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Abstract Background Research on low-protein-level diets has indicated that even though the profiles of essential amino acids (EAAs) follow the recommendation for a normal-protein-level diet, broilers fed low-protein diets failed to achieve productive performance compared to those fed normal diets. Therefore, it is imperative to reassess the optimum profile of EAAs in low-protein diets and establish a new ideal pattern for amino acid balance. Furthermore, identifying novel sensitive biomarkers for assessing amino acid balance will greatly facilitate the development of amino acid nutrition and application technology. In this study, 12 dietary treatments [Con(+), Con(-), L&A(-), L&A(+), M&C(-), M&C(+), BCAA (-), BCAA(+), Thr(-), Thr(+), Trp(-) and Trp(+)] were established by combining different EAAs including lysine and arginine, methionine and cysteine, branched-chain amino acid (BCAA), threonine, and tryptophan to observe the growth and development of the broiler chickens fed with low-protein-level diets. Based on the biochemical parameters and untargeted metabolomic analysis of animals subjected to different treatments, biomarkers associated with optimal and suboptimal amino acid balance were identified. Results Growth performance, carcass characteristics, hepatic enzyme activity, serum biochemical parameters, and breast muscle mRNA expression differed significantly between male and female broilers under different dietary amino acid patterns. Male broilers exhibited higher sensitivity to the adjustment of amino acid patterns than female broilers. For the low-protein diet, the dietary concentrations of lysine, arginine, and tryptophan, but not of methionine, cystine, or threonine, needed to be increased. Therefore, further research on individual BCAA is required. For untargeted metabolomic analysis, Con(+) was selected as a normal diet (NP) while Con(-) represented a low-protein diet (LP). L&A(+) denotes a low-protein amino acid balanced diet (LPAB) and Thr(+) represents a low-protein amino acid imbalance diet (LPAI). The metabolites oxypurinol, pantothenic acid, and D-octopine in birds were significantly influenced by different dietary amino acid patterns. Conclusion Adjusting the amino acid profile of low-protein diets is required to achieve normal growth performance in broiler chickens fed normal-protein diets. Oxypurinol, pantothenic acid, and D-octopine have been identified as potentially sensitive biomarkers for assessing amino acid balance.

Abstract There is a growing interest in the health impacts of PM2.5 originating from landscape fires. We conducted a time-series study to investigate the association between daily exposure to landscape fire PM2.5 and hospital admissions for cardiovascular events in 184 major Chinese cities. We developed a machine learning model combining outputs from chemical transport models, meteorological information and observed air pollution data to determine daily concentrations of landscape fire PM2.5. Furthermore, we fitted quasi-Poisson regression to evaluate the link between landscape fire PM2.5 concentrations and cardiovascular hospitalizations in each city, and conducted random-effects meta-analysis to pool the city-specific estimates. Here we show that, on a national scale, a rise of 1-μg/m3 in landscape fire PM2.5 concentrations is positively related to a same-day 0.16% (95% confidence interval: 0.01%–0.32%) increase in hospital admissions for cardiovascular disease, 0.28% (0.12%–0.44%) for ischemic heart disease, and 0.25% (0.02%–0.47%) for ischemic stroke. The associations remain significant even after adjusting for other sources of PM2.5. Our findings indicate that transient elevation in landscape fire PM2.5 levels may increase risk of cardiovascular diseases.

Fasting is typically used before feeding metabolizable energy assessment in broilers. Previous studies have shown that fasting cause atrophy of the intestinal villus. Whether fasting affects intestinal permeability during refeeding by altering barrier function and nutrient absorption is of concern. Here, 23-d-old broilers were randomly assigned to 5 treatments, fasted for 0, 12, 24, 36, and 48 h, respectively, and then refed for 2 d, to study the impact of different duration of fasting on the intestinal regeneration and barrier function during refeeding. Results showed that the intestinal morphology in fasted birds was recovered in 2 d of refeeding at most. As fasting durations increased, enterocytes per intestinal villus were linearly and quadratically increased (both P

Abstract Benign prostatic hyperplasia (BPH) is a prevalent condition affecting the male urinary system, with its molecular mechanisms of pathogenesis remaining unclear. Y-27632, a non-isoform-selective Rho kinase inhibitor, has shown therapeutic potential in various diseases but its effects on static factors and fibrosis in BPH remain unexplored. This study investigated human prostate tissues, human prostate cell lines, and BPH rat model using immunofluorescence, flow cytometry, quantitative reverse transcription polymerase chain reaction, western blotting, and cell counting kit-8. ROCK1 and ROCK2 were significantly up-regulated in BPH tissues, correlating with clinical parameters. Y-27632 targeted the inhibition of ROCK1 & ROCK2 expression and inhibited cell proliferation, fibrosis, epithelial-mesenchymal transition (EMT), while induced cell apoptosis in a dose-dependent manner. Moreover, knockdown of either ROCK isoform inhibited fibrosis and EMT, induced apoptosis, while ROCK overexpression had the opposite effects. ROCK downregulation inhibited the β-catenin signaling pathway (such as C-MYC, Snail and Survivin) and decreased β-catenin protein stability, while inhibiting TGF-β/Smad2/3 signaling. At the in vivo level, Y-27632 reversed prostatic hyperplasia and fibrosis in BPH model rats to some extent. Our study sheds light on the therapeutic potential of Y-27632 in regulating prostate cell growth, fibrosis and EMT, and demonstrates for the first time the regulatory effect of ROCK isoforms on prostate cells, providing the basis for future research of ROCK isoform-selective inhibitors.

Abstract Background The gut microbiota is a key regulator of bone metabolism. Investigating the relationship between the gut microbiota and bone remodeling has revealed new avenues for the treatment of bone-related disorders. Despite significant progress in understanding gut microbiota-bone interactions in mammals, research on avian species remains limited. Birds have unique bone anatomy and physiology to support egg-laying. However, whether and how the gut microbiota affects bone physiology in birds is still unknown. In this study, we utilized laying hens as a research model to analyze bone development patterns, elucidate the relationships between bone and the gut microbiota, and mine probiotics with osteomodulatory effects. Results Aging led to a continuous increase in bone mineral density in the femur of laying hens. The continuous deposition of medullary bone in the bone marrow cavity of aged laying hens led to significant trabecular bone loss and weakened bone metabolism. The cecal microbial composition significantly shifted before and after sexual maturity, with some genera within the class Clostridia potentially linked to postnatal bone development in laying hens. Four bacterial strains associated with bone development, namely Blautia coccoides CML164, Fournierella sp002159185 CML151, Anaerostipes caccae CML199 (ANA), and Romboutsia lituseburensis CML137, were identified and assessed in chicks with low bacterial loads and chicken primary osteoblasts. Among these, ANA demonstrated the most significant promotion of bone formation both in vivo and in vitro, primarily attributed to butyrate in its fermentation products. A long-term feeding experiment of up to 72 weeks confirmed that ANA enhanced bone development during sexual maturity by improving the immune microenvironment of the bone marrow in laying hens. Dietary supplementation of ANA for 50 weeks prevented excessive medullary bone deposition and mitigated aging-induced trabecular bone loss. Conclusions These findings highlight the beneficial effects of ANA on bone physiology, offering new perspectives for microbial-based interventions for bone-related disorders in both poultry and possibly extending to human health. Video Abstract Graphical Abstract

Objective The objective of this experiment was to determine the standard ileal digestibility (SID) of amino acid (AA) in 10 different sources of wheat bran fed to broilers and establish the SID AA prediction based on the chemical composition. Methods A total of 660 1-day-old broilers were randomly divided into 11 treatments with 6 replicates of 10 chickens each. Diets included 10 semi-purified mash diets and 1 nitrogen-free diet. Titanium dioxide (TiO2) 0.50% was used as an indigestible index. On day 13, 6 chickens from each replicate were selected for slaughter to collect ileal contents. On day 28, 4 chickens from each replicate were selected for slaughter to collect ileal contents. Results Results showed that the coefficient of variation of the conventional nutrients (except for gross energy, and dry matter) and all AAs was greater than 8.00%. The average SID of essential AA in wheat bran for 13-day-old broilers was 37.24% and the average SID of nonessential AA was 42.02%; the average SID of essential AA for 28-day-old broilers was 67.13% and the average SID of nonessential AA was 69.51%. A correlation was observed (p

