The Chinese keratoconus (CKC) cohort study.

The Chinese keratoconus (CKC) cohort study is a population-based longitudinal prospective cohort study in the Chinese population involving a clinical database and biobanks. This ongoing study focuses on the prevention of KC progression and is the first to involve the effect of gene‒environment interactions on KC progression. The CKC cohort is hospital-based and dynamic and was established in Zhengzhou, China; KC patients (n = 1114) from a large geographical area were enrolled from January 2019 to June 2023, with a mean age of 22.23 years (6‒57 years). Demographic details, socioeconomic characteristics, lifestyle, disease history, surgical history, family history, and visual and social function data are being collected using questionnaires. General physical examination, eye examination, biological specimen collection, and first-degree relative data were collected and analyzed in the present study. The primary focus of the present study was placed on gene, environment and the effect of gene‒environment interactions on KC progression. The follow-up of the CKC cohort study is expected to include data collection at 3 months, 6 months, and 1 year after the initial examination and then at the annual follow-up examinations. The first follow-up of the CKC cohort study was recorded. A total of 918 patients completed the follow-up by June 1, 2023, with a response rate of 82.40%. Aside from the younger age of patients who were followed up, no significant differences were found between patients who were followed up and patients who were not.

LLPS of FXR proteins drives replication organelle clustering for ß-coronaviral proliferation.

ß-Coronaviruses remodel host endomembranes to form double-membrane vesicles (DMVs) as replication organelles (ROs) that provide a shielded microenvironment for viral RNA synthesis in infected cells. DMVs are clustered, but the molecular underpinnings and pathophysiological functions remain unknown. Here, we reveal that host fragile X-related (FXR) family proteins (FXR1/FXR2/FMR1) are required for DMV clustering induced by expression of viral non-structural proteins (Nsps) Nsp3 and Nsp4. Depleting FXRs results in DMV dispersion in the cytoplasm. FXR1/2 and FMR1 are recruited to DMV sites via specific interaction with Nsp3. FXRs form condensates driven by liquid-liquid phase separation, which is required for DMV clustering. FXR1 liquid droplets concentrate Nsp3 and Nsp3-decorated liposomes in vitro. FXR droplets facilitate recruitment of translation machinery for efficient translation surrounding DMVs. In cells depleted of FXRs, SARS-CoV-2 replication is significantly attenuated. Thus, SARS-CoV-2 exploits host FXR proteins to cluster viral DMVs via phase separation for efficient viral replication.

UBAP2L ensures homeostasis of nuclear pore complexes at the intact nuclear envelope.

Assembly of macromolecular complexes at correct cellular sites is crucial for cell function. Nuclear pore complexes (NPCs) are large cylindrical assemblies with eightfold rotational symmetry, built through hierarchical binding of nucleoporins (Nups) forming distinct subcomplexes. Here, we uncover a role of ubiquitin-associated protein 2-like (UBAP2L) in the assembly and stability of properly organized and functional NPCs at the intact nuclear envelope (NE) in human cells. UBAP2L localizes to the nuclear pores and facilitates the formation of the Y-complex, an essential scaffold component of the NPC, and its localization to the NE. UBAP2L promotes the interaction of the Y-complex with POM121 and Nup153, the critical upstream factors in a well-defined sequential order of Nups assembly onto NE during interphase. Timely localization of the cytoplasmic Nup transport factor fragile X-related protein 1 (FXR1) to the NE and its interaction with the Y-complex are likewise dependent on UBAP2L. Thus, this NPC biogenesis mechanism integrates the cytoplasmic and the nuclear NPC assembly signals and ensures efficient nuclear transport, adaptation to nutrient stress, and cellular proliferative capacity, highlighting the importance of NPC homeostasis at the intact NE.

The relationship between cooking fuel use and sex hormone levels: A cross-sectional study and Mendelian randomization study.

