Metabolic Control During Macrophage Polarization by a Citrate-Functionalized Scaffold for Maintaining Bone Homeostasis.

Metabolites, as markers of phenotype at the molecular level, can regulate the function of DNA, RNA, and proteins through chemical modifications or interactions with large molecules. Citrate is an important metabolite that affects macrophage polarization and osteoporotic bone function. Therefore, a better understanding of the precise effect of citrate on macrophage polarization may provide an effective alternative strategy to reverse osteoporotic bone metabolism. In this study, we fabricated a citrate functional scaffold to control the metabolic pathway during macrophage polarization based on the metabolic differences between pro-inflammatory and anti-inflammatory phenotypes for maintaining bone homeostasis. Mechanistically, only outside M1 macrophages were accumulated high concentrations of citrate, in contrast, M2 macrophages consumed massive citrate. Therefore, citrate-functionalized scaffolds exerted more sensitive inhibitory effects on metabolic enzyme activity during M1 macrophage polarization than M2 macrophage polarization. Citrate could block glycolysis related enzymes by occupying the binding-site and ensure sufficient metabolic flux in the TCA cycle, so as to turn the metabolism of macrophages to oxidative phosphorylation of M2 macrophage, largely maintaining bone homeostasis. Our studies indicate that exogenous citrate can realize metabolic control of macrophage polarization for maintaining bone homeostasis in osteoporosis. This article is protected by copyright. All rights reserved.

Ultrasonic-assisted extraction, anti-biofilm activity, and mechanism of action of Ku Shen (Sophorae Flavescentis Radix) extracts against Vibrio parahaemolyticus.

The objective of this study is to optimize the ultrasonic-assisted extraction process of Ku Shen (Sophorae Flavescentis Radix) extracts (KSE) against Vibrio parahaemolyticus and explore their anti-biofilm activity and mechanism of action. The ultrasonic-assisted extraction process of KSE optimized by single factor experiment, Box-Behnken design and response surface methodology was as follows: 93% ethanol as solvent, liquid/material ratio of 30 mL/g, ultrasonic power of 500 W, extraction temperature of 80°C and time of 30 min. Under these conditions, the diameter of inhibition circle of KSE was 15.60 ± 0.17 mm, which had no significant difference with the predicted value. The yield of dried KSE is 32.32 ± 0.57% and the content of total flavonoids in KSE was 57.02 ± 5.54%. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of KSE against V. parahaemolyticus were 0.25 and 0.5 mg/mL, respectively. Crystal violet staining, Congo red plate, spectrophotometry, CCK-8 and scanning electron microscopy were used to investigate the activity and mechanism of action of KSE against V. parahaemolyticus biofilm. The results showed that the sub-MIC of KSE could significantly inhibit biofilm formation, reduce the synthesis of polysaccharide intercellular adhesin (PIA) and the secretion of extracellular DNA. In addition, the inhibition rate of biofilm formation and clearance rate of mature biofilm of 1.0 mg/mL KSE were 85.32 and 74.04%, and the reduction rate of metabolic activity of developing and mature biofilm were 77.98 and 74.46%, respectively. These results were confirmed by visual images obtained by scanning electron microscopy. Therefore, KSE has the potential to further isolate the anti-biofilm agent and evaluate it for the preservation process of aquatic products.

Galangin Prevents Against Ethanol-Induced Intestinal Barrier Dysfunction and NLRP3 Inflammasome Activation via NF-κB/MAPK Signaling Pathways in Mice and Caco-2 Cells.

The potential of natural phytochemicals in addressing ethanol-related public safety concerns has been garnering attention. Galangin, a potent flavonoid renowned for its antioxidative and anti-inflammatory characteristics, is derived from the galanga plant, and propolis is derived from bees. Here, we documented the effects of galangin on ethanol-stimulated intestinal tight junction damage and investigated its potential protective mechanism in both in vivo and in vitro models, which has not been extensively investigated. Our results revealed that galangin efficaciously mitigated ethanol-induced intestine injury and dysfunction of the intestinal barrier. Concurrently, galangin significantly counteracted the ethanol-induced upregulation of NLRP3 inflammasome-associated proteins and activated the mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B (NF-κB) signaling pathways in both the mouse colon and Caco-2 cells. Interestingly, similar to galangin, inhibitors of MAPKs and the NF-κB p65 reduced ethanol-induced NLRP3 inflammasome activation and intestinal tight junction damage. To sum up, our results showed that galangin blocks the ethanol-induced perturbation of the intestinal barrier and activation of the NLRP3 inflammasome via the NF-κB/MAPK signaling pathways.

