A full-length glycoprotein mRNA vaccine confers complete protection against severe fever with thrombocytopenia syndrome virus, with broad-spectrum protective effects against bandaviruses.

Highly pathogenic viruses from family Phenuiviridae, which are mainly transmitted by arthropods, have intermittently sparked epidemics worldwide. In particular, tick-borne bandaviruses, such as severe fever with thrombocytopenia syndrome virus (SFTSV), continue to spread in mountainous areas, resulting in an average mortality rate as high as 10.5%, highlighting the urgency and importance of vaccine development. Here, an mRNA vaccine developed based on the full-length SFTSV glycoprotein, containing both the receptor-binding domain and the fusion domain, was shown to confer complete protection against SFTSV at a very low dose by triggering a type 1 helper T cell-biased cellular immune response in rodents. Moreover, the vaccine candidate elicited long-term immunity and protection against SFTSV for at least 5 months. Notably, it provided complete cross-protection against other bandaviruses, such as the Heartland virus and Guertu virus, in lethal challenge models. Further research revealed that the conserved epitopes among bandaviruses within the full-length SFTSV glycoprotein may facilitate broad-spectrum protection mediated by the cellular immune response. Collectively, these findings demonstrate that the full-length SFTSV glycoprotein mRNA vaccine is a promising vaccine candidate for SFTSV and other bandaviruses, and provide guidance for the development of broad-spectrum vaccines from conserved antigens and epitopes. IMPORTANCE: Tick-borne bandaviruses, such as SFTSV and Heartland virus, sporadically trigger outbreaks in addition to influenza viruses and coronaviruses, yet there are no specific vaccines or therapeutics against them. mRNA vaccine technology has advantages in terms of enabling in situ expression and triggering cellular immunity, thus offering new solutions for vaccine development against intractable viruses, such as bandaviruses. In this study, we developed a novel vaccine candidate for SFTSV by employing mRNA vaccination technology and using a full-length glycoprotein as an antigen target. This candidate vaccine confers complete and durable protection against SFTSV at a notably low dose while also providing cross-protection against Heartland virus and Guertu virus. This study highlights the prospective value of full-length SFTSV-glycoprotein-based mRNA vaccines and suggests a potential strategy for broad-spectrum bandavirus vaccines.

Identification of tanshinone I as cap-dependent endonuclease inhibitor with broad-spectrum antiviral effect.

IMPORTANCE: The spread of avian-borne, tick-borne, and rodent-borne pathogens has the potential to pose a serious threat to human health, and candidate vaccines as well as therapeutics for these pathogens are urgently needed. Tanshinones, especially tanshinone I, were identified as a cap-dependent endonuclease inhibitor with broad-spectrum antiviral effects on negative-stranded, segmented RNA viruses including bandavirus, orthomyxovirus, and arenavirus from natural products, implying an important resource of candidate antivirals from the traditional Chinese medicines. This study supplies novel candidate antivirals for the negative-stranded, segmented RNA virus and highlights the endonuclease involved in the cap-snatching process as a reliable broad-spectrum antiviral target.

Protection of the receptor binding domain (RBD) dimer against SARS-CoV-2 and its variants.

IMPORTANCE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants achieved immune escape and became less virulent and easily transmissible through rapid mutation in the spike protein, thus the efficacy of vaccines on the market or in development continues to be challenged. Updating the vaccine, exploring compromise vaccination strategies, and evaluating the efficacy of candidate vaccines for the emerging variants in a timely manner are important to combat complex and volatile SARS-CoV-2. This study reports that vaccines prepared from the dimeric receptor-binding domain (RBD) recombinant protein, which can be quickly produced using a mature and stable process platform, had both good immunogenicity and protection in vivo and could completely protect rodents from lethal challenge by SARS-CoV-2 and its variants, including the emerging Omicron XBB.1.16, highlighting the value of dimeric recombinant vaccines in the post-COVID-19 era.

Health impacts of lifestyle and ambient air pollution patterns on all-cause mortality: a UK Biobank cohort study.

