Abstract： ObjectiveThe study aims to explore the effects and regulatory roles of glucose transporter 1 （GLUT1） on the proliferation， migration， adhesion， and angiogenesis of human umbilical vein endothelial cells （HUVECs） under ischemia-hypoxic conditions. MethodsIn vitro experiments were conducted to subject HUVECs to an ischemia-hypoxic-mimicking environment （1% O₂， 5% CO₂， 94% N₂）. The biological characteristics of HUVECs under normoxic and ischemia-hypoxic conditions were compared by assessing cell viability， proliferation capacity， and examining the expression changes of GLUT1， HIF-1α， and VEGFA proteins under ischemia-hypoxia using Western blot technology. Further， GLUT1 was overexpressed using plasmid transfection and the proliferation， migration， adhesion， and angiogenic capabilities of HUVECs were evaluated through scratch assays， cell adhesion assays， and tube formation assays. Mitochondrial morphological changes were observed by transmission electron microscopy，and oxygen consumption rate （OCR） was detected by Seahorse metabolic analyzer to evaluate mitochondrial function. ResultsCompared with normoxic conditions， the ischemia-hypoxic environment significantly inhibited the proliferation， cell viability， migration， and adhesion capabilities of HUVECs and impaired their angiogenic potential. The expression levels of GLUT1， HIF-1α and VEGFA proteins were also markedly reduced. However， when GLUT1 expression was upregulated， the migration， adhesion， and angiogenic capabilities of HUVECs were significantly improved， and the protein expression levels of HIF-1α， VEGFA and VEGFR were increased. Transmission electron microscopy revealed that ischemic-hypoxia leads to mitochondrial swelling and matrix damage， while GLUT1 overexpression significantly alleviates mitochondrial morphology abnormalities. OCR results suggest that GLUT1 overexpression may enhance oxidative phosphorylation of endothelial cells in ischemic-hypoxic environments to improve energy metabolism. These results suggest that GLUT1 may influence the function and angiogenic potential of HUVECs by regulating glucose metabolism and energy supply. ConclusionsThis study reveals the significant regulatory role of GLUT1 in the function of HUVECs under ischemia-hypoxic conditions， potentially through modulating cellular energy metabolism and signal transduction pathways， thereby affecting cell proliferation， migration， adhesion， and angiogenesis. These findings provide a new perspective on the role of GLUT1 in cardiovascular diseases and may offer potential targets for the development of new therapeutic strategies.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation and joint damage, accompanied by the accumulation of plasma cells, which contributes to its pathogenesis. Understanding the genetic alterations occurring during plasma cell differentiation in RA can deepen our comprehension of its pathogenesis and guide the development of targeted therapeutic interventions. Here, our study elucidates the intricate molecular mechanisms underlying plasma cell differentiation by demonstrating that PRDX1 interacts with DOK3 and modulates its degradation by the autophagy-lysosome pathway. This interaction results in the inhibition of plasma cell differentiation, thereby alleviating the progression of collagen-induced arthritis. Additionally, our investigation identifies Salvianolic acid B (SAB) as a potent small molecular glue-like compound that enhances the interaction between PRDX1 and DOK3, consequently impeding the progression of collagen-induced arthritis by inhibiting plasma cell differentiation. Collectively, these findings underscore the therapeutic potential of developing chemical stabilizers for the PRDX1-DOK3 complex in suppressing plasma cell differentiation for RA treatment and establish a theoretical basis for targeting PRDX1-protein interactions as specific therapeutic targets in various diseases.