The development of skeletal muscle is a crucial factor in determining the meat yield and economic benefits of broiler production. Recent research has shown that mulberry leaves and their extracts can be used to significantly improve the growth performance of livestock and poultry. The present study aims to elucidate the mechanisms involved in the regulation of skeletal muscle development in broiler offspring by dietary mulberry-leaf flavonoids (MLF) supplementation from the perspective of maternal effect theory. A total of 270 Qiling broiler breeder hens were randomly assigned to 3 treatments with different doses of MLF (0, 30, 60 mg/kg) for 8 weeks before collecting their fertilized eggs. The chicken offspring at 13 and 19 d of embryonic stage, and from 1 to 28 d old after hatching were included in this study. The results showed that maternal supplementation increased the breast muscle weight and body weight of the offspring at the embryo and chick stages (P

This study aimed to compare the effects of dietary methionine (Met) and 2-hydroxy-4-(methylthio)-butanoate (HMTBA) on the eggshell quality of broiler breeder hens and elucidate the mechanism of Met in improving eggshell quality from the perspectives of eggshell microstructure and shell gland physiological function. A total of 720 WOD188 broiler breeder hens at 40 weeks old were assigned to 3 groups, with 8 replicates per group and 30 birds per replicate. Over 7 weeks, birds were fed a basal diet or the same diet supplemented with 0.15% Met or 0.17% HMTBA. Our findings revealed significant improvements in the Met group for egg shape index, shell thickness, breaking strength, and fracture toughness (P 0.05). Met supplementation increased calcium and phosphorus levels in both serum and shell gland tissue (P

Background: Non-optimum temperatures are associated with a considerable mortality burden. However, there is a lack of evaluation of labour productivity losses related to premature deaths due to non-optimum temperatures. This study aimed to quantify the labour productivity burden associated with premature deaths related to non-optimum temperatures and explore the potential socio-economic vulnerabilities. Methods: Daily all-cause mortality data were collected from 1,066 locations in 7 countries (Australia, Brazil, Canada, Chile, New Zealand, South Korea, and Thailand). Productivity-Adjusted Life-Year (PALY) loss due to each premature death was calculated to measure the labour productivity loss, by multiplying the years of working life lost by the proportion of the equivalent full-time (EFT) workers. A two-stage times series design and the generalized linear regression model with a quasi-Poisson family were applied to assess the association between non-optimum temperatures and the PALY loss due to premature deaths. Results: We observed a U-shaped relationship between temperature and PALY lost due to premature mortality. We estimated that 2.51% (95% eCI: 2.05%, 2.92%) of PALY losses could be attributed to non-optimal temperatures, with cold-related deaths contributing 1.26% (95% eCI: 0.94%, 1.54%) and heat-related deaths contributing 1.25% (95% eCI: 0.96%, 1.51%). Cold temperature contributed to the most PALYs lost in those aged 45–54 and 55–64, while heat-related losses predominated among the 15–44 age group. We also observed that the fractions of PALY lost attributed to extreme heat were positively associated with the relative deprivation index, while negatively associated with GDP per capita. Conclusion: This multi-country study highlights that non-optimum temperatures led to a considerable labour productivity loss and socioeconomically disadvantaged communities experience greater losses.

ABSTRACT: This study aimed to investigate the effects of baicalin and chlorogenic acid (BC) on growth performance, intestinal barrier function, antioxidant capacity, intestinal microbiota, and mucosal metabolism in broilers. A total of 720 twenty-one-day-old broilers were randomly allocated into 3 groups, with 6 replicates per group and 40 chickens per replicate. They were fed a basal diet (Con group) or a basal diet supplemented with 250 or 400 mg/kg BC (BC250 and BC400 groups) for 40 consecutive days. The results revealed that 250 mg/kg BC significantly increased 60-d body weight and average daily gain during 39 to 60 d (P < 0.05). Furthermore, Supplementation with 250 mg/kg BC improved the antioxidant capacity and immunity of broilers, as evidenced by increased (P < 0.05) superoxide dismutase and decreased (P < 0.05) malondialdehyde levels in serum and ileum, as well as increased (P < 0.05) immunoglobulin G levels. Supplementation with 250 mg/kg BC enhanced intestinal development by improving intestinal morphology and promoting the proliferation of intestinal crypts. Moreover, Supplementation with 250 mg/kg BC improved (P < 0.05) intestinal permeability, up-regulated (P < 0.05) the expression of tight junction-related genes (Occludin and ZO-1), and down-regulated (P < 0.05) the expression of pro-inflammatory genes (IL-2, IL-8, and IFN-γ). 16S rRNA sequencing revealed significant enrichment of Microbacteriaceae, Micromonosporaceae, Anaerovoracaceae, and Coriobacteriaceae in the BC250 group. Metabolomics showed that 250 mg/kg BC up-regulated the lysosome, foxo signaling pathway, glycosylphosphatidylinositol (GPI)-anchor biosynthesis, and oxidative phosphorylation pathways, while down-regulating the biosynthesis of cofactors pathway. In conclusion, supplementing diets with 250 mg/kg BC is recommended to modulate intestinal microbiota, mucosal metabolism, and antioxidant capacity, thereby improving broiler growth performance and intestinal health.

Wildfires have devastating effects on society and public health. However, little evidence from population-based cohort has been performed to analyze the relationship of wildfire-related PM2.5, an important component of wildfire smoke, with cancer-specific mortality. We aimed to explore this relationship and identify vulnerable populations in UK with lower levels of wildfire-related PM2.5 exposure. The study consisted of 492394 participants (age: 38–73 years) recruited by UK Biobank during 2004–2010. The cumulative wildfire-related PM2.5 within 10 kilometers of residence over three years was used as exposure, which was assessed by chemical transport and machine learning models. A time-varying Cox regression was utilized to explore the relationship of exposure with diverse cancer-specific mortality outcomes. Subgroup analyses of a range of potential modifiers were performed. Each 10 μg/m3 increment of 3-year cumulative exposure was related to a 0.4 % greater risk of total cancer (95 %CI: 1.001–1.007), a 1.1 % greater risk of lung cancer (95 %CI: 1.004–1.018), and a 2.7 % greater risk of lip, oral cavity and pharynx (LOP) cancer (95 %CI: 1.005–1.049). Higher vulnerability in the wildfire-related PM2.5-lung cancer relationship was found among participants being retired than those with other employment status. Even lower levels of exposure to PM2.5 from wildfires were related to elevated mortality risks for cancer from total, lung, LOP, highlighting the importance of wildfire prevention and control. Further investigations are warranted to enrich and extend existing knowledge in this field.

Prior research has explored the relationship between occupational exposure to nickel and lung function. Nonetheless, there is limited research examining the correlation between blood nickel levels and lung function among young adults in the general population. The metabolomic changes associated with nickel exposure have not been well elucidated. On August 23, 2019, we enrolled 257 undergraduate participants from the Chinese Undergraduates Cohort to undergo measurements of blood nickel levels and lung function. The follow-up study was conducted in May 2021. A linear mixed-effects model was employed to assess the relationship between blood nickel levels and lung function. We also conducted stratified analyses by home address. In addition, in order to explore the biological mechanism of lung function damage caused by nickel exposure, we performed metabolomic analyses of baseline serum samples (N = 251). Both analysis of variance and mixed linear effect models were utilized to assess the impact of blood nickel exposure on metabolism. Our findings from cross-sectional and cohort analyses revealed a significant association between blood nickel levels and decreased forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) among young adults in the general population. Furthermore, we found stronger associations in urban areas. In metabolomics analysis, a total of nine metabolites were significantly changed under blood nickel exposure. The changed metabolites were mainly enriched in six pathways including carbohydrate, amino acid, and cofactor vitamin metabolism. These metabolic pathways involve inflammation and oxidative stress, indicating that high concentrations of nickel exposure can cause inflammation and oxidative stress by disrupting the above metabolism of the body.