Identifying the Spatial Architecture That Restricts the Proximity of CD8+ T Cells to Tumor Cells in Pancreatic Ductal Adenocarcinoma.

The anti-tumor function of CD8+ T cells is dependent on their proximity to tumor cells. Current studies have focused on the infiltration level of CD8+ T cells in the tumor microenvironment, while further spatial information, such as spatial localization and inter-cellular communication, have not been defined. In this study, co-detection by indexing (CODEX) was designed to characterize PDAC tissue regions with seven protein markers in order to identify the spatial architecture that regulates CD8+ T cells in human pancreatic ductal adenocarcinoma (PDAC). The cellular neighborhood algorithm was used to identify a total of six conserved and distinct cellular neighborhoods. Among these, one unique spatial architecture of CD8+ T and CD4+ T cell-enriched neighborhoods enriched the majority of CD8+ T cells, but heralded a poor prognosis. The proximity analysis revealed that the CD8+ T cells in this spatial architecture were significantly closer to themselves and the CD4+ T cells than to the tumor cells. Collectively, we identified a unique spatial architecture that restricted the proximity of CD8+ T cells to tumor cells in the tumor microenvironment, indicating a novel immune evasion mechanism of pancreatic ductal adenocarcinoma in a topologically regulated manner and providing new insights into the biology of PDAC.

Exercise-induced improvement of glycemic fluctuation and its relationship with fat and muscle distribution in type 2 diabetes.

AIMS: Management of blood glucose fluctuation is essential for diabetes. Exercise is a key therapeutic strategy for diabetes patients, although little is known about determinants of glycemic response to exercise training. We aimed to investigate the effect of combined aerobic and resistance exercise training on blood glucose fluctuation in type 2 diabetes patients and explore the predictors of exercise-induced glycemic response. MATERIALS AND METHODS: Fifty sedentary diabetes patients were randomly assigned to control or exercise group. Participants in the control group maintained sedentary lifestyle for 2 weeks, and those in the exercise group specifically performed combined exercise training for 1 week. All participants received dietary guidance based on a recommended diet chart. Glycemic fluctuation was measured by flash continuous glucose monitoring. Baseline fat and muscle distribution were accurately quantified through magnetic resonance imaging (MRI). RESULTS: Combined exercise training decreased SD of sensor glucose (SDSG, exercise-pre vs exercise-post, mean 1.35 vs 1.10 mmol/L, p = .006) and coefficient of variation (CV, mean 20.25 vs 17.20%, p = .027). No significant change was observed in the control group. Stepwise multiple linear regression showed that baseline MRI-quantified fat and muscle distribution, including visceral fat area (ß = -0.761, p = .001) and mid-thigh muscle area (ß = 0.450, p = .027), were significantly independent predictors of SDSG change in the exercise group, as well as CV change. CONCLUSIONS: Combined exercise training improved blood glucose fluctuation in diabetes patients. Baseline fat and muscle distribution were significant factors that influence glycemic response to exercise, providing new insights into personalized exercise intervention for diabetes.

Lymph-targeted high-density lipoprotein-mimetic nanovaccine for multi-antigenic personalized cancer immunotherapy.

Cancer vaccines show huge potential for cancer prevention and treatment. However, their efficacy remains limited due to weak immunogenicity regarding inefficient stimulation of cytotoxic T lymphocyte (CTL) responses. Inspired by the unique characteristic and biological function of high-density lipoprotein (HDL), we here develop an HDL-mimicking nanovaccine with the commendable lymph-targeted capacity to potently elicit antitumor immunity using lipid nanoparticle that is co-loaded with specific cancer cytomembrane harboring a collection of tumor-associated antigens and an immune adjuvant. The nanoparticulate impact is explored on the efficiency of lymphatic targeting and dendritic cell uptake. The optimized nanovaccine promotes the co-delivery of antigens and adjuvants to lymph nodes and maintains antigen presentation of dendritic cells, resulting in long-term immune surveillance as the elevated frequency of CTLs within lymphoid organs and tumor tissue. Immunization of nanovaccine suppresses tumor formation and growth and augments the therapeutic efficacy of checkpoint inhibitors notably on the high-stemness melanoma in the mouse models.

