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FUDAN University

Verified scientific contributions, CAS laboratory outputs, clinical trial papers, and engineering breakthroughs produced by researchers and faculty affiliated with FUDAN University.

Acta Biochimica et Biophysica Sinica•2026

PDK4-driven metabolic reprogramming enhances mesothelial cell invasion in colorectal cancer peritoneal metastasis

Authors: Lingyu Han, Qinyuan Zhang, Yuchen Wu, Wenqin Luo, Shaobo Mo, Hongsheng Fang, Qingguo Li, Renjie Wang, Guoxiang Cai, Weixing Dai

Mesothelial cells play an important role in colorectal cancer peritoneal metastasis (CRC-PM), where they support tumor growth and invasion. In this study, we investigate the molecular mechanisms by which mesothelial cells contribute to CRC metastasis. Using single-cell RNA sequencing (scRNA-seq) on tissue samples from 12 CRC patients with peritoneal metastasis, we identify PDK4 as a key gene in mesothelial cells during metastasis. The expression of PDK4 is significantly greater in mesothelial cells undergoing mesothelial-to-mesenchymal transition (MMT) compared to normal peritoneal cells, suggesting its involvement in mesothelial cell reprogramming during peritoneal metastasis. In vitro experiments show that coculturing mesothelial cells with CRC cells leads to increased PDK4 expression, which in turn enhances mesothelial cell migration and invasion. Knockdown of PDK4 reduces mesothelial cell invasion, while overexpression of PDK4 increases invasive ability, highlighting its critical role in mesothelial cell invasion. Additionally, PDK4 promotes metabolic changes, specifically increasing fatty acid oxidation (FAO), which is necessary for mesothelial cell invasion. Blocking FAO reduces the invasive ability of PDK4-overexpressing mesothelial cells, while restoring FAO in PDK4-knockdown cells rescues their invasion potential. Further analysis shows that PDK4 enhances the acetylation of β-catenin, a protein involved in cell movement, and that this modification is crucial for mesothelial cell invasion. Our results suggest that PDK4 regulates mesothelial cell invasion through β-catenin acetylation following metabolic reprogramming, offering a potential target for therapies aimed at inhibiting CRC-PM.

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Acta Biochimica et Biophysica Sinica•2026

Expression characteristics of serum exosomal microRNAs in patients with liver injury induced by anti-tuberculosis drugs

Authors: Yinpeng Jin, Xiaofang Yu, Mingquan Guo, Li Li, Shuangshuang Sun, Liling Yang, Ying Yuan, Qingchun Fu, Rongfeng Shi, Meng Jin

Drug-induced liver injury (DILI) caused by anti-tuberculosis drugs is a serious clinical problem that can lead to acute liver failure and even death. Early identification of anti-tuberculosis drug-induced liver injury (TB-DILI) is crucial to avoid severe outcomes. Current diagnosis relies on lagging indicators such as serum transaminase levels, which increase only 48–72 hours after liver injury. This study is the first to systematically analyze the microRNA (miRNA) expression profile of serum exosomes in patients with TB-DILI, aiming to discover early diagnostic markers. Serum samples were collected from 12 tuberculosis patients (5 with TB-DILI, 7 with normal liver function) and 6 normal controls. Extracellular vesicles were isolated via size exclusion chromatography and characterized by transmission electron microscopy, Western blot, and NanoFCM. Small RNA sequencing identified 701 miRNAs, with 128 differentially expressed between TB-DILI and TB groups (83 upregulated, 45 downregulated). Notably, miR-122-5p was upregulated and has been shown to increase within 24 hours of isoniazid administration, earlier than ALT elevation. Target gene prediction and pathway analysis revealed enrichment in PI3K/Akt, calcium, and Wnt signaling pathways. Six core miRNAs were selected to form a TB-DILI-specific diagnostic profile. These findings suggest that serum exosomal miRNAs, particularly miR-122-5p, hold promise as early biomarkers for TB-DILI, enabling timely intervention and improved patient outcomes.

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Acta Biochimica et Biophysica Sinica•2026

Bioinformatics classification of the MgtE Mg2+ channel and de novo protein design for the stabilization of its novel subclass

Authors: Zhixuan Zhao, Kimiho Omae, Wataru Iwasaki, Ziyi Zhang, Fazhi Pan, Eun-Jin Lee, Koichi Ito, Motoyuki Hattori

MgtE channels play crucial roles in Mg2+ homeostasis and are implicated in bacterial survival under antibiotic exposure. Previous structural and biophysical studies have focused predominantly on Thermus thermophilus MgtE, leaving the structural and mechanistic diversity of MgtE family proteins largely unexplored. In this study, via a genome mining approach, we identify diverse MgtE homologs, including a novel subclass termed the “mini-N type”, which lacks the canonical cytoplasmic N and CBS domains but possesses a unique small N-like domain. Despite extensive expression screening, mini-N-type homologs cannot be stably purified. To address this issue, we design a series of de novo proteins and determine their crystal structures. A selected de novo protein is fused to a mini-N-type MgtE, enabling successful purification and preliminary cryo-EM imaging. Our findings demonstrate that de novo-designed protein fusions serve as powerful tools for stabilizing and purifying otherwise unstable membrane proteins, opening new avenues for structural and functional studies of otherwise inaccessible membrane proteins.

Peer ReviewedView Paper→
Acta Biochimica et Biophysica Sinica•2026

Metabolic Reprogramming—The Nexus of Cellular Adaptations, Organ Crosstalk, and Therapeutic Innovations in Human Diseases

Authors: Jun Ren, Hartmut SchlĂĽter, Marcel Kwiatkowski, Ling Lin

For decades, cellular metabolism was viewed as a static network of biochemical pathways designed solely to produce ATP and fulfill basic energy needs. Classical pathophysiology frequently attributes systemic disorders, including cardiovascular disease, oncogenesis and tissue fibrosis, to structural defects, hormonal dysregulations or localized inflammation. However, advanced multi-omics frameworks have driven a paradigm shift, with metabolic reprogramming being recognized not merely as a passive consequence of disease but also as a primary driver of initiation, progression, and therapeutic resistance across human pathologies. This Special Issue, titled “Metabolic Reprogramming,” brings together 17 comprehensive studies alongside 3 New Phenomena exploring these transformations. The contributions span four interrelated thematic areas: (1) systemic cardiometabolic and gestational syndromes; (2) acute and chronic organ injury; (3) oncological metabolic dependencies; and (4) systemic organ-axis interdependencies. By integrating transcriptomics, metabolomics, single-cell deconvolution, and targeted biochemical analyses, these studies elucidate the precise molecular mechanisms governing metabolic remodeling. Key findings include the role of tissue-specific metabolic reprogramming in cardiometabolic syndrome, the impact of pregnancy-induced skeletal muscle reprogramming on gestational diabetes, the cardioprotective mechanisms of Levosimendan via Nrf2 in septic cardiomyopathy, the protective role of SBK3 in cardiac hypertrophy, the SENP1-DDX17 axis in carfilzomib cardiotoxicity, FGF13 as a therapeutic target in doxorubicin cardiotoxicity, and the beneficial effects of aminoguanidine in diabetic vasculopathy. These insights underscore the potential of targeting metabolic pathways for innovative therapeutic strategies.

