Associations of exposure to disinfection by-products with blood coagulation parameters among women: Results from the Tongji reproductive and environmental (TREE) study.

BACKGROUND: Experimental studies have shown that disinfection byproducts (DBPs) induce coagulotoxicity, but human evidence is scarce. OBJECTIVE: This study aimed to explore the relationships of DBP exposures with blood coagulation parameters. METHODS: Among 858 women from the Tongji Reproductive and Environmental (TREE) study, urinary dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) were detected as internal biomarkers of DBP exposures. We measured activated partial thromboplastin time (APTT), fibrinogen (Fbg), international normalized ratio (INR), prothrombin time (PT), and thrombin time (TT) as blood coagulation parameters. Multivariable linear regression models were utilized to estimate the relationships between urinary DCAA and TCAA and blood coagulation parameters. The effect modifications by demographic and lifestyle characteristics were further explored. RESULTS: Elevated tertiles of urinary DCAA concentrations were associated with increased PT and INR (11.29%, 95% CI: 1.66%, 20.92% and 0.99%, 95% CI: 0.08%, 1.90% for the third vs. first tertile, respectively; both P for trends < 0.05). Stratification analysis showed that the positive associations were only observed among younger (< 30 years), leaner (body mass index < 24.0 kg/m2), and non-passive smoking women. Moreover, elevated tertiles of urinary TCAA concentrations in positive associations with PT and INR were observed among younger women (17.89%, 95% CI: 2.50%, 33.29% and 1.82%, 95% CI: 0.34%, 3.30% for the third vs. first tertile, respectively; both P for trends < 0.05) but not among older women (both P for interactions < 0.05). CONCLUSION: Higher levels of urinary DCAA and TCAA are associated with prolonged clotting time among women.

Advanced BIFs with Co, B, N, and S for Electrocatalytic Oxygen Reduction and Oxygen Evolution Reactions.

In this work, a new alkaline-stable boron imidazolate framework (BIF-90) was rationally designed and successfully synthesized by solvothermal reaction. Due to its potential electrocatalytic active sites (Co, B, N, and S) and chemical stabilities, BIF-90 was explored as a bifunctional electrocatalyst toward electrochemical oxygen reactions, namely, oxygen evolution reaction (OER) and oxygen reduction reaction (ORR). This work will open new avenues toward the design of stable, cheap, and more active BIFs as bifunctional catalysts.

Mercury Isotopes in Deep-Sea Epibenthic Biota Suggest Limited Hg Transfer from Photosynthetic to Chemosynthetic Food Webs.

Deep oceans receive mercury (Hg) from upper oceans, sediment diagenesis, and submarine volcanism; meanwhile, sinking particles shuttle Hg to marine sediments. Recent studies showed that Hg in the trench fauna mostly originated from monomethylmercury (MMHg) of the upper marine photosynthetic food webs. Yet, Hg sources in the deep-sea chemosynthetic food webs are still uncertain. Here, we report Hg concentrations and stable isotopic compositions of indigenous biota living at hydrothermal fields of the Indian Ocean Ridge and a cold seep of the South China Sea along with hydrothermal sulfide deposits. We find that Hg is highly enriched in hydrothermal sulfides, which correlated with varying Hg concentrations in inhabited biota. Both the hydrothermal and cold seep biota have small fractions (<10%) of Hg as MMHg and slightly positive Δ199Hg values. These Δ199Hg values are slightly higher than those in near-field sulfides but are 1 order of magnitude lower than the trench counterparts. We suggest that deep-sea chemosynthetic food webs mainly assimilate Hg from ambient seawater/sediments and hydrothermal fluids formed by percolated seawater through magmatic/mantle rocks. The MMHg transfer from photosynthetic to chemosynthetic food webs is likely limited. The contrasting Hg sources between chemosynthetic and trench food webs highlight Hg isotopes as promising tools to trace the deep-sea Hg biogeochemical cycle.

Removal of nitrate by FeSiBC metallic glasses: high efficiency and superior reusability.

