Transfer of cGAMP into Bystander Cells via LRRC8 Volume-Regulated Anion Channels Augments STING-Mediated Interferon Responses and Anti-viral Immunity.

The enzyme cyclic GMP-AMP synthase (cGAS) senses cytosolic DNA in infected and malignant cells and catalyzes the formation of 2'3'cGMP-AMP (cGAMP), which in turn triggers interferon (IFN) production via the STING pathway. Here, we examined the contribution of anion channels to cGAMP transfer and anti-viral defense. A candidate screen revealed that inhibition of volume-regulated anion channels (VRACs) increased propagation of the DNA virus HSV-1 but not the RNA virus VSV. Chemical blockade or genetic ablation of LRRC8A/SWELL1, a VRAC subunit, resulted in defective IFN responses to HSV-1. Biochemical and electrophysiological analyses revealed that LRRC8A/LRRC8E-containing VRACs transport cGAMP and cyclic dinucleotides across the plasma membrane. Enhancing VRAC activity by hypotonic cell swelling, cisplatin, GTPγS, or the cytokines TNF or interleukin-1 increased STING-dependent IFN response to extracellular but not intracellular cGAMP. Lrrc8e-/- mice exhibited impaired IFN responses and compromised immunity to HSV-1. Our findings suggest that cell-to-cell transmission of cGAMP via LRRC8/VRAC channels is central to effective anti-viral immunity.

ATP-elicited Cation Fluxes Promote Volume-regulated Anion Channel LRRC8/VRAC Transport cGAMP for Antitumor Immunity.

The cyclic GMP-AMP synthase (cGAS)-stimulator of IFN genes (STING) pathway is instrumental to antitumor immunity, yet the underlying molecular and cellular mechanisms are complex and still unfolding. A new paradigm suggests that cancer cells' cGAS-synthesized cGAMP can be transferred to tumor-infiltrating immune cells, eliciting STING-dependent IFN-ß response for antitumor immunity. Nevertheless, how the tumor microenvironment may shape this process remains unclear. In this study, we found that extracellular ATP, an immune regulatory molecule widely present in the tumor microenvironment, can potentiate cGAMP transfer, thereby boosting the STING signaling and IFN-ß response in murine macrophages and fibroblasts. Notably, genetic ablation or chemical inhibition of murine volume-regulation anion channel LRRC8/volume-regulated anion channel (VRAC), a recently identified cGAMP transporter, abolished ATP-potentiated cGAMP transfer and STING-dependent IFN-ß response, revealing a crucial role of LRRC8/VRAC in the cross-talk of extracellular ATP and cGAMP. Mechanistically, ATP activation of the P2X family receptors triggered Ca2+ influx and K+ efflux, promoting reactive oxygen species production. Moreover, ATP-evoked K+ efflux alleviated the phosphorylation of VRAC's obligate subunit LRRC8A/SWELL1 on S174. Mutagenesis studies indicated that the phosphorylation of S174 on LRRC8A could act as a checkpoint for VRAC in the steady state and a rheostat of ATP responsiveness. In an MC38-transplanted tumor model, systemically blocking CD39 and ENPP1, hydroxylases of extracellular ATP and cGAMP, respectively, elevated antitumor NK, NKT, and CD8+ T cell responses and restrained tumor growth in mice. Altogether, this study establishes a crucial role of ATP in facilitating LRRC8/VRAC transport cGAMP in the tumor microenvironment and provides new insight into harnessing cGAMP transfer for antitumor immunity.

Global epidemiology of type 2 diabetes in patients with NAFLD or MAFLD: a systematic review and meta-analysis.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) and metabolic-associated fatty liver disease (MAFLD) shares common pathophysiological mechanisms with type 2 diabetes, making them significant risk factors for type 2 diabetes. The present study aimed to assess the epidemiological feature of type 2 diabetes in patients with NAFLD or MAFLD at global levels. METHODS: Published studies were searched for terms that included type 2 diabetes, and NAFLD or MAFLD using PubMed, EMBASE, MEDLINE, and Web of Science databases from their inception to December 2022. The pooled global and regional prevalence and incidence density of type 2 diabetes in patients with NAFLD or MAFLD were evaluated using random-effects meta-analysis. Potential sources of heterogeneity were investigated using stratified meta-analysis and meta-regression. RESULTS: A total of 395 studies (6,878,568 participants with NAFLD; 1,172,637 participants with MAFLD) from 40 countries or areas were included in the meta-analysis. The pooled prevalence of type 2 diabetes among NAFLD or MAFLD patients was 28.3% (95% confidence interval 25.2-31.6%) and 26.2% (23.9-28.6%) globally. The incidence density of type 2 diabetes in NAFLD or MAFLD patients was 24.6 per 1000-person year (20.7 to 29.2) and 26.9 per 1000-person year (7.3 to 44.4), respectively. CONCLUSIONS: The present study describes the global prevalence and incidence of type 2 diabetes in patients with NAFLD or MAFLD. The study findings serve as a valuable resource to assess the global clinical and economic impact of type 2 diabetes in patients with NAFLD or MAFLD.