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Chinese Journal of Tissue Engineering Research•2026

Biocompatibility and preclinical experiments of a Chinese-made 3D-printed minimally invasive tungsten alloy needle electrodes

Authors: Li Yujin, Ni Guansen, Mao Weiqing, Tang Jiayu, Li Xueqing

BACKGROUND: The increasing prevalence of minimally invasive surgery has placed higher demands on high-frequency electrosurgical equipment. Imported minimally invasive tungsten alloy electrodes offer high cutting precision, low tissue adhesion, and good biocompatibility, but their high cost limits their widespread application. Therefore, conducting biocompatibility and preclinical animal studies on Chinese-made 3D-printed minimally invasive tungsten alloy needle electrodes can provide a scientific basis for the research and development of Chinese-made minimally invasive electrodes. OBJECTIVE: To evaluate the biocompatibility and preclinical safety of Chinese-made 3D-printed tungsten alloy needle-shaped electrodes. METHODS: (1) Biocompatibility: L-929 cells were co-cultured with extracts from Chinese-made 3D-printed minimally invasive tungsten alloy needle electrodes at different concentrations (100%, 50%, 25%, and 12.5%), and the cytotoxicity of the materials was assessed using the MTT assay. Intradermal stimulation experiments were performed on New Zealand white rabbits to evaluate the skin irritation of the Chinese-made 3D-printed minimally invasive tungsten alloy needle electrodes. Skin sensitization was evaluated in albino guinea pigs. (2) Preclinical animal experiments: 36 SD rats were randomly divided into three groups (n=12 per group): 304 stainless steel electrode group, imported minimally invasive tungsten alloy needle electrode group, and Chinese-made 3D-printed minimally invasive tungsten alloy needle electrode group. The corresponding electrodes were used to cut subcutaneous tissue and abdominal wall muscle, and the incisions were sutured. The amount of adherent material on the electrode surface, intraoperative blood loss, and smoke formation were recorded. At 14 days postoperatively, wound healing, fat liquefaction, and histological morphology of the incision were observed. RESULTS AND CONCLUSION: (1) MTT assay showed that the cell survival rate in the extract group of Chinese-made 3D-printed minimally invasive tungsten alloy needle electrodes was higher than 80%, indicating no obvious cytotoxicity. Intradermal stimulation and sensitization tests showed no significant skin irritation or sensitization reaction. (2) Compared with the 304 stainless steel electrode group, the Chinese-made 3D-printed minimally invasive tungsten alloy needle electrode group had reduced electrode surface adhesion, increased intraoperative blood loss and smoke formation (P < 0.05). There were no significant differences between the Chinese-made and imported tungsten alloy needle electrode groups in terms of electrode surface adhesion, intraoperative blood loss, and smoke formation (P > 0.05). There were no significant differences among the three groups in wound healing, fat liquefaction, and incision adverse reactions (P > 0.05). Hematoxylin-eosin staining showed mild inflammatory cell infiltration in all three groups, consistent with normal wound repair pathology, with no abnormal immune reaction or delayed healing. (3) The results indicate that Chinese-made 3D-printed minimally invasive tungsten alloy needle electrodes have good biocompatibility and safety, with overall performance comparable to imported tungsten needle electrodes.

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Chinese Journal of Tissue Engineering Research•2026

Impact of HoloLens 2–assisted navigation for precision acetabular cup placement on the learning curve of surgeons with different levels of experience

Authors: Xia Qingquan, Wu Xuhua, Yin Yelin, Xu Qing, Meng Xiangchao, Rong Ke

BACKGROUND: There is a long surgical learning curve for safe and accurate placement of the acetabular prosthesis in hip replacement surgery. Mixed reality technology can fuse virtual image data models with real patient entities, which can help operations such as virtual surgery and intraoperative navigation, potentially improving the accuracy of acetabular prosthesis placement and shortening the learning curve for junior surgeons. OBJECTIVE: To use HoloLens 2 to develop a system that overlays the correct placement data of the acetabular prosthesis onto a 3D-printed pelvic model, and to evaluate the effect of mixed reality technology in training and guiding hip replacement surgery. METHODS: Senior orthopedic surgeons with experience in joint replacement and junior surgeons without experience in cup placement were selected. They performed simulated hip replacement surgery on 3D-printed pelvic models either freehand or with the guidance of HoloLens 2 head-mounted device. The abduction and anteversion angles of the acetabular cup were measured and recorded, and the accuracy of cup placement was compared between groups. RESULTS AND CONCLUSION: (1) Under freehand conditions, the experienced group had cup abduction angle of (41.52±3.76)° and anteversion angle of (21.35±3.63)°; the inexperienced group had abduction angle of (44.29±7.62)° and anteversion angle of (21.55±7.82)°, with significant differences between the two groups (P < 0.05). (2) With HoloLens assistance, the inexperienced group achieved abduction and anteversion angles of (41.10±1.28)° and (20.09±0.53)°, respectively, while the experienced group achieved (41.08±1.09)° and (20.28±0.65)°, with no significant difference between the two groups. (3) These findings indicate that for total hip replacement, the use of mixed reality technology significantly improves the accuracy of cup placement compared with freehand operation, and has obvious clinical auxiliary value in precise reaming and cup placement, shortening the learning curve for orthopedic surgeons.

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Acta Biochimica et Biophysica Sinica•2026

Glucose is a potential source of glutamate for glutamine-deprived pancreatic cancer cells with KRAS mutation

Authors: XIAO Zhiwen, LI Yiying, ZHANG Nuoyan, SHI Yang, SONG Yilin, LIU Yi, WANG Xinyue, NI Quanxing, LUO Guopei

Pancreatic cancer is a highly lethal malignancy with a five-year survival of only 13% overall and 8% for pancreatic adenocarcinoma. KRAS mutations, present in over 90% of cases, drive oncogenesis and metabolic reprogramming, including a glycolytic switch. Glutamine and glutamate play interconnected roles in pancreatic cancer metabolism, with glutamine fueling CA19-9 biosynthesis via the hexosamine pathway. Son et al. (2013) identified a non-canonical glutamine metabolism pathway regulated by KRAS, where glutamine-derived aspartate is processed by GOT1 in the cytoplasm, bypassing GLUD1. However, pancreatic tumors are often nutrient-deficient, and under glutamine deprivation, cells may rewire glucose metabolism to generate glutamate. This study analyzed 684 pancreatic adenocarcinoma patients from a prospective database (2021-2025) and found that only 19.6% had normal fasting glucose, with high fasting blood glucose (≥126 mg/dL) being an adverse prognostic factor (HR=1.41, 95% CI 1.07-1.86, P=0.015). Using isotope tracing with D-glucose-13C6 in KRAS-mutated pancreatic cancer cells deprived of glutamine, we observed that glucose-derived carbons were incorporated into glutamate and related metabolites, including glycosylation precursors (UDP-GalNAc), collagen/stroma components (proline, 5-oxoproline), cell division metabolites (adenosine, AMP, ADP, etc.), and ROS-related molecules (GSH, GSSG, γ-glutamylcysteine) at 24h, with additional labeling in UDP-GlcNAc, glycine, and citrate at 48h. These findings suggest that glucose can serve as a potential source of glutamate under glutamine deprivation, providing a metabolic adaptation mechanism for KRAS-mutated pancreatic cancer cells. This rewiring may contribute to tumor progression and represents a potential therapeutic target.

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Acta Biochimica et Biophysica Sinica•2026

Metabolic reprogramming—the nexus of cellular adaptations, organ crosstalk, and therapeutic innovations in human diseases

Authors: Jun Ren, Hartmut SchlĂĽter, Marcel Kwiatkowski, Ling Lin

For decades, cellular metabolism was viewed as a static network of biochemical pathways designed solely to produce ATP and fulfill basic energy needs. Classical pathophysiology frequently attributes systemic disorders, including cardiovascular disease, oncogenesis and tissue fibrosis, to structural defects, hormonal dysregulations or localized inflammation. However, advanced multi-omics frameworks have driven a paradigm shift, with metabolic reprogramming being recognized not merely as a passive consequence of disease but also as a primary driver of initiation, progression, and therapeutic resistance across human pathologies. This Special Issue, titled “Metabolic Reprogramming”, brings together 17 comprehensive studies alongside 3 New Phenomena exploring these transformations. The contributions span four interrelated thematic areas: (1) systemic cardiometabolic and gestational syndromes; (2) acute and chronic organ injury; (3) oncological metabolic dependencies; and (4) systemic organ-axis interdependencies. By integrating transcriptomics, metabolomics, single-cell deconvolution, and targeted biochemical analyses, these studies elucidate the precise molecular mechanisms governing metabolic remodeling.

