Objective: To investigate the prevalence of undernutrition and its associated factors among left behind and non left behind primary and secondary school students in the Nutrition Improvement Program for Rural Compulsory Education Students (NIPRCES) areas of central and western China, so as to provide evidence for improving the nutritional status of children and adolescents. Methods: A survey was conducted among 123 782 students selected by random cluster sampling method in grades 3-9 from NIPRCES in central (Hebei, Shanxi, Heilongjiang, Jilin, Anhui, Jiangxi, Henan, Hunan, Hubei, and Hainan) and western (Gansu, Guangxi, Inner Mongolia, Ningxia, Tibet, Shaanxi, Guizhou, Sichuan, Xinjiang, the Xinjiang Production and Construction Corps, Yunnan, Qinghai, and Chongqing) China in 2023. Anthropometric measurements and questionnaires were used to assess nutritional and dietary status. The prevalence of undernutrition was compared between left behind and non left behind students by Chi square test, and associated factors were analyzed by three level Logistic mixed effects model. Results: The prevalence of undernutrition was 8.5% (4 326) in left behind students and 8.1% (5 905) in non left behind students. Three level Logistic mixed effect model analysis showed that whether left behind or non left behind, the undernutrition rates of primary and secondary students in western regions were higher than those of students in central regions [ OR (95% CI )=1.72(1.57-1.87),2.25(2.07- 2.43 )]; the undernutrition risk was lower for those whose fathers had a cultural level of high school or above [ OR (95% CI )=0.69(0.62-0.77),0.90(0.82-0.98)] or junior high school [ OR (95% CI )=0.72(0.66-0.79),0.92(0.85-0.99)] compared to those with primary school or below; picky eating or selective eating increased the risk of undernutrition [ OR (95% CI )=2.36(2.07-2.68),2.28(2.04-2.55)], and primary and secondary school students without nutritional content in health education classes had higher rates of undernutrition [ OR (95% CI )=1.12(1.03-1.23),1.09(1.01-1.17)](all P <0.05). Conclusion The prevalence of undernutrition is slightly higher in left behind primary and secondary students than in non left behind primary and secondary students in central and western NIPRCES areas, with variations across different characteristics.

Objective: To analyze the trends of the frequency of meat, egg, and milk consumption among rural primary and junior high school students in central and western China covered by the Nutrition Improvement Program for Rural Compulsory Education Students (NIPRCES) from 2015 to 2023, so as to provide basis for formulating more targeted nutrition intervention policies and health education strategies. Methods: Using data from six rounds of monitoring and evaluation (2015-2021 and 2023), the study included 323 870 students from grade 3 to 9 across 22 provinces (autonomous regions and municipalities) in central and western China. The consumption frequencies of meat, egg, and milk over the past week were collected via questionnaires. The Cochran-Armitage trend test was used to analyze temporal trends, and multivariable Logistic regression models were employed to analyze factors associated with the frequency of meat, egg and milk consumption and to test for interaction effects between the year and gender, region, and grade level. Results: From 2015 to 2023, the proportion of students consuming meat, egg, and milk ≥1 time/day increased from 23.20 %, 10.71%, and 0.74% to 35.53%, 22.09%, and 26.63%, respectively. Trend tests indicated a significant upward trend for the daily intake of all three food categories for meat, egg and milk over the years ( Z =67.18, 64.90, 93.14, all P <0.01). Multivariable Logistic regression analysis showed that the daily meat intake was lower in the central region than in the western region ( OR=0.77, 95%CI =0.76-0.78), whereas the daily intake of eggs ( OR=1.19, 95%CI =1.17-1.22) and milk ( OR= 1.27 , 95%CI =1.24-1.29) was higher in the central region (all P <0.05). Compared with grade 3-4 students, junior high school students had lower daily intake of meat, eggs, and milk≥1 time/day ( OR =0.95, 0.77, 0.77, all P <0.05), with a declining trend as grade increased. Girls also had lower daily intake of meat, eggs, and milk ≥1 time/day than boys ( OR =0.95，0.93，0.91, all P < 0.05). Significant interactions were observed between year and region, as well as between year and grade (all P <0.05). Conclusion From 2015 to 2023, the NIPRCES improved the intake level of among rural students, but the situation of relatively insufficient intake of egg and milk among females, junior high school students and those in the western region still exists.