ABSTRACT: Fatty acids (FAs) can serve as energy for poultry, maintain normal cell structure and function, and support a healthy immune system. Although the addition of polyunsaturated fatty acids (PUFAs) to the diet has been extensively studied and reported, the mechanism of action of saturated fatty acids (SFAs) remains to be elucidated. We investigated the effect of 0.04% dietary myristic acid (MA) on slaughter performance, lipid components, tissue FAs, and the transcriptome profile in chickens. The results showed that dietary MA had no effect on slaughter performance (body weight, carcass weight, eviscerated weight, and pectoral muscle weight) (P > 0.05). Dietary MA enrichment increased MA (P

ABSTRACT: This study was conducted to determine the influence of dietary glucosamine sulfate sodium (GSS) on laying performance, blood profiles, eggshell and inner quality of eggs and relative expression of the genes related to eggshell in laying hens at early stage. A total of 640 twenty-weeks-old Lohmann laying hens were randomly allotted to 4 treatments with 10 replicates of 16 hens each. The experiment lasted for 8 wk, and dietary treatments were: 1) CON, basal diet; 2) G1, CON + 0.2% GSS; 3) G2, CON + 0.4% GSS; 4) G3, CON + 0.6% GSS. The inclusion of GSS increased average daily feed intake, laying rate, and egg mass (P < 0.05) linearly during wk 21 to 25, 25 to 29, and 21 to 29, egg weight during wk 21 to 25 and 25 to 29, and improved (P < 0.05) feed conversion ratio linearly during wk 21 to 25. The supplementation of GSS increased (P < 0.05) albumen height quadratically, Haugh unit, calcium content, calcium mass, phosphorus content and phosphorus mass linearly at the end of 25th and 29th wk. At the end of 29th wk, the eggshell strength, eggshell weight, eggshell ratio, and eggshell thickness were increased (P < 0.05) linearly in GSS treatments compared with CON. The addition of GSS increased (P < 0.05) serum calcium, estrogen 2, and calcitonin, while decreased (P < 0.05) serum tartrate resistant acid phosphatase (TRAP), parathormone, IL-6 and prostaglandin E2 (PGE2) at the end of 29th wk. The inclusion of GSS increased (P < 0.05) the relative expression of ovocalyxin-32 and ovocalyxin-36 linearly at the end of 29th wk, and ovalbumin, osteopontin, calbindin 1, and ovocleidin-116 linearly at the end of 25th and 29th wk. Quadratic effects were observed (P < 0.05) in the laying rate during wk 21 to 25, serum TRAP and PGE2, the relative expression of ovocleidin-116 at the end of 29th wk. In summary, the inclusion of GSS up-regulated relative expression of osteopontin, ovocleidin-116, ovocalyxin-32 and ovocalyxin-36 in uterus, promoted the serum PGE2 and calcitonin, thus increased the calcium content of eggshell and finally enhanced eggshell quality.

Abstract Background Although the association between ambient temperature and mortality of respiratory diseases was numerously documented, the association between various ambient temperature levels and respiratory emergency department (ED) visits has not been well studied. A recent investigation of the association between respiratory ED visits and various levels of ambient temperature was conducted in Beijing, China. Methods Daily meteorological data, air pollution data, and respiratory ED visits data from 2017 to 2018 were collected in Beijing. The relationship between ambient temperature and respiratory ED visits was explored using a distributed lagged nonlinear model (DLNM). Then we performed subgroup analysis based on age and gender. Finally, meta-analysis was utilized to aggregate the total influence of ambient temperature on respiratory ED visits across China. Results The single-day lag risk for extreme cold peaked at a relative risk (RR) of 1.048 [95% confidence interval (CI): 1.009, 1.088] at a lag of 21 days, with a long lag effect. As for the single-day lag risk for extreme hot, a short lag effect was shown at a lag of 7 days with an RR of 1.076 (95% CI: 1.038, 1.114). The cumulative lagged effects of both hot and cold effects peaked at lag 0–21 days, with a cumulative risk of the onset of 3.690 (95% CI: 2.133, 6.382) and 1.641 (95% CI: 1.284, 2.098), respectively, with stronger impact on the hot. Additionally, the elderly were more sensitive to ambient temperature. The males were more susceptible to hot weather than the females. A longer cold temperature lag effect was found in females. Compared with the meta-analysis, a pooled effect of ambient temperature was consistent in general. In the subgroup analysis, a significant difference was found by gender. Conclusions Temperature level, age-specific, and gender-specific effects between ambient temperature and the number of ED visits provide information on early warning measures for the prevention and control of respiratory diseases.

Abstract Background Floods are the most frequent weather-related disaster, causing significant health impacts worldwide. Limited studies have examined the long-term consequences of flooding exposure. Methods Flood data were retrieved from the Dartmouth Flood Observatory and linked with health data from 499,487 UK Biobank participants. To calculate the annual cumulative flooding exposure, we multiplied the duration and severity of each flood event and then summed these values for each year. We conducted a nested case-control analysis to evaluate the long-term effect of flooding exposure on all-cause and cause-specific mortality. Each case was matched with eight controls. Flooding exposure was modelled using a distributed lag non-linear model to capture its nonlinear and lagged effects. Results The risk of all-cause mortality increased by 6.7% (odds ratio (OR): 1.067, 95% confidence interval (CI): 1.063–1.071) for every unit increase in flood index after confounders had been controlled for. The mortality risk from neurological and mental diseases was negligible in the current year, but strongest in the lag years 3 and 4. By contrast, the risk of mortality from suicide was the strongest in the current year (OR: 1.018, 95% CI: 1.008–1.028), and attenuated to lag year 5. Participants with higher levels of education and household income had a higher estimated risk of death from most causes whereas the risk of suicide-related mortality was higher among participants who were obese, had lower household income, engaged in less physical activity, were non-moderate alcohol consumers, and those living in more deprived areas. Conclusions Long-term exposure to floods is associated with an increased risk of mortality. The health consequences of flooding exposure would vary across different periods after the event, with different profiles of vulnerable populations identified for different causes of death. These findings contribute to a better understanding of the long-term impacts of flooding exposure.

Abstract Background Under a changing climate, the joint effects of temperature and relative humidity on tuberculosis (TB) are poorly understood. To address this research gap, we conducted a time-series study to explore the joint effects of temperature and relative humidity on TB incidence in China, considering potential modifiers. Methods Weekly data on TB cases and meteorological factors in 22 cities across mainland China between 2011 and 2020 were collected. The proxy indicator for the combined exposure levels of temperature and relative humidity, Humidex, was calculated. First, a quasi-Poisson regression with the distributed lag non-linear model (DLNM) was constructed to examine the city-specific associations between humidex and TB incidence. Second, a multivariate meta-regression model was used to pool the city-specific effect estimates, and to explore the potential effect modifiers. Results A total of 849,676 TB cases occurred in the 22 cities between 2011 and 2020. Overall, a conspicuous J-shaped relationship between humidex and TB incidence was discerned. Specifically, a decrease in humidex was positively correlated with an increased risk of TB incidence, with a maximum relative risk (RR) of 1.40 (95% CI: 1.11–1.76). The elevated RR of TB incidence associated with low humidex (5th humidex) appeared on week 3 and could persist until week 13, with a peak at approximately week 5 (RR: 1.03, 95% CI: 1.01–1.05). The effects of low humidex on TB incidence vary by Natural Growth Rate (NGR) levels. Conclusion A J-shaped exposure-response association existed between humidex and TB incidence in China. Humidex may act as a better predictor to forecast TB incidence compared to temperature and relative humidity alone, especially in regions with higher NGRs.

Abstract Under long-standing threat of seasonal influenza outbreaks, it remains imperative to understand the drivers of influenza dynamics which can guide mitigation measures. While the role of absolute humidity and temperature is extensively studied, the possibility of ambient ozone (O3) as an environmental driver of influenza has received scant attention. Here, using state-level data in the USA during 2010–2015, we examined such research hypothesis. For rigorous causal inference by evidence triangulation, we applied 3 distinct methods for data analysis: Convergent Cross Mapping from state-space reconstruction theory, Peter-Clark-momentary-conditional-independence plus as graphical modeling algorithms, and regression-based Generalised Linear Model. The negative impact of ambient O3 on influenza activity at 1-week lag is consistently demonstrated by those 3 methods. With O3 commonly known as air pollutant, the novel findings here on the inhibition effect of O3 on influenza activity warrant further investigations to inform environmental management and public health protection.

Abstract The China Undergraduate Cohort (CUC) is an ambispective cohort study with its major purpose to better understand the effects of lifetime environmental exposures on health outcomes. We recruited 5322 college students with an average age of 18.3 ± 0.7 years in China from August 23, 2019 to October 28, 2019. Follow-up surveys were conducted annually. The dataset comprises individual demographic data (e.g. age, sex, height, weight, birth date, race, home address, annual family income, contact information), health-related behavior data (smoking status, smoking cessation, passive smoking exposure, drinking habit, physical activity, dietary status), lifestyle data (physical exercise, dietary habit, length of time spent outdoors), disease history (respiratory disease history, cardiovascular disease history, urinary system disease history, etc.), mental health status data (sleep quality, self-reported stress, anxiety and depression symptoms), lung function and blood samples data. Preliminary results from our cohort have found the association between air pollution, summer heat and mercury exposure and lung function among young adults in China.