Peer ReviewedView Paper→
Acta Biochimica et Biophysica Sinica•2026

Bioinformatics classification of the MgtE Mg2+ channel and de novo protein design for the stabilization of its novel subclass

Authors: Zhixuan Zhao, Kimiho Omae, Wataru Iwasaki, Ziyi Zhang, Fazhi Pan, Eun-Jin Lee, Koichi Ito, Motoyuki Hattori

MgtE channels play crucial roles in Mg2+ homeostasis and are implicated in bacterial survival under antibiotic exposure. Previous structural and biophysical studies have focused predominantly on Thermus thermophilus MgtE, leaving the structural and mechanistic diversity of MgtE family proteins largely unexplored. In this study, via a genome mining approach, we identify diverse MgtE homologs, including a novel subclass termed the “mini-N type”, which lacks the canonical cytoplasmic N and CBS domains but possesses a unique small N-like domain. Despite extensive expression screening, mini-N-type homologs cannot be stably purified. To address this issue, we design a series of de novo proteins and determine their crystal structures. A selected de novo protein is fused to a mini-N-type MgtE, enabling successful purification and preliminary cryo-EM imaging. Our findings demonstrate that de novo-designed protein fusions serve as powerful tools for stabilizing and purifying otherwise unstable membrane proteins, opening new avenues for structural and functional studies of otherwise inaccessible membrane proteins.

Peer ReviewedView Paper→
Acta Biochimica et Biophysica Sinica•2026

PDK4-driven metabolic reprogramming enhances mesothelial cell invasion in colorectal cancer peritoneal metastasis

Authors: Lingyu Han, Qinyuan Zhang, Yuchen Wu, Wenqin Luo, Shaobo Mo, Hongsheng Fang, Qingguo Li, Renjie Wang, Guoxiang Cai, Weixing Dai

Mesothelial cells play an important role in colorectal cancer peritoneal metastasis (CRC-PM), where they support tumor growth and invasion. In this study, we investigate the molecular mechanisms by which mesothelial cells contribute to CRC metastasis. Using single-cell RNA sequencing (scRNA-seq) on tissue samples from 12 CRC patients with peritoneal metastasis, we identify PDK4 as a key gene in mesothelial cells during metastasis. The expression of PDK4 is significantly greater in mesothelial cells undergoing mesothelial-to-mesenchymal transition (MMT) compared to normal peritoneal cells, suggesting its involvement in mesothelial cell reprogramming during peritoneal metastasis. In vitro experiments show that coculturing mesothelial cells with CRC cells leads to increased PDK4 expression, which in turn enhances mesothelial cell migration and invasion. Knockdown of PDK4 reduces mesothelial cell invasion, while overexpression of PDK4 increases invasive ability, highlighting its critical role in mesothelial cell invasion. Additionally, PDK4 promotes metabolic changes, specifically increasing fatty acid oxidation (FAO), which is necessary for mesothelial cell invasion. Blocking FAO reduces the invasive ability of PDK4-overexpressing mesothelial cells, while restoring FAO in PDK4-knockdown cells rescues their invasion potential. Further analysis shows that PDK4 enhances the acetylation of β-catenin, a protein involved in cell movement, and that this modification is crucial for mesothelial cell invasion. Our results suggest that PDK4 regulates mesothelial cell invasion through β-catenin acetylation following metabolic reprogramming, offering a potential target for therapies aimed at inhibiting CRC-PM.

Peer ReviewedView Paper→
Acta Biochimica et Biophysica Sinica•2026

Expression characteristics of serum exosomal microRNAs in patients with liver injury induced by anti-tuberculosis drugs

Authors: Yinpeng Jin, Xiaofang Yu, Mingquan Guo, Li Li, Shuangshuang Sun, Liling Yang, Ying Yuan, Qingchun Fu, Rongfeng Shi, Meng Jin

Drug-induced liver injury (DILI) caused by anti-tuberculosis drugs is a serious clinical problem that can lead to acute liver failure and even death. Current diagnosis relies on lagged indicators such as serum transaminase levels, which rise only 48–72 hours after liver injury. This study is the first to systematically analyze the microRNA expression profile of serum exosomes in patients with anti-tuberculosis drug-induced liver injury (TB-DILI) to discover early diagnostic markers. A total of 12 tuberculosis patients and 6 normal controls were included. Serum exosomes were isolated and characterized, and small RNA sequencing identified 701 miRNAs, with 128 differentially expressed between TB-DILI and TB groups. Notably, miR-122-5p was upregulated and has shown early warning value. Target gene prediction and enrichment analysis revealed involvement in GTPase activity regulation, cell migration, and BMP signaling. These findings suggest that exosomal miRNAs, particularly miR-122-5p, may serve as early diagnostic biomarkers for TB-DILI.

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Acta Biochimica et Biophysica Sinica•2026

MAN1A1 promotes colorectal cancer liver metastasis by maintaining TGFBR2 protein stability

Authors: Yingxi Hu, Yinwen Xu, Kai Chen, Shihua Guan, Huiling Zhou, Tao Li, Rongrui Liang, Min Tao, Yiyi Yu, Xinxin Ge, Yuanyuan Ruan

Emerging biochemical and genetic evidence has firmly established aberrant protein glycosylation as a critical regulator of oncogenic transformation, with glycocalyx remodeling profoundly influencing tumor microenvironment dynamics and metastatic progression. Despite the well-documented association between metastatic dissemination and poor clinical outcomes in patients with colorectal cancer, the underlying molecular mechanisms remain incompletely characterized. Through integrative analysis of single-cell RNA sequencing data from a public database, we identify the Golgi-resident α-1,2-mannosidase MAN1A1 as a consistently upregulated enzyme in malignant epithelial cells derived from colorectal cancer liver metastases. Clinically, elevated MAN1A1 expression is correlated with reduced overall survival, suggesting that MAN1A1 is both a prognostic biomarker and therapeutic target for colorectal cancer liver metastases. Genetic manipulation of MAN1A1 in colorectal cancer cells demonstrates that although the proliferation capacity of colorectal cancer cells remains unchanged, MAN1A1 overexpression significantly enhances migratory and invasive capacities in transwell assays, suggesting its specific involvement in metastatic progression. Mechanistic investigations reveal that MAN1A1 exerts its pro-metastatic effects by significantly prolonging the TGFBR2 protein half-life. Together, our work identifies MAN1A1 as both a prognostic biomarker and a promising therapeutic target, highlighting the critical role of glycan remodeling in the metastatic progression of colorectal cancer.

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Acta Biochimica et Biophysica Sinica•2026

Autophagy-dependent sensitization effects of PARP inhibitors on recurrent nasopharyngeal carcinoma treated with carbon ion and photon irradiation

Authors: Ziyu Le, Haojiong Zhang, Li Chen, Wanzun Lin, Qingting Huang, Shikai Geng, Wei Hu, Huaiyuan Chen, Fangzhu Wan, Xingyu Liu, Jiyi Hu, Fengtao Su, Jiade J. Lu, Lin Kong

Tumor radioresistance and severe toxicity make reirradiation for recurrent nasopharyngeal carcinoma (NPC) a significant clinical challenge. This study aims to investigate the ability of the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib to sensitize recurrent NPC cells irradiated with photon or carbon ion (C-ion), and to explore the underlying mechanism of the synergistic promotion of cell death by olaparib and ionizing radiation. The results show that olaparib has significant X-ray and C-ion radiosensitization effects on recurrent NPC cells and the associated HK-RR photon-resistant model. Radiation, particularly C-ion exposure, induces a homologous recombination (HR)-deficient gene signature in HR-proficient NPC cells, potentially increasing their sensitivity to PARP inhibition. C-ion and X-ray irradiation induces similar modes of cell death, and multiple cell death pathways [including apoptosis, necrosis, ferroptosis, senescence, and autophagic cell death (ACD)] contribute to the cytotoxic effects of radiation combined with olaparib, with ACD being the dominant pathway. Both the pharmacological and genetic inhibition of autophagy significantly attenuate the radiosensitization effect of olaparib. In conclusion, olaparib effectively sensitizes recurrent NPC cells to both X-ray irradiation and C-ion irradiation, with autophagy playing a central role in mediating this effect.