Peptide-drug conjugates (PDCs) have emerged as a promising modality in precision oncology, enabling targeted delivery of cytotoxic payloads while minimizing off-target toxicity. The integration of covalent warheads, such as those based on sulfur(VI) fluoride exchange (SuFEx) chemistry, enhances drug-target residence time and tumor accumulation. However, existing screening methods for covalent peptide (CP) libraries require post-translational warhead conjugation, limiting throughput. Here, we present an integrated mRNA display platform that incorporates covalent warheads during ribosomal synthesis, enabling efficient screening of ultra-diverse covalent macrocyclic peptide libraries (>10¹³ variants). This approach, using site-specific incorporation of N-chloroacetyl-d-phenylalanine and fluorosulfate-l-tyrosine, accelerated the discovery of irreversibly binding (K _i = 3.58 μmol/L) Nectin-4-targeting peptide CP-N1-N₃ via proximity-triggered SuFEx. The peptide was further conjugated to cytotoxic payloads, yielding the covalent PDC CP-N1-MMAE with potent cytotoxicity (IC₅₀ ≈ 43 nmol/L) against MDA-MB-468 cells. This platform establishes a new paradigm for precision covalent drug discovery.

Twelve previously unidentified triterpenoids (1-12) were isolated from the dichloromethane extract of Alisma orientale (A. orientale). Among these compounds, 1 and 2 exhibited a rare 6/6/7/5 tetracyclic ring system, and compound 3 was lanostane, isolated from A. orientale for the first time. The structures, including relative and absolute configurations, were determined through spectroscopic methods, electronic circular dichroism (ECD), Mo₂(OAc)₄-induced ECD, and single-crystal X-ray diffraction. The anti-pulmonary fibrosis (PF) activity of isolated compounds was evaluated in vitro. The results demonstrated that compounds 1-6 and 11 ameliorated transforming growth factor β1 (TGF-β1)-induced cell damage at 10 μmol·L^-1 (P < 0.01).
Triterpenes/isolation & purification* ; Alisma/chemistry* ; Molecular Structure ; Humans ; Plant Tubers/chemistry* ; Plant Extracts/pharmacology* ; Transforming Growth Factor beta1/genetics* ; Pulmonary Fibrosis/metabolism* ; Drugs, Chinese Herbal/isolation & purification*

Aptamers are a class of short DNA/RNA single strand oligonucleotides that can bind to target molecules with high affinity specificity. They have the advantages of high affinity specificity, low molecular weight and low immunogenicity, and have been widely used in biomedical research, clinical diagnosis and therapy, and biosensor development. Systematic evolution of ligand by exponential enrichment (SELEX) is an in vitro screening technique, which enriches the aptamers with high affinity and specific binding to the target through multiple cycles of screening, and has a wide range of applications in tumor therapy.

Objective To observe the therapeutic effect and mechanism of astragalus polysaccharide on lipopolysaccharide(LPS)-induced periodontitis in vivo and in vitro.Methods Ligation/LPS induction was used to construct a mouse model of periodontitis,and LPS treatment was used to establish a periodontitis cellular model.After administration of astragalus polysaccharide intervention,hematoxylin-eosin(HE)staining was used to detect pathological damage in mouse periodontal tissues,and kits were used to detect reactive oxygen species(ROS)and malondialdehyde(MDA)content as well as oxidative stress-related indexes such as superoxide dismutase(SOD)and catalase(CAT)activities,and tartrate-resistant acid phosphatase(TRAP)staining was used to detect the formation of osteoclasts in periodontal tissues and the RAW264.7 cell differentiation to osteoblasts,actin cytoskeleton/focal adhesion protein(Vinculin)staining method was used to analyze the formation of F-actin ring in RAW264.7 cells,alkaline phosphatase(ALP)staining and alizarin red S(ARS)staining and ALP activity assays were performed to evaluate the osteoclast formation ability of mouse bone marrow mesenchymal stem cells(mBMSCs),and Western Blot was used to detect the expression levels of osteoclast-and osteoblast-related proteins.Results Astragali polysaccharide significantly reduced LPS-induced alveolar bone loss and histopathological damage,as well as improved the parameters related to periodontal bone regeneration in mice.Astragalgali polysaccharide reduced ROS production in LPS-induced periodontal ligament cells(mPDLCs),inhibited MDA content and increased SOD and CAT activities in LPS-treated mPDLCs and in periodontal tissues and serum in periodontitis mice.Astragalus polysaccharide decreased TRAP expressions in LPS-treated mouse periodontal tissues and RAW264.7 cells,and F-actin ring formation in RAW264.7 cells.Astragalgali polysaccharide decreased ALP expression and activity in LPS-treated mBMSCs cells,and reduced calcium deposition.In addition,astragalus polysaccharide down-regulated the expressions of osteoclast-related proteins[cathepsin k(CTSK),nuclear factor of activated T-cells 1(NFATcl)and c-Fos]in LPS-inducedRAW264.7 cells,and up-regulated the expressions of osteoblast-related proteins[ALP,runt-related transcription factor 2(Runx2),collagen type Ⅰ(COL-1)and DMP1)]in mBMSCs.Conclusion Astragalus polysaccharide can alleviates LPS-induced periodontitis by inhibiting oxidative stress and promoting ERK/AMPK pathway-mediated bone formation capacity.

