Metabolic dysfunction-associated fatty liver disease （MAFLD）， as one of the most common chronic liver diseases in the world， poses a severe challenge to precision diagnosis and treatment due to its complex pathogenesis and highly heterogeneous disease progression. Existing clinical classification systems cannot meet the needs for comprehensively analyzing the complexity of the disease and the heterogeneity of its adverse outcomes. In recent years， data-driven prognostic risk classification methods have gradually emerged， optimizing the ability for predicting adverse outcomes and enhancing the accuracy of identifying different endpoint outcomes. However， such paradigm of “classify first， associate outcomes later” suffers from a “black-box” nature， and there are various indicators for classification， leading to limited stability and generalizability in clinical application. Future research needs to integrate or establish large-scale population cohorts， develop outcome-oriented prognostic risk classification models， incorporate dynamic data， refine classification algorithms， and validate their generalizability across multiple populations， thereby providing reliable support for the precision diagnosis and treatment of MAFLD.

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.

AIM:To investigate the current status of astigmatism and its associated factors among children and adolescents from kindergarten through senior high school in Yangpu District, Shanghai, and to provide scientific evidence for the prevention and control of refractive errors.METHODS:A cluster sampling method was employed. From September to November 2024, students from 14 randomly selected schools in Yangpu District, Shanghai, were enrolled as study subjects. Autorefraction and ocular biometry were performed under non-cycloplegic conditions, and questionnaire surveys were administered. Comparisons of astigmatism degree, detection rate, and axis were made across age groups, educational stages, and sexes. Multiple linear and logistic regression analyses were conducted to identify factors associated with astigmatism.RESULTS:A total of 7 233 students aged 4-18 y were enrolled including 3 731 males, 3 502 females, with the mean age 10.13±4.18 y, astigmatism -0.76±0.82 D, and the detection rate(≤-1.00 D)was 29.23%. Both the degree and detection rate of astigmatism were correlated with age and educational stage, peaking in senior high school, with the most pronounced changes observed during primary school. Besides age, astigmatic refractive power was influenced by spherical equivalent(β=0.105, P<0.001), mean keratometry(β=-0.118, P<0.001), sex(with boys as the reference, girls: β=0.054, P<0.001), frequent sustained near work for 30-40 min(with “almost never” as the reference, β=-0.030, P=0.038), preterm birth(β=-0.023, P=0.044), maternal myopia(β=-0.028, P=0.020), and homework completion time on rest days(β=-0.035, P=0.041). The detection rate of astigmatism was associated with maternal myopia(OR=1.130, P=0.039), male sex(OR=0.773, P<0.001), shorter sleep duration on school days(OR=0.909, P=0.028), shorter sleep duration on rest days(OR=0.937, P=0.046), preterm birth(OR=1.382, P=0.012), frequent excessive head lowering(OR=1.216, P=0.045), homework completion time on rest days(OR=1.043, P=0.046), higher spherical equivalent(OR=0.891, P<0.001), and higher mean keratometry(OR=1.188, P<0.001).CONCLUSION:The degree and detection rate of astigmatism among children and adolescents from kindergarten to senior high school in Yangpu District, Shanghai are correlated with educational stage, and primary school may represent a critical period for astigmatism prevention and control. Male sex, maternal myopia, preterm birth, high-intensity near work, and insufficient sleep and other factors may be associated with the onset and progression of astigmatism. It is recommended that education and health departments strengthen visual health screening during primary school, while promoting behavioral interventions such as scientific eye-use habits and adequate sleep across different educational stages to delay the onset and progression of astigmatism.

