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Prolonged exposure to negative stressors could be harmful if a subject cannot respond appropriately. Strategies evolved to respond to stress, including repetitive displacement behaviours, are important in maintaining behavioural homoeostasis. In rodents, self-grooming is a frequently observed repetitive behaviour believed to contribute to post-stress de-arousal with adaptive value. Here we identified a rat limbic di-synaptic circuit that regulates stress-induced self-grooming with positive affective valence. This circuit links hippocampal ventral subiculum to ventral lateral septum (LSv) and then lateral hypothalamus tuberal nucleus. Optogenetic activation of this circuit triggers delayed but robust excessive grooming with patterns closely resembling those evoked by emotional stress. Consistently, the neural activity of LSv reaches a peak before emotional stress-induced grooming while inhibition of this circuit significantly suppresses grooming triggered by emotional stress. Our results uncover a previously unknown limbic circuitry involved in regulating stress-induced self-grooming and pinpoint a critical role of LSv in this ethologically important behaviour. Self-grooming is a frequently observed repetitive behaviour in rodents that is believed to contribute to post-stress de-arousal. The authors identified a previously unknown limbic circuit that includes the ventral lateral septum in rats and is involved in regulating stress-induced self-grooming.

Retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated protein 5 (MDA5) sense viral RNA and activate antiviral immune responses. Herein we investigate their functions in human epithelial cells, the primary and initial target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A deficiency in MDA5, RIG-I or mitochondrial antiviral signaling protein (MAVS) enhanced viral replication. The expression of the type I/III interferon (IFN) during infection was impaired in MDA5 −/− and MAVS −/− , but not in RIG-I −/− , when compared to wild type (WT) cells. The mRNA level of full-length angiotensin-converting enzyme 2 (ACE2), the cellular entry receptor for SARS-CoV-2, was ~ 2.5-fold higher in RIG-I −/− than WT cells. These data demonstrate MDA5 as the predominant SARS-CoV-2 sensor, IFN-independent induction of ACE2 and anti-SARS-CoV-2 role of RIG-I in epithelial cells.

Adherence to a healthy lifestyle is associated with lower risks of adverse outcomes. However, trends in multiple lifestyle factors and overall healthy lifestyle status among US adults in recent years are unknown. To examine trends in multiple lifestyle factors and overall healthy lifestyle among US adults. This serial cross-sectional study used nationally representative data from 10 National Health and Nutrition Examination Survey (NHANES) cycles (nine 2-year cycles from 1999 to 2016 and 1 combined cycle from 2017 to March 2020) among adults 20 years or older. Data were analyzed from December 10, 2021, to January 11, 2023. Survey cycle. Five healthy lifestyle factors: never smoking, moderate or lighter alcohol consumption (for women: ≤7 drinks/wk; for men: ≤14 drinks/wk), healthy diet (Healthy Eating Index-2015 scores ≥60.0), sufficient physical activity (≥150 min/wk of equivalent moderate physical activity), and healthy weight (body mass index [calculated as weight in kilograms divided by height in meters squared] 18.5-24.9). A total of 47 852 adults were included in this study. The weighted mean [SE] age was 47.3 [0.2] years; 24 539 (weighted proportion, 51.5%) were women. From the 1999-2000 cycle to the 2017 to March 2020 cycle, the estimated prevalence of the 5 lifestyle factors showed divergent trends, with increasing prevalence of never smoking (from 49.4% [95% CI, 46.4%-52.4%] to 57.7% [95% CI, 55.5%-59.9%]; difference, 8.2% [95% CI, 4.5%-12.0%]), healthy diet (from 19.3% [95% CI, 16.0%-22.6%] to 24.5% [95% CI, 21.5%-27.5%]; difference, 5.2% [95% CI, 0.8%-9.7%]), and sufficient physical activity (from 55.7% [95% CI, 51.8%-59.6%] to 69.1% [95% CI, 67.2%-71.1%]; difference, 13.4% [95% CI, 9.0%-17.8%]), while prevalence of healthy weight decreased from 33.1% (95% CI, 30.5%-35.6%) to 24.6% (95% CI, 22.6%-26.7%; difference, -8.4% [95% CI, -11.8% to -5.1%]) (all P < .001 for trend). Meanwhile, there was no significant trend in moderate or lighter alcohol consumption. Overall, the estimated prevalence of at least 4 healthy lifestyle factors increased from 15.7% (95% CI, 12.8%-18.7%) to 20.3% (95% CI, 17.8%-22.7%; difference, 4.5% [95% CI, 0.7%-8.4%]; P < .001 for trend). Disparities in healthy lifestyle were widened by age group, with little improvement among adults 65 years and older (difference, 0.04% [95% CI, -4.28% to 4.35%]). There were persistent disparities in healthy lifestyle by race and ethnicity, educational level, and income level. The findings of this cross-sectional study of NHANES data over a 22-year period suggest diverse change patterns across 5 healthy lifestyle factors and a modest improvement in overall lifestyle existed among US adults, with worsening or persistent disparities in lifestyle.

