Multidrug-resistant (MDR) bacterial infections have emerged as a serious challenge of global public health crisis. The overuse and misuse of conventional antibiotics have dramatically accelerated the emergence, evolution and worldwide spread of drug-resistant bacterial strains, necessitating urgent exploration of novel antibacterial strategies. Bacteriophages serve as natural bacterial predators offering distinct advantages including high host specificity, autonomous self-replication capabilities and cost-effective large-scale production. However, wild-type phages present significant clinical limitations due to their narrow host ranges, susceptibility to rapid immune clearance and poor penetration of bacterial biofilms, which severely restrict their therapeutic applications. The convergence of synthetic biology, nanotechnology and advanced gene editing technologies has accelerated the development of engineered bacteriophage platforms, providing programmable, scalable and clinically translatable pathways to overcome these inherent biological constraints. Here, we systematically delineate four fundamental strategies for engineered bacteriophage development. Chemical modification utilizes reactive functional groups such as amino, carboxyl and thiol moieties on capsid proteins through esterification, amidation or click chemistry reactions to achieve precise drug conjugation and surface functionalization. In vivo editing encompasses ultraviolet or chemical mutagenesis for random mutation induction, homologous recombination for targeted genetic alterations, recombineering methodologies including electroporation-mediated bacteriophage recombination engineering, and CRISPR-Cas systems for precise genome editing to enable exact genetic reconstruction and host range reprogramming. In vitro synthesis leverages genome engineering platforms where intact phage genomes are transferred into yeast or host bacteria to facilitate highly efficient homologous recombination, enabling large DNA fragment assembly and cross-gene host range expansion without bacterial toxicity constraints. Directed evolution combines artificial selection through mutation library screening with rational design approaches involving chimeric receptor binding protein construction or site-specific mutagenesis, effectively balancing the discovery of unknown adaptive pathways with targeted host specificity modification. Moreover, we comprehensively discuss therapeutic applications across diverse clinical scenarios. Engineered bacteriophage effectively disrupt bacterial biofilms through sophisticated functionalized delivery platforms including nanozyme-conjugated phages, phage-liposome nanoconjugates and bio-responsive hydrogels, demonstrating significantly enhanced bactericidal efficiency compared to unmodified free phages. These bioengineered vectors attenuate bacterial virulence and resensitize pathogens to antibiotics by delivering CRISPR-Cas systems or base editors to disrupt critical virulence factors such as pili, capsule synthesis machineries and quorum sensing systems, or by inactivating antibiotic resistance determinants including beta-lactamase genes. As an intelligent nanomedicine delivery platform, engineered bacteriophage enable precise pathogen elimination an through photocatalytic reactive oxygen species generation, immunomodulatory interventions, or controlled release of antibacterial drugs. Furthermore, oral administration of engineered bacteriophage facilitates microbiota modulation, which selectively eliminate intestinal pathogens while preserve beneficial commensal microbiota, thereby restoring microbial community balance and preventing complications associated with dysbiosis. Finally, we critically analyze persistent challenges including host strain matching complexity, evolution of bacterial resistance mechanisms, pharmacokinetic optimization requirements, optimal administration route selection, large-scale production quality control standards and clinical dosing determination protocols. Through multidisciplinary integration of synthetic biology, infectious disease medicine and immunology, future translational medicine studies of bacteriophage should establish comprehensive technical platforms encompassing rapid phage screening, intelligent rational design, rigorous in vivo evaluation and standardized clinical validation processes, ultimately advancing engineered bacteriophage from laboratory innovations to clinically approved therapeutics for effectively combating MDR bacterial infections.

Objective To investigate gender differences and age-related changes in body composition(BC)among Miao adults in Rongshui,Guangxi Province,and to provide the basis for assessing nutritional status and health.Methods With informed consent,630 Miao adults(218 males,412 females)were randomly selected for this study.Body composition was assessed using bioelectrical impedance analysis(BIA).Results Weight,fat-free mass,muscle mass,trunk muscle mass,limb muscle mass,waist-to-hip ratio(WHR),body water,presumtion of bone mass and protein were significantly higher in males than in females.And the fat mass,trunk fat mass,limb fat mass,visceral fat content,subcutaneous fat content and percentage of body fat were significantly higher in females than in males.According to the evaluation of body mass index(BMI)and WHR,the proportion of overweight and obesity of Miao adults was higher than the average level of Miao residents,and their obesity was characterized by central obesity.With age,weight,fat mass,muscle mass,fat-free mass,limb muscle mass,limb fat mass,subcutaneous fat content,percentage of body fat,body water,presumtion of bone mass,and protein of Rongshui Miao adults showed a gradual decreasing trend,while visceral fat content and WHR increased progressively.BMI in male Miao adults,along with BMI,fat mass,trunk fat mass,subcutaneous fat content,percentage of body fat,and body water in female Miao adults,showed a trend of increasing followed by decreasing,peaking at the age of 40-49 years.Conclusion The body composition of Miao adults in Rongshui,Guangxi,exhibits significant gender differences and age-related variation change patterns,which may increase the risk of sarcopenia and metabolic diseases with aging.