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Acta Biochimica et Biophysica Sinica•2026

The lncRNA DANCR promotes breast cancer brain metastasis by acting as a ceRNA for miR-758-3p to regulate PTGS2 expression

Authors: Sen Li, Yuechao Yang, Zhisu Wang, Liangdong Li, Yang Gao, Yiqun Cao

Brain metastases in breast cancer patients are correlated with markedly lower survival rates than extracranial metastases, highlighting the critical necessity for identifying novel therapeutic targets. The functional involvement of differentiation antagonizing nonprotein coding RNA (DANCR) in the pathogenesis of breast cancer brain metastases (BCBMs) has yet to be fully elucidated. Bioinformatics analyses identify DANCR as a potential specific prognostic biomarker of BCBM. CCK-8, transwell, and wound healing assays are performed to examine the effects of DANCR on the proliferation, migration, and invasion of tumors, along with in vivo assays. Mechanistic insights are obtained through quantitative real-time polymerase chain reaction (qRT-PCR), western blot analysis, and dual-luciferase reporter assays. DANCR is markedly upregulated in BCBM and specifically correlates with the prognostic risk of BCBM. DANCR overexpression significantly enhances breast cancer cell proliferation, migration, and invasion. According to low-throughput screening, only the expression of prostaglandin-endoperoxide synthase 2 (PTGS2) consistently varies in parallel with that of DANCR, and PTGS2 silencing reverses DANCR-induced protumor effects in vitro. Additionally, in brain metastatic lesions, PTGS2 expression is also elevated in patients with increased DANCR expression. Mechanistically, DANCR and PTGS2 possess a conserved miR-758-3p response element. DANCR directly binds to and sequesters miR-758-3p, thereby alleviating the suppressive effects of miR-758-3p on both DANCR and PTGS2. When the miR-758-3p binding site on DANCR is mutated, this interaction is completely abolished. DANCR drives BCBM by functioning as a miR-758-3p sponge to upregulate PTGS2. Targeting the DANCR/miR-758-3p/PTGS2 axis represents a promising therapeutic approach.

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Chinese Journal of New Drugs•2025

Electronic Prescription System: A Comprehensive Review and Implementation Framework

Authors: Zhang Wei, Li Na, Wang Fang, Chen Yu

Electronic prescription systems (EPS) have emerged as a transformative technology in healthcare, aiming to enhance medication safety, streamline workflows, and reduce errors. This comprehensive review synthesizes current literature on EPS, focusing on implementation challenges, usability, and impact on clinical outcomes. We conducted a systematic search of databases including PubMed, Scopus, and Web of Science, identifying 45 relevant studies. Key findings indicate that EPS significantly reduces prescription errors, improves adherence to formularies, and facilitates better communication among healthcare providers. However, barriers such as high implementation costs, interoperability issues, and resistance from practitioners remain. We propose a framework for successful EPS adoption, emphasizing stakeholder engagement, training, and phased implementation. Our review underscores the need for standardized evaluation metrics and further research on long-term outcomes. This paper provides valuable insights for policymakers, healthcare administrators, and clinicians considering EPS integration.

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Chinese Journal of New Drugs•2025

Pharmaceutical Care in China: A Systematic Review of Current Status and Future Directions

Authors: Y. Zhang, L. Wang, H. Li, J. Chen

Pharmaceutical care has evolved globally as a patient-centered practice, yet its implementation in China faces unique challenges. This systematic review synthesizes evidence from 2010 to 2024 to evaluate the current status, barriers, and outcomes of pharmaceutical care in Chinese healthcare settings. A comprehensive search of PubMed, CNKI, and Wanfang databases identified 1,245 articles, of which 38 met inclusion criteria. Findings reveal that pharmaceutical care in China is predominantly hospital-based, focusing on medication reconciliation, therapeutic drug monitoring, and patient education. However, significant barriers include workforce shortages, lack of standardized protocols, and limited integration with primary care. Despite these challenges, studies demonstrate improved medication adherence, reduced adverse drug events, and enhanced patient satisfaction. The review proposes a framework for advancing pharmaceutical care through policy reforms, interprofessional collaboration, and digital health technologies. Future directions emphasize community-based services and personalized medicine to align with global standards.

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Chinese Journal of New Drugs•2025

Preparation and Evaluation of Drug-Loaded Solid Lipid Nanoparticles for Enhanced Oral Bioavailability

Authors: Y. Zhang, L. Wang, H. Li, X. Chen

The present study focuses on the preparation and evaluation of solid lipid nanoparticles (SLNs) loaded with a poorly water-soluble drug to enhance its oral bioavailability. SLNs were formulated using a high-pressure homogenization technique, and the formulation was optimized based on particle size, polydispersity index, zeta potential, and entrapment efficiency. The optimized SLNs exhibited a mean particle size of approximately 150 nm with a narrow size distribution and high drug loading. In vitro release studies demonstrated a sustained release profile over 24 hours. Pharmacokinetic studies in rats revealed a significant increase in the oral bioavailability of the drug from SLNs compared to the free drug suspension. The results suggest that SLNs are a promising carrier for enhancing the oral delivery of poorly water-soluble drugs.

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Stem Cell Research & Therapy•2025

BACH1 recruits STAT3 to enhance leukemia inhibitory factor receptor activity and augments the self-renewal capacity of mouse embryonic stem cells

Authors: Jinghua Ma, Siyu Ma, Cong Niu, Siqing Wang, Xiangxiang Wei, Dan Meng, Xiuling Zhi, Jieyu Guo

Background Genomic studies have linked single nucleotide variants in the enhancer region of the leukemia inhibitory factor receptor (Lifr) gene to chromatin accessibility and the regulation of self-renewal in mouse embryonic stem cells (mESCs). However, the underlying mechanisms remain unclear. This study investigates the role of the transcription factor BTB and CNC homology 1 (BACH1) in regulating the Lifr enhancer and its impact on mESC pluripotency. Methods We performed RNA-sequencing (RNA-seq) to assess the impact of Bach1 knockout on gene expression in mESCs. Additionally, chromatin immunoprecipitation (ChIP), co-immunoprecipitation (co-IP), and luciferase reporter gene analysis were employed to investigate the mechanism by which BACH1 regulates Lifr expression. Results Genomic analyses identified BACH1 binding at the Lifr enhancer proximal to rs50454566 in mESCs. Integrated single-cell RNA sequencing (scRNA-seq) data revealed co-upregulation of Bach1 and Lifr in inner cell mass (ICM) cells. RNA-seq analyses demonstrated that Bach1 depletion attenuated Lifr expression and impeded LIFR-signal transducer and activator of transcription 3 (STAT3) signaling. Mechanistically, BACH1 recruited STAT3 to the Lifr enhancer, driving Lifr transcription and facilitating the LIFR-STAT3 signaling pathway, thereby enhancing mESC self-renewal. Conclusion Our findings demonstrate that BACH1 enhances Lifr enhancer activity by recruiting STAT3 and activates the LIFR-STAT3 signaling pathway by promoting the LIFR expression, thereby maintaining mESC self-renewal.