PURPOSE: The aim of this study was to investigate the effect of solid fuel use on serum sex hormone levels. Furthermore, the effects of improved kitchen ventilation and duration of cooking time on the relationship between solid fuel use and serum sex hormone levels will be further explored. METHODS: In this cross-sectional study, 5386 individuals were recruited. Gender and menopausal status modified associations between solid fuel type and serum sex hormone levels was investigated through generalized linear models and further analyzed by improving kitchen ventilation and length of cooking time on the relationship between solid fuel use and serum sex hormone levels. To identify the causal association, mendelian randomization of two-sample was performed. RESULTS: In observational analyses, for ln-17-hydroxyprogesterone, ln-testosterone, and ln-androstenedione among premenopausal women, the estimated ß and 95 % CI of sex hormone levels for the effect of solid fuel users was -0.337 (-0.657, -0.017), -0.233 (-0.47, 0.005), and - 0.240 (-0.452, -0.028) respectively, and - 0.150 (-0.296, -0.004) in ln-progesterone among postmenopausal women. It was found that combining solid fuels with long cooking periods or no ventilation more effectively reduced testosterone and androstenedione in premenopausal women. We further found the adverse effects of using solid fuel on progesterone, testosterone, and androstenedione levels were enhanced with the increases of PM1, PM2.5, PM10, and NO2. Corresponding genetic, the causal risk effect of solid fuel were - 0.056 (-0.513, 0.4) and 0.026 (-3.495, 3.547) for testosterone levels and sex hormone binding globulin, respectively. CONCLUSION: Using gas or solid fuel was negatively related to sex hormone levels. A combination of using solid fuels, cooking for a long time, or cooking without ventilation had a stronger effect on sex hormone levels. However, genetic evidence did not support causality for the associations. WHAT IS ALREADY KNOWN ON THIS TOPIC?: The mechanisms underlying these associations household air pollution (HAP) from incomplete combustion of such fuels and occurrence of chronic diseases remained obscure. Recent years, extensive evidences from animal as well as human researches have suggested that progestogen and androgen hormones are involved in the development of diabetes, hypertension, and cardiovascular disease, which indicated that changes in serum progestogen and androgen hormones levels might play a role in these pathological mechanisms. However, limited evidence exists examining the effect of HAP from solid fuel use on serum sex hormone levels.

Innate immune responsive inflammation in development of progressive myopia.

PURPOSE: Inflammation has been implicated for development of myopia. It is not clear when inflammation is kicked in during the course of myopia, and what characteristics of the inflammation. In this study, we tested for cytokines from aqueous humour of eyes with wide spectrum of refractive status for profiling the inflammation. METHODS: Aqueous humour of 142 patient eyes were tested for soluble intercellular adhesion molecule 1 (sICAM-1), monocyte chemoattractant protein-1 (MCP-1), and transforming growth factor-beta 2 (TGF-ß2) using an enzyme-linked immunosorbent assay (ELISA). Eye globe axial length of these patients ranged from emmetropia to high myopia. RESULTS: Of 142 patients, an average axial length is 25.51 ± 3.31 mm, with a range of 21.56-34.37 mm. There are 36 cases in lower 25 percentile, 37 cases in upper 25 percentile, and 69 case in the middle 50 percentile. sICAM-1 and MCP-1 were significantly higher in the eyes with staphyloma (407.48 pg/mL, 312.31 pg/mL, n = 33) or macular schisis (445.86 pg/mL,345.33 pg/mL, n = 19) than that in the eyes without these changes (206.44 pg/mL, 244.76 pg/mL, n = 107). All three cytokines level was significantly associated with eye globe axial in a positive mode while adjusting for the age and sex. Strength of the association was the greatest for sICAM-1 and the weakest for TGF- ß2. MCP-1 was in between. CONCLUSION: sICAM-1 and MCP-1 in ocular fluid may be indicative biomarkers for progressive high myopia and the underneath autoimmune inflammation. sICAM-1 may be used as a monitoring biomarker for development of pathologic myopia.

Health-related quality of life assessed by EQ-5D-5L and its determinants among rural adults: result from the Henan rural cohort study.