To investigate whether Tasquinimod can influence cisplatin resistance in drug-resistant ovarian cancer (OC) cell lines by regulating histone deacetylase 4 (HDAC4) or p21, we explored its effects on the cell cycle, and associated mechanisms.RT-PCR and Western blot analyses, flow cytometry, CCK8 assay, and immunofluorescence were utilized to investigate the effects of Tasquinimod on gene expression, cell cycle, apoptosis, viability, and protein levels in OC cells. The results showed that Tasquinimod inhibited cell viability and promoted apoptosis in SKOV3/DDP (cisplatin) and A2780/DDP cells more effectively than DDP alone. In combination with cisplatin, Tasquinimod further enhanced cell apoptosis and reduced cell viability in these cell lines, an effect that could be reversed following HDAC4 overexpression. Tasquinimod treatment down-regulated HDAC4, Bcl-2, and cyclin D1, and CDK4 expression and up-regulated the cleaved-Caspase-3, and p21 expression in SKOV3/DDP and A2780/ DDP cells. Additionally, Tasquinimod inhibited DDP resistance in OC/DDP cells. These effects were similarly observed in OC mouse models treated with Tasquinimod. In conclusion, Tasquinimod can improve OC cells' sensitivity to DDP by down-regulating the HDAC4/p21 axis, offering insights into potential strategies for overcoming cisplatin resistance in OC.

Direct compression is an ideal method for tablet preparation, but it requires the powder's high functional properties. The functional properties of the powder during compression directly affect the quality of the tablet. 15 parameters such as Py, FES-8KN, FES-12KN, FES-16KN, CR-8KN, CR-12KN, and CR-16KN were used as the characteristic variables in this paper. Unsupervised learning methods like principal component analysis, cluster analysis, and factor analysis were applied to analyze and classify the compression behavior data of 36 traditional Chinese medicine powders. The results showed that both different dimensionality reduction classification methods could effectively differentiate the compression behavior characteristics of 36 traditional Chinese medicine compound powders. The hierarchical cluster analysis results showed a better agreement with the actual compression phenomena of the powders, where group 1 was high elasticity and low compressibility, group 2 was easily compressed and hard to break, group 3 was excellent compressibility and compactibility. This study is expected to provide references and ideas for predicting the behavior of traditional Chinese medicine powders and the screening of tablet formulations.

To investigate whether Tasquinimod can influence cisplatin resistance in drug-resistant ovarian cancer (OC) cell lines by regulating histone deacetylase 4 (HDAC4) or p21, we explored its effects on the cell cycle, and associated mechanisms.RT-PCR and Western blot analyses, flow cytometry, CCK8 assay, and immunofluorescence were utilized to investigate the effects of Tasquinimod on gene expression, cell cycle, apoptosis, viability, and protein levels in OC cells. The results showed that Tasquinimod inhibited cell viability and promoted apoptosis in SKOV3/DDP (cisplatin) and A2780/DDP cells more effectively than DDP alone. In combination with cisplatin, Tasquinimod further enhanced cell apoptosis and reduced cell viability in these cell lines, an effect that could be reversed following HDAC4 overexpression. Tasquinimod treatment down-regulated HDAC4, Bcl-2, and cyclin D1, and CDK4 expression and up-regulated the cleaved-Caspase-3, and p21 expression in SKOV3/DDP and A2780/ DDP cells. Additionally, Tasquinimod inhibited DDP resistance in OC/DDP cells. These effects were similarly observed in OC mouse models treated with Tasquinimod. In conclusion, Tasquinimod can improve OC cells' sensitivity to DDP by down-regulating the HDAC4/p21 axis, offering insights into potential strategies for overcoming cisplatin resistance in OC.

To investigate whether Tasquinimod can influence cisplatin resistance in drug-resistant ovarian cancer (OC) cell lines by regulating histone deacetylase 4 (HDAC4) or p21, we explored its effects on the cell cycle, and associated mechanisms.RT-PCR and Western blot analyses, flow cytometry, CCK8 assay, and immunofluorescence were utilized to investigate the effects of Tasquinimod on gene expression, cell cycle, apoptosis, viability, and protein levels in OC cells. The results showed that Tasquinimod inhibited cell viability and promoted apoptosis in SKOV3/DDP (cisplatin) and A2780/DDP cells more effectively than DDP alone. In combination with cisplatin, Tasquinimod further enhanced cell apoptosis and reduced cell viability in these cell lines, an effect that could be reversed following HDAC4 overexpression. Tasquinimod treatment down-regulated HDAC4, Bcl-2, and cyclin D1, and CDK4 expression and up-regulated the cleaved-Caspase-3, and p21 expression in SKOV3/DDP and A2780/ DDP cells. Additionally, Tasquinimod inhibited DDP resistance in OC/DDP cells. These effects were similarly observed in OC mouse models treated with Tasquinimod. In conclusion, Tasquinimod can improve OC cells' sensitivity to DDP by down-regulating the HDAC4/p21 axis, offering insights into potential strategies for overcoming cisplatin resistance in OC.

