The Role of JAK/STAT Signaling Pathway and Its Downstream Influencing Factors in the Treatment of Atherosclerosis.

Atherosclerosis is now widely considered to be a chronic inflammatory disease, with increasing evidence suggesting that lipid alone is not the main factor contributing to its development. Rather, atherosclerotic plaques contain a significant amount of inflammatory cells, characterized by the accumulation of monocytes and lymphocytes on the vessel wall. This suggests that inflammation may play a crucial role in the occurrence and progression of atherosclerosis. As research deepens, other pathological factors have also been found to influence the development of the disease. The Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway is a recently discovered target of inflammation that has gained attention in recent years. Numerous studies have provided evidence for the causal role of this pathway in atherosclerosis, and its downstream signaling factors play a significant role in this process. This brief review aims to explore the crucial role of the JAK/STAT pathway and its representative downstream signaling factors in the development of atherosclerosis. It provides a new theoretical basis for clinically affecting the development of atherosclerosis by interfering with the JAK/STAT signaling pathway.

Longitudinal Associations Between Physical Activity and Depressive Symptoms in Chinese Children: Evidence from the Tongji Mental Health Cohort Study.

BACKGROUND: We aimed to examine the associations between depressive symptoms and physical activity parameters (e.g., intensity, frequency, and duration) among Chinese school-aged children. METHOD: Participants in this study were extracted from the Tongji Mental Health Cohort Study. The baseline survey was conducted in June 2020 involving 2588 school-aged children from two primary schools in Hubei Province, China. A total of 2435 children were followed up successfully in December 2020. The Children's Depression Inventory Short Form (CDI-S) was applied to evaluate depressive symptoms among school-aged children. The Physical Activity Rating Scale-3 (PARS-3) was adopted to estimate children's physical activity parameters including the intensity, frequency, and duration. Generalized estimation equation models were used to explore the longitudinal associations between physical activity and depressive symptoms among school-aged children. RESULTS: Engaging in moderate levels of physical activity (OR, 0.800; 95%CI, 0.692-0.924) or high levels of physical activity (OR, 0.808; 95%CI, 0.689-0.947) in the baseline survey was associated with a reduced risk of developing depressive symptoms in the follow-up survey compared with children engaging in low levels of physical activity. Stratified analyses revealed that the associations between physical activity and depressive symptoms exhibited a significant correlation among boys and children in the older age group (11-12 years). Our findings showed that engaging in physical activity more than once a week, with each session lasting 20 min or longer, was related to significant reductions in depressive symptoms by 43.8% and 22.3%, respectively. CONCLUSION: Self-reported physical activity is positively associated with improved mental health among Chinese school-aged children, especially when considering parameters such as frequency and duration. The association between vigorous-intensity physical activity and depressive symptoms in children should be cautiously interpreted. Future research should continue to explore the effects of vigorous-intensity physical activity on depressive symptoms in children.

Association between urinary BTEX metabolites and dyslexic odds among school-aged children.

Benzene, toluene, ethylbenzene, and xylene (BTEX) are ubiquitous in the environment, and all of them can cause neurotoxicity. However, the association between BTEX exposure and dyslexia, a disorder with language network-related regions in left hemisphere affected, remains unclear. We aimed to assess the relationship between BTEX exposure and dyslexic odds among school-aged children. A case-control study, including 355 dyslexics and 390 controls from three cities in China, was conducted. Six BTEX metabolites were measured in their urine samples. Logistic regression model was used to explore the association between the BTEX metabolites and the dyslexic odds. Urinary trans,trans-muconic acid (MU: a metabolite of benzene) was significantly associated with an increased dyslexic odds [odds ratio (OR) = 1.23, 95% confidence interval (CI): 1.01, 1.50], and the adjusted OR of the dyslexic odds in the third tertile was 1.72 (95% CI: 1.06, 2.77) compared to that in the lowest tertile regarding urinary MU concentration. Furthermore, the association between urinary MU level and the dyslexic odds was more pronounced among children from low-income families based on stratified analyses. Urinary metabolite levels of toluene, ethylbenzene, and xylene were not found to be associated with the dyslexic odds. In summary, elevated MU concentrations may be associated with an increased dyslexic odds. We should take measures to reduce MU related exposure among children, particularly those with low family income.

