Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025150
Rapid identification of pathogens responsible for bloodstream infection is critical for early intervention and effective treatment. Reporter phages, which are known for their exceptional sensitivity and specificity in pathogen detection, have garnered significant interest. In this study, we systematically evaluate phage genome editing strategies that combine homologous recombination with the CRISPR-Cas9 system. We investigate the impacts of homologous arm length, sgRNA activity, target site, and plasmid interactions on editing efficiency. Our results demonstrate that successful genome editing depends on both sufficient cleavage pressure and optimal homologous arm length, particularly when using low-activity sgRNAs. On the basis of these findings, we develop a highly efficient gene editing strategy TPMSR (triple-plasmid-mediated synchronous recombination) that overcomes the limitations of conventional methods that rely on high-activity sgRNA and restricted editing sites. Using the TPMSR strategy, we integrate the Nluc gene into phage T7, generating the reporter phage T7::Nluc, which is then incorporated into a microfluidic chip. Validation with 51 clinical isolates demonstrates outstanding sensitivity, specificity, and accuracy in detecting Escherichia coli in blood within 1.5 h at concentrations less than 30 CFU/mL. This study presents a robust strategy for phage genome engineering and develops a promising method for the rapid diagnosis of bloodstream infections caused by E. coli.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025192
Gut inflammatory diseases, including inflammatory bowel disease (IBD), infectious enteritis, and other inflammatory conditions, are among the most common non-neoplastic intestinal disorders. Their pathogenesis is often driven by an imbalance between pro-inflammatory and anti-inflammatory signals, with immune cells playing pivotal roles in maintaining this equilibrium. Immune cells in the gut exhibit complex, multifaceted functions: they eliminate pathogens, promote tissue repair, and counteract tumors, but excessive immune activation can exacerbate tissue damage and disease progression. Notably, metabolic reprogramming in inflammatory contexts serves as a key regulator of immune cell function and phenotypic switching. This includes alterations in cellular energy metabolism (e.g., macrophage polarization via disrupted glycolysis or fatty acid oxidation) and the modulation of immune responses by microenvironmental metabolites (e.g., bile acid-mediated Th17/Treg balance). While alterations in immune cell function and composition within the inflammatory milieu are well-established, the significance of disease-associated metabolic reprogramming—specifically how metabolism regulates immune cell function—has garnered increasing attention. This review explores how cellular metabolic reprogramming, changes in the metabolic microenvironment, and gut dysbiosis collectively influence the differentiation, proliferation, and function of immune cells in various intestinal inflammatory diseases, as well as their impact on disease progression.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026081
Multiple myeloma (MM) patients frequently experience relapse, disease progression, and drug resistance, necessitating novel therapeutic strategies. This study investigates the role of peptidylprolyl isomerase A (PPIA) in mediating dihydroartemisinin (DHA)-induced ferroptosis in MM. Building on our previous work establishing the prognostic relevance of ferroptosis in MM, we elucidate the mechanism by which DHA triggers this form of cell death through the disruption of iron metabolism and redox homeostasis. DHA significantly reduces the viability of MM cell lines and primary CD138+ cells derived from patient bone marrow samples and attenuates tumor burden in orthotopic MM models. Mechanistically, DHA upregulates the iron-regulatory genes transferrin receptor 1 (TFRC) and heme oxygenase-1 (HMOX1), thereby perturbing iron homeostasis and promoting ferroptosis. Crucially, DHA targets the oxidized form of PPIA, a redox-sensitive chaperone, binding to it and preventing its reduction, which elevates intracellular reactive oxygen species (ROS). Combined treatment with DHA and erastin, which concurrently disrupt iron and amino acid metabolism, exerts synergistic cytotoxicity and enhances MM inhibition. Furthermore, in a syngeneic mouse model, DHA promotes T-cell activation and augments tumor suppression. Collectively, these findings underscore PPIA’s pivotal role in a novel ferroptotic cell death pathway and reveal new therapeutic opportunities for MM.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025213