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Acta Biochimica et Biophysica Sinica•2025

Ageing-associated gut dysbiosis deteriorates mouse cognition

Authors: Huihui Ju, Yile Zhou, Wanting Wei, Yan Hu, Hongwei Fang, Zhouyi Chen, Xia Sun, Yi Shi, Hao Fang

Ageing is an independent factor for cognitive dysfunction. Ageing-associated alterations in the gut microbiota also affect cognition. The present study is designed to investigate changes in the gut microbiota and their participation in ageing-associated cognitive impairment. Both 10-week-old and 18-month-old mice are used. Mouse cognition is examined by novel object recognition and T-maze tests. Mouse feces are collected for sequencing and transplantation. Protein expression in the mouse intestine and hippocampus is studied using immunohistochemistry and immunofluorescence staining. Senescent neurons are induced by hydrogen peroxide in vitro. The cell lysates are used for western blot analysis and adenosine triphosphate (ATP) measurement. Our results show that 18-month-old mice exhibit cognitive dysfunction compared with young mice. In aged mice, transplanting the microbiota of young mice increases the protein presence of synaptophysin in the hippocampus and partially restores cognition. The protein expressions of mucin-2 and E-cadherin in the intestine are reduced in aged mice but are increased by transplantation. Gut microbiota analyses reveal that the reduced abundance of the microbe Bacilli-Lactobacillales-Lactobacillaceae-Lactobacillus in aged mice is restored by transplantation. Fecal microbiota transplantation in young mice increases the serum level of acetic acid in aged mice. Hydrogen peroxide stimulation induces senescence and reduces the protein expression levels of synaptophysin and acetyl-coenzyme A synthetase member 2 (ACSS2) in primary neurons. Incubation with acetic acid upregulates the protein expressions of ACSS2 and synaptophysin and further increases ATP production in senescent neurons. In summary, gut microbiota transplantation increases the abundance of Lactobacillales, elevates serum acetic acid level, and improves cognitive function in aged mice. Gut microbiota transplantation has therapeutic importance for ageing-associated cognitive decline.

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Acta Biochimica et Biophysica Sinica•2025

Macrophage NLRP3-dependent IL-1β production contributes to aortic fibrosis in heart failure with preserved ejection fraction

Authors: Sheng Chen, Zhiqiang Lu

Fibrosis is the main pathological feature of aortic stiffness, which is a common extracardiac comorbidity of heart failure with preserved ejection fraction (HFpEF) and a contributor to left ventricular (LV) diastolic dysfunction. Systemic low-grade inflammation plays a crucial role in the pathogenesis of HFpEF and the development of vascular fibrosis. In this study, we investigate the inflammatory mechanism of aortic fibrosis in HFpEF using a novel mouse model. LV diastolic dysfunction with preserved ejection fraction and aortic fibrosis induced by a high-fat diet (HFD) combined with subcutaneous aldosterone infusion are utilized. The constructed model exhibits augmented macrophage recruitment and NLR family pyrin domain containing 3 (NLRP3)-dependent interleukin (IL)-1β production in fibrotic aortas. In addition, a bone marrow transplant is employed to induce macrophage-specific NLRP3 deficiency in the HFpEF mouse model. These mice show almost completely suppressed cleaved-caspase-1 and mature IL-1β protein expression in the aortas, indicating that macrophage NLRP3 inflammasome activation enhances the IL-1β overproduction in fibrotic aortas. Furthermore, we show that macrophage NLRP3 inflammasome inhibition improves aortic fibrosis and LV diastolic dysfunction. In conclusion, this study demonstrates the pivotal effect of macrophage NLRP3-dependent IL-1β production on aortic fibrosis and cardiac function in HFpEF, suggesting a potential target for HFpEF therapy.

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Acta Biochimica et Biophysica Sinica•2025

Antitumor potential of polyamines in cancer

Authors: He Liu, Yi Liu, Xinyue Wang, Zhiwen Xiao, Quanxing Ni, Xianjun Yu, Guopei Luo

The dysregulation of polyamines in tumors has made polyamine metabolism an appealing target for cancer therapy. Gene mutations drive the reprogramming of polyamine metabolism in tumors, presenting promising opportunities for clinical treatment. The proposed strategies involve inhibiting polyamine biosynthesis while also targeting the polyamine transport system as antitumor approaches. A growing number of drugs aimed at polyamine biosynthesis and transport systems are undergoing clinical trials. Polyamine metabolism plays a role in regulating cancer signaling pathways, suggesting potential combination therapies for cancer treatment. Furthermore, supplemental polyamine substances have demonstrated antitumor activity, indicating that combining polyamines with downstream targets or immunotherapy could offer significant clinical benefits. These discoveries open new avenues for leveraging polyamine metabolism in anticancer therapy.

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Acta Biochimica et Biophysica Sinica•2025

Immune signatures of megakaryocytes in persistent inflammation-immunosuppression and catabolism syndrome

Authors: Xingfeng Sun, Ke Nan, Ziwen Zhong, Zhiqiang Liu, Changhong Miao

Persistent inflammation-immunosuppression and catabolism syndrome (PICS) is a severe condition that may follow sepsis and is characterized by ongoing inflammation and immune suppression, diminishing quality of life and potentially causing death. The role of megakaryocytes (MKs) in PICS, despite their association with thrombopoiesis, is not well understood. In this study, we use single-cell RNA sequencing to profile MKs in peripheral blood mononuclear cell samples obtained from 11 patients, including six with PICS, five with sepsis, and five healthy controls, to determine the diversity and molecular signatures of the MKs. Five subgroups of MKs are identified (MK1–MK5), and their proportions vary across the groups. MK1 and MK2 are predominant in PICS. Gene Ontology analysis shows that genes related to antigen processing and presentation and IL-17 signaling are enriched in MK1, whereas genes associated with platelet degranulation and neutrophil activation are enriched in MK2. Moreover, the expression level of CCL5 is markedly increased in MKs. Ligand-receptor analysis reveals dynamic interactions among MKs and T cells, B cells, natural killer cells, monocytes, and macrophages, suggesting a broad role of MKs in immune homeostasis. In PICS model mice, MKs regulate systemic inflammation by reducing the levels of the proinflammatory cytokines TNF-α and IL-17A and promoting lung tissue repair. Our findings establish MKs as essential components of the immune system in PICS and provide new insights into their potential as therapeutic targets for post-sepsis immune dysfunction.

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Acta Biochimica et Biophysica Sinica•2025

miR-32-5p suppresses the progression of hepatocellular carcinoma by regulating the GSK3β/NF-κB signaling

Authors: Guangzhi Wang, Qianqian Yang, Yaqi Han, Yunlong Zhang, Wei Pan, Zhongliang Ma, Hui Tian, Xudong Qu

Hepatocellular carcinoma (HCC) is a highly fatal form of malignancy that seriously threatens patient survival. The global 5-year survival rate for HCC patients ranges from 15% to 19%, and nearly 80% of patients are diagnosed at an advanced stage. Therefore, exploring the mechanism of HCC development and identifying biomarkers and therapeutic targets for HCC are vital. MicroRNAs (miRNAs), a class of noncoding single-stranded RNAs, are 20–24 nucleotides (nt) long. They play pivotal roles in modulating the progression of diverse diseases. The specific role of miR-32-5p in the development of HCC remains unclear. In this study, qRT-PCR is utilized to precisely determine the downregulated expression levels of miR-32-5p in HCC. Subsequently, functional analysis reveals the suppressive role of miR-32-5p in modulating the proliferative and migratory capabilities of HCC cells. Glycogen synthase kinase 3β (GSK3β) has emerged as a potential target of miR-32-5p, which is confirmed through a dual-luciferase reporter assay. Notably, the expression of GSK3β in HCC tissue specimens is negatively correlated with the abundance of miR-32-5p, and patients with high GSK3β expression have shorter survival time. Furthermore, the targeted downregulation of GSK3β remarkably impedes the proliferation and migration of tumor cells. This study suggests that miR-32-5p inhibits the proliferation and migration of HCC through regulating the GSK3β/NF-κB signaling pathway. Therefore, this study reveals that miR-32-5p exerts its suppressive effect on HCC progression, suggesting that it is a promising target for both diagnostic and targeted therapeutic interventions against HCC.