OBJECTIVES: Evidence on the health-related quality of life (HRQoL) among Chinese rural populations and its influence factors were limited. This study aimed to describe the distribution of HRQoL assessed by EQ-5D-5L and its determinants among a Chinese rural population. METHODS: A total of 23,510 eligible participants (9542 men and 13,968 women) from the Henan rural cohort study were included. Tobit regression and generalized linear models were performed to investigate the associations between demographic characteristics, lifestyle factors, common chronic diseases, and HRQoL. RESULTS: Of all respondents, the most frequently reported problem was pain/discomfort dimension (23.05%), followed by mobility (12.72%), anxiety/depression (7.77%), and usual activities (6.45%), while the least reported was the self-care dimension (3.84%). The more problems reported in all dimensions with age increased except anxiety/depression. The mean (standard deviation) utility index and VAS score were 0.954 (0.111) and 78.34 (14.80), respectively. The regression analysis indicated that increasing age, former drinkers, poor sleep quality, and suffering from common chronic diseases were significantly associated with low HRQoL, while high education level, average monthly income, and physical activity were significantly associated with high HRQoL. CONCLUSION: This study described the distribution of HRQoL and its influence factors among the Chinese rural population, which was helpful for medical institutions and policymakers to allocate medical resources and better understand HRQoL among the Chinese rural population.

Hollow Spherical Heterostructured FeCo-P Catalysts Derived from MOF-74 for Efficient Overall Water Splitting.

The design of catalysts with tunable active sites in heterogeneous interface structures is crucial for addressing challenges in the water-splitting process. Herein, a hollow spherical heterostructure FeCo-P is successfully prepared by hydrothermal and phosphorization methods. This hollow structure, along with the heterogeneous interface between Co2 P and FeP, not only facilitates the exposure of more active sites, but also increases the contact area between the catalyst and the electrolyte, as well as shortens the distance for mass/electron transfer. This enhancement promotes electron transfer to facilitate water decomposition. FeCo-P exhibits excellent hydrogen evolution (HER) and oxygen evolution (OER) performance when reaching @ 10 mA cm-2 in 1 mol L-1  KOH, with overpotentials of 131/240 mV for HER/OER. Furthermore, when FeCo-P is used as both the cathode and anode for overall water splitting (OWS), it only requires low voltages of 1.49, 1.55, and 1.57 V to achieve CDs of 10, 100, and 300 mA cm-2 , respectively. Density functional theory calculations indicate that constructing a Co2 P and FeP heterogeneous interface with good lattice matching can facilitate electron redistribution, thereby enhancing the electrocatalytic performance of OWS. This work opens up new possibilities for the rational design of efficient water electrolysis catalysts derived from MOFs.

Sheet-Isolated MoS2 Used for Dispersing Pt Nanoparticles and its Application in Methanol Fuel Cells.

It is highly challenging to activate the basal plane and minimize the π-π stacking of MoS2 sheets, thus enhancing its catalytic performance. Here, we display an approach for making well-dispersed MoS2 . By using the N-doped multi-walled carbon nanotubes (NMWCNTs) as an isolation unit, the aggregation of MoS2 sheets was effectively reduced, favoring the dispersion of Pt nanoparticles (noted as Pt/NMWCNTs-isolated-MoS2 ). Excellent bifunctional catalytic performance for methanol oxidation and oxygen reduction reaction (MOR/ORR) were demonstrated by the produced Pt/NMWCNTs-isolated-MoS2 . In comparison to Pt nanoparticles supported on MoS2 (Pt/MoS2 ), the MOR activity (2314.14 mA mgpt -1 ) and stability (317.69 mA mgpt -1 after 2 h of operation) on Pt/NMWCNTs-isolatedMoS2 were 24 and 232 times higher, respectively. As for ORR, Pt/NMWCNTs-isolated-MoS2 holds large half-wave potential (0.88 V) and high stability (92.71 % after 22 h of operation). This work presents a tactic for activating the basal planes and reducing the π-π stacking of 2D materials to satisfy their applications in electrocatalysis. In addition, the proposed sheet-isolation method can be used for fabricating other 2D materials to promote the dispersion of nanoparticles, which assist its application in other fields of energy as well as the environment.

Differential contributions of the C5b-9 and C5a/C5aR pathways to microvascular and macrovascular thrombosis in complement-mediated thrombotic microangiopathy patients.