Myocardial infarction (MI) causes irreversible cardiomyocyte loss, creating a need for cardiac repair therapies. The role of cell division cycle 5-like (CDC5L), a cell cycle regulator, in cardiac repair is unknown. This study aims to define the role of CDC5L in mitigating ischemia-reperfusion (I/R) injury by assessing its impact on cardiomyocyte proliferation and apoptosis and to determine the mechanism involving the FGF10-YAP axis. We model cardiac injury using in vitro oxygen-glucose deprivation/reoxygenation (OGD/R) in neonatal mouse cardiomyocytes and in vivo I/R in adult mice. To investigate CDC5L function, we modulate its expression via adenoviral or AAV9-mediated overexpression or knockdown. Proliferation markers (EdU+, Ki67+, pH3+), apoptosis (TUNEL staining, Bax/Bcl-2 ratio), and cardiac function (echocardiography) are assessed. Through transcriptomic screening, we identify CDC5L downstream targets and validate their functional roles using FGF10 knockdown rescue assays. We find that CDC5L is upregulated in the post-I/R murine myocardium. Its overexpression enhances cardiomyocyte proliferation, preserves cardiac function, reduces apoptosis, and diminishes infarct size. Transcriptomic analysis identifies FGF10 as a key downstream effector, and we confirm that CDC5L upregulates FGF10 expression. Notably, FGF10 knockdown reverses the proliferative and anti-apoptotic effects of CDC5L. Moreover, the CDC5L-mediated reduction in YAP phosphorylation is also dependent on FGF10, as this effect is abolished upon FGF10 knockdown. In conclusion, CDC5L attenuates cardiac I/R injury by promoting cardiomyocyte proliferation and inhibiting apoptosis through the FGF10-YAP pathway. This CDC5L-FGF10-YAP axis represents a promising therapeutic target to improve myocardial regeneration and recovery after myocardial infarction.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2025156
CD19-directed chimeric antigen receptor T (CAR-T) cell therapy is promising for treating relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL), yet its long-term efficacy remains limited by CAR-T-cell exhaustion. Given the broad immunomodulatory activities of vitamin D, we investigate whether its active form, 1α,25(OH)2D3, enhances CAR-T-cell functionality and improves therapeutic outcomes. We demonstrate that 1α,25(OH)2D3 treatment significantly mitigates exhaustion and enhances the antitumor activity of CD19 CAR-T cells derived from both healthy donors and DLBCL patients, which is further validated in xenograft mouse models. Mechanistically, we show that 1α,25(OH)2D3 upregulates the expression of the vitamin D receptor (VDR), promoting transcriptional reprogramming associated with memory-like differentiation and downregulation of exhaustion-related genes, thereby reshaping the functional heterogeneity of CAR-T cells under tumor stimulation. Our study highlights 1α,25(OH)2D3 supplementation as a safe and accessible approach to mitigate terminal differentiation and exhaustion of CAR-T cells, offering a promising strategy to enhance the clinical efficacy of CAR-T therapy in patients with R/R DLBCL.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2024174
Berberine (BBR) is used to treat diarrhea clinically. However, its reproductive toxicity is unclear. This study aims to investigate the impact of BBR on the male reproductive system. Intragastric BBR administration for 14 consecutive days results in a significant decrease in the serum testosterone concentration, epididymal sperm concentration, mating rate and fecundity of male mice. Testicular treatment with testosterone propionate (TP) partially reverses the damage caused by BBR to the male reproductive system. Mechanistically, the decrease in Muribaculaceae abundance in the gut microbiota of mice is the principal cause of the BBR-induced decrease in the sperm concentration. Both fecal microbiota transplantation (FMT) and polyethylene glycol (PEG) treatment demonstrate that Muribaculaceae is necessary for spermatogenesis. The intragastric administration of Muribaculaceae intestinale to BBR-treated mice restores the sperm concentration and testosterone levels. Metabolomic analysis reveals that BBR affects arginine and proline metabolism, of which ornithine level is downregulated. Combined analysis via 16S rRNA metagenomics sequencing and metabolomics shows that Muribaculaceae regulates ornithine level. The transcriptomic results of the testes indicate that the expressions of genes related to the low-density lipoprotein receptor (LDLR)-mediated testosterone synthesis pathway decrease after BBR administration. The transcriptional activity of the Ldlr gene in TM3 cells is increased with increased ornithine supplementation in the culture media, leading to increased testosterone synthesis. Overall, this study reveals an association between a BBR-induced decrease in Muribaculaceae abundance and defective spermatogenesis, providing a prospective therapeutic approach for addressing infertility-related decreases in serum testosterone triggered by changes in the gut microbiota composition.