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Acta Biochimica et Biophysica Sinica•2025

The combination of fatigue with the serum GCSF improves the performance of serological screening for frailty

Authors: Jiaming Yu, Jie Chen, Xueying Ji, Yixuan Qiu, Yan Zhang, Jiaofeng Wang, Xiangqi Li, Chaobao Zhang, Zhijun Bao

Frailty is a common geriatric disease characterized by accelerated aging and the loss of biological reserves across multiple organs. Approximately 10% of people aged 65 years and older and 25%–50% of people older than 85 years are in a frail state. The increasing institutionalization, hospitalization, and mortality caused by frailty incur massive medical costs and impose a heavy health service burden. For elderly individuals with chronic and/or infectious diseases, such as COVID-19, concomitant frailty can lead to extremely high mortality rates. Moreover, except exercise and nutritional intervention, no effective medicine for treating frailty is available. However, frailty can be prevented, and prefrailty can be reversed. Therefore, effectively screening frailty in elderly individuals is a public health priority. Two main methods for assessing frailty exist: the Fried phenotype and the Rockwood frailty index. The Fried phenotype uses five items, namely, fatigue, weakness, slowness, low physical activity, and weight loss, whereas the Rockwood frailty index is based on the accumulation of age-related deficits. However, these two diagnostic tools are subjective, challenging to use and time-consuming, and are therefore unsuitable for simple, rapid, and extensive screening of frailty in clinical practice. Here, we propose a new strategy to address the above issue. We first harnessed common professional databases to perform inflammatory niche analysis for plasma proteomics from normal aging and frailty patients. We subsequently performed frailty screening and blood sample collection. A total of 852 elderly people were included in the study from January 2018 to August 2018. The assessments included demographic information collection, frailty evaluation, and physical and body composition tests. Blood samples for the determination of inflammatory cytokines were taken from 67 participants. We utilized ELISA to detect the expressions of inflammatory cytokines and chemokines. All blood samples were collected and centrifuged at 4°C and 2000 g for 20 min. The serum was aliquoted and stored properly for ELISA. Inflammatory cytokines in human sera were quantified using corresponding human ELISA kits according to the manufacturer’s protocols. The following markers were measured: IL1A, IL2, IL6, IL8, IL10, IL17, TNFα, IFNγ, GCSF, MCP2, CXCL1, CX3CL1, MMP7, and SOD1. All the statistical analyses were performed with Prism v.6.0. P < 0.05 was considered statistically significant. The receiver operating characteristic (ROC) curve was used to evaluate the performance of all the screening tools. Our inflammatory niche analysis revealed intriguing results when five datasets containing a large number of proteins related to normal aging and inflammation were utilized. The Venn diagrams in Figure 1 show 77 human senescence-associated secretory phenotype genes. Among these genes, 26 are positively correlated with normal aging, whereas 8 are negatively correlated with normal aging. However, neither are positively correlated with frailty, and only two genes are negatively correlated with frailty. Therefore, frailty is obviously distinct from normal aging. Given that most of these differential proteins are inflammatory factors, frailty and normal aging may involve different inflammatory niches. These results suggest that inflammatory factors may be candidates for frailty screening. Our ELISA detection of 15 frailty-related inflammatory factors in the serum of frailty patients screened from 852 volunteers also provided valuable results. The prevalence of frailty was 7.16% (61/852), and that of prefrailty was 41.90% (357/852). The volunteers were 65.22% female and 34.78% male, with a mean age of 70.18 ± 0.73 years. As shown in Table 1, the frail and prefrail groups were significantly older than the robust group (P < 0.001). We observed statistically significant differences in RASM, gait speed, CCI, SARC-F, ADL and MNA scores (P < 0.05), whereas no significant differences were detected with respect to sex, WHR, grip strength or drug count among the three groups. A total of 67 serum samples (nonfrail, n = 20; prefrail, n = 28; and frail, n = 19) were subjected to inflammatory factor screening. No significant difference in the expression of most inflammatory factors was detected.

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Acta Biochimica et Biophysica Sinica•2025

The host gene CSTF2 regulates HBV replication via HBV PRE-induced nuclear export

Authors: Jinyu Wang, Jing Li, Wentao Xie, Zhongliang Shen, Jingwen Wu, Richeng Mao, Mengji Lu, Jiming Zhang

The persistent global burden of hepatitis B virus (HBV) infection has prompted ongoing investigations into host determinants of viral control. In this study, we investigate the regulatory influence of the host gene cleavage stimulation factor subunit 2 (CSTF2) on HBV replication dynamics. We demonstrate differential CSTF2 expression across the spectrum of HBV infection phases, with upregulated expression noted during the immune-reactive and inactive carrier states compared with the immune-tolerant phase. Notably, dose-responsive attenuation of HBV DNA, as well as surface and core protein levels, is observed subsequent to CSTF2 overexpression, whereas HBV RNA levels remain unaffected. Upon HBV transfection, a notable alteration in CSTF2 subcellular localization is discerned, suggesting active relocalization to the cytoplasm, potentially mediated through interaction with the HBV posttranscriptional regulatory element (PRE). This interaction appears to impede the nuclear export of HBV RNA. Additionally, distinct antiviral efficacies are attributed to the functional domains of the CSTF2 protein, indicating a multifaceted host defense mechanism. These insights increase the understanding of host-virus interplay and identify CSTF2 as a candidate for antiviral therapeutic strategies.

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Acta Biochimica et Biophysica Sinica•2025

Structures and mechanisms of the RNA m6A writer

Authors: Ting Deng, Jinbiao Ma

N6-methyladenosine (m6A) is the most prevalent epigenetic modification found in eukaryotic mRNAs and plays a crucial role in regulating gene expression by influencing numerous aspects of mRNA metabolism. The m6A writer for mRNAs and long non-coding RNAs consists of the catalytic subunit m6A-METTL complex (MTC) (including METTL3/METTL14) and the regulatory subunit m6A-METTL-associated complex (MACOM) (including HAKAI, WTAP, VIRMA, ZC3H13, and RBM15/15B). In this review, we focus on recent advances in our understanding of the structural and functional properties of m6A writers and the possible mechanism by which they recognize RNA substrates and perform selective m6A modifications.

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Acta Biochimica et Biophysica Sinica•2025

ZIPK collaborates with STAT5A in p53-mediated ROS accumulation in hyperglycemia-induced vascular injury

Authors: Qichao Wu, Tingting Xie, Chang Fu, Chenyu Sun, Yan Ma, Zhengzhe Huang, Jiao Yang, Xiaoxiao Li, Wenqian Li, Changhong Miao

In this study we investigate the role of Zipper-interacting protein kinase (ZIPK) in high glucose-induced vascular injury, focusing on its interaction with STAT5A and its effects on p53 and inducible nitric oxide synthase (NOS2) expression. Human umbilical vein endothelial cells (HUVECs) are cultured under normal (5 mM) and high (25 mM) glucose conditions. Protein and gene expression levels are assessed by western blot analysis and qPCR respectively, while ROS levels are measured via flow cytometry. ZIPK expression is manipulated using overexpression plasmids, siRNAs, and shRNAs. The effects of the ZIPK inhibitor TC-DAPK6 are evaluated in a diabetic rat model. Our results show that high glucose significantly upregulates ZIPK, STAT5A, p53, and NOS2 expressions in HUVECs, thus increasing oxidative stress. Silencing of STAT5A reduces p53 and NOS2 expressions and reactive oxygen species (ROS) accumulation. ZIPK is essential for high glucose-induced p53 expression and ROS accumulation, while silencing of ZIPK reverses these effects. Overexpression of ZIPK combined with STAT5A silencing attenuates glucose-induced alterations in p53 and NOS2 expression, thereby preventing cell damage. Coimmunoprecipitation reveals a direct interaction between ZIPK and STAT5A in the nucleus under high-glucose condition. In diabetic rats, TC-DAPK6 treatment significantly decreases ZIPK, p53, and NOS2 expressions. Our findings suggest that ZIPK plays a critical role in high glucose-induced vascular injury via STAT5A-mediated pathways, proposing that ZIPK is a potential therapeutic target for diabetic vascular complications.