Study on multi-target effects of the novel HDAC6 inhibitor W5 on Aß/Cu2+-induced Alzheimer's disease model of rats.

Histone deacetylase 6 (HDAC6) is a key therapeutic target in neurodegenerative diseases such as Alzheimer's disease (AD), which has been demonstrated to play an essential role in memory function and microtubule-associated tau physiology. In this study, W5 was used to treat AD model rats induced by Aß/Cu2+ to study the improving effect of W5 on learning and memory impairment in AD rats and its related mechanism, to provide the basis for the subsequent development of W5 as an anti-AD drug. Results showed that W5 could decrease the expression of Aß, Tau, and p-Tau proteins in the hippocampus of AD rats to inhibit the formation of senile plaques and neurofibrillary tangles, down-regulate the expression of Bax mRNA and Caspase-3 mRNA, and up-regulate the expression of Bcl-2 mRNA to reduce the apoptosis of neuron cells, reverse the expression of TNF-α, IL-1ß and IL-6 mRNA to regulate neuroinflammatory response in AD rat brain. W5 also could regulate the oxidative stress state of AD rats, and balance the neurotransmitter disorder in AD rats' brain tissue. Overall, W5 could recover the morphology of hippocampal neurons and improve the learning and memory dysfunction in AD rats by regulating multiple targets in AD rats, providing a promising therapeutic avenue for the treatment of AD.

Mitochondrial biogenesis in white adipose tissue mediated by JMJD1A-PGC-1 axis limits age-related metabolic disease.

Mitochondria play a vital role in non-shivering thermogenesis in both brown and subcutaneous white adipose tissues (BAT and scWAT, respectively). However, specific regulatory mechanisms driving mitochondrial function in these tissues have been unclear. Here we demonstrate that prolonged activation of ß-adrenergic signaling induces epigenetic modifications in scWAT, specifically targeting the enhancers for the mitochondria master regulator genes Pgc1a/b. This is mediated at least partially through JMJD1A, a histone demethylase that in response to ß-adrenergic signals, facilitates H3K9 demethylation of the Pgc1a/b enhancers, promoting mitochondrial biogenesis and the formation of beige adipocytes. Disruption of demethylation activity of JMJD1A in mice impairs activation of Pgc1a/b driven mitochondrial biogenesis and limits scWAT beiging, contributing to reduced energy expenditure, obesity, insulin resistance, and metabolic disorders. Notably, JMJD1A demethylase activity is not required for Pgc1a/b dependent thermogenic capacity of BAT especially during acute cold stress, emphasizing the importance of scWAT thermogenesis in overall energy metabolism.

Prenatal, perinatal and parental risk factors for autism spectrum disorder in China: a case- control study.

BACKGROUND: Autism spectrum disorder (ASD) is heritable neurodevelopmental disorders (NDDs), but environmental risk factors have also been suggested to a play a role in its development. Prenatal, perinatal and parental factors have been associated with an increased risk of ASD in children. The aim of the present study was to explore the prenatal, perinatal, and parenting risk factors in children with autism spectrum disorder (ASD) from Beijing, China by comparing them with typically developing (TD) children. METHODS: A sample of 151 ASD children's parents who from rehabilitation institutions in Beijing were enrolled in this study, and an additional 151 children from kindergartens in Beijing were recruited as a control group (child age: mean = 4.4 years). TD children were matched according to age, sex and maternal education. We explored the maternal AQ (Autism Spectrum Quotient) scores (mean:19.40-19.71, no significant difference between two groups) to referring the genetic baseline. This study evaluated 17 factors with unadjusted and adjusted analyses. RESULTS: Birth asphyxia was associated with a more than a thirteen-fold higher risk of ASD (adjusted odds ratio (AOR) = 13.42). Breastfeeding difficulties were associated with a higher risk of ASD(AOR = 3.46). Parenting influenced the risk of ASD, with low responding (LR) and harsh or neglectful parenting associated with a higher risk of ASD in offspring (AOR = 2.37 for LR, AOR = 3.42 for harsh parenting and AOR = 3.01 for neglectful parenting). Maternal fever during pregnancy was associated with a higher risk of ASD in offspring (AOR = 3.81). CONCLUSIONS: Many factors were associated with ASD in offspring. Further assessment is needed to elucidate the role of modifiable environmental factors to inform prevention strategies.