Phenethyl isothiocyanate inhibits metastasis potential of non-small cell lung cancer cells through FTO mediated TLE1 m6A modification.

N6-methyladenosine (m6A) modification is a prevalent RNA epigenetic modification, which plays a crucial role in tumor progression including metastasis. Isothiocyanates (ITCs) are natural compounds and inhibit the tumorigenesis of various cancers. Our previous studies show that ITCs inhibit the proliferation and metastasis of non-small cell lung cancer (NSCLC) cells, and have synergistic effects with chemotherapy drugs. In this study, we investigated the molecular mechanisms underlying the inhibitory effects of ITCs on cancer cell metastasis. We showed that phenethyl isothiocyanate (PEITC) dose-dependently inhibited the cell viability of both NSCLC cell lines H1299 and H226 with IC50 values of 17.6 and 15.2 µM, respectively. Furthermore, PEITC dose-dependently inhibited the invasion and migration of H1299 and H226 cells. We demonstrated that PEITC treatment dose-dependently increased m6A methylation levels and inhibited the expression of the m6A demethylase fat mass and obesity-associated protein (FTO) in H1299 and H226 cells. Knockdown of FTO significantly increased m6A methylation in H1299 and H226 cells, impaired their abilities of invasion and migration in vitro, and enhanced the inhibition of PEITC on tumor growth in vivo. Overexpression of FTO promoted the migration of NSCLC cells, and also mitigated the inhibitory effect of PEITC on migration of NSCLC cells. Furthermore, we found that FTO regulated the mRNA m6A modification of a transcriptional co-repressor Transducin-Like Enhancer of split-1 (TLE1) and further affected its stability and expression. TCGA database analysis revealed TLE1 was upregulated in NSCLC tissues compared to normal tissues, which might be correlated with the metastasis status. Moreover, we showed that PEITC suppressed the migration of NSCLC cells by inhibiting TLE1 expression and downstream Akt/NF-κB pathway. This study reveals a novel mechanism underlying ITC's inhibitory effect on metastasis of lung cancer cells, and provided valuable information for developing new therapeutics for lung cancer by targeting m6A methylation.

Association of birth weight with type 2 diabetes mellitus and the mediating role of fatty acids traits: a two-step mendelian randomization study.

BACKGROUND: Observational studies have suggested an association between birth weight and type 2 diabetes mellitus, but the causality between them has not been established. We aimed to obtain the causal relationship between birth weight with T2DM and quantify the mediating effects of potential modifiable risk factors. METHODS: Two-step, two-sample Mendelian randomization (MR) techniques were applied using SNPs as genetic instruments for exposure and mediators. Summary data from genome-wide association studies (GWAS) for birth weight, T2DM, and a series of fatty acids traits and their ratios were leveraged. The inverse variance weighted (IVW) method was the main analysis approach. In addition, the heterogeneity test, horizontal pleiotropy test, Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) test, and leave-one-out analysis were carried out to assess the robustness. RESULTS: The IVW method showed that lower birth weight raised the risk of T2DM (ß: -1.113, 95% CI: -1.573 ∼ -0.652). Two-step MR identified 4 of 17 candidate mediators partially mediating the effect of lower birth weight on T2DM, including ratio of polyunsaturated fatty acids to monounsaturated fatty acids (proportion mediated: 7.9%), ratio of polyunsaturated fatty acids to total fatty acids (7.2%), ratio of omega-6 fatty acids to total fatty acids (8.1%) and ratio of linoleic acid to total fatty acids ratio (6.0%). CONCLUSIONS: Our findings supported a potentially causal effect of birth weight against T2DM with considerable mediation by modifiable risk factors. Interventions that target these factors have the potential to reduce the burden of T2DM attributable to low birth weight.