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Acta Biochimica et Biophysica Sinica•2025

Early RSV infection aggravates asthma-related Th2 responses by increasing the number of CD4+ TRM cells through upregulation of PLZF

Authors: Meng Zhang, Jiafeng Sha, Na Li, Jingjing Feng, Tianyun Shi, Yunxia Yu, Xiaoting Ren, Zhoufang Mei, Zhijun Jie

Respiratory syncytial virus (RSV) infection is correlated with the chronic pathogenesis and exacerbation of asthma. However, the mechanism remains unclear. In this study, acute and memory (Mem) asthma models with early RSV infection are established to explore the persistence of the effects of RSV infection on asthma. Intravascular injection of an anti-CD45 antibody is performed to define CD4+ TRM cells accurately. RSV infection has a sustained impact on asthma exacerbation for at least six weeks, with high Th2 cytokine secretion in lung tissue instead of IgE response-related B cells. CD45–CD4+ TRM cells are positively correlated with RSV-related asthma exacerbation and severe airway inflammation. Mechanistically, overexpression of the transcription factor PLZF in vitro increases the number of CD4+ TRM cells, and conditional knockout of Zbtb16 (encoding PLZF) can decrease the number of CD4+ TRM cells to aggravate allergic inflammation and reduce Th2 responses. This study provides evidence for potential combined strategies that might benefit asthma patients.

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Acta Biochimica et Biophysica Sinica•2025

HADHA promotes esophageal cancer progression by activating mTOR signaling and the SP1/MDM2 axis

Authors: Xusheng Ding, Longlong Shao, Jie Wang, Yongwei Jin, Haiqing Chen, Bin Li

Esophageal cancer (EC) is one of the most recalcitrant cancers, with a 5-year survival rate of < 30%. The hydroxyacyl-CoA dehydrogenase alpha subunit (HADHA) plays an essential role in long-chain fatty acid metabolism, and dysregulation of HADHA has been demonstrated to be involved in a series of metabolic diseases and cancers. However, its role in cancers remains controversial. HADHA has seldom been investigated in EC, and little is known about how HADHA regulates the malignant progression of EC. In this study, we find that HADHA is significantly upregulated in EC tissues and is correlated with poor survival. HADHA knockdown markedly inhibits EC cell proliferation both in vitro and in vivo. The loss of HADHA also induces EC cell apoptosis, causes cell cycle arrest and inhibits cell migration. Additionally, RNA profiling reveals that mTOR signaling is significantly suppressed after HADHA knockdown. Mechanistically, HADHA interacts with SP1 and induces MDM2 expression. In conclusion, both mTOR signaling and the SP1-MDM2 axis participate in the HADHA-induced malignant behavior of EC cells.

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Genomics, Proteomics & Bioinformatics•2024

Correction to: dbDEMC 3.0: Functional Exploration of Differentially Expressed miRNAs in Cancers of Human and Model Organisms

Authors: Feng Xu, Yifan Wang, Yunchao Ling, Chenfen Zhou, Haizhou Wang, Andrew E. Teschendorff, Yi Zhao, Haitao Zhao, Yungang He, Guoqing Zhang, Zhen Yang

This is a correction to: Feng Xu, Yifan Wang, Yunchao Ling, Chenfen Zhou, Haizhou Wang, Andrew E. Teschendorff, Yi Zhao, Haitao Zhao, Yungang He, Guoqing Zhang, Zhen Yang, dbDEMC 3.0: Functional Exploration of Differentially Expressed miRNAs in Cancers of Human and Model Organisms, Genomics, Proteomics & Bioinformatics, Volume 20, Issue 3, June 2022, Pages 446–454, https://doi.org/10.1016/j.gpb.2022.04.006. The published version of this manuscript contained errors in the author affiliation listings. The corrected affiliations are as follows: Feng Xu1,#, Yifan Wang2,#, Yunchao Ling2, Chenfen Zhou2, Haizhou Wang1, Andrew E. Teschendorff3, Yi Zhao4, Haitao Zhao5, Yungang He6,*, Guoqing Zhang2,*, Zhen Yang1,* 1 Center for Medical Research and Innovation of Pudong Hospital, Fudan University Pudong Medical Center, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China 2 Bio-Med Big Data Center, CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China 3 CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China 4 Institute of Computing Technology, Chinese Academy of Sciences, Beijing 100190, China 5 Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China 6 Shanghai Fifth People’s Hospital, and Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology), Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China These details have been corrected only in this correction notice to preserve the published version of record.

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Acta Biochimica et Biophysica Sinica•2024

Glycosylation in aging and neurodegenerative diseases

Authors: Weilong Zhang, Tian Chen, Huijuan Zhao, Shifang Ren

Aging, a complex biological process, involves the progressive decline of physiological functions across various systems, leading to increased susceptibility to neurodegenerative diseases. In society, demographic aging imposes significant economic and social burdens due to these conditions. This review specifically examines the association of protein glycosylation with aging and neurodegenerative diseases. Glycosylation, a critical post-translational modification, influences numerous aspects of protein function that are pivotal in aging and the pathophysiology of diseases such as Alzheimer’s disease, Parkinson’s disease, and other neurodegenerative conditions. We highlight the alterations in glycosylation patterns observed during aging, their implications in the onset and progression of neurodegenerative diseases, and the potential of glycosylation profiles as biomarkers for early detection, prognosis, and monitoring of these age-associated conditions, and delve into the mechanisms of glycosylation. Furthermore, this review explores their role in regulating protein function and mediating critical biological interactions in these diseases. By examining the changes in glycosylation profiles associated with each part, this review underscores the potential of glycosylation research as a tool to enhance our understanding of aging and its related diseases.

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Acta Biochimica et Biophysica Sinica•2024

Glyco-signatures in patients with advanced lung cancer during anti-PD-1/PD-L1 immunotherapy

Authors: Xinyi Cao, Zhihuang Hu, Xiangying Sheng, Zhenyu Sun, Lijun Yang, Hong Shu, Xiaojing Liu, Guoquan Yan, Lei Zhang, Chao Liu, Ying Zhang, Huijie Wang, Haojie Lu

Immune checkpoint inhibitors (ICIs) targeting programmed cell death 1/programmed cell death ligand-1 (PD-1/PD-L1) have significantly prolonged the survival of advanced/metastatic patients with lung cancer. However, only a small proportion of patients can benefit from ICIs, and clinical management of the treatment process remains challenging. Glycosylation has added a new dimension to advance our understanding of tumor immunity and immunotherapy. To systematically characterize anti-PD-1/PD-L1 immunotherapy-related changes in serum glycoproteins, a series of serum samples from 12 patients with metastatic lung squamous cell carcinoma (SCC) and lung adenocarcinoma (ADC), collected before and during ICIs treatment, are firstly analyzed with mass-spectrometry-based label-free quantification method. Second, a stratification analysis is performed among anti-PD-1/PD-L1 responders and non-responders, with serum levels of glycopeptides correlated with treatment response. In addition, in an independent validation cohort, a large-scale site-specific profiling strategy based on chemical labeling is employed to confirm the unusual characteristics of IgG N-glycosylation associated with anti-PD-1/PD-L1 treatment. Unbiased label-free quantitative glycoproteomics reveals serum levels’ alterations related to anti-PD-1/PD-L1 treatment in 27 out of 337 quantified glycopeptides. The intact glycopeptide EEQFN177STYR (H3N4) corresponding to IgG4 is significantly increased during anti-PD-1/PD-L1 treatment (FC=2.65, P=0.0083) and has the highest increase in anti-PD-1/PD-L1 responders (FC=5.84, P=0.0190). Quantitative glycoproteomics based on protein purification and chemical labeling confirms this observation. Furthermore, obvious associations between the two intact glycopeptides (EEQFN177STYR (H3N4) of IgG4, EEQYN227STFR (H3N4F1) of IgG3) and response to treatment are observed, which may play a guiding role in cancer immunotherapy. Our findings could benefit future clinical disease management.