The Role of H3K27me3-Mediated Th17 Differentiation in Ankylosing Spondylitis.

Ankylosing spondylitis (AS) is a common chronic progressive inflammatory autoimmune disease. T helper 17 (Th17) cells are the major effector cells mediating AS inflammation. Histone 3 Lys 27 trimethylation (H3K27me3) is an inhibitory histone modification that silences gene transcription and plays an important role in Th17 differentiation. The objective of this study was to investigate the expression of H3K27me3 in patients with AS and to explore its epigenetic regulation mechanism of Th17 differentiation during AS inflammation. We collected serum samples from 45 patients with AS at various stages and 10 healthy controls to measure their Interleukin-17 (IL-17) levels using ELISA. A quantitative polymerase chain reaction was used to quantify the mRNA levels of RORc and the signaling molecules of the JAK2/STAT3 pathway, JMJD3, and EZH2. Additionally, Western blot analysis was performed to quantify the protein levels of H3K27me3, RORγt, JAK2, STAT3, JMJD3, and EZH2 in cell protein extracts. The results showed that H3K27me3 expression in peripheral blood mononuclear cells (PBMCs) was significantly lower in patients with active AS compared to both the normal control groups and those with stable AS. Moreover, a significant negative correlation was observed between H3K27me3 expression and the characteristic transcription factor of Th17 differentiation, RORγt. We also discovered that patients with active AS exhibited significantly higher levels of JMJD3, an inhibitor of H3K27 demethylase, compared to the normal control group and patients with stable AS, while the expression of H3K27 methyltransferase (EZH2) was significantly lower. These findings suggest that H3K27me3 may be a dynamic and important epigenetic modification in AS inflammation, and JMJD3/EZH2 regulates the methylation level of H3K27me3, which may be one of the key regulatory factors in the pathogenesis of AS. These findings contribute to our understanding of the role of epigenetics in AS and may have implications for the development of novel therapeutic strategies for AS.

Gastrodin ameliorates depressive-like behaviors via modulating gut microbiota in CUMS-induced mice.

PURPOSE: Depression is a psychiatric disorder and the treatment of depression is an urgent problem that need to be solved. Gastrodin (GAS) is a Traditional Chinese Medicine from an orchid and is used for neurological diseases, including depressive disorders. METHODS: To assess the effect of GAS on gut microbiota of depressive mice, we established a chronic unpredictable mild stress (CUMS)-induced mouse model, and GAS was administered to one group of the mice. Animal behavior experiments were used to detect depressive-like behaviors, and 16 S rRNA gene analysis was applied to detect the gut microbiota of each group. All raw sequences were deposited in the NCBI Sequence Read Archive under accession number SRP491061. RESULTS: GAS treatment significantly improved depressive-like behaviors as well as the diversity and abundance of the gut microbiota. The depressive-like behaviors of the CUMS-GAS group were improved in different degrees compared with the CUMS group. The linear discriminant analysis (LDA) of the gut microbiota showed that the makeup of the gut microbiota in mice changed dramatically in the CUMS-GAS group, compared with the CUMS group, Bacteroides (LDA = 3.94, P < 0.05) were enriched in the CUMS-GAS group at the genus level. In comparison to the CUMS group, the CUMS-GAS group had a greater concentration numbers of Lactobacillus, Corynebacterium, Staphylococcus, Bacteroides, Psychrobacter, and Alistipes. CONCLUSION: Our results suggested that GAS improved depressive-like behaviors in mice and impacted the microbial composition of the gut. Our research indicated that dysbiosis of the gut microbiota may be affected by GAS treatment, which improved depressive-like behaviors in the CUMS-induced mouse model of depression.