Coronavirus-related diseases pose a significant challenge to the global health system. Given the diversity of coronaviruses and the unpredictable nature of disease outbreaks, the traditional "one bug, one drug" paradigm struggles to address the growing number of emerging crises. Therefore, there is an urgent need for therapeutic agents with broad-spectrum anti-coronavirus activity. Here, we provide evidence that ATV006, an anti-SARS-CoV-2 nucleoside analog targeting RNA-dependent RNA polymerase (RdRp), has broad antiviral activity against human and animal coronaviruses. Using mouse hepatitis virus (MHV) and human coronavirus NL63 (HCoV-NL63) as a model, we show that ATV006 has potent prophylactic and therapeutic activity against murine coronavirus infection in vivo. Remarkably, ATV006 successfully inhibits viral replication in mice even when administered 96 h after infection. Due to its oral bioavailability and potency against multiple coronaviruses, ATV006 has the potential to become a useful antiviral agent against SARS-CoV-2 and other circulating and emerging coronaviruses in humans and animals.

Objective:To investigate the pathways involved in bisphenol S(BPS)and bisphenol F(BPF)induced male reproductive injury by bioinformatics methods and experimental verification.Methods:Bioinformatics analysis was conducted to screen the genes related to male reproductive system diseases associated with BPF and BPS from the Comparative Toxicogenomics Database(CTD).Functional enrichment using Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed to predict potential signaling pathways and key genes.Cell counting kit-8(CCK-8)method was used to assess the cell viability in various groups treated with different concentrations of BPS and BPF(1×10-3,1×10-2,1×10-1,1×100,1×101,and 1×102 μmol·L-1).TM3 cells were divided into control group(0.1％DMSO),different doses of BPS groups,and different doses of BPF groups.The cells were treated with 20,40,and 80 μmol·L-1 of BPS and BPF for 72 h,respectively.Real-time fluorescence quantitative PCR(RT-qPCR)and Western blotting method were used to detect the expression levels of key genes mRNA and proteins in various groups.Results:The bioinformatics analysis results revealed that 507 and 447 male systemic disease genes related to BPS and BPF were screened by CTD,respectively.The GO enrichment analysis results showed that the selected genes were primarily enriched in biological processes(BP)such as reproductive system development and reproductive structure development.The KEGG pathway analysis results indicated that these genes were significantly enriched in signaling pathways such as phosphatidylinositol 3-kinase/protein kinase B(PI3K/AKT),hypoxia-inducible factor-1(HIF-1),and cellular senescence(P＜0.001).The CCK-8 method results showed that compared with control group,the cell viabilities in 1× 102 μmol·L-1 BPF and BPS groups were significantly decreased(P＜0.05),while the viabilities of TM3 cells in other groups had no significant changes(P＞0.05).After BPS treatment,compared with control group,the expression levels of PI3K,AKT,hypoxia-inducible factor-1α(HIF-1α),and CREB-binding protein(CBP)mRNA in low,medium,and high doses of BPS groups were decreased(P＜0.05),the expression levels of PI3K protein were decreased(P＜0.05),the expression levels of B-cell lymphoma-2-associated X protein(Bax)protein were increased(P＜0.05),and the expression levels of serine protease inhibitor clade B,member 10(SERPINB10)mRNA were increased(P＜0.01);the expression levels of Bax and intraflagellar transport 80 homolog(IFT80)mRNA in the cells in medium and high doses of BPS groups were increased(P＜0.05);the expression levels of B-cell lymphoma-2(Bcl-2)mRNA and protein in low and high doses of BPS groups were decreased(P＜0.05);the expression levels of additional sex combs like 2(ASXL2)mRNA in low and medium doses of BPS groups were decreased(P＜0.01).After BPF treatment,compared with control group,the expression levels of Bcl-2,HIF-1α,and structural maintenance of chromosomes protein 1B(SMC1B)mRNA in low,medium,and high doses of BPF groups were decreased(P＜0.05),and the expression levels of IFT80 mRNA(P＜0.01)and Bax protein(P＜0.01)were increased;the expression levels of PI3K,AKT,and ring finger protein 130(RNF130)mRNA in low and high doses of BPF groups were decreased(P＜0.05);the expression level of CBP mRNA in medium dose of BPF group was decreased(P＜0.05),while the expression level of RNF130 mRNA was increased(P＜0.05);the expression levels of PI3K and Bcl-2 proteins in high dose of BPF group were decreased(P＜0.05).Conclusion:BPF and BPS may cause cell cytotoxicity and impair male reproductive health through PI3K/AKT and HIF-1 signaling pathways.RNF130 and SMC1B may be important targets for their induction of male reproductive toxicity.