Importance Although the EAT-Lancet Commission has recently proposed a planetary health diet (PHD) to promote human and environmental health, little is known about how PHD affects environment and mortality risk among an Asian population. Objective To investigate whether a PHD score is associated with environmental impacts and mortality outcomes in a Chinese cohort living in Singapore. Design, Setting, and Participants This cohort study used data from the Singapore Chinese Health Study. Eligible participants were without known cardiovascular disease and cancer at baseline; they were recruited between 1993 and 1998 and followed up using record linkage data until 2020. Data were analyzed from September 2022 to April 2023. Exposures PHD score was calculated based on the reference consumption of 14 dietary components in PHD and individual energy intake assessed using a validated food frequency questionnaire in this cohort. Main Outcomes and Measures Diet-related environmental impacts were estimated using a food frequency questionnaire. Mortality outcomes (all-cause, cardiovascular disease, cancer, and respiratory disease) were identified via linkage with a nationwide registry. Results A total of 57 078 participants were included in this study (mean [SD] age, 56.1 (7.9) years; 31 958 women [56.0%]). During a median (IQR) follow-up of 23.4 (18.7-26.2) years, 22 599 deaths occurred. Comparing the highest and lowest quintiles, higher PHD scores were associated with lower greenhouse gas emissions (β = −0.13 kg CO2equivalent; 95% CI, −0.14 to −0.12 kg CO2equivalent), but with higher total water footprint (β = 0.12 m3; 95% CI, 0.11-0.13 m3) and land use (β = 0.29 m2; 95% CI, 0.28-0.31 m2). In the adjusted multivariable model, compared with the lowest quintile, participants in the highest quintile of PHD score had lower risk of all-cause mortality (hazard ratio [HR], 0.85; 95% CI, 0.81-0.89), cardiovascular disease mortality (HR, 0.79; 95% CI, 0.73-0.85), cancer mortality (HR, 0.93; 95% CI, 0.86-1.00), and respiratory disease mortality (HR, 0.81; 95% CI, 0.74-0.89). Conclusions and Relevance In this study of Singapore Chinese adults, higher adherence to PHD was associated with reduced risk of chronic disease mortality. However, environmental impacts were uncertain, as higher adherence was associated with lower greenhouse gas emissions but higher total water footprint and land use.

Improved understanding of trends in the proportion of individuals with metabolically healthy obesity (MHO) may facilitate stratification and management of obesity and inform policy efforts. To characterize trends in the prevalence of MHO among US adults with obesity, overall and by sociodemographic subgroups. This survey study included 20 430 adult participants from 10 National Health and Nutrition Examination Survey (NHANES) cycles between 1999-2000 and 2017-2018. The NHANES is a series of cross-sectional and nationally representative surveys of the US population conducted continuously in 2-year cycles. Data were analyzed from November 2021 to August 2022. National Health and Nutrition Examination Survey cycles from 1999-2000 to 2017-2018. Metabolically healthy obesity was defined as a body mass index of 30.0 (calculated as weight in kilograms divided by height in meters squared) without any metabolic disorders in blood pressure, fasting plasma glucose (FPG), high-density lipoprotein cholesterol (HDL-C), or triglycerides based on established cutoffs. Trends in the age-standardized prevalence of MHO were estimated using logistic regression analysis. This study included 20 430 participants. Their weighted mean (SE) age was 47.1 (0.2) years; 50.8% were women, and 68.8% self-reported their race and ethnicity as non-Hispanic White. The age-standardized prevalence (95% CI) of MHO increased from 3.2% (2.6%-3.8%) in the 1999-2002 cycles to 6.6% (5.3%-7.9%) in the 2015-2018 cycles (P < .001 for trend). There were 7386 adults with obesity. Their weighted mean (SE) age was 48.0 (0.3) years, and 53.5% were women. The age-standardized proportion (95% CI) of MHO among these 7386 adults increased from 10.6% (8.8%-12.5%) in the 1999-2002 cycles to 15.0% (12.4%-17.6%) in the 2015-2018 cycles (P = .02 for trend). Substantial increases in the proportion of MHO were observed for adults aged 60 years or older, men, non-Hispanic White individuals, and those with higher income, private insurance, or class I obesity. In addition, there were significant decreases in the age-standardized prevalence (95% CI) of elevated triglycerides (from 44.9% [40.9%-48.9%] to 29.0% [25.7%-32.4%]; P < .001 for trend) and reduced HDL-C (from 51.1% [47.6%-54.6%] to 39.6% [36.3%-43.0%]; P = .006 for trend). There was also a significant increase in elevated FPG (from 49.7% [95% CI, 46.3%-53.0%] to 58.0% [54.8%-61.3%]; P < .001 for trend) but no significant change in elevated blood pressure (from 57.3% [53.9%-60.7%] to 54.0% [50.9%-57.1%]; P = .28 for trend). The findings of this cross-sectional study suggest that the age-standardized proportion of MHO increased among US adults from 1999 to 2018, but differences in trends existed across sociodemographic subgroups. Effective strategies are needed to improve metabolic health status and prevent obesity-related complications in adults with obesity.