The development of sustainable technologies for efficient nitrate removal has attracted increasing attention, because excessive nitrate emissions can result in serious environmental, economic, and health effects. Herein, we propose to utilize FeSiBC metallic glass (MG) powders as a potential solution for nitrate removal. In terms of removal efficiency and reusability, our results show that the MG powders, as special zero-valent iron carriers, are 2-3 orders of magnitude more efficient in nitrate removal than the previous studies, while maintaining more than 50% nitrate removal efficiency after 9 cycles of reaction. Moreover, the optimal FeSiBC MG dosage, pH value, and temperature for nitrate removal are determined. The mechanism of nitrate removal is also revealed. The present study offers a promising approach to remediate nitrate, one of the world's most widespread water pollutants.

Associations between phthalate metabolites and cytokines in the follicular fluid of women undergoing in vitro fertilization.

Many studies have showed that phthalates have reproductive and embryonic toxicity, while the potential mechanisms are mostly unknown. Inflammation may play a mediating part in phthalate exposure and adverse reproductive endpoints. A cross-sectional survey was conducted to investigate the associations of phthalate metabolites with inflammatory cytokines in the follicular fluid (FF) of women undergoing in vitro fertilization (IVF). We determined the levels of eight phthalate metabolites and five cytokines in the FF of 76 women, including interleukin (IL)- 6, IL-8, IL-10, monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α). The associations of individual phthalate exposure with cytokines in FF samples were explored by multiple linear regression. We further evaluated the combined effects of multiple phthalate exposures on FF levels of cytokines by using Bayesian kernel machine regression (BKMR) models. We found that there was a positive relationship between mono-ethyl phthalate (MEP) and IL-6 in the FF (percent change:12.4%; 95% CI: 1.3%, 24.9%). In contrast, elevated mono-benzyl phthalate (MBzP), mono(2-ethylhexyl) phthalate (MEHP) and %MEHP levels were associated with decreased MCP-1. In the BKMR models, phthalate metabolite mixtures were positively associated with TNF-α when the mixtures were lower than 65th percentile compared with their medians. In the stratified analyses, MEHP was inversely associated with MCP-1 among women with BMI ≥ 23 kg/m2 (test for interaction <0.05). Our results suggest that certain phthalate metabolites or their mixtures may alter levels of inflammatory cytokines in the FF, and further research is necessary to elucidate the mechanisms underlying the relationship between phthalates exposure, ovarian dysfunction and adverse pregnancy outcomes.

Anti-müllerian hormone as a predictor for live birth among women undergoing IVF/ICSI in different age groups: an update of systematic review and meta-analysis.

PURPOSE: To update the evidence of anti-müllerian hormone (AMH) as predictive factors for live birth outcome in women undergoing assisted conception and discover the modulating effect of age. METHODS: PubMed, Embase, Medline, and Web of Science were searched for studies published until June 2021. We included studies that measured serum AMH levels and reported the subsequent live birth outcomes. Random effects models and hierarchical summary receiver operating characteristics (HSROC) models were used. The QUADAS-2 checklist was employed to assess the quality of the included studies. RESULTS: We included 27 studies (27,029 women) investigating the relationship between AMH and live birth outcome after assisted conception. The diagnostic odds ratios (DOR) from random effects models were ruled out due to high heterogeneity. Our findings suggested that AMH was associated with live birth. The DOR was 2.21 (95% CI 1.89-2.59), and 2.49 (95% CI 1.26-4.91) for studies on women with unspecified ovarian reserve and women with low ovarian reserve, respectively. The DOR of those with advanced ages was 2.50 (95% CI 1.87-2.60). For younger women, the DOR was 1.41 (95% CI 0.99-2.02). HSROCs showed that AMH had no predictive ability towards live birth in women with diminished ovarian reserve or younger age. Exclusion of Chinese cohorts lowered the heterogeneity. CONCLUSIONS: This study revealed that AMH had better prediction for live birth in advanced-age women. AMH may have implicative predictive value for assisted conception counseling of couples of advanced ages.

Effects of water-soluble chitosan on Hylotelephium spectabile and soybean growth, as well as Cd uptake and phytoextraction efficiency in a co-planting cultivation system.