This experiment aimed to discuss and reveal the effect and mechanism of mannanase on intestinal inflammation in broilers triggered by a soybean meal diet. In this experiment, 384 Arbor Acres broilers at 1 d old were randomly divided into 3 treatment groups. The broilers were fed a corn-soybean meal basal diet, a low-energy diet (metabolizable energy reduced by 50 kcal/kg), and a low-energy diet supplemented with 100 mg/kg mannanase for 42 d. The low-energy diet increased feed conversion ratio from 0 to 42 d, reduced ileal villus height and villus height-to-crypt depth ratio and upregulated the expression of nuclear factor kappa B (NF-κB) in the ileum (P

Chromium (Cr) exposure is associated with various respiratory system diseases, but there are limited studies investigating its impact on lung function in young adults. The Cr exposure-related metabolomic changes are not well elucidated. This study recruited 608 students from a university in Shandong Province, China in 2019. We used cohort design fitted with linear mixed-effects models to assess the association between blood Cr concentration and lung function. In addition, we performed metabolomic and lipidomic analyses of baseline serum samples (N = 582) using liquid chromatography-mass spectrometry. Two-step statistical analysis (analysis of variance and mixed-linear effect model) was used to evaluate the effect of blood Cr exposure on metabolites. We found that blood Cr was associated with decreased lung function in young adults. Each 2-fold increase in blood Cr concentrations was significantly associated with decreased FEV1 and FVC by 35.26 mL (95 % CI: −60.75, −9.78) and 38.56 mL (95 % CI: −66.60, −10.51), respectively. In the metabolomics analysis, blood Cr exposure was significantly associated with 14 key metabolites. The changed metabolites were mainly enriched in six pathways including lipid metabolism, amino acid metabolism, and cofactor vitamin metabolism. Blood Cr may affect lung function through oxidative stress and inflammation related pathways.

Objective: Drug-induced liver injury (DILI), a type of acute inflammation, has sparked significant concern owing to its unpredictability and severity. Psoraleae Fructus (PF), an edible Chinese herb widely used in traditional Chinese medicine (TCM), causes liver injury. Therefore, the elucidation of the mechanism underlying PF-induced liver injury and the search for more effective means of detoxification using herbal compatibility has become an urgent issue. This study evaluated the hepatoprotective effects of Paeoniae Radix Alba (PRA), a hepatoprotective Chinese medicine, on PF-induced liver injury and explored the underlying mechanisms. Methods: A rat model of lipopolysaccharide (LPS)-induced immune stress was established to evaluate the hepatotoxicity of PF and the detoxifying effect of PRA. Subsequently, inflammatory pathways were identified using network pharmacology. Finally, the molecular mechanism by which PRA alleviates PF-induced liver injury was validated using an inflammasome activation model in bone marrow-derived macrophages (BMDMs). Results: In vivo, hepatocytes in rats treated with LPS + PF exhibited massive inflammatory infiltration and apoptosis, and the expression of liver injury indicators and inflammatory factors was significantly upregulated, which was reversed by PRA pretreatment. Network pharmacology showed that PRA alleviated PF-induced liver injury and was associated with the NOD-like receptor signaling pathway. Moreover, PF directly induced inflammasome activation in LPS-primed BMDMs which in turn induced caspase-1 activation and the secretion of downstream effector cytokines such as IL-1β. PRA pretreatment inhibited PF-induced activation of the NLRP3 inflammasome by mitigating the accumulation of mitochondrial reactive oxygen species (mtROS). Conclusions: The present study demonstrates that PRA alleviated PF induced-liver injury by inhibiting NLRP3 inflammasome activation. The results of this study are expected to inform the prevention and control of PF-induced hepatotoxicity in clinical practice.

Pulmonary fibrosis (PF) is a fatal interstitial lung disease associated with declining pulmonary function but currently with few effective drugs. Cellular senescence has been implicated in the pathogenesis of PF and could be a potential therapeutic target. Emerging evidence suggests wogonin, the bioactive compound isolated from Scutellaria baicalensis, owns the anti-senescence properties, however, the possible impact of wogonin on PF and the potential mechanisms remain unclear. In this study, a well-established mouse model of PF was utilized which mice were administrated with bleomycin (BLM). Strikingly, wogonin treatment significantly reduced fibrosis deposition in the lung induced by BLM. In vitro, wogonin also suppressed fibrotic markers of cultured epithelial cells stimulated by BLM or hydrogen peroxide. Mechanistic investigation revealed that wogonin attenuated the expressions of DNA damage marker γ-H2AX and senescence-related markers including phosphorylated p53, p21, retinoblastoma protein (pRB), and senescence-associated β-galactosidase (SA-β-gal). Moreover, wogonin, as a direct and selective inhibitor of cyclin-dependent kinase 9 (CDK9), exhibited anti-fibrotic capacity by inhibiting CDK9 and p53/p21 signalling. In conclusion, wogonin protects against BLM-induced PF in mice through the inhibition of cell senescence via the regulation of CDK9/p53 and DNA damage pathway. This is the first study to demonstrate the beneficial effect of wogonin on PF, and its implication as a novel candidate for PF therapy.

Background Baicalin and probiotic cocktails are promising feed additives with broad application prospects. While probiotic cocktails are known to enhance intestinal health, the potential synergistic impact of combining baicalin with probiotic cocktails on the gut health of broiler chickens remains largely unexplored. Therefore, this study aims to investigate the influence of the combined administration of baicalin and probiotic cocktails on the composition of ileal and cecal microbiota in broiler chickens to elucidate the underlying mechanisms responsible for the health-promoting effects. Results A total of 320 1-day-old male Arbor Acres broilers were divided into 4 groups, each with 8 replicates of 10 chicks per replicate. Over a period of 42 d, the birds were fed a basal diet or the same diet supplemented with 37.5 g/t baicalin (BC), 1,000 g/t probiotic cocktails (PC), or a combination of both BC (37.5 g/t) and PC (1,000 g/t). The results demonstrated that BC + PC exhibited positive synergistic effects, enhancing intestinal morphology, immune function, and barrier function. This was evidenced by increased VH/CD ratio, sIgA levels, and upregulated expression of occludin and claudin-1 (P

Abstract Background Increasing evidence is appearing that ozone has adverse effects on health. However, the association between long-term ozone exposure and lung function is still inconclusive. Objectives To investigate the associations between long-term exposure to ozone and lung function in Chinese young adults. Methods We conducted a prospective cohort study among 1594 college students with a mean age of 19.2 years at baseline in Shandong, China from September 2020 to September 2021. Lung function indicators were measured in September 2020 and September 2021, including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), forced expiratory flow at the 25th, 50th, and 75th percentile of the FVC (FEF25, FEF50, and FEF75) and mean flow rate between 25% and 75% of the FVC (FEF25-75) were measured. Daily 10 km×10 km ozone concentrations come from a well-validated data-fusion approach. The time-weighted average concentrations in 12 months before the lung function test were defined as the long-term ozone exposure. The associations between long-term ozone exposure and lung function indicators in Chinese young adults were investigated using a linear mixed effects model, followed by stratified analyses regarding sex, BMI and history of respiratory diseases. Results Each interquartile range (IQR) (8.9 µg/m3) increase in long-term ozone exposure were associated with a -204.3 (95% confidence interval (CI): -361.6, -47.0) ml/s, -146.3 (95% CI: -264.1, -28.4) ml/s, and − 132.8 (95% CI: -239.2, -26.4) ml/s change in FEF25, FEF50, and FEF25-75, respectively. Stronger adverse associations were found in female participants or those with BMI ≥ 24 kg/m2 and history of respiratory diseases. Conclusion Long-term exposure to ambient ozone is associated with impaired small airway indicators in Chinese young adults. Females, participants with BMI ≥ 24 kg/m2 and a history of respiratory disease have stronger associations.

Abstract The Sanxingdui site (4.4–2.9 ka B.P.) in southwestern China is considered one of the most significant archaeological discoveries of the twentieth century, which contains numerous codes for interpreting the origin and development of the Yangtze River civilization. Remains found in Sanxingdui burial pits are keys to deciphering some of these codes. From the characters of the charcoal fragments, ashes and jades in the Sanxingdui buried pits, at the same time, comprehensively analyzing archaeological evidence and previous research results, we speculate that the temperature of ancient Shu people burning sacrifices could be 600–800 ℃. However, the values of magnetic properties and chroma of soils near the ash layers in the pits, and Guanghan Clay near the pits, do not show obvious changes caused by such high-temperature annealing. Combined with the geographical location of the pits and the accumulation characteristics of ash layers and artifacts in the pits, we consider that the Sanxingdui burial pits were not trash pits but sacrificial pits, and they were used for burying sacrifice after burning sacrifice. Although the ritual of burying sacrifice after burning sacrifice dates back to the Longshan period (4.3–4.0 ka B.P.) in China’s Central Plain, the Sanxingdui sacrificial pits, which began to occur in the late Shang Dynasty (~ 3.0 ka B.P.) with such a large scale, and the sacrifices unearthed from the pits, are unique. So, we believe that although influenced by the Central Plain culture, the ancient Shu people in the late Shang Dynasty have unique characteristics of culture and religion.