Background Observational studies have illustrated that maternal central obesity is associated with birth size, including of birth weight, birth length and head circumference, but the causal nature of these associations remains unclear. Our study aimed to test the causal effect of maternal central obesity on birth size and puberty height growth using a Mendelian randomization (MR) analysis. Methods We performed two-sample MR using summary-level genome-wide public data. Thirty-five single nucleotide polymorphisms (SNPs), 25 SNPs and 41 SNPs were selected as instrumental variables for waist-to-hip ratio adjusted for BMI, waist circumference adjusted for BMI and hip circumference adjusted for BMI, respectively to test the causal effects of maternal central obesity on birth size and puberty height using an inverse-variance-weighted approach. Results In this MR analysis, we found no evidence of a causal association between waist circumference or waist-to-hip ratio and the outcomes. However, we observed that one standard deviation (SD) increase in hip circumference (HIP) was associated with a 0.392 SD increase in birth length ( p  = 1.1 × 10 − 6 ) and a 0.168 SD increase in birth weight ( p  = 7.1 × 10 − 5 ), respectively at the Bonferroni-adjusted level of significance. In addition, higher genetically predicted maternal HIP was strongly associated with the puberty heights (0.835 SD, p  = 8.4 × 10 − 10 ). However, HIP was not associated with head circumference ( p  = 0.172). Conclusions A genetic predisposition to higher maternal HIP was causally associated with larger offspring birth size independent of maternal BMI. However, we found no evidence of a causal association between maternal waist circumference, waist-to-hip ratio and birth size.

PurposeWe performed a systematic review and meta-analysis of available literature to investigate the efficacy of the intracytoplasmic sperm injection (ICSI) in couples with non-male factor with respect to the clinical outcomes.MethodsThe literature search was based on EMBASE, PubMed, and the Cochrane Library. All studies published after 1992 until February 2020 and written in English addressing patients in the presence of normal semen parameters subjected to ICSI and in vitro fertilization (IVF) were eligible. Reference lists of retrieved articles were hand-searched for additional studies. The primary outcomes were fertilization rate, clinical pregnancy rate, and implantation rate; the secondary outcomes were good-quality embryo rate, miscarriage rate, and live birth rate.ResultsFour RCTs and twenty-two cohort studies fulfilling the inclusion criteria were included. Collectively, a meta-analysis of the outcomes in RCTs showed that compared to IVF, ICSI has no obvious advantage in fertilization rate (RR = 1.16, 95% CI: 0.83–1.62), clinical pregnancy rate (RR = 1.04, 95% CI: 0.66–1.64), implantation rate (RR = 1.12, 95% CI: 0.67–1.86), and live birth rate (RR = 1.17, 95% CI: 0.43–3.15). Pooled results of cohort studies demonstrated a statistically significant higher fertilization rate (RR = 1.16, 95% CI: 1.03–1.31) and miscarriage rate (RR = 1.04, 95% CI: 1.01–1.06) in the ICSI group; furthermore, higher clinical pregnancy rate (RR = 0.85, 95% CI: 0.77–0.94), implantation rate (RR = 0.78, 95% CI: 0.65–0.95), and live birth rate (RR = 0.86, 95% CI: 0.79–0.94) was founded in the IVF group; no statistically significant difference was observed in good-quality embryo rate (RR = 0.98, 95% CI: 0.93–1.04).ConclusionICSI has no obvious advantage in patients with normal semen parameters. Enough information is still not available to prove the efficacy of ICSI in couples with non-male factor infertility comparing to IVF.