Objective To explore the efficacy of goal management training(GMT)on core symptoms and mental status in college students with attention deficit hyperactivity disorder(ADHD)inattentive type.Methods Delphi method was used to construct a GMT program for college students with inattentive ADHD.Then,totally 68 college students with inattentive ADHD were recruited through advertisements published by hospitals and universities(Second Affiliated Hospital of Army Medical University,and 3 universities in Chongqing from March to June 2024.The subjects were randomly divided into an intervention group(n=34)and a control group(n=34).The intervention group received GMT for 2 h,once a week,for 7 weeks,and the control group did not receive training for the time being.The 2 groups were evaluated within 1 week before and in 7 weeks after intervention by using Adult ADHD Self-Report Scale(ASRS),Dysregulation of Emotions Rating Scale(DERS),Generalized Anxiety Disorde-7(GAD-7),Patient Health Questionnaire-9(PHQ-9),Self-Compassion Scale(SCS),and Satisfaction with Life Scale(SWLS).Results ① The expert authority coefficient(Cr)of 2 rounds of expert consultation was 0.83,with a questionnaire recovery rate of 100%and 95%,respectively,the Kendall's coordination coefficient was 0.081(P<0.01)and 0.226(P<0.01),and the coefficient of variation was<0.3,indicating the results of the expert consultation were reliable.The constructed GMT program includes 1 first-level indicator,7 second-level indicators,and 20 third-level indicators.② After 7 weeks of GMT intervention,the interaction between the 2 groups and time showed that the experimental group obtained significant improvements than the control group in terms of inattention symptoms(Wald Chi-square=28.35,P<0.001),dysregulation of emotions(Wald Chi-square=23.81,P<0.001),anxiety(Wald Chi-square=22.79,P<0.001),depression(Wald Chi-square=20.52,P<0.001),self-compassion(Wald Chi-square=9.36,P<0.01),and life satisfaction(Wald Chi-square=3.97,P<0.05).Conclusion GMT intervention can significantly improve the core symptoms of college students with inattentive ADHD,reduce anxiety and depression levels,enhance their emotion regulation and self-compassion abilities,and improve their life satisfaction.

Widespread utilization of glyphosate has led to environmental residues,posing potential threats to ecological systems and human health.Traditional methods for detection of glyphosate are limited by specialized equipment and operational techniques,resulting in inefficient responses.Therefore,it is urgent to develop a convenient,sensitive and accurate detection method for detection of glyphosate.Herein,a new naphthalenesulfonamide-based"Turn-on"fluorescent probe was synthesized using 2-chloroaniline and dansyl chloride as raw materials through a one-step process,which showed a good linear relationship between the glyphosate concentration in concentration range of 0.003-70 μmol/L and the fluorescence intensity(R2=0.995),with a detection limit of 2.73 nmol/L(S/N=3).Analytical techniques such as nuclear magnetic resonance(NMR)spectroscopy and high-resolution mass spectrometry(HRMS)were used to investigate the interaction mechanism between the fluorescent probe and glyphosate.The results indicated that a nucleophilic substitution reaction occurred between the probe and the secondary amine(—NH—)of glyphosate,inducing a photoinduced electron transfer(PET)effect which enhanced the fluorescence intensity by 11.2 times.The probe showed good anti-interference ability towards coexisting metal ions,anions and pesticides in water.When applied to determination of glyphosate in the samples such as tap water,river water(Xiangxi River Reservoir),soil,soybeans,and corn,the spiking recoveries ranged from 94.7％to 109.9％,demonstrating the high accuracy and broad applicability of this detection method.A portable test strip based on this fluorescent probe was developed for rapid semi-quantitative analysis of glyphosate.The developed method was rapid,sensitive,and portable,providing theoretical and technical support for on-site measurement of environmental contaminants.