To clarify the role of the C5a/C5aR (C5a receptor) and C5b-9 pathways in macrovascular thrombosis (MAT) and renal microthrombosis (MIT), 73 renal biopsy-proven complement-mediated thrombotic microangiopathy (C-TMA) patients were enrolled; 9 patients with pure MAT and 13 patients with pure MIT were selected for further study. Twenty-five external C-TMA patients were selected as the validation cohort. Plasma C5a and sC5b-9 (soluble C5b-9) levels were significantly higher in patients with MAT than in those with MIT (P = 0.008, P = 0.041, respectively). The mean optical density of C5aR1 in the kidney was significantly higher in MAT patients than in those with MIT (P < 0.001). Both urinary sC5b-9 levels (MIT: P < 0.001, MAT: P = 0.004) and renal deposition of C5b-9 (MIT: P < 0.001, MAT: P = 0.001) were significantly higher in C-TMA patients compared to normal control, but were similar between MAT and MIT groups. In the correlation analysis within 22C-TMA patients, urinary sC5b-9 levels and renal deposition of C5b-9 were positively correlated to renal MIT formation (P = 0.009 and P = 0.031, respectively). Furthermore, the renal citrullinated histone H3 (CitH3)- and neutrophil elastase (NE)-positive area ratios were both significantly higher in the MAT group than in the MIT group (P = 0.006 and P = 0.020, respectively). Therefore, the local C5b-9 and C5a/C5aR1 pathways might have differential contributions to MIT and MAT formation in the disease.

Adenosine A2A receptor antagonist KW6002 protects against A53T mutant alpha-synuclein-induced brain damage and neuronal apoptosis in Parkinson's disease mice by restoring autophagic flux.

BACKGROUND: Protein misfolding and inclusion body aggregation caused by α-Syn mutations in the brain often cause neurodegeneration and cognitive impairment, among which the A53T point mutation is more common. Inhibition of adenosine A2A receptor (A2AR) can alleviate the pathological symptoms of brain dysfunction caused by A53T-α-Syn protofibrils, but the mechanism of action is still unclear. AIM: This studies aimed to investigate the potential therapeutic role of the A2AR inhibitor KW6002 in a mouse model of brain synucleinopathy. METHODS: A53T-α-Syn fibre precursor cell nuclear protein was injected into the bilateral prefrontal cortex of mice to establish a synucleinopathy animal model, and the A2AR inhibitor KW6002 (5 mg/kg) was injected intraperitoneally to intervene. RESULT: The intracerebral injection of A53T-α-Syn protofibrils triggers the formation of inclusion bodies in the brain, leading to astrocyte activation, an increased number of apoptotic cells, and suppression of autophagic flux. The administration of KW6002 significantly reversed these phenomena. In vitro experiments revealed that A53T-α-Syn protofibrils inhibited HT-22 autophagy in mouse hippocampal neuronal cells, whereas KW6002 increased cellular autophagic flux, upregulated the expression of LAMP2A and Hsc70 proteins and inhibited the expression of SQSTM1 protein. The present study suggests that KW6002 reduces the level of α-Syn phosphorylation by inhibiting A2AR protein, at the same time, enhances the autophagic flux of neuronal cells, resulting in the degradation of A53T-α-Syn protofibrils and thus reducing the neuronal toxicity and apoptosis induced by A53T-α-Syn protofibrils. CONCLUSION: KW6002 has a significant protective effect on neuronal injury induced by A53T-α-Syn.

Progress of Dispersants for Coal Water Slurry.

Dispersants, serving as an essential raw material in the formulation of coal water slurry, offer an economical and convenient solution for enhancing slurry concentration, thus stimulating significant interest in the development of novel and efficient dispersants. This paper intends to illuminate the evolution of dispersants by examining both the traditional and the newly conceived types and elaborating on their respective mechanisms of influence on slurry performance. Dispersants can be classified into anionic, cationic, amphoteric, and non-ionic types based on their dissociation properties. They can be produced by modifying either natural or synthetic products. The molecular structure of a dispersant allows for further categorization into one-dimensional, two-dimensional, or three-dimensional structure dispersants. This document succinctly outlines dispersants derived from natural products, three-dimensional structure dispersants, common anionic dispersants such as lignin and naphthalene, and amphoteric and non-ionic dispersants. Subsequently, the adsorption mechanism of dispersants, governed by either electrostatic attraction or functional group effects, is elucidated. The three mechanisms through which dispersants alter the surface properties of coal, namely the wetting dispersion effect, electrostatic repulsion effect, and steric hindrance effect, are also explained. The paper concludes with an exploration of the challenges and emerging trends in the domain of dispersants.