Spectral data fusion in nondestructive detection of food products: Strategies, recent applications, and future perspectives.

In recent years, the food industry has shown a growing interest in the development of rapid and nondestructive analytical methods. However, the utilization of a solitary nondestructive detection technique offers only a constrained extent of physical or chemical insights regarding the sample under examination. To overcome this limitation, the amalgamation of spectroscopy with data fusion strategies has emerged as a promising approach. This comprehensive review delves into the fundamental principles and merits of low-level, mid-level, and high-level data fusion strategies within the domain of food analysis. Various data fusion techniques encompassing spectra-to-spectra, spectra-to-machine vision, spectra-to-electronic nose, and spectra-to-nuclear magnetic resonance are summarized. Moreover, this review also provides an overview of the latest applications of spectral data fusion techniques (SDFTs) for classification, adulteration, quality evaluation, and contaminant detection within the purview of food safety analysis. It also addresses current challenges and future prospects associated with SDFTs in real-world applications. Despite the extant technical intricacy, the ongoing evolution of online data fusion platforms and the emergence of smartphone-based multi-sensor fusion detection technology augur well for the pragmatic realization of SDFTs, endowing them with formidable capabilities for both qualitative and quantitative analysis in the realm of food analysis.

The specific biopanning of single-domain antibody against haptens based on a functionalized cryogel.

Phage display technology is commonly applied for high-throughput screening of single-domain antibodies (sdAbs), and the problem of non-specific adsorption caused by carrier proteins seriously affects the biopanning of single-domain antibodies specific to haptens. In this paper, enrofloxacin (ENR)-functionalized cryogels were prepared by the ethylenediamine (EDA) and carbodiimide methods for application in the biopanning of ENR-specific phages. To improve the efficiency of biopanning, double blocking, a wash solution flow rate of 1 mL/min, and phage pre-incubation were applied to the biopanning process through single-factor experiments. Results of flat colony counting showed that the phage output of AG-ENR cryogels was 15 times higher than that of AG cryogels for the same input amount. And seven complete sequences of ENR-specific shark sdAbs were obtained by monoclonal phage ELISA and sequence alignment. All these results indicate that functionalized cryogels could be used as a novel and efficient method for phage biopanning for single-domain antibodies to haptens.

Efficient Hapten-Specific Biopanning Strategy Based on the Fe3O4@ENR-Functionalized Core-Shell Magnetic Nanoparticles.

The biopanning of target-specific phages is one of the most critical steps in the preparation of single-domain antibodies. In the traditional biopanning of haptens, the nonspecific binding of library phages to macromolecular proteins is one of the most challenging problems in preparing single-domain antibodies. In this research, Fe3O4@ENR-functionalized core-shell magnetic nanoparticles (FMNPs) were silylated and aminated by tetraethyl orthosilicate and (3-aminopropyl)triethoxysilane, and target enrofloxacin was coupled onto the surface by the carbodiimide method. The magnetic nanoparticles were characterized by Fourier transform infrared spectroscopy, particle size distribution, zeta potential, transmission electron microscopy observation, and indirect enzyme-linked immunosorbent assay (ELISA). A biopanning strategy based on Fe3O4@ENR FMNPs was then established to solve the problem in the traditional solid-phase biopanning process. The results showed that a considerable number of enrofloxacin (ENR)-positive phages were screened by only one round of biopanning. Finally, two ENR-specific shark-derived single-domain genes were identified and validated by monoclonal phage ELISA, gene sequencing, and biolayer interferometry technology. Our study provides a new biopanning strategy based on Fe3O4@ENR FMNPs for efficiently providing phages specific to haptens.

Regulation of Anion Channel LRRC8 Volume-Regulated Anion Channels in Transport of 2'3'-Cyclic GMP-AMP and Cisplatin under Steady State and Inflammation.