Enhancing photodynamic immunotherapy by reprograming the immunosuppressive tumor microenvironment with hypoxia relief.

Tumor hypoxia impairs the generation of reactive oxygen species and the induction of immunogenic cell death (ICD) for photodynamic therapy (PDT), thus impeding its efficacy and the subsequent immunotherapy. In addition, hypoxia plays a critical role in forming immunosuppressive tumor microenvironments (TME) by regulating the infiltration of immunosuppressive tumor-associated macrophages (TAMs) and the expression of programmed death ligand 1 (PD-L1). To simultaneously tackle these issues, a MnO2-containing albumin nanoplatform co-delivering IR780, NLG919, and a paclitaxel (PTX) dimer is designed to boost photodynamic immunotherapy. The MnO2-catalyzed oxygen supply bolsters the efficacy of PDT and PTX-mediated chemotherapy, collectively amplifying the induction of ICD and the expansion of tumor-specific cytotoxic T lymphocytes (CTLs). More importantly, hypoxia releif reshapes the immunosuppressive TME via down-regulating the intratumoral infiltration of M2-type TAMs and the PD-L1 expression of tumor cells to enhance the infiltration and efficacy of CTLs in combination with immune checkpoint blockade (ICB) by NLG919, consequently eradicating primary tumors and almost completely preventing tumor relapse and metastasis. This study sets an example of enhanced immunotherapy for breast cancers through dual ICD induction and simultaneous immunosuppression modulation via both hypoxia relief and ICB, providing a strategy for the treatment of other hypoxic and immunosuppressive cancers.

Protective effects of myricetin and morin on neurological damage in Aß1-42/Al3+ -induced Alzheimer's disease model of rats.

Alzheimer's disease (AD) is a degenerative neurological disorder with unclear pathogenesis. Single-target drugs have very limited efficacy in treating AD, but synthetic multi-target drugs have poor efficacy and safety. Therefore, finding suitable natural multi-target drugs against AD is of great interest for research studies. We chose two flavonols, myricetin and morin, for the relevant study. In this study, we used microinjection of Aß1-42 oligomers into the CA1 region of rat hippocampus, combined with gavage of Aluminum chloride hexahydrate (AlCl3·6H2O) solution to establish AD rat models, and myricetin and morin were selected as intervening drugs to explore the protective effects against neurological impairment. Experimental results showed that myricetin or morin could reduce the production of Aß, Tubulin-associated unit (Tau), and Phosphorylated tubulin-associated unit (p-Tau), down-regulate the expression of relevant inflammatory factors, reduce hippocampal cell apoptosis in rats. There was a significant increase in the activity of adenosine triphosphatase, catalase, total superoxide dismutase, and the content of glutathione in the brain tissue. However, the content of malondialdehyde, inducible nitric oxide synthase, and the activity of acetylcholinesterase were decreased in the brain tissue. These two flavonols can regulate the imbalance of monoamine and amino acid neurotransmitter levels. In conclusion, Myricetin or morin can effectively improve learning and memory dysfunction in AD rats induced by Aß1-42/Al3+ through anti-oxidative stress and anti-apoptotic features.

Determination and analysis of patulin in apples, hawthorns, and their products by high-performance liquid chromatography.

This study aimed to establish a high-performance liquid chromatography (HPLC) method to investigate the residues of patulin in apples, hawthorns, and their products. A total of 400 samples were collected from online shopping plats and supermarkets in China, including apples (n = 50), hawthorns (n = 50), and their products (apple juice, apple puree, apple jam, hawthorn juice, hawthorn chips, and hawthorn rolls, n = 300). In this experiment, this method had good linearity and a recovery of 82.3-94.4% for patulin. The limit of detection (LOD) was 0.2 µg/kg for liquid samples, while it was 0.3 µg/kg for solid and semi-fluid samples. The frequencies of patulin were 79.8% in 400 samples, and the patulin concentration is from 0.6 to 126.0 µg/kg. Two samples (0.5%) for patulin exceeded the regulatory limit (50 µg/kg) in 400 samples. The frequencies of patulin in kinds of samples were 32.0-98.0% (p < 0.05), and the percentage of samples exceeding the limit was not more than 2.0%. The frequencies of patulin in domestic samples were 83.0%, while they were 57.7% in imported samples. Two domestic samples (0.6%) contained patulin above the regulatory limit, while none of the imported samples exceeded the limit. Among the online and offline samples, the frequencies of patulin were 76.4 and 82.1%. Two online samples (1.0%) for patulin exceeded the regulatory limit, whereas none of the offline samples exceeded the limit. These results showed it is important to monitor regularly the content of patulin in apples, hawthorns, and their products to ensure consumer food safety.