BACKGROUND: Extensive evidence indicates that both lifestyle factors and air pollution are strongly associated with all-cause mortality. However, little studies in this field have integrated these two factors in order to examine their relationship with mortality and explore potential interactions. METHODS: A cohort of 271,075 participants from the UK Biobank underwent analysis. Lifestyles in terms of five modifiable factors, namely smoking, alcohol consumption, physical activity, diet, and sleep quality, were classified as unhealthy (0-1 score), general (2-3 score), and healthy (4-5 score). Air pollution, including particle matter with a diameter ≤ 2.5 µm (PM2.5), particulate matter with a diameter ≤ 10 µm (PM10), particulate matter with a diameter 2.5-10 µm (PM2.5-10), nitrogen dioxide (NO2), and nitrogen oxides (NOx), was divided into three levels (high, moderate, and low) using Latent Profile Analysis (LPA). Cox proportional hazard regression analysis was performed to examine the links between lifestyle, air pollution, and all-cause mortality before and after adjustment for potential confounders. Restricted cubic spline curves featuring three knots were incorporated to determine nonlinear relationships. The robustness of the findings was assessed via subgroup and sensitivity analyses. RESULTS: With unhealthy lifestyles have a significantly enhanced risk of death compared to people with general lifestyles (HR = 1.315, 95% CI, 1.277-1.355), while people with healthy lifestyles have a significantly lower risk of death (HR = 0.821, 95% CI, 0.785-0.858). Notably, the difference in risk between moderate air pollution and mortality risk remained insignificant (HR = 0.993, 95% CI, 0.945-1.044). High air pollution, on the other hand, was independently linked to increased mortality risk as compared to low air pollution (HR = 1.162, 95% CI, 1.124-1.201). The relationship between NOx, PM10, and PM2.5-10 and all-cause mortality was found to be nonlinear (p for nonlinearity < 0.05). Furthermore, no significant interaction was identified between lifestyle and air pollution with respect to all-cause mortality. CONCLUSIONS: Exposure to ambient air pollution elevated the likelihood of mortality from any cause, which was impacted by individual lifestyles. To alleviate this hazard, it is crucial for authorities to escalate environmental interventions, while individuals should proactively embrace and sustain healthy lifestyles.

Task Assignment and Path Planning Mechanism Based on Grade-Matching Degree and Task Similarity in Participatory Crowdsensing.

Participatory crowdsensing (PCS) is an innovative data sensing paradigm that leverages the sensors carried in mobile devices to collect large-scale environmental information and personal behavioral data with the user's participation. In PCS, task assignment and path planning pose complex challenges. Previous studies have only focused on the assignment of individual tasks, neglecting or overlooking the associations between tasks. In practice, users often tend to execute similar tasks when choosing assignments. Additionally, users frequently engage in tasks that do not match their abilities, leading to poor task quality or resource wastage. This paper introduces a multi-task assignment and path-planning problem (MTAPP), which defines utility as the ratio of a user's profit to the time spent on task execution. The optimization goal of MATPP is to maximize the utility of all users in the context of task assignment, allocate a set of task locations to a group of workers, and generate execution paths. To solve the MATPP, this study proposes a grade-matching degree and similarity-based mechanism (GSBM) in which the grade-matching degree determines the user's income. It also establishes a mathematical model, based on similarity, to investigate the impact of task similarity on user task completion. Finally, an improved ant colony optimization (IACO) algorithm, combining the ant colony and greedy algorithms, is employed to maximize total utility. The simulation results demonstrate its superior performance in terms of task coverage, average task completion rate, user profits, and task assignment rationality compared to other algorithms.

Sertraline Is an Effective SARS-CoV-2 Entry Inhibitor Targeting the Spike Protein.