Intercropping a Cd-accumulator with economically valuable crops is common in slightly or moderately Cd-polluted farmland soils. A field experiment was conducted to evaluate the effects of water-soluble chitosan (WSC) on the growth and Cd uptake of the Cd-accumulator Hylotelephium spectabile and soybean (Glycine max) during a co-cultivation in Cd-contaminated agricultural soil (WSC, 0 and 10 g·m-2). The results indicated that soybean yields were highest in response to the intercropping and WSC treatment. The results from the field trials generally showed that intercropping and WSC treatments significantly decreased Cd concentrations in inedible parts of soybean by 42.9-72.1% (except for stems), in the meantime, increased 95.8%-334.6% in shoot and root tissues of H. spectabile compared with the control (p < 0.05). The data revealed that Cd uptake was highest for H. spectabile during the intercropping and WSC treatment. The application of WSC in the intercropping system significantly increased the uptake of Cd by H. spectabile, but not by soybean. The findings of this study suggest that combining an intercropping system with a WSC treatment may be better for remediating Cd-contaminated soils than other methods involving the growth of a single hyperaccumulator.

This paper clearly focused on the accumulation and uptake of Cd in the system of intercropping of Cd-accumulator (Hylotelephium spectable) and soybean (Glycine max) grown in Cd-polluted farmland soils supplied with water-soluble chitosan (WSC) under field conditions. Some studies mainly focused on active agent to promote remediation efficiency of (hyper) accumulators. This study indicated that combining the intercropping system with WSC may be better for remediating Cd-contaminated soils than the methods involving a single hyperaccumulator.

Associations of sleep characteristics with outcomes of IVF/ICSI treatment: a prospective cohort study.

STUDY QUESTION: Are sleep characteristics associated with outcomes of IVF/ICSI treatment? SUMMARY ANSWER: Nocturnal sleep <7 h/night and disturbed sleep are related to impaired oocyte and embryo yield, while longer nocturnal sleep might reduce the chance of a successful pregnancy, and the associations between nocturnal sleep duration and IVF/ICSI outcomes are modified by maternal age and subjective sleep quality. WHAT IS KNOWN ALREADY: Disturbed sleep and circadian rhythm contribute to impaired fecundity in the general population, but the effects of sleep characteristics on IVF/ICSI outcomes are largely unknown. STUDY DESIGN, SIZE, DURATION: This study was conducted among 1276 women undergoing IVF/ICSI treatment between December 2018 and September 2019 based on the Tongji Reproductive and Environmental cohort. Owing to the limited number of multiple cycles, we included only the outcomes of their first IVF/ICSI cycle in the current analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data on sleep characteristics were collected via questionnaires on the day of oocyte retrieval. IVF/ICSI outcomes were abstracted from medical records. Quasi-Poisson, quasi-binomial or logistic regression models were used to assess the relations between sleep characteristics and reproductive outcomes after adjusting for relevant confounders. We also performed stratified analyses by subjective sleep quality (good versus poor) and maternal age (≤30 versus >30 years). MAIN RESULTS AND THE ROLE OF CHANCE: Compared with women who slept 7 to <8 h/night, those who slept <7 h/night exhibited decreases in the number of retrieved and mature oocytes of 11.5% (95% CI: -21.3%, -0.48%) and 11.9% (95% CI: -22.4%, -0.03%), respectively. A mid-sleep time (MST) earlier than 2:21 a.m. (<2:21 a.m.) or later than 3:00 a.m. (≥3:00 a.m.) and poor subjective sleep quality were inversely associated with the fertilization rate. Women who had trouble falling asleep more than three times per week had a lower number of mature oocytes (-10.5%, 95% CI: -18.6%, -1.6%), normal fertilized oocytes (-14.8%, 95% CI: -23.7%, -4.8%) and good-quality embryos (-15.1%, 95% CI: -25.4%, -3.5%) than those who had no such trouble. In addition, women who slept 9 to <10 h/night had a lower chance of clinical pregnancy compared to women who slept 7 to <8 h/night (odds ratio = 0.65, 95% CI: 0.44, 0.98). In the stratified analyses, the positive associations of nocturnal sleep duration with the number of good-quality embryos and fertilization rate existed only among the women with poor subjective sleep quality (P for interaction = 0.02 and 0.03, respectively). Additionally, we found that the positive associations of nocturnal sleep duration with implantation or clinical pregnancy only existed among women aged over 30 years (P for interaction = 0.04 and 0.01, respectively). LIMITATIONS, REASONS FOR CAUTION: Sleep characteristics are self-reported, which may lead to misclassification. MST serves as a proxy of chronotype and may be non-differentially misclassified resulting in an underestimate of the association of interest. Measuring sleep characteristics on the day of oocyte retrieval may lead to bias. Chance findings cannot be excluded because of the limited number of women with <7 h or ≥10 h nocturnal sleep and multiple testing. Our results may be biased by other confounders and may not be generalizable to women of other ethnicities. WIDER IMPLICATIONS OF THE FINDINGS: Unhealthy sleep characteristics, including short nocturnal sleep, inappropriate sleep time, poor subjective sleep quality and having trouble falling asleep, may impair oocyte quantity and its potential to mature or be fertilized. Long nocturnal sleep might reduce the chance of clinical pregnancy among infertile females, especially women younger than 30 years old. Prolonged nocturnal sleep duration may be a potential beneficial behavior for improving IVF/ICSI outcomes for women aged over 30 years and women with poor subjective sleep quality, which requires further investigation. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Natural Science Foundation of China (81771654) and the National Key R&D Program of China (No. 2018YFC1004201). There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Genetic spectrum of CAKUT and risk factors for kidney failure: a pediatric multicenter cohort study.