Given the key role of methionine in biological processes, adequate methionine should be provided to meet the nutritional requirements. DL-2-hydroxy-4-(methylthio)-butanoic acid (DL-HMTBA) has been considered as an important source of methionine. However, the effects of different sources and levels of methionine on the intestinal health status have not been clarified yet. An experiment was carried out to investigate the effects of different dietary sources and levels of methionine on the intestinal epithelial barrier, inflammatory cytokines expression, ileal morphology, microbiota composition, and cecal short chain fatty acids (SCFA) profiles. For this purpose, 720 male Arbor Acre broiler chicks at 1 d old were randomly assigned to a 2 × 3 factorial arrangement with 2 methionine sources (DL-methionine and DL-HMTBA) and 3 total sulfur amino acids (TSAA) levels (80%, 100%, and 120% of Arbor Acre recommendation). The results showed that DL-HMTBA supplementation promoted intestinal physical barrier at both gene expression level of claudin-1 and serum diamine oxidase level (P

To investigate the possible protective effect of hesperidin on intestinal damage caused by high-temperature heat stress in yellow-feathered broilers, 960 broilers aged 21 days were randomly divided into four groups: HT, HT300, HT450, and HT600, with each group receiving different amounts of hesperidin supplementation (0, 300, 450, and 600 mg/kg). The dietary supplementation of hesperidin could mitigate the elevation of corticosterone (CORT) and adrenocorticotropic hormone (ATCH) levels in serum from yellow-feathered broilers induced by heat stress. The supplementation of 300 mg/kg and 450 mg/kg of hesperidin reduced crypt depth and increased the V/C ratio in the small intestine compared to the HT group. The dietary supplementation of hesperidin decreased endotoxin and D-lactic acid levels in the blood, and dietary supplementation of 300 mg/kg of hesperidin increased the expression of claudin-1 and ZO-1 mRNA in the jejunum compared with the HT group. Furthermore, the dietary supplementation of 300 mg/kg of hesperidin decreased serum IL-1β and IL-6 levels. In comparison, supplementation with 300 mg/kg and 450 mg/kg of hesperidin decreased serum TNF-α levels in yellow-feathered broilers compared to the HT group. Moreover, the dietary supplementation of hesperidin decreased NF-κB mRNA levels. Overall, these data suggest that dietary supplementation with hesperidin potentially improves intestinal injury caused by heat stress in yellow-feathered broilers.

BackgroundThe regional disparity of heatwave-related mortality over a long period has not been sufficiently assessed across the globe, impeding the localisation of adaptation planning and risk management towards climate change. We quantified the global mortality burden associated with heatwaves at a spatial resolution of 0.5°×0.5° and the temporal change from 1990 to 2019.Methods and findingsWe collected data on daily deaths and temperature from 750 locations of 43 countries or regions, and 5 meta-predictors in 0.5°×0.5° resolution across the world. Heatwaves were defined as location-specific daily mean temperature ≥95th percentiles of year-round temperature range with duration ≥2 days. We first estimated the location-specific heatwave-mortality association. Secondly, a multivariate meta-regression was fitted between location-specific associations and 5 meta-predictors, which was in the third stage used with grid cell-specific meta-predictors to predict grid cell-specific association. Heatwave-related excess deaths were calculated for each grid and aggregated. During 1990 to 2019, 0.94% (95% CI: 0.68-1.19) of deaths [i.e., 153,078 cases (95% eCI: 109,950-194,227)] per warm season were estimated to be from heatwaves, accounting for 236 (95% eCI: 170-300) deaths per 10 million residents. The ratio between heatwave-related excess deaths and all premature deaths per warm season remained relatively unchanged over the 30 years, while the number of heatwave-related excess deaths per 10 million residents per warm season declined by 7.2% per decade in comparison to the 30-year average. Locations with the highest heatwave-related death ratio and rate were in Southern and Eastern Europe or areas had polar and alpine climates, and/or their residents had high incomes. The temporal change of heatwave-related mortality burden showed geographic disparities, such that locations with tropical climate or low incomes were observed with the greatest decline. The main limitation of this study was the lack of data from certain regions, e.g., Arabian Peninsula and South Asia.ConclusionsHeatwaves were associated with substantial mortality burden that varied spatiotemporally over the globe in the past 30 years. The findings indicate the potential benefit of governmental actions to enhance health sector adaptation and resilience, accounting for inequalities across communities.

Background: Temperature variability (TV) is associated with increased mortality risk. However, it is still unknown whether intra-day or inter-day TV has different effects. Objectives: We aimed to assess the association of intra-day TV and inter-day TV with all-cause, cardiovascular, and respiratory mortality. Methods: We collected data on total, cardiovascular, and respiratory mortality and meteorology from 758 locations in 47 countries or regions from 1972 to 2020. We defined inter-day TV as the standard deviation (SD) of daily mean temperatures across the lag interval, and intra-day TV as the average SD of minimum and maximum temperatures on each day. In the first stage, inter-day and intra-day TVs were modelled simultaneously in the quasi-Poisson time-series model for each location. In the second stage, a multi-level analysis was used to pool the location-specific estimates. Results: Overall, the mortality risk due to each interquartile range [IQR] increase was higher for intra-day TV than for inter-day TV. The risk increased by 0.59% (95% confidence interval [CI]: 0.53, 0.65) for all-cause mortality, 0.64% (95% CI: 0.56, 0.73) for cardiovascular mortality, and 0.65% (95% CI: 0.49, 0.80) for respiratory mortality per IQR increase in intra-day TV0–7 (0.9 °C). An IQR increase in inter-day TV0–7 (1.6 °C) was associated with 0.22% (95% CI: 0.18, 0.26) increase in all-cause mortality, 0.44% (95% CI: 0.37, 0.50) increase in cardiovascular mortality, and 0.31% (95% CI: 0.21, 0.41) increase in respiratory mortality. The proportion of all-cause deaths attributable to intra-day TV0–7 and inter-day TV0–7 was 1.45% and 0.35%, respectively. The mortality risks varied by lag interval, climate area, season, and climate type. Conclusions: Our results indicated that intra-day TV may explain the main part of the mortality risk related to TV and suggested that comprehensive evaluations should be proposed in more countries to help protect human health.

Assessing the association between temperature frequency and mortality can provide insights into human adaptation to local ambient temperatures. We collected daily time-series data on mortality and temperature from 757 locations in 47 countries/regions during 1979–2020. We used a two-stage time series design to assess the association between temperature frequency and all-cause mortality. The results were pooled at the national, regional, and global levels. We observed a consistent decrease in the risk of mortality as the normalized frequency of temperature increases across the globe. The average increase in mortality risk comparing the 10th to 100th percentile of normalized frequency was 13.03% (95% CI: 12.17–13.91), with substantial regional differences (from 4.56% in Australia and New Zealand to 33.06% in South Europe). The highest increase in mortality was observed for high-income countries (13.58%, 95% CI: 12.56–14.61), followed by lower-middle-income countries (12.34%, 95% CI: 9.27–15.51). This study observed a declining risk of mortality associated with higher temperature frequency. Our findings suggest that populations can adapt to their local climate with frequent exposure, with the adapting ability varying geographically due to differences in climatic and socioeconomic characteristics.

Summary: Background: Non-optimum temperatures are associated with a considerable mortality burden. However, evidence of temperature with all-cause and cause-specific hospital admissions in tropical countries like Thailand is still limited. Methods: Daily all-cause and cause-specific hospital admissions for outpatient and inpatient visits were collected from 77 provinces in Thailand from January 2013 to August 2019. A two-stage time-series approach was applied to assess the association between non-optimum temperatures and hospital admission. We first fitted the province-specific temperature-morbidity association and then obtained the national association in the second stage using a random-effects meta-analysis regression. The attributable fraction (AF) of hospital admissions with 95% empirical confidence interval (eCI) was calculated. Findings: A total of 878,513,460 all-cause outpatient admissions and 32,616,600 all-cause inpatient admissions were included in this study. We observed a J-shaped relationship with the risk of hospital admissions increasing for both cold and hot temperatures. The overall AFs of all-cause hospital admissions due to non-optimum temperatures were 7.57% (95% eCI: 6.47%, 8.39%) for outpatient visits and 6.17% (95% eCI: 4.88%, 7.20%) for inpatient visits. Hot temperatures were responsible for most of the AFs of hospital admissions, with 6.71% (95% eCI: 5.80%, 7.41%) for outpatient visits and 4.50% (95% eCI: 3.62%, 5.19%) for inpatient visits. The burden of hospital admissions was greater in females and in children and adolescents (0–19 years). The fractions of hospital admissions attributable to non-optimum temperatures exhibited variation among disease categories and geographical areas. Interpretation: The results indicate that low and high temperature has a significant impact on hospital admissions, especially among the females, and children and adolescents (0–19 years). The current investigation could provide evidence for policymakers to develop adaptation strategies and mitigate the adverse effects of climate change on public health in Thailand and other tropical countries. Funding: National Research Council of Thailand (NRCT): E-Asia Joint Research Program: Climate change impact on natural and human systems (N33A650979).