The global spread of the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the continuously emerging new variants underscore an urgent need for effective therapeutics for the treatment of coronavirus disease 2019 (COVID-19). Here, we screened several FDA-approved amphiphilic drugs and determined that sertraline (SRT) exhibits potent antiviral activity against infection of SARS-CoV-2 pseudovirus (PsV) and authentic virus in vitro. It effectively inhibits SARS-CoV-2 spike (S)-mediated cell-cell fusion. SRT targets the early stage of viral entry. It can bind to the S1 subunit of the S protein, especially the receptor binding domain (RBD), thus blocking S-hACE2 interaction and interfering with the proteolysis process of S protein. SRT is also effective against infection with SARS-CoV-2 PsV variants, including the newly emerging Omicron. The combination of SRT and other antivirals exhibits a strong synergistic effect against infection of SARS-CoV-2 PsV. The antiviral activity of SRT is independent of serotonin transporter expression. Moreover, SRT effectively inhibits infection of SARS-CoV-2 PsV and alleviates the inflammation process and lung pathological alterations in transduced mice in vivo. Therefore, SRT shows promise as a treatment option for COVID-19. IMPORTANCE The study shows SRT is an effective entry inhibitor against infection of SARS-CoV-2, which is currently prevalent globally. SRT targets the S protein of SARS-CoV-2 and is effective against a panel of SARS-CoV-2 variants. It also could be used in combination to prevent SARS-CoV-2 infection. More importantly, with long history of clinical use and proven safety, SRT might be particularly suitable to treat infection of SARS-CoV-2 in the central nervous system and optimized for treatment in older people, pregnant women, and COVID-19 patients with heart complications, which are associated with severity and mortality of COVID-19.

A precise and efficient adenine base editor.

Adenine base editors (ABEs) are novel genome-editing tools, and their activity has been greatly enhanced by eight additional mutations, thus named ABE8e. However, elevated catalytic activity was concomitant with frequent generation of bystander mutations. This bystander effect precludes its safe applications required in human gene therapy. To develop next-generation ABEs that are both catalytically efficient and positionally precise, we performed combinatorial engineering of NG-ABE8e. We identify a novel variant (NG-ABE9e), which harbors nine mutations. NG-ABE9e exhibits robust and precise base-editing activity in human cells, with more than 7-fold bystander editing reduction at some sites, compared with NG-ABE8e. To demonstrate its practical utility, we used NG-ABE9e to correct the frequent T17M mutation in Rhodopsin for autosomal dominant retinitis pigmentosa. It reduces bystander editing by ∼4-fold while maintaining comparable efficiency. NG-ABE9e possesses substantially higher activity than NG-ABEmax and significantly lower bystander editing than NG-ABE8e in rice. Therefore, this study provides a versatile and improved adenine base editor for genome editing.

Secular trend of non-communicable chronic disease prevalence throughout the life span who endured Chinese Great Famine (1959-1961).

BACKGROUND: Famine is a risk factor for non-communicable chronic diseases (NCDs), which account for over 80% of deaths in China. The effect of famine on the prevalence of NCDs in terms of various age groups, time periods and cohorts is currently poorly understood. OBJECTIVE: This study aims to explore long-term trends in the impact of China's Great Famine (1959-1961) on NCDs in China. METHODS: This study used data from the 2010-2020 China Family Panel Longitudinal Survey across 25 provinces in China. The subjects were aged 18-85 years, and the total number of subjects was 174,894. The prevalence of NCDs was derived from the China Family Panel Studies database (CFPS). An age-period-cohort (APC) model was used to estimate the age, period and cohort effects of NCDs in 2010-2020 and the effect of famine on the risk of NCDs in terms of cohort effects. RESULTS: The prevalence of NCDs increased with age. Additionally, the prevalence did not clearly decrease over the survey period. Regarding the cohort effect, people born in the years adjacent to the famine period had a higher risk of NCDs; additionally, females, those born in rural areas, and those who lived in provinces with severe famine and post-famine had a higher likelihood of NCDs. CONCLUSIONS: Experiencing famine at an early age or the experience of famine in a close relative's generation (births after the onset of famine) are associated with an increased risk of NCDs. Additionally, more severe famine is associated with a higher risk of NCDs.

Association of living arrangements with all-cause mortality among older adults: a propensity score-matched cohort study.

