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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Correction: Ye et al. Investigation of the JASMONATE ZIM-DOMAIN Gene Family Reveals the Canonical JA-Signaling Pathway in Pineapple. Biology 2022, 11, 445.

The authors would like to make the following correction to the published paper [...].

Association between changes in social capital and mental well-being among older people in China.

Background: The mental well-being of older people has become social concern under aging times in China. Social capital has been linked to mental well-being. Our aims were to explore how social capital and the state of mental well-being of older people were changing and what the relationship between them was. Methods: Data were from six waves of the China Family Panel Studies that were conducted between 2010 and 2020, and a total of 1,055 participants aged 60 and over were included in the analysis. The Generalized Estimated Equation model (GEE) was used to clarify the long-term relationship, and to use GEE we first defined how time points were related, in other words, an appropriate working correlation structure was supposed to choose. Therefore, correlation coefficient between measurements at two time points was calculated to choose the exchange structure. All the analyses were performed in the statistical software Stata 15.0. Results: The mental well-being of older people has deteriorated over time, especially we found that between 2014 and 2016, the mental well-being of older people plummeted. In addition, cognitive social capital was positively correlated with mental well-being, while structural social capital was inverse. Conclusions: Policymakers are supposed to take into account the long-term impact of cognitive and structural social capital on the mental well-being of older people and to provide them with projects aimed at increasing cognitive social capital and turning the pressure of structural social capital into a source of happiness in life.

Effects of oral exposure to leachate from boiled-water treated plastic products on gut microbiome and metabolomics.

By simulating plastic exposure patterns in modern society, the impact of daily exposure to plastic products on mammals was explored. 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. Feces and urine of mice were collected for gut microbiome and metabolomics analysis. Our results showed that the diversity and composition of gut microbiota changed at genus level compared to control group. Lactobacillus, Parabacteroides, Escherichia-shigella and Staphylococcus decreased while Lachnospiraceae increased treated with non-woven tea bags. Escherichia-shigella and Alistipes increased while Parabacteroides decreased treated with food grade plastic bags. Muribaculaceae decreased in the gut microbiota of mice treated with disposable paper cups. Metabolomics has seen changes in the number of metabolites and enrichment of metabolic pathways related to inflammatory responses and immune function. Inflammatory responses were found in histological and biochemical examination. In summary, this study demonstrated that long-term oral exposure to leachate form boiled-water treated plastic products might have effects on gut microbiome and metabolome, which further provided new insights about potential adverse effects for human beings.

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.

Happiness, depression, physical activity and cognition among the middle and old-aged population in China: a conditional process analysis.

Background: Happiness is one variable of subjective well-being, which has been increasingly shown to have protective effects on health. Although the association between happiness and cognition has been established, the mechanism by which happiness leads to cognition remains unclear. Since happiness, depression, and physical activity may all be related to cognition, and happiness is related to depression and physical activity, this study explored the effect of depression and physical activity on the relationship between happiness and cognition among middle and old-aged individuals in China. Methods: Data on 14,344 participants above 45 years of age were obtained from the 2018 China Family Panel Studies survey. A multiple linear regression analysis was performed to identify the correlation factors of cognition. The conditional process analysis was used to assess the mediatory effect of depression and physical activity on the relationship between happiness and cognition. Results: Residence, age, sex, income level, social status, smoking, napping, reading, education, exercise times, satisfaction, happiness, and depression had associations with cognition. When other variables were held constant, cognition score increased by 0.029 standard deviation(SD) for every 1 SD increased in happiness. Mediation analysis showed that happiness had a significant positive total effect on cognition. The direct effect of happiness was significant and accounted for 57.86% of the total effect. The mediatory effect of depression (path of happiness→depression→cognition) accounted for 38.31% of the total effect, whereas that of physical activity (path of happiness→exercise times→cognition) accounted for 3.02% of the total effect. Conclusion: Happiness has a positive correlation with cognitive function, and depression and physical activity play mediatory roles in this association. Effective interventions to improve happiness levels of middle and old-aged population will not only improve their subjective well-being but also improve their cognitive function, which carries great potential for reducing public health burdens related to cognitive aging.

Association of outdoor artificial light at night with mental health among China adults: a prospective ecology study.