ABSTRACT: To develop effective antibiotics alternatives is getting more and more important to poultry healthy production. The study investigated the effects of a microencapsulated essential oils and organic acids preparation (EOA) on growth performance, slaughter performance, nutrient digestibility and intestinal microenvironment of broilers. A total of 624 1-day-old male Arbor Acres broilers were randomly divided into 6 groups including the control group (T1) fed with basal diet, the antibiotic group (T2) supplemented with basal diet with 45 mg/kg bacitracin methylene disalicylate (BMD), and 4 inclusion levels of EOA-treated groups (T3, T4, T5, T6 groups) chickens given basal diet with 200, 400, 600, and 800 mg EOA/kg of diet, respectively. Results showed that compared with the control, the 200 mg/kg EOA group increased average daily gain (ADG) and average body weight (ABW) during the early stage (P < 0.05). EOA addition decreased crypt depth of the ileum (P < 0.05), but villus height to crypt depth ratio was increased by EOA addition at 200 and 400 mg/kg at d 21 (P < 0.05). Compared with the control, dietary addition EOA at 200, 400 and 600 mg/kg increased the lipase activity in the duodenum at d 21 (P < 0.05). Increased lactic acid bacteria population was found in cecal digesta of the 400 mg/kg EOA group at d 21 (P < 0.05), and higher concentration of butyric acid level was observed in cecal digesta at d 21 and d 42 in the 200 mg/kg EOA group compared with the control (P < 0.05). RT-PCR analysis found that dietary EOA addition decreased the gene expression of IL-1β, COX-2 and TGF-β4 in the ileum at d 21 (P < 0.05), while only the 200 mg/kg EOA increased the gene expression of IL-10, TGF-β4, Claudin-1, ZO-1, CATH-1, CATH-3, AvBD-1, AvBD-9 and AvBD-12 in the ileum at d 42 (P < 0.05) compared with the control. In summary, adding 200 mg/kg and 400 mg/kg of the EOA to the diet could improve the growth performance and intestinal microenvironment through improving intestinal morphology, increasing digestive enzymes activity and cecal lactic acid bacteria abundance and butyric acid content, improving intestinal barrier function as well as maintaining intestinal immune homeostasis. The improving effect induced by EOA addition in the early growth stage was better than that in the later growth stage. Overall, the EOA product might be an effective antibiotic alternative for broiler industry.

ABSTRACT: As an enzyme, β-mannanase (BM) can be widely used as feed additive to improve the growth performance of animals. This experiment aimed to determine the effect of the addition of BM to low-energy diet on the immune function and intestinal microflora of broiler chickens. In this study, 384 one-day-old Arbor Acres broilers were randomly divided into 3 groups (8 replicates per group): positive control (PC, received a corn-soybean meal basal diet), negative control (NC, received a low-energy diet with Metabolizable Energy (ME) reduced by 50 kcal/kg) and NC + BM group (NC birds + 100 mg/kg BM). All birds were raised for 42 d. The results showed that BM mitigated the damage of immune function in peripheral blood of broilers caused by the decrease of dietary energy level by increasing the Concanavalin A (Con A) index of stimulation (SI) and macrophages phagocytic activity in the peripheral blood of broilers at 42 d (P < 0.05). The analysis of cecum flora showed that the low-energy diet significantly reduced the observed_species index (P < 0.01), Chao1 index and ACE index (P < 0.05), which reduced the abundance and evenness of species in the cecum of broilers at 21 d. It also significantly reduced the relative abundance of Candidatus_Arthromitus and significantly increased the relative abundance of Pseudomonas in the cecum of broilers at 21 d, while also significantly increasing the relative abundance of Monoglobus at 42 d. BM significantly increased the relative abundance of Lachnospiraceae_UCG-001 and Lachnospiraceae_bacterium_615 in the cecum of broilers at 21 d. In addition, BM inhibited microbial Fatty acid degradation by decreasing the activity of glutaryl-CoA dehydrogenase. Collectively, BM could improve intestinal health by enhancing the immune function of broilers, promoting the proliferation of beneficial bacteria and reducing the number of harmful bacteria, regulating intestinal flora, thereby alleviating the adverse effects of lower dietary energy levels.

Background: Mounting evidence has demonstrated that high temperature was associated with adverse health outcomes, especially morbidity and mortality. Nonetheless, the impact of extreme high temperature on cognitive performance, which is the fundamental capacity for interpreting one's surroundings, decision-making, and acquiring new abilities, has not been thoroughly investigated. Methods: We aimed to assess associations between extreme high temperature at different time scales and poor cognitive function. We used longitudinal survey data from the three waves of data from China Family Panel Study, providing an 8-year follow-up of 53,008 participants from China. We assessed temperature and extreme high temperature exposure for each participant based on the residential area and date of cognitive test. We defined the proportion of days/hours above 32 °C as the metric of the exposure to extreme high temperature. Then we used generalized additive model and difference-in-differences approach to explore the associations between extreme high temperature and cognitive function. Results: Our results demonstrated that either acute exposure or long-term exposure to extreme high temperature was associated with cognitive decline. At hourly level, 0–1 hour acute exposure to extreme high temperature would induce −0.93 % (95 % CI: −1.46 %, −0.39 %) cognitive change. At annual level, 10 percentage point increase in the hours proportion exceeding 32 °C in the past two years induced −9.87 % (95 % CI: −13.99 %, −5.75 %) cognitive change. Furthermore, subgroup analyses indicated adaptation effect: for the same 10 percentage increase in hours proportion exceeding 32 °C, people in warmer areas had cognitive change of −6.41 % (-11.22 %, −1.61 %), compared with −15.30 % (-21.07 %, −9.53 %) for people in cool areas. Conclusion: Our results demonstrated that extreme high temperature was associated with reduced cognitive function at hourly, daily and annual levels, warning that people should take better measures to protect the cognitive function in the context of climate change.

ABSTRACT: This experiment aimed to investigate the effect of Lonicerae flos and Turmeric extracts (LTE) added to diets on growth performance and intestinal health of broilers. A total of 720 healthy 21-day-old yellow-feathered broilers were randomly divided into 3 treatment groups, with 6 replicates and 40 broilers per replicate. These 3 dietary treatments included a basal diet + 0 g/t LTE (CON), a basal diet + 300 g/t LTE (LTE300), and a basal diet + 500 g/t LTE (LTE500). The results showed that dietary supplementation of LTE linearly increased (P < 0.05) average daily gain (d 21–38) and average daily feed intake (d 21–60). At d 60, LTE300 had the highest serum total antioxidant capacity and total superoxide dismutase (P < 0.05), and LTE500 had the lowest malondialdehyde level (P < 0.05) among the three groups. Moreover, compared to CON, LTE300 significantly (P < 0.05) reduced endotoxin (d 38 and d 60) and diamine oxidase activity (d 38); LTE500 significantly (P < 0.05) reduced endotoxin (d 38 and d 60) and diamine oxidase levels (d 60) in the serum. LTE groups significantly (P < 0.05) increased ileal the ratio of villus height to crypt depth and serum immunoglobulin G. Furthermore, dietary supplementation of LTE also improved the intestinal epithelial barrier by the up-regulated mRNA expression of Claudin-1, Occludin and zonula occludens-1, and decreased the mRNA expression of interleukin-2, interleukin-8, tumor necrosis factor-α, nuclear factor κB, myeloid differentiation factor 88 and toll-like receptor 4. Compared to CON, 16S rRNA sequencing analysis showed that LTE300 had a better effect on the microbial diversity and composition in the ileum, and Bacillus and Lactobacillus_agilis were significantly enriched in LTE300. PICRUSt results showed that LTE300 was significantly (P < 0.05) enriched in four pathway pathways at KEGG level 2. In conclusion, dietary supplementation with LTE improved growth performance and intestinal health by enhancing antioxidant capacity, intestinal barrier and immune function, and regulating intestinal flora of yellow-feathered broilers.