Early-Stage Application of Agomir-137 Promotes Locomotor Recovery in a Mouse Model of Motor Cortex Injury.

Traumatic brain injury (TBI) is a significant risk factor for neurodegenerative disorders, and patients often experience varying degrees of motor impairment. MiR-137, a broadly conserved and brain-enriched miRNA, is a key regulator in neural development and in various neurological diseases. Following TBI, the expression of miR-137 is dramatically downregulated. However, whether miR-137 is a therapeutic target for TBI still remains unknown. Here, for the first time, we demonstrate that intranasal administration of miR-137 agomir (a mimic) in the early stage (0-7 days) of TBI effectively inhibits glial scar formation and improves neuronal survival, while early-stage administration of miR-137 antagomir (an inhibitor) deteriorates motor impairment. This study elucidates the therapeutic potential of miR-137 mimics in improving locomotor recovery following motor cortex injury.

Associations of Long-Term Exposure to PM2.5 and Its Constituents with Erythrocytosis and Thrombocytosis in Rural Populations.

Evidence on the effect of long-term exposure to fine particulate matter (PM2.5) on erythrocytosis and thrombocytosis prevalence was limited. We aimed to investigate the association of PM2.5 and its constituents with the risks of erythrocytosis and thrombocytosis. The present study included a total of 33,585 participants from the Henan Rural Cohort at baseline between 2015 and 2017. A hybrid satellite-based model was employed to estimate the concentrations of PM2.5 mass and its constituents (including black carbon [BC], nitrate [NO3-], ammonium [NH4+], inorganic sulfate [SO42-], organic matter [OM], and soil particles [SOIL]). The logistic regression model was used to assess the associations of single exposure to PM2.5 and its constituents with the risks of erythrocytosis and thrombocytosis, and the quantile G-computation method was applied to evaluate their joint exposure risk. For the independent association, the odds ratios for erythrocytosis/thrombocytosis with 1 µg/m3 increase was 1.049/1.043 for PM2.5 mass, 1.596/1.610 for BC, 1.410/1.231 for NH4+, 1.205/1.139 for NO3-, 1.221/1.359 for OM, 1.300/1.143 for SO42-, and 1.197/1.313 for SOIL. Joint exposure to PM2.5 and its components was also positively associated with erythrocytosis and thrombocytosis. The estimated weight of NH4+ was found to be the largest for erythrocytosis, while OM had the largest weight for thrombocytosis. PM2.5 mass and its constituents were positively linked to prevalent erythrocytosis and thrombocytosis, both in single-exposure and joint-exposure models. Additionally, NH4+/OM was identified as a potentially responsible component for the association between PM2.5 and erythrocytosis/thrombocytosis.

The associations between sleep timing and night sleep duration with dyslipidemia in a rural population: The Henan Rural Cohort Study.