The recently identified anion channel LRRC8 volume-regulated anion channels (VRACs) are heteromeric hexamers constituted with the obligate LRRC8A subunit paired with at least one of the accessory LRRC8B to LRRC8E subunits. In addition to transport chloride, taurine, and glutamate, LRRC8 VRACs also transport the anticancer agent cisplatin and STING agonists 2'3'-cyclic GMP-AMP (cGAMP) and cyclic dinucleotides; hence, they are implicated in a variety of physiological and pathological processes, such as cell swelling, stroke, cancer, and viral infection. Although the subunit composition largely determines VRAC substrate specificity, the opening of various VRAC pores under physiological and pathological settings remains enigmatic. In this study, we demonstrated that VRACs comprising LRRC8A and LRRC8E (LRRC8A/E-containing VRACs), specialized in cGAMP transport, can be opened by a protein component present in serum under resting condition. Serum depletion ablated the tonic activity of LRRC8A/E-containing VRACs, decreasing cGAMP transport in various human and murine cells. Also, heating or proteinase K treatment abolished the ability of serum to activate VRAC. Genetic analyses revealed a crucial role for cGAMP synthase (cGAS) in serum/TNF-promoted VRAC activation. Notably, the presence of cGAS on the plasma membrane, rather than its DNA-binding or enzymatic activity, enabled VRAC activation. Moreover, phospholipid PIP2 seemed to be instrumental in the membrane localization of cGAS and its association with VRACs. Corroborating a role for LRRC8A/D-containing VRACs in cisplatin transport, serum and TNF markedly potentiated cisplatin uptake and killing of cancer cells derived from human or mouse. Together, these observations provide new insights into the complex regulation of VRAC activation and suggest a novel approach to enhance the efficacy of cGAMP and cisplatin in treating infection and cancer.

Analysis of Cognition, Protection, Psychological, and Job-search Intentions Among Medical and Nonmedical College Students During COVID-19 Epidemic.

Context: Since December 2019, medical practitioners discovered a novel coronavirus causing an acute respiratory-tract infection in some hospitals in Wuhan, Hubei Province. COVID-19 has spread globally, making it an epidemic worldwide at present. Understanding the mental-health responses of college students to COVID-19 can help a school staff to better guide students seeking education. Objective: The study aimed to explore the differences between nonmedical and medical college students during the COVID-19 epidemic in their cognitive interest about the disease, preventive behaviors, psychological effects, and job-search intentions, hoping to provide more targeted measures for virus-coping education for college students. Design: The research team conducted a cross-sectional study, using an anonymous online questionnaire. Setting: The study took place at Shanghai, China. Participants: Participants were 1648 college students studying different specialties in various provinces of China, 485 nonmedical students and 1163 medical students. Outcome Measures: The survey's questions covered the respondents': (1) general demographic characteristics, (2) cognitive interest and knowledge about COVID-19 and its infectiousness as well as efforts at active learning about infectious diseases and viruses, (3) awareness of precautionary behaviors against COVID-19, (4) effects on mental health, and (5) effects on job-search intentions. The research team used descriptive statistics and Chi-square tests to analyze the survey data. Results: Among nonmedical students: (1) 297 participants (61.2%) were interested in learning about COVID-19, (2) 321 participants (66.2%) took the initiative to learn about the virus, (3) 301 participants (62.1%) took the initiative to learn about infectious disease, and (4) 151 participants (31.1%) watched medical-themed movies or TV series about COVID-19. Among medical students, the corresponding proportions were 772 participants (66.4%), 855 participants (73.5%), 791 participants (68.1%), and 791 participants (68.1%), respectively. Among nonmedical students, 223 participants (46.0%) had N95 masks available, 429 participants (88.5%) had disinfectant supplies available, 271 participants (55.9%) wore goggles in public places, 75 participants (15.5%) chose public transportation, and 77 participants (15.9%) were exposed to public places in the week prior to the survey. Among medical students, the corresponding proportions were 470 participants (40.4%), 935 participants (80.4%), 575 participants (49.4%), 243 participants (20.9%), and 297 participants (25.5%), respectively. Furthermore, COVID-19 had a stronger effect on medical students' psychology and job-search ambitions. Conclusions: The news about COVID-19 piqued the interest of medical students. Nonmedical students had stronger protective behavior than medical students. The COVID-19 outbreak had a significant influence on medical students' lives, studies, and moods. In addition, COVID-19 had a greater impact on the job-search intentions of medical students.

Employment Intention of Chinese Medical Students During the COVID-19 Epidemic: A Cross-Sectional Survey.