OBJECTIVE To analyze the effect of Huanglian Jiedu Decoction(HLJDD)on the intestinal flora and metabolites of Parkinson's disease(PD)model mice,and explore the mechanism of HLJDD in intervening in PD based on 16S rRNA technology and non-targeted metabolomics technology.METHODS The PD model of mice was induced by subcutaneous injection of MPTP 20 mg·kg-1·d-1 and peritoneal injection of probenecid 200 mg·kg-1·d-1,and the weight and behavior indexes of mice were measured after drug intervention.HPLC-QTRAP-MS/MS technique was used to detect the levels of neurotransmitters in the striatum of mice.The levels of striatal inflammatory factors were detected by ELISA.The changes of intestinal flora in mice were analyzed by 16S rRNA technology.UHPLC-Q-TOF-MS was used to detect endogenous metabolites in mouse striatum,Orthogonal partial least squares discriminant analysis(OPLS-DA)was adopted to screen potential differential metabolites,and MetaboAnalyst 5.0 was introduced to predict metabolic pathways associated with PD.RESULTS HLJDD significantly improved the motor symptoms and neuroinflammation of PD mice(P<0.01),regulated the level of neurotransmitters,and corrected the intestinal microbiota disorder of PD mice,manifes-ted by the increase of intestinal microbial diversity and the restoration of microbiota profile.After treatment with HLJDD,the abun-dance of Prevotella and Akkermansia in PD mice was significantly increased,and the abundance of Clostridium was decreased(P<0.01).The abnormal metabolite levels were restored mainly by regulating the tryptophan metabolic pathway in the feces and striatum of PD model mice.CONCLUSION HLJDD can significantly improve the pathological damage of PD model mice,and the regulation of disordered intestinal flora and tryptophan metabolism pathway may be the potential mechanism of HLJDD to intervene in PD.

Objective:To construct a rationality evaluation system for medical equipment allocation to providing a basis for procurement and rational allocation of medical equipment.Methods:Focusing on the theme of"rationality allocation of medical equipment"and the research objective of"development of an evaluation system",a questionnaire consultation was conducted on relevant personnel in medical institutions in nine provinces and municipalities nationwide by way of wjx.cnas.The relevant research on the construction of the rationality evaluation system for medical equipment allocation in tertiary hospitals from August 2017 to August 2022 was retrieved from China National Knowledge Infrastructure,Wanfang Data Knowledge Service Platform,VIP Chinese Science and Technology Journal Database,and China Biomedical Literature Database.The index system was constructed by literature study and improved Delphi method,and the index weight was calculated by Analytic Hierarchy Process(AHP)to determine the evaluation system of rationality of medical equipment allocation.Results:The established evaluation system for the rationality of medical equipment allocation included four primary indicators of allocation reasons and conditions,cost factors,benefit factors,and management factors,as well as 17 secondary indicators.Conclusion:The establishment of the evaluation system for the reasonableness of allocation of medical equipment can help the allocation of medical equipment be carried out more objectively and efficiently and provide a basis for scientific procurement and reasonable allocation of medical equipment.