Evidence linking sleep timing and night sleep duration to dyslipidemia was limited and inconclusive, especially among low- and middle-income adults. The aims were to evaluate the associations between sleep timing, night sleep duration and dyslipidemia in a rural population. Based on the Henan Rural Cohort Study, a total of 37 164 participants were included. The Pittsburgh Sleep Quality Index was used to collect sleep information. Logistic regression and restrictive cubic splines were conducted to explore the associations. Of the 37 164 enrolled participants, 13881 suffered from dyslipidemia. Compared to the reference groups, people who went to sleep after 23:00 or woke up after 7:30 had higher prevalence of dyslipidemia, the adjusted odds ratios (ORs) and 95% confidence intervals (CIs)were 1.30 (1.20-1.41) and 1.34 (1.19-1.50). The adjusted OR (95%CI) of participants in the Late-sleep/Late-rise category compared to the Early-sleep/Early-rise category was 1.55 (1.08-1.23). Compared to the reference (7~≤8 h), the adjusted OR (95%CI) was 1.11 (1.03-1.20) for longer (>9 h) night sleep duration. Moreover, the combined effects of sleep duration (>9 h) with sleep time (22:00~) (OR = 1.46, 95%CI: 1.16-1.84), sleep duration (>9 h) with wake-up time (≥7:30) (OR = 1.28, 95%CI: 1.08-1.51), and sleep duration (>9 h) with the Late-sleep/Late-rise category (OR = 1.41, 95%CI: 1.14-1.75) increased the prevalence of dyslipidemia. Accordingly, our results indicate that delayed sleep timing and longer night sleep duration had independent and joint effects on higher risks of dyslipidemia in rural population.

Association between snoring, daytime sleepiness and cardiovascular disease in Chinese rural adults.

BACKGROUNDS AND AIMS: Evidence on the association between habitual snoring, excessive daytime sleepiness (EDS), and cardiovascular diseases (CVDs) remains uncertain and limited. The study aimed to explore the independent and joint association between habitual snoring, EDS, and CVDs in rural Chinese adults. METHODS AND RESULTS: A total of 28,140 participants from the Henan rural cohort study were included. Sleep status information was obtained by self-reported. Based on their sleep status, the participants were classified into four groups: "no snoring and no EDS (NSNS) (reference group)", "snoring and no EDS (SNS)", "no snoring and EDS (NSS)", "snoring and EDS (SS)." The logistic regression models were used to calculate independent and joint odds ratios (OR) and 95% confidence intervals (CI) between the snoring, EDS status and stroke, CHD, and CVD. Of the 28,140 participants, 740 subjects reported snoring and sleepiness. The ORs and (95% CIs) for CVDs in the adjusted model were 1.31 (1.20-1.43) for participants who snored frequently and 2.44 (1.76-3.39) for frequent sleepiness compared with no snoring and no sleepiness. Individuals with both snoring and sleepiness had higher odds of CVDs compared with no snoring and no sleepiness (OR: 2.18, 95%CI: 1.80-2.62). CONCLUSION: Habitual snoring and excessive daytime sleepiness were independently and jointly associated with CVDs in the Chinese rural population. More studies are needed to explore the mechanisms of the relationship. CLINICAL TRIAL REGISTRATION: The Henan Rural Cohort Study has been registered at the Chinese Clinical Trial Register (Registration number: ChiCTR-OOC-15006699). Date of registration: 2015-52 07-06. http://www.chictr.org.cn/showproj.aspx?proj=11375.

Gender-specific associations between mixture of polycyclic aromatic hydrocarbons and telomere length.

Evidence shows the relationships of individual environmental PAHs by their urinary metabolites with relative telomere length (RTL), which may be affected by biological gender differences. Since plasma parent PAHs are not metabolized, it may reflect human exposure to PAHs more realistically in daily life. Thus, exploring joint associations between plasma parent PAHs and RTL is urgent, which may identify the major contributor to its adverse effect. In this study, 2577 participants were obtained from the Henan Rural Cohort. The level of PAHs in blood samples was detected by gas chromatography coupled with tandem mass spectrometry. RTL in blood samples was detected by quantitative polymerase chain reaction. Generalized linear models or quantile g-computation were performed to evaluate the associations between the individual or a mixture of PAHs and RTL. Results from generalized linear models showed that each unit increment in BghiP value corresponded to a 0.098 (95%CI: 0.067, 0.129) increment in RTL for men; each unit increment in BaP, BghiP and Flu value corresponded to a 0.041 (95%CI: 0.014, 0.068), 0.081 (95%CI: 0.055, 0.107) and 0.016 (95%CI: 0.005, 0.027) increment in RTL for women. Results from quantile-g computation revealed that each one-quantile increment in the mixture of 10 PAHs corresponded to a 0.057 (95%CI: 0.021, 0.094) and 0.047 (95%CI: 0.003, 0.091) increment in RTL values of women and men, but these associations were mainly ascribed to three PAHs for women (BaP, Flu and BghiP) and men (BaP, BghiP and Pyr), respectively. Similar results were found in smoking men and cooking women without smoking. Our study found that exposure to 10 PAHs mixture was positively associated with RTL across gender, mainly attributed to Flu, BaP and BghiP, implicating that gender-specific associations may be ascribed to tobacco and cooking smoke pollution. The findings provided clues for effective measures to control PAHs pollutants-related aging disease.Clinical trial registration The Henan Rural Cohort Study has been registered at the Chinese Clinical Trial Register (Registration number: ChiCTR-OOC-15006699). Date of registration: 06 July 2015. http://www.chictr.org.cn/showproj.aspx?proj=11375 .