BACKGROUND: Many studies exist on the living arrangements and health status of older adults, but the findings have been inconsistent. Therefore, we examined the relationship between living arrangements and all-cause mortality in older adults. METHODS: This perspective study was based on the Chinese Longitudinal Healthy Longevity Survey (CLHLS) from 2011 to 2018. We used a sample aged 65 years and over included in the study in 2011. Propensity score matching was performed to minimize bias and Cox proportional hazards regression models were conducted. RESULTS: A total of 7,963 participants were included. Of these, 1,383 were living alone, 6,424 were living with families, and 156 were living in nursing homes. In the propensity score-matched cohort, older adults living alone had a significantly lower risk of all-cause mortality than those living with families (hazard ratio 0.85; 95% confidence intervals 0.76 to 0.95). Living alone was prominently associated with a decline in mortality compared with living in nursing homes (hazard ratio 0.61; 95% confidence intervals 0.44 to 0.84). There was no significant difference in mortality between living in nursing homes and living with families (hazard ratio 1.19; 95% confidence intervals 0.89 to 1.60). Subgroup analyses indicated that there was no significant interaction with age, sex, education, or residence. CONCLUSIONS: The risk of all-cause mortality was significantly lower in older adults living alone than in those living with families or living in nursing homes. This article's findings suggest the need to adopt multiple approaches to meet the needs of senior care services.

Effects of common plastic products heat exposure on cognition: Mediated by gut microbiota.

Considering plastic exposure patterns in modern society, the effects of exposure to leachate from boiled-water treated plastic products on cognitive function was probed in mice through changes in gut microbiota diversity. In this study, Institute for Cancer Research (ICR) mice were used to establish drinking water exposure models of three popular kinds of plastic products, including non-woven tea bags, food-grade plastic bags and disposable paper cups. 16S rRNA was used to detect changes in the gut microbiota of mice. Behavioral, histopathology, biochemistry, and molecular biology experiments were used to evaluate cognitive function in mice. Our results showed that the diversity and composition of gut microbiota changed at genus level compared to control group. Nonwoven tea bags-treated mice were proved an increase in Lachnospiraceae and a decreased in Muribaculaceae in gut. Alistipes was increased under the intervention of food grade plastic bags. Muribaculaceae decreased and Clostridium increased in disposable paper cups group. The new object recognition index of mice in the non-woven tea bag and disposable paper cup groups decreased, and amyloid ß-protein (Aß) and tau phosphorylation (P-tau) protein deposition. Cell damage and neuroinflammation were observed in the three intervention groups. Totally speaking, oral exposure to leachate from boiled-water treated plastic results in cognitive decline and neuroinflammation in mammals, which is likely related to MGBA and changes in gut microbiota.

Assembly and comparative analysis of the complete mitochondrial genome of Suaeda glauca.

BACKGROUND: Suaeda glauca (S. glauca) is a halophyte widely distributed in saline and sandy beaches, with strong saline-alkali tolerance. It is also admired as a landscape plant with high development prospects and scientific research value. The S. glauca chloroplast (cp) genome has recently been reported; however, the mitochondria (mt) genome is still unexplored. RESULTS: The mt genome of S. glauca were assembled based on the reads from Pacbio and Illumina sequencing platforms. The circular mt genome of S. glauca has a length of 474,330 bp. The base composition of the S. glauca mt genome showed A (28.00%), T (27.93%), C (21.62%), and G (22.45%). S. glauca mt genome contains 61 genes, including 27 protein-coding genes, 29 tRNA genes, and 5 rRNA genes. The sequence repeats, RNA editing, and gene migration from cp to mt were observed in S. glauca mt genome. Phylogenetic analysis based on the mt genomes of S. glauca and other 28 taxa reflects an exact evolutionary and taxonomic status of S. glauca. Furthermore, the investigation on mt genome characteristics, including genome size, GC contents, genome organization, and gene repeats of S. gulaca genome, was investigated compared to other land plants, indicating the variation of the mt genome in plants. However, the subsequently Ka/Ks analysis revealed that most of the protein-coding genes in mt genome had undergone negative selections, reflecting the importance of those genes in the mt genomes. CONCLUSIONS: In this study, we reported the mt genome assembly and annotation of a halophytic model plant S. glauca. The subsequent analysis provided us a comprehensive understanding of the S. glauca mt genome, which might facilitate the research on the salt-tolerant plant species.