Socioeconomic disparities in education placement for children of primary school age with autism spectrum disorder in China.

Relatively little is known about education placements for children with autism spectrum disorder (ASD) in China. While disparities in ASD diagnoses and services for the population broadly are often documented, the presence and determinants of differences in the educational placement of ASD children are less studied and understood. By identifying who is likely to be in segregated settings, we can discern how to best support them and facilitate a possible transition to a less restrictive setting. This study describes four placements (regular schools, special schools, institutions, homes) and their influencing factors retrospectively in a large sample (n = 2,190) of Chinese primary school-aged children (6-12 years old). We divided ASD into severe and mild to moderate categories for analysis. Children with ASD were more likely to study in a regular school (48.60%), while 13.88% were in a special school. Children with severe ASD were placed in less regular settings than children with mild to moderate ASD. However, families with higher socioeconomic status (SES) were more likely to place their children in regular schools than lower SES families if their children experienced mild to moderate symptoms. Children with severe ASD were more likely to be placed in expensive institutions for families with higher SES than those with lower SES. SES disparities in educational placement existed and had two manifestations. It is important to characterize educational placements of students with ASD to determine the extent to which they are placed in general education settings, which are often the preferred placement.

Greatly Improved the Tunable Amplitude of Ferromagnetism Based on Interface Effect of Flexible Pt/YIG Heterojunctions.

Flexible quantum spin electronic devices based on ferromagnetic insulators have attracted wide attention due to their outstanding advantages of low-power dissipation and noncontact sensing. However, ferromagnetic insulators, such as monocrystalline yttrium iron garnet (Y3Fe5O12, YIG), hve weak stress effects with a small magnetostrictive coefficient (λ110, 10 ppm), making it difficult to achieve a large magnetic tunable amplitude. In this paper, large-scale (with a diameter of 40 mm), flexible Pt/YIG heterojunctions were obtained by double-cavity magnetron sputtering technology, indicating typical soft magnetism and good bending fatigue characteristics. Here, the 3 nm thickness of the Pt layer triggers an obvious magnetic proximity effect, in which the in-plane ferromagnetic resonance field is decreased by 70 Oe compared to flexible Cu/YIG heterojunctions. Meanwhile, it shows a wide tunable amplitude of 110 Oe under the flexible bending stresses, which is induced by the sensitive interface effect of Pt (3 nm)/YIG heterojunctions. The saturation magnetization of Pt/YIG heterojunctions is negatively correlated with Pt thickness rather than the relative stability of Cu/YIG heterojunctions, depending on the magnetic proximity effect. It brings greater application possibilities for flexible stress-sensitive magnetic oxides in spin logic electronic devices.

Carbapenem-resistant Escherichia coli exhibit diverse spatiotemporal epidemiological characteristics across the globe.

Carbapenem-resistant Escherichia coli (CREC) poses a severe global public health risk. This study reveals the worldwide geographic spreading patterns and spatiotemporal distribution characteristics of resistance genes in 7918 CREC isolates belonging to 497 sequence types (ST) and originating from 75 countries. In the last decade, there has been a transition in the prevailing STs from highly virulent ST131 and ST38 to higher antibiotic-resistant ST410 and ST167. The rise of multi-drug resistant strains of CREC carrying plasmids with extended-spectrum beta-lactamase (ESBL) resistance genes could be attributed to three important instances of host-switching events. The spread of CREC was associated with the changing trends in blaNDM-5, blaKPC-2, and blaOXA-48, as well as the plasmids IncFI, IncFII, and IncI. There were intercontinental geographic transfers of major CREC strains. Various crucial transmission hubs and patterns have been identified for ST131 in the United Kingdom, Italy, the United States, and China, ST167 in India, France, Egypt, and the United States, and ST410 in Thailand, Israel, the United Kingdom, France, and the United States. This work is valuable in managing CREC infections and preventing CREC occurrence and transmission inside healthcare settings and among diverse hosts.