BACKGROUND: Congenital anomalies of the kidney and urinary tracts (CAKUT) are the leading cause of kidney failure in children with phenotypic and genotypic heterogeneity. Our objective was to describe the genetic spectrum and identify the risk factors for kidney failure in children with CAKUT. METHODS: Clinical and genetic data were derived from a multicenter network (Chinese Children Genetic Kidney Disease Database, CCGKDD) and the Chigene database. A total of 925 children with CAKUT who underwent genetic testing from 2014 to 2020 across China were studied. Data for a total of 584 children wereobtained from the CCGKDD, including longitudinal data regarding kidney function. The risk factors for kidney failure were determined by the Kaplan-Meier method and Cox proportional hazards models. RESULTS: A genetic diagnosis was established in 96 out of 925 (10.3%) children, including 72 (8%) with monogenic variants, 20 (2%) with copy number variants (CNVs), and 4 (0.4%)with major chromosomal anomalies. Patients with skeletal abnormalities were more likely to have large CNVs or abnormal karyotypes than monogenic variants. Eighty-two patients from the CCGKDD progressed to kidney failure at a median age of 13.0 (95% confidence interval, 12.4-13.6) years, and twenty-four were genetically diagnosed with variants of PAX2, TNXB, EYA1, HNF1B and GATA3 or the 48, XXYY karyotype. The multivariate analysis indicated that solitary kidney, posterior urethral valves, bilateral hypodysplasia, the presence of certain variants and premature birth were independent prognostic factors. CONCLUSIONS: The genetic spectrum of CAKUT varies among different subphenotypes. The identified factors indicate areas that require special attention.

Active Sites In Situ Implanted Hybrid Zeolitic Imidazolate Frameworks for a Water Oxidation Catalyst.

Metal-organic frameworks (MOFs) have been a focus of research because of their unique porous structure, but they are usually not directly for electrocatalysis. Herein, we prepared a special class of Fe/Zn/Mo-based trimetallic hybrid zeolitic imidazolate frameworks by in situ solvothermal synthesis that have the potential to act directly as highly efficient oxygen evolution reaction electrocatalysts. This work provides a foundation for the preparation of multimetal MOFs and expands the investigation of electrocatalysts.

Mitochondria homeostasis: Biology and involvement in hepatic steatosis to NASH.

Mitochondrial biology and behavior are central to the physiology of liver. Multiple mitochondrial quality control mechanisms remodel mitochondrial homeostasis under physiological and pathological conditions. Mitochondrial dysfunction and damage induced by overnutrition lead to oxidative stress, inflammation, liver cell death, and collagen production, which advance hepatic steatosis to nonalcoholic steatohepatitis (NASH). Accumulating evidence suggests that specific interventions that target mitochondrial homeostasis, including energy metabolism, antioxidant effects, and mitochondrial quality control, have emerged as promising strategies for NASH treatment. However, clinical translation of these findings is challenging due to the complex and unclear mechanisms of mitochondrial homeostasis in the pathophysiology of NASH.