Complementary Oxidative Generation of Iminyl Radicals from α-Imino-oxy Acids: Silver-Catalyzed C-H Cyanoalkylation of Heterocycles and Quinones.

A complementary and general strategy for the oxidative generation of iminyl radicals from the readily available α-imino-oxy acids has been established through silver-catalyzed decarboxylation. To demonstrate its synthesis utility, the direct C-H cyanoalkylation of heterocycles and quinones with cyclic α-imino-oxy acids via the iminyl radical-mediated C-C bond cleavage is developed. This cost-effective method takes place under mild reaction conditions and exhibits a broad substrate scope.

Protective Effect of Hesperidin Against Sepsis-Induced Lung Injury by Inducing the Heat-Stable Protein 70 (Hsp70)/Toll-Like Receptor 4 (TLR4)/ Myeloid Differentiation Primary Response 88 (MyD88) Pathway.

BACKGROUND Sepsis-induced lung injury is associated with high mortality. The present investigation evaluated the protective effect of hesperidin against sepsis-induced lung injury and also postulates the possible mechanism of its action. MATERIAL AND METHODS Lung injury was induced by sepsis in all animals, in which sepsis was produced by cecal ligation and puncture (CLP). Animals were treated with hesperidin 10 and 20 mg/kg i.v. 30 min after the surgery. Oxygenation index and lung injury score were determined and levels of pro-inflammatory mediators and markers of oxidative stress were also estimated in the lung tissues. Moreover, expression of caspase-3, B-cell lymphoma (Bcl-2), Toll-like receptor 4 (TLR4), heat-stable protein 70 (Hsp70) and myeloid differentiation primary response 88 (MyD88) protein was estimated by Western blot assay and immunofluorescence assay. RESULTS Hesperidin attenuated the partial pressure of arterial oxygen/fraction of inspired oxygen (PaO2/FiO2) ratio and lung injury score in CLP-induced lung injury mice. There was a significant (p<0.01) decrease in the level of pro-inflammatory mediators in the lung tissue of CLP-induced lung injury mice. Moreover, markers of oxidative stress were attenuated in the hesperidin-treated group. Treatment with hesperidin attenuated the expression of caspase-3, Bcl-2, TLR4, Hsp70, and MyD88 protein in the lung tissue of CLP-induced lung injury mice. CONCLUSIONS Hesperidin protects against lung injury by attenuating the Hsp70/TLR4/MyD88 pathway in CLP-induced lung injury mice.

miR-203 inhibits cell proliferation, invasion, and migration of non-small-cell lung cancer by downregulating RGS17.

Involvement of the RGS17 oncogene in the promotion of non-small-cell lung cancer (NSCLC) has been reported, but the regulation mechanism in NSCLC remains unclear. MicroRNAs (miRNAs) negatively regulate gene expression, and their dysregulation has been implicated in tumorigenesis. To understand the role of miRNAs in Regulator of G Protein Signaling 17 (RGS17)-induced NSCLC, we showed that miR-203 was downregulated during tumorigenesis, and inhibited the proliferation and invasion of lung cancer cells. We then determined whether miR-203 regulated NSCLC by targeting RGS17. To characterize the regulatory effect of miR-203 on RGS17, we used lung cancer cell lines, A549 and Calu-1, and the constructed miR-203 and RGS17 overexpression vectors. The CCK8 kit was used to determine cell proliferation, and the Transwell® assay was used to measure cell invasion and migration. RT-PCR, western blots, and immunofluorescence were used to analyze expression of miR-203 and RGS17, and the luciferase reporter assay was used to examine the interaction between miR-203 and RGS17. Nude mice were used to characterize in vivo tumor growth regulation. Expression of miR-203 inhibited proliferation, invasion, and migration of lung cancer cell lines A549 and Calu-1 by targeting RGS17. The regulatory effect of miR-203 was inhibited after overexpression of RGS17. The luciferase reporter assay showed that miR-203 downregulated RGS17 by direct integration into the 3'-UTR of RGS17 mRNA. In vivo studies showed that expression of miR-203 significantly inhibited growth of tumors. Taken together, the results suggested that expression of miR-203 inhibited tumor growth and metastasis by targeting RGS17.