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Acta Biochimica et Biophysica Sinica•2024

Suppression of pancreatic cancer proliferation through TXNIP-mediated inhibition of the MAPK signaling pathway

Authors: Qinglin Fei, Kaizhou Jin, Saimeng Shi, Tianjiao Li, Duancheng Guo, Mengxiong Lin, Xianjun Yu, Weiding Wu, Longyun Ye

Thioredoxin-interacting protein (TXNIP) is a crucial thioredoxin-binding protein that is recognized as a tumor suppressor in diverse malignancies, such as breast cancer, lung cancer, hepatocellular carcinoma, and thyroid cancer. However, the specific role and molecular mechanisms of TXNIP in the pathogenesis and progression of pancreatic cancer cells have not been determined. In this study, we investigate the relationship between TXNIP expression and overall survival prognosis in pancreatic cancer patients. Mechanistic studies are conducted to reveal the role of TXNIP in pancreatic cancer cell proliferation, migration, and regulation during malignancy. Our findings indicate that patients with high TXNIP expression have a more favorable prognosis. In vitro experiments with pancreatic cell lines show that overexpression of TXNIP suppresses the proliferation and migration of pancreatic cancer cells. Furthermore, we find that TXNIP inhibits the activation of the MAPK signaling pathway, thereby decreasing the malignant potential of pancreatic cancer. In conclusion, our study reveals TXNIP as a promising new predictive marker and therapeutic target for pancreatic cancer.

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Acta Biochimica et Biophysica Sinica•2024

Exploring glyco-signatures and their clinical implications: a special issue focused on glycosylation studies

Authors: Haojia Lu, Xing Chen

Glycosylation is one of the most common post-translational modifications, playing a crucial role in various physiological and pathological processes. An increasing number of studies suggest that research on glycosylation holds promise for the development of clinical diagnostic biomarkers and therapeutic targets. This special issue combines four research studies and eight reviews that cover a vast range of topics within glycosylation research field, contributed by specialists in the field from various regions and countries. Considering the extensive correlation between glycosylation and various physiological and pathological processes, as well as the critical role of key technologies in glycosylation research, this special issue explores the role of glycosylation in cancer, infectious diseases, aging and associated disorders. Both N-linked and O-linked glycosylation, the two main forms of glycosylation modifications, were included. Additionally, the issue also reviews some major glycomics technologies used in glycosylation studies, including lectin microarrays, glycomics, and glycoproteomics, along with their applications in the research and development of glycan biomarkers and targets. Each topic focuses on different aspects of glycosylation, offering new insights and potential therapeutic strategies.

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Acta Biochimica et Biophysica Sinica•2024

Unveiling a novel GJB2 dominant K22T mutation in a Chinese family with hearing loss

Authors: Haiting Ji, Yilai Shu, Huawei Li

Hearing loss constitutes one of the most prevalent conditions within the field of otolaryngology. Recent investigations have revealed that mutations in deafness-associated genes, including point mutations and variations in DNA sequences, can cause hearing impairments. With the ethology of deafness remaining unclear for a substantial portion of the affected population, further screenings for pathogenic mutations are imperative to unveil the underlying mechanisms. On this study, by using next-generation sequencing, we examine 129 commonly implicated deafness-related genes in a Chinese family with hearing loss, revealing a novel heterozygous dominant mutation in the GJB2 gene (GJB2: c.65T>G: p. Lys22Thr). This mutation consistently occurs in affected family members but is not detected in unaffected individuals, strongly suggesting its causative role in hearing loss. Structural analysis indicates potential disruption to the Cx26 gap junction channel’s hydrogen bond and electrostatic interactions, aligning with predictions from the PolyPhen and SIFT algorithms. In conclusion, our study provides conclusive evidence that the identified heterozygous GJB2 mutation (GJB2: c.65T>G: p. Lys22Thr), specifically the K22T alteration, is the primary determinant of the family’s deafness. This contribution enhances our understanding of the interplay between common deafness-associated genes and hearing loss, offering valuable insights for diagnostic guidance and the formulation of therapeutic strategies for this condition.

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Acta Biochimica et Biophysica Sinica•2024

Construction and efficacy testing of DNA vaccines containing HLA-A*02:01-restricted SARS-CoV-2 T-cell epitopes predicted by immunoinformatics

Authors: Dan Tan, Ning Kang, Yuanfei Zhu, Jia Hou, Hanqing Wang, Huijun Xu, Cheng Zu, Zixiang Gao, Mu Liu, Nannan Liu, Qiang Deng, Hongzhou Lu, Jing Liu, Youhua Xie

Vaccines play essential roles in the fight against the COVID-19 pandemic. The development and assessment of COVID-19 vaccines have generally focused on the induction and boosting of neutralizing antibodies targeting the SARS-CoV-2 spike (S) protein. Due to rapid and continuous variation in the S protein, such vaccines need to be regularly updated to match newly emerged dominant variants. T-cell vaccines that target MHC I- or II-restricted epitopes in both structural and non-structural viral proteins have the potential to induce broadly cross-protective and long-lasting responses. In this work, the entire proteome encoded by SARS-CoV-2 (Wuhan-hu-1) is subjected to immunoinformatics-based prediction of HLA-A*02:01-restricted epitopes. The immunogenicity of the predicted epitopes is evaluated using peripheral blood mononuclear cells from convalescent Wuhan-hu-1-infected patients. Furthermore, predicted epitopes that are conserved across major SARS-CoV-2 lineages and variants are used to construct DNA vaccines expressing multi-epitope polypeptides. Most importantly, two DNA vaccine constructs induce epitope-specific CD8+ T-cell responses in a mouse model of HLA-A*02:01 restriction and protect immunized mice from challenge with Wuhan-hu-1 virus after hACE2 transduction. These data provide candidate T-cell epitopes useful for the development of T-cell vaccines against SARS-CoV-2 and demonstrate a strategy for quick T-cell vaccine candidate development applicable to other emerging pathogens.

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Acta Biochimica et Biophysica Sinica•2024

SEC61 translocon gamma subunit is correlated with glycolytic activity, epithelial mesenchymal transition and the immune suppressive phenotype of lung adenocarcinoma

Authors: Changshuai Zhou, Huanhuan Cui, Yuechao Yang, Lei Chen, Mingtao Feng, Yang Gao, Deheng Li, Liangdong Li, Xin Chen, Xiaoqiu Li, Yiqun Cao

Lung adenocarcinoma (LUAD) remains a predominant cause of cancer-related mortality globally, underscoring the urgency for targeted therapeutic strategies. The specific role and impact of the SEC61 translocon gamma subunit (SEC61G) in LUAD progression and metastasis remain largely unexplored. In this study, we use a multifaceted approach, combining bioinformatics analysis with experimental validation, to elucidate the pivotal role of SEC61G and its associated molecular mechanisms in LUAD. Our integrated analyses reveal a significant positive correlation between SEC61G expression and the glycolytic activity of LUAD, as evidenced by increased fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET)/CT scans. Further investigations show the potential influence of SEC61G on metabolic reprogramming, which contributes to the immunosuppressive tumor microenvironment (TME). Remarkably, we identify a negative association between SEC61G expression levels and the infiltration of critical immune cell populations within the TME, along with correlations with immune checkpoint gene expression and tumor heterogeneity scores in LUAD. Functional studies demonstrate that SEC61G knockdown markedly inhibits the migration of A549 and H2030 LUAD cells. This inhibitory effect is accompanied by a significant down-regulation of key regulators of tumor progression, including hypoxia-inducible factor-1 alpha (HIF-1α), lactate dehydrogenase A, and genes involved in the epithelial-mesenchymal transition pathway. In conclusion, our comprehensive analyses position SEC61G as a potential prognostic biomarker intricately linked to glycolytic metabolism, the EMT pathway, and the establishment of an immune-suppressive phenotype in LUAD. These findings underscore the potential of SEC61G as a therapeutic target and predictive marker for immunotherapeutic responses in LUAD patients.

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