Exposure to disinfection by-products and reproductive hormones among women: Results from the Tongji Reproductive and Environmental (TREE) study.

BACKGROUND: Disinfection by-products (DBPs) have been shown to impair female reproductive function. However, epidemiological evidence on reproductive hormones is scarce. OBJECTIVE: To investigate the associations between DBP exposures and reproductive hormones among women undergoing assisted reproductive technology. METHODS: We included 725 women from the Tongji Reproductive and Environmental (TREE) Study, an ongoing cohort conducted in Wuhan, China during December 2018 and January 2020. Urine samples collected at recruitment were quantified for dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) as biomarkers of DBP exposures. At day 2-5 of menstruation, serum reproductive hormones including luteinizing hormone (LH), estradiol (E2), total testosterone (T), progesterone (PRGE), and prolactin (PRL) were determined. Multivariate linear regression models were performed to assess the associations of urinary DCAA and TCAA concentrations with reproductive hormone levels. Dose-response relationships were investigated using natural cubic spline (NCS) and restricted cubic spline (RCS) models. RESULTS: After adjusting for relevant confounders, we observed that higher urinary DCAA levels were associated with increased serum PRGE (9.2%; 95% CI: -0.55%, 19.8% for the highest vs. lowest tertile; P for trend = 0.06). Based on NCS models, we observed U-shaped associations of urinary DCAA with serum PRGE and PRL; each ln-unit increment in urinary DCAA concentrations above 3.61 µg/L and 6.30 µg/L was associated with 18.9% (95% CI: 4.8%, 34.7%) and 23.3% (95% CI: -0.92%, 53.5%) increase in serum PRGE and PRL, respectively. The U-shaped associations were further confirmed in RCS models (P for overall association ≤0.01 and P for non-linear associations ≤0.04). We did not observe evidence of associations between urinary TCAA and reproductive hormones. CONCLUSION: Urinary DCAA but not TCAA was associated with altered serum PRGE and PRL levels among women undergoing assisted reproductive technology.

Pharmacokinetic evaluation and relative bioavailability pilot study of fidaxomicin in healthy Chinese subjects: An open, randomized, single-dose, cross-over study.

OBJECTIVE: To compare the pharmacokinetic (PK) characteristics, investigate relative bioavailability, and provide data for potential additional bioequivalence trials between generic fidaxomicin (test (T) formulation) and the original brand (reference (R) formulation) in healthy Chinese subjects. MATERIALS AND METHODS: An open, randomized, single-dose, cross-over study was conducted in 18 healthy Chinese subjects. The subjects randomly received T or R formulations and the alternative formulations were received after a 14-day wash-out period. Blood and fecal samples were collected and tested by liquid chromatography-tandem mass spectrometry (LC-MS/MS). PK parameters were calculated using a non-compartmental model. Relative bioavailability considering commonly established bioequivalence criteria was assessed. RESULTS: Cmax were 3.58 ± 2.74 ng/mL and 6.01 ± 3.93 ng/mL, and AUC0-∞ were 35.71 ± 18.68 h×ng/mL and 52.15 ± 31.31 h×ng/mL for the T and R formulations, respectively. The tmax of both formulations was 5.00 hours. The cumulative fecal excretion rate (Fe0-96h/F) of fidaxomicin and its main active metabolite OP-1118 were similar for both formulations. The geometric mean ratios and 90% confidence intervals (CI) of AUC0-t, AUC0-∞, and Cmax were not completely within the range of 80.00 - 125.00%. Significant within-subject and inter-subject coefficients of variation (> 30%) were found. CONCLUSION: Despite the differences in exposure, PK characteristics and fecal recovery of the two formulations were similar, suggesting that an effective concentration of the generic fidaxomicin could be achieved locally in the gastrointestinal tract. Fidaxomicin was a highly viable drug, thus providing reference for future clinical study design.

Nano-WSe2 Is Absorbable and Transformable by Rice Plants.