Higher HDL-C levels attenuated the association of plasma polybrominated diphenyl ethers with prediabetes and type 2 diabetes mellitus in rural Chinese adults.

BACKGROUND: Plasma polybrominated diphenyl ethers (PBDE) were used as flame retardants widely, however, epidemiological evidence for the association between PBDEs and type 2 diabetes mellitus (T2DM) is inconsistent. Moreover, the combined effects of PBDEs and blood lipid indicators on impaired fasting glucose (IFG) and T2DM remains largely unknown in rural areas lacking good waste recycling infrastructure. METHODS: In this study, a total of 2607 subjects aged 18-79 years were included from the Henan Rural Cohort. Generalized linear and logistic regression models were applied to evaluate the associations of various PBDE pollutants on IFG and T2DM. Quantile g-computation regression and PBDE pollution score created by the adaptive elastic net were applied to evaluate the impact of PBDEs mixtures on IFG and T2DM. Interaction effects of individual PBDE pollutants and blood lipid indicators on IFG and T2DM were assessed by using Interaction plots. RESULTS: The geometric mean concentrations (detection rates) were 0.09 ng/mL (100.0%), 0.12 ng/mL (97.8%), 0.22 ng/mL (94.7%), 0.16 ng/mL (99.2%) and 0.28 ng/mL (100.0%) for PBDE-28, PBDE-47, PBDE-99, and PBDE-153 respectively. However, PBDE-28, PBDE-99, PBDE-100, and ΣPBDEs were positively associated with IFG (odds ratios (ORs) (95% confidence intervals (CIs)): 1.14 (1.06, 1.23), 1.16 (1.04, 1.29), 1.25 (1.14, 1.37), and 1.27 (1.08, 1.50)). Similarly, PBDE-28, PBDE-47, PBDE-99, PBDE-100, and ΣPBDEs were positively associated with T2DM (ORs (95% CIs): 1.30 (1.10, 1.54), 1.13 (1.06, 1.22), 1.27 (1.13, 1.43), 1.27 (1.15, 1.40), and 1.30 (1.10, 1.54)). Moreover, five PBDE mixtures or jointly as PBDE pollution score, were significantly associated with an increased risk of T2DM (P < 0.05 for all). In addition, the harmful effect of PBDE exposure on T2DM was decreased with accompanying high-density lipoprotein cholesterol (HDL-C) levels increased. CONCLUSIONS: Our findings highlight the importance of managing PBDEs contamination and suggest that HDL-C may be a novel way to prevent T2DM.

Transcriptomic and genetic approaches reveal that the pipecolate biosynthesis pathway simultaneously regulates tomato fruit ripening and quality.

Pipecolic acid (Pip) and N-hydroxypipecolic acid (NHP) have been found to accumulate during the ripening of multiple types of fruits; however, the function and mechanism of pipecolate pathway in fruits remain unclear. Here study was conducted on fruits produced by the model plant tomato, wherein the NHP biosynthesis-related genes, Slald1 and Slfmo1, were mutated. The results showed that the fruits of both the Slald1 and the Slfmo1 mutants exhibited a delayed onset of ripening, decreased fruit size, nutrition and flavor. Exogenous treatment with Pip and NHP promoted fruit ripening and improved fruit quality. Transcriptomic analysis combined with weighted gene co-expression network analysis revealed that the genes involved in the biosynthesis of amino acids, carbon metabolism, photosynthesis, starch and sucrose metabolism, flavonoid biosynthesis, and plant hormone signal transduction were affected by SlFMO1 gene mutation. Transcription factor prediction analysis revealed that the NAC and AP2/ERF-ERF family members are notably involved in the regulation pathway. Overall, our results suggest that the pipecolate biosynthesis pathway is involved in the simultaneous regulation of fruit ripening and quality and indicate that a regulatory mechanism at the transcriptional level exists. However, possible roles of endogenously synthesized Pip and NHP in these processes remain to be determined. The biosynthesis pathway genes SlALD1 and SlFMO1 may be potential breeding targets for promoting fruit ripening and improving fruit quality with concomitant yield increases.