Context: In the process of combating the coronavirus disease 2019 (COVID-19) epidemic, medical personnel were at the forefront of the fight. As the future medical workforce, medical students often experienced firsthand how their seniors and teachers had to commit to working hard in combating the epidemic. Many were directly involved in the front line of the fight and that experience could easily have affected their intention to seek employment in a medically related career. Objective: The study intended to evaluate the impact of the COVID-19 pandemic on Chinese medical students' employment intentions and the factors associated with them to put forward relevant suggestions to provide a basis for medical education in the future. Design: The research team conducted a cross-sectional study, using an anonymous online questionnaire. Setting: The study took place in many provinces and cities in China and was conducted in an online questionnaire. Participants: Participants were 1114 college students studying clinical medicine, college students studying nursing, and students interning during standardized resident training, medical interns. Outcome Measures: The participants completed a self-administered questionnaire, which investigated their psychological statuses related to anxiety and depression as well as COVID-19's impact on their intentions related to job searches, regarding their willingness to engage in clinical or basic research in epidemic-related specialties and epidemic-related work. Results: Compared to college students studying clinical medicine, the employment intentions of nursing students and medical interns were more vulnerable to the epidemic. Females and nursing students were more reluctant to choose clinical work, and the choice was associated with depression. Nursing college students and medical interns were significantly less willing to engage in infection medicine, respiratory medicine, and intensive care medicine (all P < .001). Medical students with a bachelor's degree and postgraduate degrees were significantly less willing to engage in infection medicine and respiratory medicine (all P < .001), but medical students from regions with stable epidemics were more willing to engage in intensive care medicine. Medical students with a bachelor's degree were significantly less likely to be involved in epidemiology-related work than undergraduate students, and students from severe epidemic regions were significantly less willing to work in isolation wards or to go to Wuhan as volunteers. Conclusions: Participants' psychological statuses related to anxiety and depression, genders, degrees, current educational statuses, and regions affected employment intentions during the epidemic.

Adherence to a vegetable dietary pattern attenuates the risk of non-alcoholic fatty liver disease in incident type 2 diabetes: The TCLSIH cohort study.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a strong risk factor for type 2 diabetes. However, no study has investigated whether dietary intake can modify this effect. Therefore, we aimed to investigate the effect of dietary pattern modification on the association between NAFLD and type 2 diabetes. METHODS: A large prospective cohort study (n = 24,602) was conducted in China. NAFLD was diagnosed using liver ultrasonography considering alcohol consumption. Dietary data were assessed using a validated self-administered food frequency questionnaire. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Following a 93,873 person-year follow-up, 787 (3.20%) participants developed type 2 diabetes. In a multivariable adjusted model, compared with participants without NAFLD, the HR (95% CI) of incident type 2 diabetes for NAFLD patients was 3.04 (2.51, 3.68). On subgroup analyses, the adjusted HRs (95% CIs) of incident type 2 diabetes for NAFLD patients with low (≤median score) and high (>median score) vegetable pattern intakes were 4.08 (3.05, 5.46) and 2.38 (1.85, 3.07) (p for interaction <0.01), respectively. Higher vegetable intake was also found to attenuate the risk effect of phenotype groups of NAFLD on incident type 2 diabetes, especially in the lean NAFLD group. CONCLUSIONS: The present study demonstrated that NAFLD is a strong risk factor for type 2 diabetes in the Chinese population. Notably, adherence to a dietary pattern rich in vegetables can attenuate this risk, especially in lean NAFLD patients.

Indoor air pollution and frailty: A cross-sectional and follow-up study among older Chinese adults.