Objective To investigate the effect of miR-185-5p-mediated targeted negative regulation of transmembrane 9 superfamily member 1(TM9SF1)on proliferation,migration and autophagy in lung adenocarcinoma cells.Methods The expression of miR-185-5p in lung adenocarcinoma tissues was analyzed using dataset GSE51853 downloaded from the Gene Expression Omnibus(GEO)database.Potential target proteins of miR-185-5p were predicted using online databases(miRTargetLink,miRTarbase,and DIANA-microT-CD),and autophagy-related proteins were obtained from HADb.The intersected results from these four databases was identified,and survival curves of vascular endothelial growth factor A(VEGFA)and TM9SF1 within the overlapping candidates were analyzed using the StarBase database.TM9SF1 3'UTR wild-type(WT)or TM9SF1 3'UTR mutant(MUT)reporter plasmids were separately co-transfected with miR-185-5p control plasmid(CON)or miR-185-5p overexpression plasmid(over-miR-185-5p)into HEK-293T cells.A dual-luciferase reporter gene assay was employed to assess the binding interaction between miR-185-5p and TM9SF1 and quantify the subsequent luciferase activity.Western blotting was used to assess TM9SF1 protein expression levels in A549 cells transfected with over-miR-185-5p.A549 cells were divided into three groups:(1)CON+NC group,co-transfected with miR-185-5p control plasmid and TM9SF1 control plasmid;(2)over-miR-185-5p+NC group,co-transfected with over-miR-185-5p and TM9SF1 control plasmid;(3)over-miR-185-5p+over-TM9SF1 group,co-transfected with both miR-185-5p and TM9SF1 overexpression plasmids.EdU cell proliferation assay,wound healing assay,and Transwell migration assay were performed to validate the effects of miR-185-5p targeted binding to TM9SF1 on proliferation and migration capacities in lung adenocarcinoma.Changes in autophagic flux and mitochondrial membrane potential(MMP)of lung adenocarcinoma cells were detected using stubRFP-sensGFP-LC3 lentivirus and JC-1 assays,respectively.Results In the GSE51853 dataset,miR-185-5p expression level was significantly lower in lung adenocarcinoma tissues compared with normal lung tissues(P<0.01).qRT-PCR analysis revealed that miR-185-5p expression was downregulated in lung adenocarcinoma cell lines NCI-H1299 and A549 compared with normal lung epithelial cells BEAS-2B(P<0.01).Bioinformatics predictions using miRTargetLink,miRTarbase,DIANA-microT-CD,and HADb databases indicated that miR-185-5p could target and regulate the autophagy-related protein TM9SF1.Dual-luciferase reporter assays and Western blotting demonstrated that miR-185-5p directly bound to the 3'UTR region of TM9SF1 mRNA,and overexpression of miR-185-5p significantly reduced the expression of target protein TM9SF1(P<0.05).EdU cell proliferation,wound healing,and Transwell migration assays demonstrated that miR-185-5p overexpression inhibited proliferation and migration capacities of lung adenocarcinoma cells,whereas TM9SF1 overexpression could attenuate this inhibition effect(P<0.05).Results of stubRFP-sensGFP-LC3 for autophagic flux analysis demonstrated that overexpression of miR-185-5p enhanced autophagic flux in A549 cells,whereas co-overexpression of miR-185-5p and TM9SF1 suppressed autophagic flux.JC-1 assays showed a decreased MMP level in A549 cells after miR-185-5p overexpression,with higher MMP level observed when miR-185-5p and TM9SF1 were co-overexpressed.Conclusion miR-185-5p may suppress proliferation,migration,and autophagy capacities in lung adenocarcinoma cells by targeting TM9SF1 through negative regulation.