Multiple environmental changes are related to mental disorders. However, research on the association between artificial light at night (ALAN) and mental health in China is limited, particularly at the national level. We used a "difference-in-differences" design and logistic regression to explore the relationship between ALAN changes and scores on self-assessed mental health. Participants were drawn from the China Family Panel Studies of adults in 2012 and 2018. The final analysis was based on 21,036 adults from 25 provinces throughout China. The brighter the ALAN, the worse was the mental health, and this connection was unaffected by particulate matter 2.5 (PM2.5) or temperature. ALAN sensitivity may differ among populations. Our findings suggest that exposure to brighter ALAN is associated significantly with worse mental health among Chinese adults. Environmental policies that reduce ALAN could improve the mental health of the Chinese public.

The tRNA-Derived Fragment tRF-24-V29K9UV3IU Functions as a miRNA-like RNA to Prevent Gastric Cancer Progression by Inhibiting GPR78 Expression.

Emerging studies have proved that tRNA-derived fragments (tRFs) play vital roles in tumor metastasis; however, the function of tRFs in gastric cancer (GC) remains largely unclear. We investigated the role of tRF-24-V29K9UV3IU in growth and metastasis of GC using a xenograft mouse model. Differential gene expression downstream of tRF-24-V29K9UV3IU was identified by transcriptome sequencing, and interaction was then verified by a dual luciferase reporter and RNA immunoprecipitation. MKN-45 cells were also used to explore the biological functions of tRF-24-V29K9UV3IU in vitro. Here, knockdown of tRF-24-V29K9UV3IU promoted tumor growth and metastasis of GC in vivo. The expression of tRF-24-V29K9UV3IU and E-cadherin (epithelial cell marker) was down-regulated in tumors of mice following tRF-24-V29K9UV3IU knockdown, whereas the mesenchymal cell markers N-cadherin and vimentin displayed an opposite trend. Transcriptome sequencing identified 87 differentially expressed genes (DEGs) down-regulated in the tRF-24-V29K9UV3IU-overexpressed groups compared with the control group. Among them, G-protein-coupled receptor 78 (GPR78), the most significantly down-regulated DEG, was also predicted to be a target of tRF-24-V29K9UV3IU. Moreover, tRF-24-V29K9UV3IU could function as a miRNA-like fragment and bind to AGO2 and directly silence GPR78 expression by complementing with the 3'-untranslated region of the GPR78 mRNA. Functionally, overexpression of tRF-24-V29K9UV3IU significantly suppressed proliferation, migration, and invasion and promoted apoptosis of MKN-45 cells, whereas GPR78 attenuated these effects. Therefore, our data suggest that tRF-24-V29K9UV3IU functions as a miRNA-like fragment to suppress GPR78 expression and thus inhibit GC progression. These observations suggest that the tRF-24-V29K9UV3IU/GPR78 axis serves as a potential therapeutic target in GC.

Investigation of the JASMONATE ZIM-DOMAIN Gene Family Reveals the Canonical JA-Signaling Pathway in Pineapple.

JASMONATE ZIM-DOMAIN (JAZ) proteins are negative regulators of the jasmonate (JA)-signaling pathway and play pivotal roles in plant resistance to biotic and abiotic stresses. Genome-wide identification of JAZ genes has been performed in many plant species. However, systematic information about pineapple (Ananas comosus L. Merr.) JAZ genes (AcJAZs) is still not available. In this study, we identified 14 AcJAZ genes and classified them into five groups along with the Arabidopsis and rice orthologs. The AcJAZ genes have 3-10 exons, and the putative AcJAZ proteins have between two and eight conserved regions, including the TIFY motif and Jas domain. The cis-acting element analysis revealed that the putative promoter regions of AcJAZs contain between three and eight abiotic stress-responsive cis-acting elements. The gene-expression analysis suggested that AcJAZs were expressed differentially during plant development and subjected to regulation by the cold, heat, salt, and osmotic stresses as well as by phytohormones. Moreover, the BiFC analysis of protein interactions among the central JA-signaling regulators showed that AcJAZ4, AcMYC2, AcNINJA, and AcJAM1 could interact with AcJAZ5 and AcJAZ13 in vivo, indicating a canonical JA-signaling pathway in pineapple. These results increase our understanding of the functions of AcJAZs and the responses of the core players in the JA-signaling pathway to abiotic stresses.