As typical transition metal dichalcogenides (TMDC), tungsten selenide (WSe2) nanosheets (nano-WSe2) are widely used in various fields due to their layered structures and highly tunable electronic and magnetic properties, which results in the unwanted release of tungsten (W) and selenium (Se) into the environment. However, the environmental effects of nano-WSe2 in plants are still unclear. Herein, we evaluated the impacts and fate of nano-WSe2 and micro-WSe2 in rice plants (Oryza sativa L.). It was found that both nano-WSe2 and micro-WSe2 did not affect the germination of rice seeds up to 5000 mg/L but nano-WSe2 affected the growth of rice seedlings with shortened root lengths. The uptake and transportation of WSe2 was found to be size-dependent. Moreover, W in WSe2 was oxidized to tungstate while Se was transformed to selenocysteine, selenomethionine, SeIV and SeVI in the roots of rice when exposed to nano-WSe2, suggesting the transformation of nano-WSe2 in rice plants. The exposure to nano-WSe2 brought lipid peroxidative damage to rice seedlings. However, Se in nano-WSe2 did not contribute to the synthesis of glutathione peroxidase (GSH-Px) since the latter did not change when exposed to nano-WSe2. This is the first report on the impacts and fate of nano-WSe2 in rice plants, which has raised environmental safety concerns about the wide application of TMDCs, such as WSe2 nanosheets.

[Correlation of neck circumference with body mass index in preschool children]. / å­¦é¾„å‰å„¿ç«¥é¢ˆå›´ä¸Žä½“é‡æŒ‡æ•°çš„ç›¸å ³æ€§.

OBJECTIVES: To study the correlation between neck circumference and body mass index and the value of neck circumference in identifying overweight and obesity in preschool children. METHODS: The stratified cluster sampling method was used to recruit 3 719 children under 7 years from 10 kindergartens in Urumqi, China. General data were collected, and physical measurements were performed. A Pearson correlation analysis was used to evaluate the correlation between neck circumference and body mass index. The receiver operating characteristic (ROC) curve was used to assess the accuracy of neck circumference in identifying overweight/obesity. The Kappa consistency test was used to assess the consistency of neck circumference and body mass index in identifying overweight/obesity. RESULTS: There was a positive correlation between neck circumference and body mass index in boys and girls of all ages (r≥0.50, P<0.001). According to body mass index as the criteria for overweight/obesity, the children were divided into an overweight/obesity group and a non-overweight/obesity group, and the analysis showed that the overweight/obesity group had a significantly larger neck circumference than the non-overweight/obesity group (P<0.001). The ROC curve analysis showed that neck circumference had an area under the ROC curve of >0.7 in identifying overweight/obesity for boys and girls. The Kappa consistency test showed that the neck circumference and body mass index had a Kappa value of >0.40 in identifying overweight/obesity in boys and girls of all ages. CONCLUSIONS: Neck circumference is positively correlated to body mass index, and neck circumference can be used to identify overweight/obesity in preschool children.

Well-Aligned Ni-Heteroatom (N, S) MOF Arrays Enhanced Electrocatalytic Oxygen Evolution Reaction.

A two-dimensional Ni-heteroatom-based metal-organic framework (MOF) array was directly grown on C paper (Ni-MOF-A/CP) via one-pot solvothermal reaction. According to the strategy for MOF self-assembly on C paper, Ni-MOFs were also synthesized on Ni foam (Ni-MOF/NF) with different sizes and morphologies. The newly resulting MOFs with ternary (Ni, S, and N) active sites exhibited enhanced activity toward oxygen evolution reaction [e.g., Ni-MOF-A/CP: E(5 mA cm-2) = 333 mV and a low Tafel slope of 80 mV dec-1].

Co-Heteroatom-Based MOFs for Bifunctional Electrocatalysts for Oxygen and Hydrogen Evolution Reactions.

Herein, a Co(II) heteroatom metal-organic framework was successfully post-modified via unsaturated coordinated S precisely capturing Ni2+ on the surface of the porous structure. The newly pristine bimetallic MOFs have increasing active edge sites (Ni(II) and S), boosting electrocatalytic activity toward oxygen evolution reaction and hydrogen evolution reaction.