BACKGROUND: Previous studies have suggested that ambient air pollution negatively affects frailty, but whether indoor air pollution exposure affects frailty is unknown. METHOD: This study was conducted on 4946 older adults (≥60 years) followed from baseline to 4 years in the Chinese Longitudinal Healthy Longevity Survey. Household fuel types and frailty were assessed with self-rated questionnaires and physical examination. The relationships between indoor air pollution and frailty via phenotypic frailty and a frailty index were explored with logistic regression models and Cox proportional hazard regression models in both a cross-sectional and follow-up design. Additionally, the effects of indoor air pollution on phenotypic frailty together with mild cognitive impairment (MCI) were further investigated. RESULTS: In the cross-sectional study, the adjusted ORs (95% CIs) for frailty assessment with the frailty index and phenotypic frailty were 1.28 (1.12, 1.46) and 1.36 (1.18, 1.57), respectively. Solid fuel use was a risk factor in prefrail/frail patients with [OR and 95% CI, 1.88 (1.41, 2.50)], or without MCI [OR and 95% CI, 1.37 (1.17, 1.61)], as compared with the groups with no phenotypic prefrailty/frailty and no MCI. Moreover, solid cooking fuel use was positively associated with the incidence of phenotypic prefrailty and frailty. The adjusted HRs (95% CIs) for phenotypic prefrailty and frailty were 1.26 (1.03, 1.55). CONCLUSIONS: Solid cooking fuels can be regarded as a risk factor for frailty. Moreover, our findings suggest that more attention should be paid to solid cooking fuel using as it relates to phenotypic frailty together with MCI.

Associations between household solid fuel use and hearing loss in a Chinese population: A population-based prospective cohort study.

Hearing loss, a common chronic condition, severely affects the quality of human life. However, the longitudinal relationships between household solid fuel use and hearing loss are unclear. To explore the associations between household solid fuel use and hearing loss in a Chinese population. There were 8835 participants enrolled in this prospective cohort study. Hearing function was assessed by asking the following self-reported question. Cox proportional hazards regression models were used to examine the relationships between baseline household solid fuel use and hearing loss incidence. After 6 (range, 2-7) years of follow-up, 1654 (18.72%) of 8835 participants developed hearing loss. This study demonstrated that increasing baseline solid fuel exposure was associated with a higher rate of poor hearing function (P for trend < 0.01). Compared with the clean fuel group (both cooking and heating), the hazard ratios (HR) (95% confidence intervals) of poor hearing function for the solid fuel group (cooking or heating) and both solid fuel groups (both cooking and heating) were 1.17 (1.01, 1.37) and 1.26 (1.09, 1.45) after adjustments, respectively. In subgroup analysis of household energy sources, the use of solid fuels for both heating (HR, 1.21; 1.07, 1.37) and cooking (HR, 1.12; 1.01, 1.26) was related to a higher incidence of poor hearing function. In subgroup analysis of place of residence, more solid fuel use was associated with a higher rate of poor hearing function in urban communities (HR, 1.39; 1.12, 1.74) but not in rural villages (HR, 1.18; 0.97, 1.45). Moreover, compared with the population that used solid fuel for cooking at both baseline and follow-up, those who switched from solid to clean fuel had a lower risk of developing poor hearing function (HR, 0.54, 0.46-0.63). This study demonstrates that household solid fuel use is closely associated with poor hearing function. Programs that educate individuals on the effects of household fuel use on hearing function should be established, especially in urban communities.

The effect of water source on cognitive functioning in Chinese adults: A cross-sectional and follow-up study.

The effect of water source on cognitive functioning is poorly understood. The present study explored the associations between water source and cognition in 9921 participants from the China Health and Retirement Longitudinal Study (CHARLS). Cognitive functioning was measured from three aspects: orientation and attention, episodic memory, and visuo-construction. Water sources included tap and non-tap water. Generalized linear models and multiple logistic regression models were conducted to investigate the associations of cognitive scores with water source among the whole population and different subgroups. Results from cross-sectional analysis reported that participants without access to tap water showed a lower cognitive score (ß = - 0.57; 95% CI: - 0.74, - 0.39) than those with tap water as a water source; and this phenomenon was pronounced for both sexes and across all residences. During 4-years' follow-up, a greater decline of cognitive score was associated with no tap water use in the lowest quartile of baseline cognitive scores (ß = - 0.67; 95% CI: - 1.26, - 0.08). Additionally, the utilization rate of tap water was lower in rural areas compared to urban areas. The lowest utilization rates were observed in urban areas of the Anhui province (0.38 in 2011 and 0.55 in 2015) and in rural areas of Inner Mongolia (0.09 in 2011 and 0.20 in 2015). These findings suggest that having no tap water may be a risk factor for cognition impairment, particularly for those with a low basic cognition score. Additionally, our results support the need to expand tap water use in China.

Associations between long term exposures to outdoor air pollution and indoor solid fuel use and depression in China.