Objective To investigate the influence of type 2 diabetes mellitus(T2DM)on cognitive function and the effective connectivity with in the default mode network(DMN)in the brain.Methods A total of 93 hospitalized patients diagnosed with T2DM were enrolled in this study as T2DM group from The First Affiliated Hospital of Guangzhou University of Chinese Medicine during September 2021 to December 2022.Simultaneously,108 healthy individuals were recruited from the community as normal control(NC)group.The cognitive functions were evaluated in the two groups.A random dynamic causal modeling approach was employed to analyze the effective connectivity within DMN in both groups.Additionally,Pearson correlation analysis was performed to examine the association between differential connectivity,clinical indicators,and cognitive scores in both groups.Results In comparison to the NC group,T2DM individuals exhibited statistically significant reductions in scores in the auditory verbal learning test(AVLT)for immediate recall and the digit symbol substitution test(DSST)(P＜0.05).Additionally,they displayed a notable decrease in effective connectivity from the left lateral parietal cortex(LLPC)to the posterior cingulate cortex(PCC),as well as from the LLPC to the right lateral parietal cortex(RLPC)within the DMN(P＜0.05).Pearson correlation analysis unveiled a negative association between HbA1c levels and the strength of effective connectivity from LLPC to PCC.Conversely,a positive correlation was observed between AVLT(immediate)scores and the strength of effective connectivity from LLPC to PCC and LLPC to RLPC.Additionally,DSST scores displayed a positive correlation with the strength of effective connectivity from LLPC to PCC(P＜0.05).Conclusion Patients with T2DM display compromised effective connectivity from LLPC to PCC and LLPC to RLPC within the DMN network,and this alteration may associated with cognitive impairment.

Objective To study the use of phospholipase A2(PLA2)to open blood brain barrier(BBB)by affecting the physiological barrier function and promote the antidote drug asoxime(HI-6)to take effect in brain,providing a new research idea for the treatment of central nervous system organophosphorus poisoning.Methods The stability of the complex of PLA2-HI-6 was characterized through methods such as release and stability experiments.The cerebral delivery ability of the complex was evaluated through brain tissue FLU fluorescence pathology.The effect of PLA2 on cell membrane permeability was evaluated by observation with propidium iodide(PI)staining.The mouse model of soman poisoning was established to evaluate cerebral effects of the complex against soman central poisoning:(1)measuring the reactivation rate of mouse brain acetylcholinesterase(AChE);(2)observing pathological sections of mouse brain tissues;(3)calculating the survival time of mice in different groups.The safety of PLA2 was evaluated at both cellular and animal levels.Results Releasing and stability test results showed that the addition of PLA2 didn't affect the release and degradation of HI-6.PLA2 helped FLU transport into brain tissues,demonstrating excellent central delivery capability.The complex of PLA2-H1-6 significantly increased the reactivation rate of AChE in the brain of poisoned mice to 50％,about 12 times higher than that treated by HI-6 alone.Pathological results of mouse brain tissue showed that the complex effectively counteracted the cerebral nervous system damage caused by organophosphorus poisoning,significantly prolonged the survival time of mice at three times the lethal dose,and significantly alleviated symptoms of central toxicity.Research on delivery mechanisms found that complex achieved central delivery by increasing the permeability of the cell membrane to crossing the cell.Safety tests at the cellular and animal levels showed that the dosage of PLA2 used in this study was safe and reliable,and did not cause any adverse reactions.Conclusion By using PLA2 as an open material,combined with the therapeutic drug of HI-6,a complexcapable of effectively penetrating the BBB was successfully constructed.This complex has a certain central targeting ability and significantly improves the reactivation rate of AChE in the brain after organophosphorus poisoning,whichprovides a referencefor solving the difficult problem of enzyme reactivation incentral nervous system organophosphorus poisoning.

