第四军医大学

Paired immunoglobulin-like receptor B (PirB) has been identified as a new receptor for myelin-associated inhibitory (MAI) proteins, which may play important role in axonal regeneration and corticospinal tract (CST) projection associated with neurobehavioral function recovery after stroke. Here, we found that the expression of PirB was increased in the cortical penumbra from 1 to 28 days after transient focal cerebral ischemic reperfusion of rats. Then, transactivator of transcription-PirB extracellular peptide (TAT-PEP) was generated that might block the interactions between MAIs and PirB. The results showed that TAT-PEP displayed high affinity for MAIs and ameliorated their inhibitory effect on neurite growth. Furthermore, TAT-PEP can widely distribute in the penumbra after intraperitoneal injection. Then, we found that TAT-PEP enhanced neurite growth and alleviated growth cone collapse after oxygen glucose deprivation (OGD) injury. In addition, TAT-PEP promoted long-term neurobehavioral functional recovery through enhancing axonal regeneration and CST projection. Finally, the observations demonstrated that POSH/RhoA/growth-associated protein 43 (GAP43) as PirB-associated downstream signaling molecules played important role in neurobehavioral functional recovery after stroke. Moreover, the underlying mechanism associated with TAT-PEP-mediated promoting axonal regeneration and CST projection was by intervening in the expression of POSH, RhoA, and GAP43. These studies suggest that TAT-PEP may represent an attractive therapeutic strategy against stroke.

Optimizing the immune microenvironment is essential for successful implant osseointegration. In this study, four different nano/microstructures were fabricated on polyetheretherketone (PEEK) substrates by varying the agitation speed during sulfonation to influence osteoimmunomodulation and implant integration. The results indicate that nano/microstructures with minimal dimensions (SP450) inhibit actin polymerization by reducing calcium influx through PIEZO1, activating the anti-inflammatory M2 macrophage phenotype. Among the tested specimens, SP450 exhibited the lowest expression levels of tumor necrosis factor-α and interleukin-1β while releasing the highest levels of anti-inflammatory factors, including interleukin-4 and interleukin-10. This optimized immune environment promotes the osteogenesis of MC3T3-E1 pre-osteoblasts and enhances the osseointegration of PEEK implants. Transcriptomic analysis and validation experiment further revealed that SP450 inhibits osteoclastic differentiation by down-regulating transforming growth factor-β2 and suppressing the NF-κB signaling pathway. These findings suggest that manipulating the surface topography of PEEK implants is an effective strategy for enhancing osseointegration with promising clinical applications.

Background The burden of gastric cancer remains substantial in Asia. Gastric premalignant conditions, including chronic atrophic gastritis, intestinal metaplasia and dysplasia, are important intermediate stages in the gastric carcinogenesis cascade. The sojourn time allows endoscopic surveillance to have a pivotal role in early detection and timely intervention.Objective This task force was commissioned by the Asian Pacific Association of Gastroenterology to formulate recommendations for the surveillance and management of Helicobacter pylori associated gastric premalignant conditions in the region.Design A systematic literature review was conducted across multiple databases, including PubMed, Cochrane Library and Embase, focusing on studies related to gastric premalignant conditions and their surveillance, particularly from Asia. The evidence quality and strength of recommendations were appraised using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system.Results These recommendations address four key aspects of gastric premalignant condition surveillance: (1) epidemiology and risk factors; (2) endoscopic and histopathological diagnosis; (3) risk stratification and endoscopic surveillance strategies; and (4) management strategies. 28 statements were made after multiple rounds of voting by experts. The statements offer a comprehensive, evidence based framework designed to assist clinicians in the Asia Pacific region on the early detection and management of gastric premalignant conditions.Conclusion These statements aim to provide a structured, evidence based surveillance framework for clinical practice in the Asia Pacific region, while also identifying priority areas for future research.

The development of wearable electronics calls for materials that can concurrently manage electromagnetic interference (EMI) and microbial threats across different interfaces. Herein, we fabricate an asymmetric sandwich-structured film (CSP/MXC/CNF) through a rational layer-by-layer design. The film comprises a hydrophilic cellulose nanofiber (CNF) substrate, a conductive MXene@CuS (MXC) heterojunction interlayer, and a superhydrophobic CNF@SiO2@PDMS (CSP) top layer. This architecture enables spatially segregated functions: the bottom CNF captures bacteria from skin for subsequent eradication via photothermal/photodynamic/chemodynamic effects (>99 % inhibition against S. aureus and E. coli), while the top CSP repels airborne contaminants (0 % bacterial adhesion). The MXC interlayer concurrently provides efficient EMI shielding (33.64 dB in Xband) and high electrical conductivity (303 S/m). With good mechanical flexibility and deformation stability, the film establishes a "interface-segregated defense" paradigm, offering an integrated solution for next-generation wearable devices that require simultaneous electromagnetic compatibility and directional biological safety, such as intelligent healthcare monitors and personal protective electronics.

Nucleolar stress has emerged as a critical regulatory mechanism linking ribosome biogenesis defects to apoptotic cell death in various pathological conditions. Fibrillarin (FBL), the catalytic component of box C/D small nucleolar ribonucleoproteins, participates in multiple forms of programmed cell death through both p53-dependent and p53-independent pathways across diverse disease contexts including cancer and neurodegeneration. In malignancies including breast cancer, colorectal cancer, and hepatocellular carcinoma, FBL overexpression promotes apoptosis resistance, whereas in Alzheimer’s disease and ALS/FTD, FBL dysfunction contributes to pathological neuronal death. Dysregulation of FBL can lead to excessive apoptosis or apoptosis resistance depending on cellular context and disease state. Various cellular stressors trigger aberrant FBL function, disrupting rRNA processing and ribosome assembly, which then activates nucleolar stress responses that culminate in cell death through ribosomal protein-MDM2-p53 axis activation or selective translational control of survival factors in a context-dependent manner. Therefore, targeting FBL-mediated apoptotic pathways is considered an important avenue for the treatment of various cancers and neurodegenerative diseases. In this review, we summarize the major and recent findings focusing on the mechanisms of FBL-regulated apoptosis in disease pathogenesis and provide a systematic overview of current therapeutic strategies targeting nucleolar stress pathways, including RNA polymerase I inhibitors and precision medicine approaches based on p53 status, which may provide important therapeutic targets that merit further investigation.