To investigate the effects of Biyan Jiedu Capsules on the proliferation and apoptosis of nasopharyngeal carcinoma cells and their molecular mechanism, nasopharyngeal carcinoma cells CNE1 and CNE2 were used. They were divided into control group(30% blank serum medium), low-(10% drug-containing serum + 20% blank serum medium), medium-(20% drug-containing serum + 10% blank serum medium), and high-(30% drug-containing serum medium) concentration group of Biyan Jiedu Capsules according to in vitro experiment. After 24 h of intervention, the effects of Biyan Jiedu Capsules on the proliferation of CNE1 and CNE2 were detected by CCK-8 assay, clonal formation experiment, and EdU staining. The effect of Biyan Jiedu Capsules on apoptosis of CNE1 and CNE2 was detected by flow cytometry. Western blot was used to detect the effect of Biyan Jiedu Capsules on the expression of X-linked apoptosis inhibitor protein(XIAP), survivin, proliferating cell nuclear antigen(PCNA), and PI3K/Akt pathway-related proteins in CNE1 and CNE2. The results showed that compared with the control group, the survival rate of CNE1 and CNE2 in the medium and high concentration groups of Biyan Jiedu Capsules could be decreased in a concentration-dependent way(P<0.05, P<0.01). At the same time, EdU staining and clonal formation experiments showed that the proliferation of CNE1 and CNE2 was significantly inhibited in the medium and high concentration groups of Biyan Jiedu Capsules(P<0.05, P<0.01). Flow cytometry showed that the apoptosis rate of CNE1 and CNE2 was significantly increased in all concentration groups of Biyan Jiedu Capsules(P<0.01), and the apoptosis rate was concentration-dependent. Western blot showed that the expressions of XIAP, survivin, PCNA, p-PI3K, and p-Akt in all concentration groups of Biyan Jiedu Capsules were significantly down-regulated(P<0.05, P<0.01). In conclusion, Biyan Jiedu Capsules can inhibit the proliferation and induce apoptosis of nasopharyngeal carcinoma cells possibly by down-regulating the PI3K/Akt signaling pathway.
Humans ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Nasopharyngeal Carcinoma ; Nasopharyngeal Neoplasms/physiopathology* ; Proto-Oncogene Proteins c-akt/genetics* ; Cell Line, Tumor ; Drugs, Chinese Herbal/pharmacology* ; Phosphatidylinositol 3-Kinases/genetics* ; Signal Transduction/drug effects* ; Capsules ; Carcinoma/drug therapy*

Cryopreservation is the primary technique for in vitro preservation of allogeneic tissue. However, its success is often hindered by factors such as low temperature, ischemia, and hypoxia. This study investigated the potential of Sini Decoction, known for its antioxidant and anti-apoptotic properties, to reduce cryopreservation-induced injury in rats' sciatic nerves. Sini Decoction was prepared according to the Chinese Pharmacopoeia, and its cytotoxicity on Rsc96 cells was assessed by using the CCK-8 method. Sini Decoction at concentrations of 4, 8, and 16 mg·mL~(-1), termed as low-(SL), medium-(SM), and high-(SH) doses group, was used for cryopreservation of rats' sciatic nerves. A normal control(NC) group and a fresh nerve control(fresh) group were set. Flow cytometry and TUNEL staining were used to detect the apoptosis of neural tissue cells after cryopreservation. Western blot was used to detect the expression of apoptosis-related proteins(Bcl-2, Bax, caspase-3, and caspase-8) and nerve regeneration proteins(NGF and BDNF) in vitro after cryopreservation. Oxidative damage of neural tissue after cryopreservation was evaluated by measuring levels of GSH, SOD, MDA, ROS, and ATP. Cryopreserved nerves were then used for allogeneic transplantation. One week after transplantation, CD4~+ and CD8~+ fluorescent double staining assessed inflammatory cell invasion in the transplanted nerve segment, and ELISA evaluated the expression of serum inflammatory factors(IL-1, IFN-γ, and TNF-α) in recipients. Twenty weeks after transplantation, electrophysiology and NF200 neurofilament staining were used to evaluate nerve regeneration. RESULTS:: showed that Sini Decoction at concentrations of below 32 mg·mL~(-1) exhibited no cytotoxicity to Rsc96 cells. During in vitro nerve cryopreservation, Sini Decoction significantly reduced cell apoptosis, ROS, and MDA production compared to the NC group. In the SH group, the protein expression of NGF and BDNF in vitro, as well as ATP, SOD, and GSH production, were significantly increased. In the rejection reaction one week after transplantation, compared to the fresh nerve transplantation group, the SL and SM groups showed reduced CD4~+ and CD8~+ T cell invasion in the transplanted nerve segment and down-regulated IL-1, IFN-γ, and TNF-α expression in recipient serum. Twenty weeks after transplantation, the electrophysiological test results of CMAP, NCV, and NF200 neurofilament protein fluorescent staining in the SM and SH groups were superior to those in the NC and fresh groups. These findings indicate that Sini Decoction offers protective benefits in the cryopreservation of rats' sciatic nerves and holds significant potential for the in vitro preservation of tissue and organs.
Animals ; Apoptosis/drug effects* ; Rats ; Oxidative Stress/drug effects* ; Sciatic Nerve/cytology* ; Cryopreservation ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Rats, Sprague-Dawley ; Protective Agents/pharmacology*