Acta Biochimica et Biophysica Sinica•2024•DOI: 10.3724/abbs.2024132
Through genome-wide association studies (GWAS) and integrated expression quantitative trait locus (eQTL) analyses, numerous susceptibility genes (“eGenes”, whose expressions are significantly associated with common variants) associated with systemic lupus erythematosus (SLE) have been identified. Notably, a subset of these eGenes is correlated with disease activity. However, the precise mechanisms through which these genes contribute to the initiation and progression of the disease remain to be fully elucidated. In this investigation, we initially identify SPATS2L as an SLE eGene correlated with disease activity. eSignaling and transcriptomic analyses suggest its involvement in the type I interferon (IFN) pathway. We observe a significant increase in SPATS2L expression following type I IFN stimulation, and the expression levels are dependent on both the concentration and duration of stimulation. Furthermore, through dual-luciferase reporter assays, western blot analysis, and imaging flow cytometry, we confirm that SPATS2L positively modulates the type I IFN pathway, acting as a positive feedback regulator. Notably, siRNA-mediated intervention targeting SPATS2L, an interferon-inducible gene, in peripheral blood mononuclear cells (PBMCs) from patients with SLE reverses the activation of the interferon pathway. In conclusion, our research highlights the pivotal role of SPATS2L as a positive-feedback regulatory molecule within the type I IFN pathway. Our findings suggest that SPATS2L plays a critical role in the onset and progression of SLE and may serve as a promising target for disease activity assessment and intervention strategies.
Chinese Traditional and Herbal Drugs•2026•DOI: 10.7501/j.issn.0253-2670.2026.15.20261510
This study evaluated the quality of Fagopyri Dibotryis Rhizoma Tablets (FDRT) from two manufacturers. Eighteen batches from company A and twenty from company B were analyzed. HPLC fingerprints were established, and 33 common peaks were assigned. Quadrupole time-of-flight mass spectrometry (Q-TOF-MS/MS) identified 53 constituents, including 21 tannins, 12 phenolics, 7 flavonoids, 7 phenylpropanoid glycosides, 2 amino acids, 2 organic acids, 1 alkaloid, and 1 terpenoid. Among these, 3 phenolics (gallic acid, protocatechuic acid, protocatechualdehyde), 5 tannins (procyanidin B1, B2, B3, C1, C2), and 4 flavonoids (catechin, epicatechin, epicatechin gallate, rutin) were confirmed by reference substances. Nine constituents with good separation (excluding procyanidin C2, B2, and rutin) were quantified. The average content of these nine constituents in company B tablets was significantly higher than in company A (P < 0.01). Hierarchical cluster analysis (HCA), principal component analysis (PCA), and orthogonal partial least squares-discriminant analysis (OPLS-DA) consistently discriminated the two manufacturers into distinct clusters. Common peaks 30, 29, 16, 17, 2, 21, 10, 11, 18, 20, and 27, corresponding to procyanidin C2, B2, C1, B1, B3, gallic acid, epicatechin, etc., were identified as marker constituents responsible for quality differences. The results demonstrate significant quality divergence between FDRT from the two manufacturers.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026081