MALDI-TOF-MS and XAS analysis of complexes formed by metallothionein with mercury and/or selenium.

Mercury (Hg) is highly toxic while selenium (Se) has been found to antagonize Hg. Both Hg and Se have been found to induce metallothioneins (MTs). In this study, the complexes formed by metallothionein-1 (MT-1) with HgCl2 and/or Na2SeO3 was studied using matrix-assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS) and X-ray absorption spectrometry (XAS). MALDI-TOF-MS and XAS indicated the formation of Hg-S bond or Se-S bond when MT-1 reacted with HgCl2 or Na2SeO3, respectively. The bond lengths of Hg-S and coordination number in MT-Hg are 2.41 ± 0.02 Å and 3.10 and in MT-Se are 2.50 ± 0.03 Å and 2.69. A MT-Se-Hg complex was formed when MT-1 reacted with both HgCl2 and Na2SeO3, in which the neighboring atom of Hg is Se, while the neighboring atoms of Se are S and Hg. Our study is an important step towards a better understanding of the interaction of HgCl2 and/or Na2SeO3 with proteins like MT-1.

Sarsasapogenin improves adipose tissue inflammation and ameliorates insulin resistance in high-fat diet-fed C57BL/6J mice.

Insulin resistance is a major cause of type 2 diabetes and metabolic syndrome. Macrophage infiltration into obese adipose tissue promotes inflammatory responses that contribute to the pathogenesis of insulin resistance. Suppression of adipose tissue inflammatory responses is postulated to increase insulin sensitivity in obese patients and animals. Sarsasapogenin (ZGY) is one of the metabolites of timosaponin AIII in the gut, which has been shown to exert anti-inflammatory action. In this study, we investigated the effects of ZGY treatment on obesity-induced insulin resistance in mice. We showed that pretreatment with ZGY (80 mg·kg-1·d-1, ig, for 18 days) significantly inhibited acute adipose tissue inflammatory responses in LPS-treated mice. In high-fat diet (HFD)-fed obese mice, oral administration of ZGY (80 mg·kg-1·d-1, for 6 weeks) ameliorated insulin resistance and alleviated inflammation in adipose tissues by reducing the infiltration of macrophages. Furthermore, we demonstrated that ZGY not only directly inhibited inflammatory responses in macrophages and adipocytes, but also interrupts the crosstalk between macrophages and adipocytes in vitro, improving adipocyte insulin resistance. The insulin-sensitizing and anti-inflammatory effects of ZGY may result from inactivation of the IKK /NF-κB and JNK inflammatory signaling pathways in adipocytes. Collectively, our findings suggest that ZGY ameliorates insulin resistance and alleviates the adipose inflammatory state in HFD mice, suggesting that ZGY may be a potential agent for the treatment of insulin resistance and obesity-related metabolic diseases.

Circ-sirt1 inhibits growth and invasion of gastric cancer by sponging miR-132-3p/miR-212-3p and upregulating sirt1 expression.

circRNAs have been considered as a rising factor in cancers. However, the roles and mechanisms of circ-sirt1 in gastric cancer (GC) remain largely unknown. In this study, we found that the expressions of sirt1 and circ-sirt1 are decreased in tissues or serums of GC patients by real-time quantitative PCR (RT-qPCR). The expressions of miR-132-3p/miR-212-3p showed an opposite tendency in these samples. The co-transfection of miR-132-3p/miR-212-3p mimics counteracted the enhancement of sirt1 expression induced by circ-sirt1. The results of cell colony-formation assay and transwell assays demonstrated that the proliferation, migration, and invasion activities of BGC-823 cells were inhibited by circ-sirt1 overexpression or miR-132-3p/miR-212-3p knockdown, respectively. The xenograft tumor model result indicated that the circ-sirt1 overexpression suppressed the tumor growth of BGC-823 cells. The regulation of miR-132-3p/miR-212-3p between circ-sirt1 and sirt1 was verified in the mice tumor tissues. Thus, circ-sirt1 inhibited tumor growth and invasion probably by sponging miR-132-3p/miR-212-3p and upregulating sirt1 expression in GC. These findings may provide a theoretical basis for the classification of GC and a novel therapeutic target for GC patients.