Hidden dangers: Does multisensory impairments accompanying visual impairment increase dementia risk.

BACKGROUND: Growing evidence suggests that sensory impairment, particularly in the form of visual impairment, may contribute to the development of dementia. However, it remains unclear whether experiencing concurrent visual impairment in combination with other types of multisensory impairments may further increase this risk. METHODS: The study used data from the UK Biobank cohort study, which recruited 500,000 adults. With meticulous screening procedures in place, individuals with visual impairment, hearing impairment, and oral health issues were identified for further follow-up evaluations. A multivariable regression analysis was conducted to investigate the relationship between multisensory impairments concurrent with visual impairment and cognitive function. Cox proportional hazard models were used to estimate hazard ratios and 95% confidence intervals to evaluate the association between multisensory impairments concurrent with visual impairment and dementia risk. RESULTS: Subjects experiencing multisensory impairments concurrent with visual impairment demonstrated a negative association with cognitive function. Notably, individuals who have both vision and hearing impairments had a significantly higher risk of developing dementia (HR 1.28, 95% CI [1.01-1.63]). Additionally, individuals who experience vision impairment and oral health issues simultaneously were also at higher risk for dementia (HR 1.61, 95% CI [1.32-1.97]). Furthermore, the risk of dementia among individuals with vision impairment, hearing impairment, and oral health issues further escalated to an even higher level (HR 1.63, 95% CI [1.19-2.24]). CONCLUSIONS: The correlation between the presence of multisensory impairments concurrent with visual impairment and cognitive decline is highly significant. Those with multisensory impairments concurrent with visual impairment are at a significantly increased risk of developing dementia.

The association between urbanization and adolescent depression in China.

Background: With the rapid urbanization in many countries, more attention is being paid to the relationship between urbanization and mental health, especially depression. However, in countries with rapid urbanization, few empirical studies exist on the relationship between urbanization and adolescent depression. Methods: Nationally representative survey data from the China Family Panel Studies in 2012, 2016 and 2018 were used. Data of 1,588 adolescents were obtained from 25 provinces. Depression was measured using the Center for Epidemiology Studies of Depression 20-item score. The urbanization rate was obtained from the National Bureau of Statistics of China. The generalized estimating equation was used to estimate the statistical relationship. Results: The participants' mean age at baseline was 15 years, and 51.2% (813/1,588) of participants were male. After adjusting for all covariates (gender, age, ethnicity, level of education, marital status, urban/rural areas, body mass index, self-rated health, academic pressure, smoking, drinking and exercise), the rate of urbanization was monotonically and negatively associated with adolescent depression (odds ratio 0.34, 95% CI [0.14-0.79]). Compared with female adolescents, male adolescents had a lower risk of depression (odds ratio 0.80, 95% CI [0.67-0.97]). Conclusion: In the context of China, urbanization has a positive effect on the mental health of adolescents. Female adolescents are more likely to experience depression than male adolescents.

Discovery of a novel flavonol O-methyltransferase possessing sequential 4'- and 7-O-methyltransferase activity from Camptotheca acuminata Decne.