Depression is one of the most common mental disorders. Effects of air pollution from outdoor and indoor on depression were inconsistent. We assessed 30,139 participants from Northeast China to explore the associations between long term exposures of outdoor and indoor solid fuel use and depressive symptoms. Multiple logistic regressions models as well as multiplicative interaction and additive interaction analysis were used. Outdoor exposures to air pollutants of particulate matter (with an aerodynamic diameter <2.5 µm, [PM2.5], odds ratio [OR] = 1.98 per standard deviation [SD], 95% confidence interval [CI]: 1.78, 2.19; with an aerodynamic diameter <10 µm, [PM10], OR = 1.83, 95% CI:1.68, 2.00), sulfur dioxide (SO2, OR = 1.42, 95% CI: 1.33, 1.52), and nitrogen dioxide (NO2, OR = 1.62, 95% CI: 1.49, 1.76) were significantly associated with higher occurrence of depressive symptoms. A significant linear trend for increased occurrence of depressive symptoms was observed in participants using both solid fuels for cooking and heating (P = 0.04). Indoor air pollution exposures from solid fuel use for heating (OR = 1.16, 95%CI: 1.00, 1.35) and high cooking frequency (OR = 1.17, 95%CI: 1.00, 1.37) were significantly associated with increased occurrence of depressive symptoms. We observed significant interactions of indoor solid fuel use and outdoor air pollution exposures on depressive symptoms (indoor fuel use for cooking and SO2, P value = 0.04; solid fuel use for heating and NO2, P value = 0.02). Solid fuel use for cooking weakened the associations between SO2(relative excess risk due to interaction [RERI] = -1.37, 95% CI: -1.88, -0.86) and depressive symptoms. Solid fuel use for heating weakened the associations between NO2 (RERI = -1.91, 95% CI: -2.55, -1.27) and depressive symptoms. Compared with individual associations, antagonistic interactions of outdoor air pollution and indoor solid fuel use on depressive symptoms might exist. Our findings contribute to better understandings for the associations between air pollution and depressive symptoms, which might be useful for developing effective strategies for depression prevention and air pollution control.

The effect of chlorophyll on the enzyme-linked immunosorbent assay (ELISA) of procymidone in vegetables and the way to overcome the matrix interference.

BACKGROUND: There is now an increasing demand for the immunoassay of procymidone residue in foodstuffs. However, the matrix interference could significantly affect the analysis. Till now there is no detailed information on the source of the interference and the mechanism involved, which greatly limits the real application of these techniques. RESULTS: Significant matrix effect was observed in the enzyme-linked immunosorbent assay (ELISA) of procymidone in negative vegetable samples (leek, broccoli and cucumber). By the investigation with both vegetable extracts and standard solutions, the chlorophyll was confirmed as an important source of the matrix effect. Therefore, a new strategy was proposed for the pretreatment based on the exploitation of 5-sulfosalicylic acid. It was demonstrated to effectively eliminate chlorophyll and exhibited little effect on procymidone and the competitive indirect ELISA (ci-ELISA) performance. The established technique was validated with different vegetables. With the spiking concentration of procymidone investigated, the recovery rate of ci-ELISA was 71.52-120.37%, and the relative standard deviation was 4.05-17.61%. CONCLUSION: Chlorophyll was for the first time illuminated as an important source of matrix interference to the immunoassay of procymidone in vegetables. A new pretreatment based on 5-sulfosalicylic acid was established to remove chlorophyll and therefore eliminate the matrix effect. Validated with different vegetable samples, the new technique was demonstrated much better efficiency in comparison to conventional methods, which indicated its promising application for the development of immunoassays of herb-origin samples. © 2021 Society of Chemical Industry.

Household solid fuel use and peak expiratory flow in middle-aged and older adults in China: A large cohort study (2011-2015).