OBJECTIVES: To investigate the causal relationship between Helicobacter pylori (Hp) infection and immune thrombocytopenia (ITP) using Mendelian randomization (MR), as well as the association between Hp infection and chronic ITP (cITP) through a clinical study. METHODS: The datasets from genome-wide association studies were used to select the single nucleotide polymorphism loci significantly associated with Hp infection as genetic instrumental variables. The MR analysis model was used to investigate the causal relationship between ITP and Hp infection. A retrospective analysis was conducted on the medical data of 316 children with newly diagnosed ITP at the First Affiliated Hospital of Xinjiang Medical University from January 2020 to December 2023. The children were followed up for 1 year, and a multivariate logistic regression analysis was used to investigate the risk factors for cITP. RESULTS: The inverse variance weighted analysis revealed that Hp infection was significantly associated with an increased risk of ITP (OR=1.280, 95%CI: 1.098-1.492, P=0.002). There was no heterogeneity or pleiotropy in this MR study (P>0.05), and the model was stable. The "leave-one-out" sensitivity analysis verified the reliability of the results. The multivariate logistic regression analysis demonstrated that Hp infection was an independent risk factor for progression to cITP (OR=7.916, 95%CI: 3.327-18.832, P<0.001). CONCLUSIONS Hp infection is a risk factor for the onset of ITP and is an independent risk factor for cITP in children.
Humans ; Helicobacter Infections/complications* ; Purpura, Thrombocytopenic, Idiopathic/etiology* ; Child ; Male ; Female ; Helicobacter pylori ; Prognosis ; Child, Preschool ; Logistic Models ; Retrospective Studies ; Risk Factors ; Polymorphism, Single Nucleotide ; Adolescent ; Infant

Ribonucleic acid(RNA)molecules with repeat expansion sequences can liquid-liquid phase separate into droplet-like condensates,which usually have good fluidity and can dynamically exchange matter and energy with the outside world,so as to play physiological functions.However,when the conditions are changed,the droplets will undergo a phase transition,forming gel-like or solid-like condensates.The change in the morphology of the condensates is closely related to many diseases.In this work,the effects of the RNA repeat length,concentration,cation and pH value on the liquid-liquid phase separation(LLPS)of RNA with CAG repeats were systematically studied,and the molecular structure of the condensates formed by LLPS was analyzed by Raman spectroscopy.This study revealed the molecular basis of the formation of different condensates from the perspective of structural biology,and provided new insights for in-depth understanding of the molecular assembly of RNA phase separation and phase transition.