Multiple myeloma (MM) patients frequently experience relapse, disease progression, and drug resistance, necessitating novel therapeutic strategies. This study investigates the role of peptidylprolyl isomerase A (PPIA) in mediating dihydroartemisinin (DHA)-induced ferroptosis in MM. Building on our previous work establishing the prognostic relevance of ferroptosis in MM, we elucidate the mechanism by which DHA triggers this form of cell death through the disruption of iron metabolism and redox homeostasis. DHA significantly reduces the viability of MM cell lines and primary CD138+ cells derived from patient bone marrow samples and attenuates tumor burden in orthotopic MM models. Mechanistically, DHA upregulates the iron-regulatory genes transferrin receptor 1 (TFRC) and heme oxygenase-1 (HMOX1), thereby perturbing iron homeostasis and promoting ferroptosis. Crucially, DHA targets the oxidized form of PPIA, a redox-sensitive chaperone, binding to it and preventing its reduction, which elevates intracellular reactive oxygen species (ROS). Combined treatment with DHA and erastin, which concurrently disrupt iron and amino acid metabolism, exerts synergistic cytotoxicity and enhances MM inhibition. Furthermore, in a syngeneic mouse model, DHA promotes T-cell activation and augments tumor suppression. Collectively, these findings underscore PPIA's pivotal role in a novel ferroptotic cell death pathway and reveal new therapeutic opportunities for MM.
Chinese Journal of Tissue Engineering Research•2026•DOI: 10.12307/2026.21579
BACKGROUND: The enormous impact acceleration experienced by the human body during ejection is a major risk factor for spinal injury. Therefore, optimizing the cushioning and energy absorption design of ejection seat cushions is crucial for ensuring the safety of pilots. OBJECTIVE: To construct a human-seat cushion coupled finite element model based on ABAQUS to quantitatively evaluate the impact of a double-layer cushion, which combines the advantages of high and slow rebound, on lumbar spine biomechanical response and spinal injury risk under ejection conditions, and to quantify its safety margin. METHODS: CT imaging data of the entire spine and legs from one male pilot volunteer were selected. Three-dimensional anatomical reconstruction, geometric repair, and finite element meshing were completed to construct a highly biologically faithful digital human model encompassing the entire spine, pelvis, both femurs, and skin soft tissues. A geometric model of the dual-layer seat cushion was also established. Subsequently, a human-chair system coupled model was assembled in ABAQUS. Dynamic simulations were conducted by applying an ejection acceleration time history. Stress responses in the L4–L5 and L5–S1 intervertebral discs were compared between the high-resilience and dual-layer cushion designs. Injury probability was predicted using the Spinal Injury Dynamic Response Index. RESULTS AND CONCLUSION: The simulation results showed good agreement with experimental data, validating the model's accuracy. Performance comparison indicated that, compared with the traditional high-resilience cushion, the double-layer cushion reduced peak stresses in the L4–L5 and L5–S1 intervertebral discs, decreased the Dynamic Response Index by 1.8%, and reduced the spinal injury probability by 10.6%. While meeting relevant limits, it provided a higher safety margin and effectively reduced the risk of spinal injury under ejection impact loads.