Abstract: Chronic infection of hepatitis B virus (HBV) is the major cause of hepatocellular carcinoma (HCC) in China. The occurrence of HCC through chronic inflammation follows the Darwinian evolutionary law, known as "mutation-selection-adaptation". Inflammatory mutagenic molecules promote the generation of somatic mutations, and the most mutant cells are eliminated by inflammatory microenvironment. However, a minority of mutant cells survive the selective pressure and develop to tumor initial cells by activating oncogenic signaling pathway and acquiring "stemness" characteristics. Alongside this process, HBV also evolves under the pressure of inflammatory microenvironment, which is characterized by the accumulation of cancer-promoting viral mutations, reducing the ability to infect new individuals. The high-risk mutant strains are eliminated with the death of hosts, leading to a phenomenon termed as "dead-end evolution". HBV evolution contributes to cancer evolution by maintaining the inflammatory microenvironment, activating oncogenic pathways, inducing somatic cell mutations, and altering metabolic patterns. The combo mutations of HBV and HBV integrations can be applied to predict the occurrence and prognosis of HCC. Anti-viral treatment reduces the risk of HCC by relieving inflammation. This article reviews the molecular epidemiological evidence and mechanistic advances related to the co-evolution of HBV and HCC. Clarifying the co-evolutionary pattern of virus and cancer and the key molecular events involved, is beneficial for identifying new biomarkers and therapeutic targets, thus improving the prevention and treatment strategies for HCC.

As a limiting factor in telomerase activity,telomerase reverse transcriptase(TERT)controls cellular senescence and apoptosis by maintaining telomere length.TERT is not expressed or little expressed in most normal cells.However,the abnormal overexpression of TERT promotes the ability of tumor cells to replicate indefinitely.This review summarizes the regulatory mechanisms of TERT expression,including the main transcription factor families,single nucleotide polymorphism sites,and epigenetic modification changes such as DNA methylation,histone modification,and non-coding RNA.The role of these molecular mechanisms as well as significant TERT single-base variants and virus integration variants in the occurrence and development of cancer are reviewed.On this basis,its application in tumor diagnosis and prognosis is discussed.

With the widespread use of mobile phones, laptops, and WIFI, the effects of radio frequency radiation (RFR) on human health are of increasing concern, and there are particular concerns about its reproductive toxicity. Studies have shown that the reproductive system is a sensitive target for RFR. In males, RFR is associated with decreased sperm quality and serum testosterone levels, but there are few studies on the biological effects of RFR by altering physical parameters on the male reproductive system. This paper introduced common sources of RFR, reviewed the toxic effects and mechanisms of RFR targeting male reproductive system from the aspects of spermatogenic cells, sperm structure, blood-testicular barrier, and testicular function, and analyzed male reproductive system related toxic effects of RFR by varying physical parameters including frequency, treatment duration, and specific absorption rate, so as to provide a theoretical basis and scientific basis for the safe and reasonable use of radio frequency electromagnetic field by humans and subsequent in-depth research.

The severe acute respiratory syndrome coronavirus 2 （SARS-CoV-2） and its variants are still globally spreading. Vaccines can reduce the mortality， but cannot eliminate the risk of infection. The identification and protection of the high-risk susceptible population remains of great importance for the prevention and control of SARS-CoV2 and other coronavirus infections. Smoking is an important risk factor for many respiratory diseases， and therefore may also influence the risk of SARS-CoV2 infection and the disease progression after infection. This study reviewed the epidemiological and mechanistic evidence supporting the relationship between tobacco exposure and SARS-CoV2 infection， summarized the contributing effects of tobacco exposure to the infection risk， disease severity， and mortality of COVID-19， and analyzed the molecular mechanisms by which cigarette smoking affects COVID-19 through regulating inflammatory microenvironment and gene expression.