Background Accelerated aging is a dynamic process, yet few studies examined the association of changes in accelerated aging with cardiovascular disease (CVD) and mortality. This study aims to evaluate this association in three prospective cohorts from China and the UK. Methods Data were drawn from the Kailuan cohort ( n  = 107,830), the Dongfeng-Tongji (DFTJ) cohort ( n  = 14,032), and the UK Biobank ( n  = 316,087). Accelerated aging was assessed by PhenoAge and Klemera-Doubal method (KDM) age, measured at baseline (Kailuan cohort: 2006–2009; DFTJ cohort: 2008–2010; UK Biobank: 2006–2010) and the first follow-up (Kailuan cohort: 2010–2013; DFTJ cohort: 2013; UK Biobank: 2012–2013). Changes in accelerated aging were classified as persistent accelerated aging, recovery from accelerated aging, delayed accelerated aging, and stable non-accelerated aging. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Meta-analysis was performed to summarize estimates across three cohorts. Results Median follow-up periods were 10.3–15.9 years across three cohorts. When defining accelerated aging by PhenoAge, baseline accelerated aging was significantly associated with increased risks of CVD (pooled HR: 1.41, 95% CI: 1.25, 1.60) and mortality (pooled HR: 1.47, 95% CI: 1.33, 1.63). Compared to participants with persistent accelerated aging, participants recovering from accelerated aging (pooled HR of CVD: 0.76, 95% CI: 0.72, 0.81; pooled HR of mortality: 0.84, 95% CI: 0.78, 0.89), delaying accelerated aging (pooled HR of CVD: 0.75, 95% CI: 0.70, 0.79; pooled HR of mortality: 0.77, 95% CI: 0.72, 0.83) or maintaining non-accelerated aging (pooled HR of CVD: 0.59, 95% CI: 0.48, 0.71; pooled HR of mortality: 0.58, 95% CI: 0.55, 0.62) exhibited decreased risks of both CVD and mortality. When defining accelerated aging by KDM age, the results remained consistent with those of PhenoAge. Conclusions Accelerated aging is a significant risk factor for CVD and mortality. Recovering from or delaying accelerated aging, or maintaining non-accelerated aging, was associated with reduced risks of CVD and mortality.  Graphical Abstract

Agricultural straw, a massive lignocellulosic by-product, requires high-value utilization strategies, and larvae of Protaetia brevitarsis (a resource insect) can convert straw into two valuable products: insect protein and frass rich in humic acid (HA). In this study, we investigated the interactions among multiple parameters affecting HA extraction efficiency and optimized the extraction process. The resulting extract was characterized by elemental analysis to determine nutrient elements, trace elements, and heavy metals; by 13C nuclear magnetic resonance (13C NMR) spectroscopy to identify the main categories of bioactive molecules; and by pot experiments to evaluate its effects on plant growth and quality. The optimized extraction conditions yielded extracts with a total organic carbon (TOC) concentration of 46.8 g/L, meeting the Chinese standard for water-soluble humic acid fertilizers (NY 1106-2010). Elemental analysis indicated that the extract was rich in trace elements, and heavy metal contents met the limitation requirements of toxic and harmful substances in fertilizers (GB 38400-2019). 13C NMR analysis revealed that the extract was enriched in aliphatic and methoxyl carbons, while pot experiments with cherry radish demonstrated that application of the extract at appropriate dosages significantly promoted plant growth and improved crop quality. These findings provide scientific support for circular agriculture and arable land protection, highlighting both their academic significance and broad application prospects.

Background Experimental studies have shown that exposure to incense burning may have deleterious effects on kidney function and architecture. However, the association between chronic exposure to incense smoke and risk of end-stage renal disease (ESRD) has not been reported in epidemiologic studies. Methods We investigated this association in the Singapore Chinese Health Study, a prospective population-based cohort of 63,257 Chinese men and women of 45–74 years of age in Singapore during recruitment from 1993 to 1998. Information on the practice of incense burning at home, diet, lifestyle and medical history was collected at baseline interviews. ESRD cases were identified through linkage with the nationwide Singapore Renal Registry through 2015. We used Cox proportional hazards regression analysis to estimate hazard ratio (HR) and 95% confidence interval (CI) of ESRD associated with domestic incense burning. Results Among cohort participants, 76.9% were current incense users. After an average 17.5 years of follow-up, there were 1217 incident ESRD cases. Compared to never users, the multivariable-adjusted HR for ESRD risk was 1.05 (95% CI, 0.80 to 1.38) for former users and 1.26 (95% CI, 1.02 to1.57) for current users of incense. In analysis by daily or non-daily use and duration, the increased ESRD risk was observed in daily users who had used incense for > 20 years; HR was 1.25 (95% CI, 1.07 to 1.46). Conversely, the risk was not increased in those who did not use incense daily or who had used daily but for ≤20 years. Conclusions Our findings demonstrate that long-term daily exposure to domestic incense burning could be associated with a higher risk of ESRD in the general population.