Acta Biochimica et Biophysica Sinica•2026•DOI: 10.3724/abbs.2026082
E74-like ETS transcription factor 3 (ELF3) has been implicated in various tumorigenesis and inflammatory diseases. However, its expression profile and role in lung adenocarcinoma (LUAD) remain poorly defined. In the present study, through comprehensive clinical and experimental analyses, we aim to clarify the association between ELF3 overexpression in LUAD tissues and poor prognosis. Functional assays reveal that ELF3 knockdown inhibits the proliferation, migration, and invasion of LUAD cells, while ELF3 overexpression enhances these functions. Pathway enrichment analysis indicates that ELF3 influences the metabolic processes of LUAD. Mechanistically, ELF3 exerts oncogenic effects by regulating the transcription of hexokinase 2 (HK2) and glucose transporter type 1 (GLUT1). High-throughput screening reveals that dacinostat, by targeting the active site of the ELF3 protein, attenuates the glycolytic, proliferative, and metastatic abilities of LUAD cells. Additionally, ubiquitin-specific peptidase 18 (USP18) strengthens the stability of the ELF3 protein and influences the malignant biological behavior of LUAD through ELF3. In conclusion, the USP18/ELF3/HK2 and USP18/ELF3/GLUT1 axes play critical roles in glucose metabolism, proliferation, and metastasis of LUAD cells. Dacinostat inhibits the malignant progression of LUAD by targeting ELF3, providing strong evidence for developing novel therapeutic strategies targeting ELF3.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025213
Myocardial infarction (MI) causes irreversible cardiomyocyte loss, and current reperfusion therapies fail to regenerate necrotic myocardium. Cell division cycle 5-like (CDC5L), a cell cycle regulator, has an undefined role in cardiac repair. This study investigates CDC5L in mitigating ischemia-reperfusion (I/R) injury by assessing cardiomyocyte proliferation and apoptosis, and delineates the FGF10-YAP mechanism. In vitro oxygen-glucose deprivation/reoxygenation (OGD/R) in neonatal mouse cardiomyocytes and in vivo I/R in adult mice were employed. CDC5L was modulated via adenoviral or AAV9-mediated overexpression or knockdown. Proliferation markers (EdU+, Ki67+, pH3+), apoptosis (TUNEL, Bax/Bcl-2 ratio), and cardiac function (echocardiography) were quantified. Transcriptomic screening identified downstream targets, validated by FGF10 knockdown rescue. CDC5L was upregulated in post-I/R murine myocardium. Overexpression enhanced cardiomyocyte proliferation, preserved cardiac function, reduced apoptosis, and diminished infarct size. FGF10 was identified as a key downstream effector; CDC5L upregulated FGF10 expression. FGF10 knockdown reversed the proliferative and anti-apoptotic effects of CDC5L. The CDC5L-mediated reduction in YAP phosphorylation was abolished upon FGF10 knockdown. CDC5L attenuates cardiac I/R injury by promoting cardiomyocyte proliferation and inhibiting apoptosis through the FGF10-YAP pathway. This CDC5L-FGF10-YAP axis represents a promising therapeutic target to improve myocardial regeneration and recovery after myocardial infarction.
Acta Biochimica et Biophysica Sinica•2025•DOI: 10.3724/abbs.2025057
MEIOB and SPATA22 are gonad-specific proteins essential for meiotic recombination, with mutations linked to oligospermia and azoospermia in human males. The heterodimer recognizes and binds single-stranded DNA (ssDNA) protected by replication protein A (RPA) to promote homologous recombination repair. However, sequence divergence between human and rodent orthologs leads to functional differences. Here, human MEIOB (hMEIOB) and SPATA22 (hSPATA22) were expressed and purified for electrophoretic mobility shift assay (EMSA), magnetic tweezer (MT) assay, and bio-layer interferometry (BLI) to dissect ssDNA binding patterns. hMEIOB alone exhibits low ssDNA-binding affinity and stability, whereas hSPATA22 binds ssDNA faster and more stably, promoting ssDNA condensation. The hMEIOB-hSPATA22 heterodimer displays strong binding affinity and stability. Multiple heterodimers spontaneously aggregate in vitro, with BLI response signals of ~4.31 nm for hSPATA22 alone versus ~19.5 nm for the heterodimer, indicating polymer formation. The hRPA complex weakens the binding affinity of hMEIOB, hSPATA22, and the heterodimer to ssDNA, and binds to hSPATA22 and the heterodimer in vitro, consistent with RPA's role in protecting ssDNA and recruiting repair proteins. This study provides the first single-molecule elucidation of hMEIOB and hSPATA22 binding to ssDNA and verifies their relationship with the RPA complex.