The biosynthetic route for flavonol in Camptotheca acuminata has been recently elucidated from a chemical point of view. However, the genes involved in flavonol methylation remain unclear. It is a critical step for fully uncovering the flavonol metabolism in this ancient plant. In this study, the multi-omics resource of this plant was utilized to perform flavonol O-methyltransferase-oriented mining and screening. Two genes, CaFOMT1 and CaFOMT2 are identified, and their recombinant CaFOMT proteins are purified to homogeneity. CaFOMT1 exhibits strict substrate and catalytic position specificity for quercetin, and selectively methylates only the 4'-OH group. CaFOMT2 possesses sequential O-methyltransferase activity for the 4'-OH and 7-OH of quercetin. These CaFOMT genes are enriched in the leaf and root tissues. The catalytic dyad and critical substrate-binding sites of the CaFOMTs are determined by molecular docking and further verified through site-mutation experiments. PHE181 and MET185 are designated as the critical sites for flavonol substrate selectivity. Genomic environment analysis indicates that CaFOMTs evolved independently and that their ancestral genes are different from that of the known Ca10OMT. This study provides molecular insights into the substrate-binding pockets of two new CaFOMTs responsible for flavonol metabolism in C. acuminata.

A predictive model for the risk of cognitive impairment in community middle-aged and older adults.

Identifying individuals at high risk of cognitive impairment is essential for treatment and prevention strategies. We aimed to develop and validate a prediction model for evaluating the risk of cognitive impairment. Data were from the China Family Panel Studies (CFPS) and China Health and Retirement Longitudinal Study (CHARLS). A total of 14,265 subjects were selected for model development. The area under the curve(AUC) for the training, internal, and external validation sets were 0.775, 0.920, and 0.727, respectively. This model could be used to identify middle-aged and older adults aged 45 years and older at high risk of cognitive impairment.

Exposure to outdoor artificial light at night increases risk and burden of metabolic disease in Ningxia, China.

Nearly a quarter of the world's land has already been polluted by artificial light. And numerous human and animal studies have corroborated that light at night can disrupt metabolism. Therefore, we aimed to estimate the association between outdoor artificial light at night (ALAN) and the presence of metabolic disease. Daily hospital admission cases from Ningxia, China, between 2014 and 2020 were included. Cumulative associations between outdoor ALAN and metabolic disease were estimated using logistic regression and distributed lagged non-linear models (DLNM) with lags of 0-30 days and stratified analysis by age groups and gender. The results suggest that 26.80% of metabolic disease cases in Ningxia can be attributed to outdoor ALAN and that men, especially in men aged 46-59 years, are more susceptible to lighting. Policymakers need to develop measures and facilities in corresponding areas, such as universal access to indoor blackout curtains. In particular, men should be urged to minimize going outside at night and to develop protective measures specifically for men.

Metabolomic analysis of vascular cognitive impairment due to hepatocellular carcinoma.

Introduction: Screening for metabolically relevant differentially expressed genes (DEGs) shared by hepatocellular carcinoma (HCC) and vascular cognitive impairment (VCI) to explore the possible mechanisms of HCC-induced VCI. Methods: Based on metabolomic and gene expression data for HCC and VCI, 14 genes were identified as being associated with changes in HCC metabolites, and 71 genes were associated with changes in VCI metabolites. Multi-omics analysis was used to screen 360 DEGs associated with HCC metabolism and 63 DEGs associated with VCI metabolism. Results: According to the Cancer Genome Atlas (TCGA) database, 882 HCC-associated DEGs were identified and 343 VCI-associated DEGs were identified. Eight genes were found at the intersection of these two gene sets: NNMT, PHGDH, NR1I2, CYP2J2, PON1, APOC2, CCL2, and SOCS3. The HCC metabolomics prognostic model was constructed and proved to have a good prognostic effect. The HCC metabolomics prognostic model was constructed and proved to have a good prognostic effect. Following principal component analyses (PCA), functional enrichment analyses, immune function analyses, and TMB analyses, these eight DEGs were identified as possibly affecting HCC-induced VCI and the immune microenvironment. As well as gene expression and gene set enrichment analyses (GSEA), a potential drug screen was conducted to investigate the possible mechanisms involved in HCC-induced VCI. The drug screening revealed the potential clinical efficacy of A-443654, A-770041, AP-24534, BI-2536, BMS- 509744, CGP-60474, and CGP-082996. Conclusion: HCC-associated metabolic DEGs may influence the development of VCI in HCC patients.