Objective To investigate the expression of the histone deacetylase SIRT7 in glioma cells and its impact on epithelial-mesenchymal transformation(EMT),as well as its effects on proliferative,migratory and invasive capabilities of glioma cells.Methods Bioinformatics analysis was conducted on data from glioma patients in the Cancer Genome Atlas(TCGA)and the Chinese glioma Genome Atlas(CGGA)databases to explore the expression of SIRT7 gene in gliomas and its correlation with tumor grading,molecular characteristics and patient clinical prognosis.Glioma cells were randomly divided into control,SIRT7 knockdown,SIRT7 overexpression,drug treatment(10 μmol/L hydrochlorothiazide)and drug(10 μmol/L hydrochlorothiazide)+SIRT7 overexpression groups.The CCK-8 assay,cell scratch assay and Transwell assay were used to observe the effects of upregulating and downregulating SIRT7 expression on glioma cell proliferation,migration and invasion.RT-qPCR and Western blotting were employed to detect the effects of SIRT7 on the expression of neural cadherin(N-cadherin),Vimentin,E-cadherin,transforming growth factor-β(TGF-β),Ki-67,and Smad3 protein in glioma cells.Nude mouse tumor-bearing experiments were conducted to observe the effect of SIRT7 knockdown on glioma growth.Results Higher expression levels of SIRT7 gene were associated with poorer clinical prognosis(P＜0.0001).SIRT7 expression levels were significantly correlated with tumor grading and 1p19q coding status(P＜0.01).Compared with normal HA cells,glioma cells showed significantly increased SIRT7 expression levels(P＜0.01).CCK-8 assay results indicated that,compared with control group,the proliferation activity of glioma cells in SIRT7 knockout group was significantly decreased(P＜0.01),while SIRT7 overexpression group showed significantly increased proliferation activity(P＜0.01).EdU assay results showed that,compared with control group,the proportion of glioma cells in the proliferative stage was significantly decreased in SIRT7 knockdown group(P＜0.01),and significantly increased in SIRT7 overexpression group(P＜0.01).Western blotting results revealed that,compared with control group,the protein expression levels of TGF-β,Smad3,N-cadherin and Vimentin were significantly decreased in SIRT7 knockdown group(P＜0.01),while the expression level of E-cadherin protein was significantly increased(P＜0.05).SIRT7 overexpression group showed significantly increased protein expression levels of TGF-β,Smad3,N-cadherin and Vimentin(P＜0.05),and a significantly decrease in E-cadherin protein expression level(P＜0.05).Scratch assay results indicated that,compared with control group,the migration ability of cells in SIRT7 knockdown group and drug group was significantly decreased(P＜0.01),and SIRT7 overexpression group showed significantly increased cell migration ability(P＜0.05).Compared with drug group,drug+SIRT7 overexpression group exhibited significantly increased cell migration ability(P＜0.01).Transwell assay results showed that,compared with control group,the migration and invasion abilities of cells in SIRT7 knockdown group and drug group were significantly decreased(P＜0.01),and SIRT7 overexpression group exhibited significantly increased migration and invasion abilities(P＜0.01).Compared with drug group,drug+SIRT7 overexpression group showed significantly increased migration and invasion abilities(P＜0.01).Nude mouse tumor-bearing assay results indicated that the volume and weight of glioma in SIRT7 knockdown group were significantly reduced compared with control group(P＜0.01).Conclusions Glioma patients with high SIRT7 expression have poorer clinical prognosis.SIRT7 can regulate the TGF-β/Smad3 pathway to mediate EMT,promoting the proliferation and migration of glioma cells.SIRT7 knockdown can inhibit the growth of transplanted gliomas in nude mice.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43％(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38％,9.73％,and 8.47％,respectively.The prevalence of CRE strains in Escherichia coli was 1.99％.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)％,followed by blood(20.88±3.40)％and urine(18.40±3.45)％.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)％.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.

Objective To characterize the changing species distribution and antibiotic resistance profiles of respiratory isolates in hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Methods Commercial automated antimicrobial susceptibility testing systems and disk diffusion method were used to test the susceptibility of respiratory bacterial isolates to antimicrobial agents following the standardized technical protocol established by the CHINET program.Results A total of 589 746 respiratory isolates were collected from 2015 to 2021.Overall,82.6％of the isolates were Gram-negative bacteria and 17.4％were Gram-positive bacteria.The bacterial isolates from outpatients and inpatients accounted for(6.0±0.9)％and(94.0±0.1)％,respectively.The top microorganisms were Klebsiella spp.,Acinetobacter spp.,Pseudomonas aeruginosa,Staphylococcus aureus,Haemophilus spp.,Stenotrophomonas maltophilia,Escherichia coli,and Streptococcus pneumoniae.Each microorganism was isolated from significantly more males than from females(P＜0.05).The overall prevalence of methicillin-resistant S.aureus(MRSA)was 39.9％.The prevalence of penicillin-resistant S.pneumoniae was 1.4％.The prevalence of extended-spectrum β-lactamase(ESBL)-producing E.coli and K.pneumoniae was 67.8％and 41.3％,respectively.The overall prevalence of carbapenem-resistant E.coli,K.pneumoniae,Enterobacter cloacae,Pseudomonas aeruginosa,and Acinetobacter baumannii was 3.7％,20.8％,9.4％,29.8％,and 73.3％,respectively.The prevalence of β-lactamase was 96.1％in Moraxella catarrhalis and 60.0％in Haemophilus influenzae.The H.influenzae isolates from children(＜18 years)showed significantly higher resistance rates to β-lactam antibiotics than the isolates from adults(P＜0.05).Conclusions Gram-negative bacteria are still predominant in respiratory isolates associated with serious antibiotic resistance.Antimicrobial resistance surveillance should be strengthened in clinical practice to support accurate etiological diagnosis and appropriate antimicrobial therapy based on antimicrobial susceptibility testing results.