Age at Menarche, Menopause Status and Metabolic Syndrome and its Components: Findings from the Henan Rural Cohort Study.

INTRODUCTION: To evaluate the effect of age at menarche on metabolic syndrome (Mets) and its components and explore the impact of menopause status on the association between age at menarche and Mets in rural Chinese women. METHODS: This cross-sectional study enrolled 23382 women from the Henan Rural Cohort study. The relationship between age at menarche and Mets was assessed using logistic regression and restricted cubic spline. Interaction plots were used to describe interactive effects of age at menarche and menopause status on Mets. RESULTS: Age at menarche was inversely associated with the risk of Mets with the adjusted OR of 1.16, 0.98, 1.00, 0.82, and 0.77, respectively, for those with age at menarche≤13, 14, 15-16 (reference), 17, and≥18 years. Each year of delay in menarche age correlated with a 6.2% (P<0.001) lower risk of Mets. Among the components of Mets, an inverse association was observed between age at menarche and central obesity (OR (95% CI): 0.92 (0.90, 0.94)), abnormal FPG (OR (95% CI): 0.96 (0.94, 0.97)), abnormal BP (OR (95% CI): 0.967 (0.95, 0.98)), abnormal TG (OR (95% CI): 0.96 (0.94, 0.97)), and abnormal HDL-C (OR (95% CI): 0.96 (0.95, 0.98)). Significant interactions were discovered between age at menarche, menopause status, and the risk of Mets, central obesity, abnormal FPG, abnormal BP, and abnormal TG (all P interaction<0.001). The adverse effect of menopausal status on Mets, central obesity, abnormal FPG, abnormal BP, and abnormal TG decreased with delayed age at menarche. CONCLUSIONS: Later menarche was associated with a lower risk of Mets. More importantly, the deleterious effect of menopause status on Mets decreased with the increase in age at menarche.

Mediation effect of JAK2 methylation on the association between sitting time and abdominal obesity in rural adults.

BACKGROUND: Sitting time may affect health by altering the methylation of certain genes. This research aimed to estimate the association of sitting time with abdominal obesity and the role of Janus kinase 2 (JAK2) methylation in the association among rural adults. METHODS: A total of 1062 rural adults from the Henan Rural Cohort Study were included. Whole blood was used to extract genomic DNA. JAK2 DNA methylation level was assessed by MethylTargetTM. The logistic regression model was utilized to assess the association of sitting time with abdominal obesity, and the possible effect of JAK2 DNA methylation on the association were conducted by using mediation analyses. RESULTS: Average time of sitting of participants was 7.28 ± 3.37 h/d. For per 1 h increment in sitting time, the odd ratio (OR) and 95% confidence interval (CI) of abdominal obesity was 1.153 (1.095, 1.214) after controlling potential risk factors. Simultaneously, the methylation levels of Chr9: 4985407 site and Chr9: 4985238-4985455 region were negatively correlated with abdominal obesity (OR: 0.549, 95% CI: 0.394, 0.765; OR: 0.189, 95% CI: 0.056, 0.640, respectively). Moreover, Chr9: 4985407 site and Chr9: 4985238-4985455 region methylation levels mediated the association of sitting time with abdominal obesity, and the indirect effects account for 6.78% and 4.24%, respectively. CONCLUSIONS: Longer sitting time was positively correlated with abdominal obesity in the rural population, and methylation level of JAK2 may be an underlying mediation of the effect.