The economic burden of autism spectrum disorder with and without intellectual disability in China: A nationwide cost-of-illness study.

OBJECTIVE: The economic burden of autism spectrum disorder (ASD) on individuals, their families and society as a whole is poorly understood. Accurate figures are crucial for economic estimates and service planning. METHODS: The total lifetime individual costs and annual societal costs of ASD in China were estimated with a prevalence-based, gross cost of illness approach and data from multiple sources. The direct medical costs in outpatient and inpatient settings from the electronic health records (EHRs) of hospitals, and direct nonmedical costs from a national survey were included. The indirect costs were from both the national survey and the estimation using human capital methods. Age-specific lifetime incremental societal costs were measured. Comorbidity-related and unrelated costs were analyzed separately. RESULTS: The discounted lifetime cost for an individual with ASD in China was $2.65 million (at 2020 prices, $) for those without intellectual disability (ID) and $4.61 million (at 2020 prices, $) for those with ID. The total cost of ASD amounted to $41.8 billion in 2020. Productivity loss were major cost drivers for ASD individuals without ID. Direct nonmedical costs (rehabilitation or adult care costs etc.) were major drivers for ASD individuals with ID. In a lifetime course, the total annual costs for middle aged and elderly (>42 years) were highest, followed by transitional adults (18-29 years) and preschoolers, both for individuals with or without ID. The distribution of costs over the lifespan varied by the cost category. CONCLUSIONS: ASD imposes a substantial economic burden on families and health care systems. Sectors and services coordination should be given policy considerations.

Exposure to PM2.5 and its five constituents is associated with the incidence of type 2 diabetes mellitus: a prospective cohort study in northwest China.

Studies have demonstrated that fine particulate matter (PM2.5) is an underlying risk factor for type 2 diabetes mellitus (T2DM), but evidence exploring the relationship between PM2.5 chemical components and T2DM was extremely limited, to investigate the effects of long-term exposure to PM2.5 and its five constituents (sulfate [SO42-], nitrate [NO3-], ammonium [NH4+]), organic matter [OM] and black carbon [BC]) on incidence of T2DM. Based on the "Jinchang Cohort" platform, a total of 19,884 participants were selected for analysis. Daily average concentrations of pollutants were gained from Tracking Air Pollution in China (TAP). Cox proportional hazards regression models were utilized to estimate the hazard ratios (HR) and 95% confidence interval (CI) in single-pollutant models, restricted cubic splines functions were used to examine the dose-response relationships, and quantile g-computation (QgC) was applied to evaluate the combined effect of PM2.5 compositions on T2DM. Stratification analysis was also considered. A total of 791 developed new cases of T2DM were observed during a follow-up period of 45254.16 person-years. The concentrations of PM2.5, NO3-, NH4+, OM and BC were significantly associated with incidence of T2DM (P-trend < 0.05), with the HRs in the highest quartiles of 2.16 (95% CI 1.79, 2.62), 1.43 (95% CI 1.16, 1.75), 1.75 (95% CI 1.45, 2.11), 1.31 (95% CI 1.08, 1.59) and 1.79 (95% CI 1.46, 2.21), respectively. Findings of QgC model showed a noticeably positive joint effect of one quartile increase in PM2.5 constituents on increased T2DM morbidity (HR 1.27, 95% CI 1.09, 1.49), and BC (32.7%) contributed the most to the overall effect. The drinkers, workers and subjects with hypertension, obesity, higher physical activity, and lower education and income were generally more susceptible to PM2.5 components hazards. Long-term exposure to PM2.5 and its components (i.e., NO3-, NH4+, OM, BC) was positively correlated with T2DM incidence. Moreover, BC may be the most responsible for the association between PM2.5 constituents and T2DM. In the future, more epidemiological and experimental studies are needed to identify the link and potential biological mechanisms.