Abstract Deubiquitinases (DUBs) play important roles in various human cancers and targeting DUBs is considered as a novel anticancer therapeutic strategy. Overexpression of ubiquitin specific protease 7 and 22 (USP7 and USP22) are associated with malignancy, therapy resistance, and poor prognosis in many cancers. Although both DUBs are involved in the regulation of similar genes and signaling pathways, such as histone H2B monoubiquitination (H2Bub1), c-Myc, FOXP3, and p53, the interdependence of USP22 and USP7 expression has never been described. In the study, we found that targeting USP7 via either siRNA-mediated knockdown or pharmaceutical inhibitors dramatically upregulates USP22 in cancer cells. Mechanistically, the elevated USP22 occurs through a transcriptional pathway, possibly due to desuppression of the transcriptional activity of SP1 via promoting its degradation upon USP7 inhibition. Importantly, increased USP22 expression leads to significant activation of downstream signal pathways including H2Bub1 and c-Myc, which may potentially enhance cancer malignancy and counteract the anticancer efficacy of USP7 inhibition. Importantly, targeting USP7 further suppresses the in vitro proliferation of USP22-knockout (USP22-Ko) A549 and H1299 lung cancer cells and induces a stronger activation of p53 tumor suppressor signaling pathway. In addition, USP22-Ko cancer cells are more sensitive to a combination of cisplatin and USP7 inhibitor. USP7 inhibitor treatment further suppresses in vivo angiogenesis and tumor growth and induced more apoptosis in USP22-Ko cancer xenografts. Taken together, our findings demonstrate that USP7 inhibition can dramatically upregulate USP22 in cancer cells; and targeting USP7 and USP22 may represent a more effective approach for targeted cancer therapy, which warrants further study. Video Abstract

Abstract Accumulated evidence supports the beneficial role of inulin in alleviating metabolic dysfunction-associated fatty liver disease (MAFLD) by modulating gut microbiota. However, the underlying mechanisms are not fully understood. Here we used high-fat diet (HFD)-induced laying hen model of MAFLD to investigate the effect of inulin on ameliorating MAFLD and found that the inulin-enriched Megamonas genus was inversely correlated with hepatic steatosis-related parameters. Oral administration of a newly isolated commensal bacterium by culturomics, M. funiformis CML154, to HFD-fed hens and mice ameliorated MAFLD, changed liver gene expression profiles, and increased intestinal propionate concentration. Further evidence demonstrated that the anti-MAFLD effect of M. funiformis CML154 is attributed to propionate-mediated activation of the APN-AMPK-PPARα signaling pathway, thereby inhibiting fatty acid de novo synthesis and promoting β-oxidation. These findings establish the causal relationships among inulin, M. funiformis, and MAFLD, and suggest that M. funiformis CML154 is a probiotic candidate for preventative or therapeutic intervention of MAFLD.

Abstract. Background. The outbreak and prevalence of the Omicron variant have threatened human health since March 2022 in mainland China. In this study, we aimed to investigate the clinical characteristics and outcomes of patients with coronavirus disease 2019 (COVID-19) in the Beijing region. Methods. In this retrospective study, we enrolled inpatients admitted for COVID-19 in the Fifth Medical Center of Chinese PLA General Hospital in Beijing between November 10, 2022, and January 30, 2023. Demographic and clinical features and treatment outcomes were comprehensively analyzed. We used logistic regression and linear regression analyses to explore the risk factors associated with disease severity and time of nucleic acid conversion, respectively. Results. A total of 1010 hospitalized patients with COVID-19 were enrolled. The median age was 43.0 years (interquartile range, 28.0–63.0), and patients aged 7 pg/mL, lactic dehydrogenase level >245 U/L, cough, and fever at admission. Age ≥80 years and chronic lung disease were independent risk factors in the nonmild group in elderly patients. In addition, the duration for nucleic acid to turn negative was approximately 5.0 d (interquartile range, 3.0–7.0). Prolonged time of nucleic acid conversion was associated with age ≥60 years, serum urea nitrogen level >8.2 mmol/L, neutrophil count >7 ×109/L, and the presence of a chronic lung disease or carcinoma. Finally, unvaccinated patients accounted for 37.3% of enrolled patients; children and the elder people accounted for approximately half of that. The univariable analysis found that booster doses reduced disease severity and shortened the time of nucleic acid conversion in elderly patients. Conclusions. The outbreak of Omicron rapidly increased the number of patients with COVID-19 in Beijing. In elderly patients, booster doses may reduce disease severity and shorten the time of nucleic acid conversion. Healthcare systems should be optimized before an emerging epidemic outbreak.

Abstract Background The pathogenesis of benign prostatic hyperplasia (BPH) has not been fully elucidated. Ras homology family member A (RhoA) plays an important role in regulating cell cytoskeleton, growth and fibrosis. The role of RhoA in BPH remains unclear. Methods This study aimed to clarify the expression, functional activity and mechanism of RhoA in BPH. Human prostate tissues, human prostate cell lines, BPH rat model were used. Cell models of RhoA knockdown and overexpression were generated. Immunofluorescence staining, quantitative real time PCR (qRT-PCR), Western blotting, cell counting kit-8 (CCK-8), flow cytometry, phalloidine staining, organ bath study, gel contraction assay, protein stability analysis, isolation and extraction of nuclear protein and cytoplasmic protein were performed. Results In this study we found that RhoA was localized in prostate stroma and epithelial compartments and was up-regulated in both BPH patients and BPH rats. Functionally, RhoA knockdown induced cell apoptosis and inhibited cell proliferation, fibrosis, epithelial-mesenchymal transformation (EMT) and contraction. Consistently, overexpression of RhoA reversed all aforementioned processes. More importantly, we found that β-catenin and the downstream of Wnt/β-catenin signaling, including C-MYC, Survivin and Snail were up-regulated in BPH rats. Downregulation of RhoA significantly reduced the expression of these proteins. Rho kinase inhibitor Y-27632 also down-regulated β-catenin protein in a concentration-dependent manner. However, overexpression of β-catenin did not affect RhoA-ROCK levels, suggesting that β-catenin was the downstream of RhoA-ROCK regulation. Further data suggested that RhoA increased nuclear translocation of β-catenin and up-regulated β-catenin expression by inhibiting its proteasomal degradation, thereby activating Wnt/β-catenin signaling. Overexpression of β-catenin partially reversed the changes in cell growth, fibrosis and EMT except cell contraction caused by RhoA downregulation. Finally, Y-27632 partially reversed prostatic hyperplasia in vivo, further suggesting the potential of RhoA-ROCK signaling in BPH treatment. Conclusion Our novel data demonstrated that RhoA regulated both static and dynamic factors of BPH, RhoA-ROCK-β-catenin signaling axis played an important role in the development of BPH and might provide more possibilities for the formulation of subsequent clinical treatment strategies.

Abstract Heat-related mortality has been identified as one of the key climate extremes posing a risk to human health. Current research focuses largely on how heat mortality increases with mean global temperature rise, but it is unclear how much climate change will increase the frequency and severity of extreme summer seasons with high impact on human health. In this probabilistic analysis, we combined empirical heat-mortality relationships for 748 locations from 47 countries with climate model large ensemble data to identify probable past and future highly impactful summer seasons. Across most locations, heat mortality counts of a 1-in-100 year season in the climate of 2000 would be expected once every ten to twenty years in the climate of 2020. These return periods are projected to further shorten under warming levels of 1.5 °C and 2 °C, where heat-mortality extremes of the past climate will eventually become commonplace if no adaptation occurs. Our findings highlight the urgent need for strong mitigation and adaptation to reduce impacts on human lives.