Indoor air pollution caused by solid fuel use in cooking and heating in China is common. The relationship between household solid fuel use and peak expiratory flow (PEF) in middle-aged and older adults in China has not been clarified. The aim of this study was to assess the relationship between long-term household solid fuel use (clean for both cooking and heating, solid for either cooking or heating, and solid for both cooking and heating) and PEF changes in middle-aged and older adults using a nationally representative prospective cohort. Covariance analysis was used to compare PEF changes in different indoor air pollution exposure groups. Separate analysis of cooking and heating as well as sub-group analyses by age, sex and smoking status were conducted, linear mixed growth model analysis was used to evaluate the association between cooking fuel type and PEF. A total of 6818 participants were enrolled in the cohort analysis. Results revealed that solid fuel use in cooking and heating separately or conjointly were associated with reduced PEF (solid fuel use in cooking: least square mean [LSM] = 19.9, 95% confidence interval [CI]: 11.5-28.2, P = 0.03; solid fuel use in heating: LSM = 19.4, 95% CI:11.2-27.5, P = 0.04; both solid fuel use: LSM = 17.6, 95% CI: 9.3-25.9, P for trend <0.0001), especially in participants aged >65 years (LSM = -9.22, 95% CI: 27.9-69.52, P for trend <0.0001), females (LSM = -6.41, 95% CI: 19.12-6.30, P for trend <0.0001) and current or former smokers (LSM = -21.55, 95% CI: 36.14 to -6.97, P < 0.02). Compared to that of participants using clean fuels for cooking, PEF of participants using solid fuels were decreased by 3.5 l/min per 2 years over a 4-year follow-up. This cohort study highlights the adverse effects of indoor air pollution on lung function in middle aged and older adults in China.

Peripheral white blood cell counts mediated the associations of sleep duration with atherosclerotic cardiovascular disease risk: a cross-sectional study of middle-aged and older Chinese.

PURPOSE: To investigate the associations between sleep duration and atherosclerotic cardiovascular disease (ASCVD) risk and the potential mechanism. METHODS: Overall, 24,471 subjects without ASCVD were included from Dongfeng-Tongji (DFTJ) cohort. Data collection included questionnaires and general medical examinations. We used logistic regression models and generalized linear models to examine the associations between sleep duration, peripheral white blood cell (WBC) counts, and 10-year ASCVD risk. Mediation analyses were further performed to assess the potential role of peripheral WBC counts in the associations between sleep duration and 10-year ASCVD risk. RESULTS: Increased risk of 10-year ASCVD was observed as sleep duration extended. After adjusting for potential confounders, the odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of 10-year ASCVD were 1.24 (1.11-1.38), 1.12 (1.03-1.22), and 1.21(1.08-1.36) for individuals with nighttime sleeping duration of ≥ 9 h, daytime napping duration of > 30 min, and daily sleep duration of ≥ 9 h, respectively. Peripheral WBC counts mediated 14.1%, 14.5%, and 12.6% in the associations of nighttime sleep duration of ≥ 9 h, daytime napping duration of > 30 min and daily sleep duration of ≥ 9 h with 10-year ASCVD risk, respectively. CONCLUSIONS: Extended sleep durations are associated with the increased 10-year ASCVD risk, and the associations are partially mediated by peripheral WBC counts.

The effects of household solid fuel use on self-reported and performance-based physical functioning in middle-aged and older Chinese populations: A cross-sectional study.

BACKGROUND: Physical limitation, which has been linked to outdoor air pollution exposure in previous studies, is a risk factor for disability and even for premature death. Although people often spend more time indoors, the relationship between indoor air pollution and physical function has not been fully explored. METHODS: The associations of household fuel types with self-reported and performance-based physical functioning were tested on a total of 12,458 participants in the China Health and Retirement Longitudinal Study (CHARL), using generalized linear models and logistic regression models. Additionally, subgroup analyses according to smoking status and number of chronic diseases, were performed regarding these associations. RESULTS: Our results revealed that after adjusting for potential confounds, solid fuel use in cooking showed -0.08 (-0.13, -0.04) and -0.15 (-0.23, -0.06) declines in self-reported and performance-based physical functioning scores (higher scores means fewer physical limitations), when compared with cleaner groups, respectively. Considering these outcomes as binary variables, the ORs (95% CIs) for abnormal self-reported and performance-based physical functioning in the solid fuel cooking group were 1.226 (1.053-1.427) and 1.194 (1.072-1.330), respectively. No significant association between heating fuel use and physical functioning was observed. Additionally, no modification effect of smoking status and the number of chronic diseases on the association between cooking fuel use and performance-based physical functioning was observed (P > 0.05). CONCLUSION: Our findings suggested that solid cooking fuel use may be associated with self-reported and performance-based physical functioning decline of middle-aged and elder Chinese populations.