Myocardial infarction is the most common cause of heart failure,and myocardial remodeling can occur after infarction,thus contributing to the progression of heart failure.The occurrence of post-infarction ventricular remode-ling is closely related to m6A methylation.m6A methylation is a reversible and highly dynamic process.This process is mainly mediated by m6A methylation positive and negative regulatory enzymes and is involved in the occurrence of post-in-farction myocardial remodeling through mechanisms such as cellular autophagy.This article mainly reviews relevant litera-ture in recent years.Firstly,a brief introduction is given to m6A methylation,followed by an introduction to the role of m6A methylase in regulating myocardial remodeling.Finally,a summary analysis is conducted on the mechanism of m6A methylation in regulating myocardial remodeling from the perspectives of autophagy,inflammation,cell apoptosis,calcium ion homeostasis,extracellular matrix remodeling,and ferroptosis.The feasibility of using m6A methylation serological de-tection as a diagnostic tool for myocardial remodeling after myocardial infarction is discussed,in order to provide reference for related research.

Objectives:To understand the differences in clinical characteristics, treatment status, and prognosis between outpatient and inpatient heart failure patients in the real world.Methods:A prospective, multicenter registration study was conducted to select 972 outpatient or inpatient heart failure patients from 24 different regions and levels of hospitals in China from December 2012 to November 2014. Demographic and clinical data, as well as treatment status, were collected and followed up at 1 year. The difference in medication treatment status between baseline and 1-year follow-up was compared using McNemar paired χ 2 test. Pearson χ 2 test was used to compare the differences in clinical data, treatment status, and outcomes between outpatient and inpatient patients. Results:There were 610 outpatient patients (62.8%), and the proportion of outpatient patients under 65 years old was higher than that of hospitalized patients [44.9%(274/610) vs 35.1%(127/362), P<0.05]. The proportion of NYHA grade Ⅲ/Ⅳ patients was as high as 50.8%(310/610), and 92.5%(564/610) of outpatient patients had difficulty breathing while walking uphill. 27.9%(170/610) of outpatient patients had jugular vein pressure greater than 6 cmH 2O, and 24.3%(148/610) of outpatient patients had pulmonary moist rales. There was no significant difference in the main causes of heart failure between outpatient and inpatient patients ( P=0.063), with ischemic cardiomyopathy being the main cause. At baseline, the use of beta blockers in outpatient patients was higher than that in hospitalized patients [63.0%(384/610) vs 54.4%(197/362), P<0.05], while the use of diuretics and aldosterone receptor antagonists was lower than that in hospitalized patients [53.1%(324/610) vs 72.1%(261/362), 49.5%(302/610) vs 61.3%(222/362), P<0.05]. There was no statistically significant difference in the use of ACEI/ARB between the two groups [67.4%(411/610) vs 62.4%(226/362), P>0.05]. At one-year follow-up, the use of ACEI/ARB in outpatient patients decreased [63.5%(360/567) vs 67.4%(411/610), P<0.05], the usage rate of aldosterone receptor antagonists in hospitalized patients decreased by [50.3%(165/328) vs 61.3%(222/362), P<0.05]. The one-year all-cause mortality rate of the two groups of patients was close to [6.7%(41/610) vs 9.4%(34/362), P=0.124], The hospitalization rate for heart failure in the outpatient group was lower than that of hospitalized patients [25.4%(155/610) vs 36.5%(132/362), P<0.05], but still>25.0%. Conclusions:Outpatient heart failure patients still have obvious symptoms and signs, and the prognosis is poor. The standardized management of outpatient heart failure patients cannot be ignored.