Abstract Background Benign prostatic hyperplasia (BPH) is a common disease in elderly men, mainly resulted from an imbalance between cell proliferation and death. Glutathione peroxidase 3 (GPX3) was one of the differentially expressed genes in BPH identified by transcriptome sequencing of 5 hyperplastic and 3 normal prostate specimens, which had not been elucidated in the prostate. This study aimed to ascertain the mechanism of GPX3 involved in cell proliferation, apoptosis, autophagy and ferroptosis in BPH. Methods Human prostate tissues, GPX3 silencing and overexpression prostate cell (BPH-1 and WPMY-1) models and testosterone-induced rat BPH (T-BPH) model were utilized. The qRT-PCR, CCK8 assay, flow cytometry, Western blotting, immunofluorescence, hematoxylin and eosin, masson’s trichrome, immunohistochemical staining and transmission electron microscopy analysis were performed during in vivo and in vitro experiments. Results Our study indicated that GPX3 was localized both in the stroma and epithelium of prostate, and down-regulated in BPH samples. Overexpression of GPX3 inhibited AMPK and activated ERK1/2 pathway, thereby inducing mitochondria-dependent apoptosis and G0/G1 phase arrest, which could be significantly reversed by MEK1/2 inhibitor U0126 preconditioning. Moreover, overexpression of GPX3 further exerted anti-autophagy by inhibiting AMPK/m-TOR and up-regulated nuclear factor erythroid 2-related factor 2 (Nrf2)/glutathione peroxidase 4 (GPX4, mitochondrial GPX4 and cytoplasmic GPX4) to antagonize autophagy-related ferroptosis. Consistently, GPX3 deficiency generated opposite changes in both cell lines. Finally, T-BPH rat model was treated with GPX3 indirect agonist troglitazone (TRO) or GPX4 inhibitor RAS-selective lethal 3 (RSL3) or TRO plus RSL3. These treatments produced significant atrophy of the prostate and related molecular changes were similar to our in vitro observations. Conclusions Our novel data manifested that GPX3, which was capable of inducing apoptosis via AMPK/ERK1/2 pathway and antagonizing autophagy-related ferroptosis through AMPK/m-TOR signalling, was a promising therapeutic target for BPH in the future.

Abstract Background Ginkgo biloba extract (GBE) is evidenced to be effective in the prevention and alleviation of metabolic disorders, including obesity, diabetes and fatty liver disease. However, the role of GBE in alleviating fatty liver hemorrhagic syndrome (FLHS) in laying hens and the underlying mechanisms remain to be elucidated. Here, we investigated the effects of GBE on relieving FLHS with an emphasis on the modulatory role of GBE in chicken gut microbiota. Results The results showed that GBE treatment ameliorated biochemical blood indicators in high-fat diet (HFD)-induced FLHS laying hen model by decreasing the levels of TG, TC, ALT and ALP. The lipid accumulation and pathological score of liver were also relieved after GBE treatment. Moreover, GBE treatment enhanced the antioxidant activity of liver and serum by increasing GSH, SOD, T-AOC, GSH-PX and reducing MDA, and downregulated the expression of genes related to lipid synthesis (FAS, LXRα, GPAT1, PPARγ and ChREBP1) and inflammatory cytokines (TNF-α, IL-6, TLR4 and NF-κB) in the liver. Microbial profiling analysis revealed that GBE treatment reshaped the HFD-perturbed gut microbiota, particularly elevated the abundance of Megasphaera in the cecum. Meanwhile, targeted metabolomic analysis of SCFAs revealed that GBE treatment significantly promoted the production of total SCFAs, acetate and propionate, which were positively correlated with the GBE-enriched gut microbiota. Finally, we confirmed that the GBE-altered gut microbiota was sufficient to alleviate FLHS by fecal microbiota transplantation (FMT). Conclusions We provided evidence that GBE alleviated FLHS in HFD-induced laying hens through reshaping the composition of gut microbiota. Our findings shed light on mechanism underlying the anti-FLHS efficacy of GBE and lay foundations for future use of GBE as additive to prevent and control FLHS in laying hen industry.

Abstract Background Alginate oligosaccharide (AOS) holds great potential as a novel feed supplement in farm animals. However, the effects of AOS on chicken health and the underlying mechanisms are not fully understood. This study aimed to optimize the enzymatic preparation of AOS by using bacterial alginate lyases expressed in yeast, investigate the effects of the prepared AOS on the growth performance and gut health of broiler chickens, and reveal the underlying mechanisms. Results Five alginate lyases from bacteria were cloned into Pichia pastoris GS115 and the alginate lyase PDE9 was expressed at relatively high yield, activity and stability in P. pastoris. Animal trials were carried out using 320 1-day-old male Arbor Acres broilers (four groups; 8 replicates/group × 10 chicks/replicate) receiving either a basal diet or the same diet supplemented with 100, 200 and 400 mg/kg PDE9-prepared AOS for 42 d. The results showed that dietary supplementation of 200 mg/kg AOS displayed the highest activity in promoting the birds’ ADG and ADFI (P

Abstract Background Reducing Salmonella infection in broiler chickens by using effective and safe alternatives to antibiotics is vital to provide safer poultry meat and minimize the emergence of drug-resistant Salmonella and the spread of salmonellosis to humans. This study was to first evaluate the protective efficacy of feeding coated essential oils and organic acids mixture (EOA) on broiler chickens infected with Salmonella Enteritidis (S. Enteritidis, SE), and then its action mechanism was further explored. Methods A total of 480 1-day-old Arbor Acres male chickens were randomly assigned into five treatments with six replicates, including non-challenged control fed with basal diet (A), SE-challenged control (B), and SE-infected birds fed a basal diet with 300 mg/kg of EOA (BL), 500 mg/kg of EOA (BM) and 800 mg/kg of EOA (BH), respectively. All birds on challenged groups were infected with Salmonella Enteritidis on d 13. Results Feeding EOA showed a reversed ability on negative effects caused by SE infection, as evidenced by decreasing the feed conversion rate (FCR) and the ratio of villus height to crypt depth (VH/CD) (P

Abstract The gut microbiota (GM) plays a crucial role in maintaining the overall health and well-being of the host. Recent studies have demonstrated that the GM may significantly influence bone metabolism and degenerative skeletal diseases, such as osteoporosis (OP). Interventions targeting GM modification, including probiotics or antibiotics, have been found to affect bone remodeling. This review provides a comprehensive summary of recent research on the role of GM in regulating bone remodeling and seeks to elucidate the regulatory mechanism from various perspectives, such as the interaction with the immune system, interplay with estrogen or parathyroid hormone (PTH), the impact of GM metabolites, and the effect of extracellular vesicles (EVs). Moreover, this review explores the potential of probiotics as a therapeutic approach for OP. The insights presented may contribute to the development of innovative GM-targeted therapies for OP.

Objectives To assess the association between ambient temperature and diurnal temperature range (DTR) on emergency admissions for hyperventilation syndrome (HVS).Design Distributed lag non-linear model design was used with a lag time to 5 days.Setting Emergency admission data used were from the Beijing Red Cross Emergency Centre (2017–2018).Participants and exposure Cases were those with emergency visits to the Beijing Emergency Center during the period 2017–2018 and who were given the primary outcome indicator defined as HVS according to the International Classification of Diseases, 10th edition code F45.303. Ambient temperature and DTR were used as exposure factors with adjustments for relative humidity, wind speed, precipitation, seasonality long-term trend and day of the week.Main outcome measure We used the minimum emergency visits temperature as a reference to indicate the relative risk with 95% CI of exposure–response for the risk of HVS visits at different temperatures.Results A u-shape was described between ambient temperature and HVS visits, with a minimum risk at 12°C. Moderate heat (23°C) at lag (0–3) days, extreme heat at lag 0 days, had greatest relative risks on HVS visits, with 2.021 (95% CI 1.101 to 3.71) and 1.995 (95% CI 1.016 to 3.915), respectively. A stronger association between HVS visits and temperature was found in women and aged ≤44 years. Notably, the relationship between DTR and HVS visits appeared a reverse u-shaped. Low DTR (4°C) effect appeared at lag (0–1) days with 0.589 (95% CI 0.395 to 0.878), lasting until lag (0–3) days with 0.535 (95% CI 0.319 to 0.897) and was associated with a reduced risk of HVS visits in women and those aged ≤44 years.Conclusions Ambient temperature and DTR were associated with HVS visits, appearing a differentiation in gender and age groups. Timely prevention strategies during high temperatures and control mild changes in temperature might reduce the risk of HVS.

Climate change triggered more environmental extremes. The joint events of air pollution wave and cold wave showed higher health risks than independent events, but little evidence is available for the spatiotemporal features of their co-occurrence. To better understand and forecast the joint events, a method framework was developed in this study. The temporal trend and spatial distribution of count and duration for joint events were measured at each grid cell (0.5°×0.5°) by integrating the PM2.5 air pollution wave and cold wave. The generalized linear mixed model was used to screen influencing variables that took into account socioeconomic characteristics, meteorological variables, and annual PM2.5 levels. During 2000 and 2018, the average annual count of joint events was 4.1 ± 6.8 days and the average duration ranged from 1.0 to 9.7 days. High spatial heterogeneity was observed throughout China, with a significant increase in joint events observed in Xinjiang area (the largest province in China). The most average count of joint events was observed in Henan province (one of the most populous provinces), while the longest duration was in Chongqing (a municipality, one of the megacities). Areas with higher PM2.5 levels, prolonged air pollution wave, and cold wave durations would experience more joint events. These findings can assist China in locating vulnerable areas and establishing effective local early warning systems. The method framework offers broader perspectives on mitigating health risks associated with extreme events in other countries and regions.