Association of exposure to phthalates and phthalate alternatives with dyslexia in Chinese primary school children.

Previous studies have shown associations between children's exposure to phthalates and neurodevelopmental disorders. Whereas the impact of exposure to phthalate alternatives is understudied. This study aimed to evaluate the association of exposure to phthalates/their alternatives with the risk of dyslexia. We recruited 745 children (355 dyslexia and 390 non-dyslexia) via the Tongji Reading Environment and Dyslexia Research Project, and their urine samples were collected. A total of 26 metabolites of phthalates/their alternatives were measured. Multivariate logistic regression and quantile-based g-computation were used to estimate the associations of exposure to the phthalates/their alternatives with dyslexia. More than 80% of the children had 17 related metabolites detected in their urine samples. After adjustment, the association between mono-2-(propyl-6-hydroxy-heptyl) phthalate (OH-MPHP) with the risk of dyslexia was observed. Compared with the lowest quartile of OH-MPHP levels, the odds of dyslexia for the third quartile was 1.93 (95% CI 1.06, 3.57). Regarding mixture analyses, it was found that OH-MPHP contributed the most to the association. Further analyses stratified by sex revealed that this association was only observed in boys. Our results suggested a significantly adverse association of di-2-propylheptyl phthalate exposure with children's language abilities. It highlights the necessity to prioritize the protection of children's neurodevelopment by minimizing their exposure to endocrine-disrupting chemicals like di-2-propylheptyl phthalate.

Dyslexia is associated with urinary polycyclic aromatic hydrocarbon metabolite concentrations of children from China: Data from the READ program.

It has been found that exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with the risk of certain childhood neurodevelopmental disorders. However, no research has investigated the relationship between exposure to PAHs and children's dyslexia odds. The objective of this research was to investigate whether urinary mono-hydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) are associated with increased dyslexia odds in Chinese children. We recruited 1,089 children (542 dyslexic children and 547 non-dyslexic children) for this case-control study. Ten OH-PAHs were measured in the participants' urine samples, which were collected between November 2017 and March 2023. Odds ratios (ORs) of the associations between the OH-PAHs and dyslexia were calculated using logistic regression models, after adjustment for the potential confounding factors. A significant association was found between urinary concentrations of 2-hydroxynaphthalene (2-OHNap) and the elevated odds of dyslexia. The children in the highest quartile of 2-OHNap had a higher OR of dyslexia (1.87, 95% CI: 1.07-3.27) than those in the lowest quartile (P-trend = 0.02) after adjustment for the covariates. After excluding children with maternal disorders during pregnancy, logistic regression analyses showed similar results. Our results suggested a possible association between PAH exposure and the elevated odds of dyslexia.

Image-Guided Photothermal and Immune Therapy of Tumors via Melanin-Producing Genetically Engineered Bacteria.

Photothermal therapy (PTT) is a new treatment modality for tumors. However, the efficient delivery of photothermal agents into tumors remains difficult, especially in hypoxic tumor regions. In this study, an approach to deliver melanin, a natural photothermal agent, into tumors using genetically engineered bacteria for image-guided photothermal and immune therapy is developed. An Escherichia coli MG1655 is transformed with a recombinant plasmid harboring a tyrosinase gene to produce melanin nanoparticles. Melanin-producing genetically engineered bacteria (MG1655-M) are systemically administered to 4T1 tumor-bearing mice. The tumor-targeting properties of MG1655-M in the hypoxic environment integrate the properties of hypoxia targeting, photoacoustic imaging, and photothermal therapeutic agents in an "all-in-one" manner. This eliminates the need for post-modification to achieve image-guided hypoxia-targeted cancer photothermal therapy. Tumor growth is significantly suppressed by irradiating the tumor with an 808 nm laser. Furthermore, strong antitumor immunity is triggered by PTT, thereby producing long-term immune memory effects that effectively inhibit tumor metastasis and recurrence. This work proposes a new photothermal and immune therapy guided by an "all-in-one" melanin-producing genetically engineered bacteria, which can offer broad potential applications in cancer treatment.

A Self-Accelerating Naphthalimide-Based Probe Coupled with Upconversion Nanoparticles for Ultra-Accurate Tri-Mode Visualization of Hydrogen Peroxide.

The design and development of ultra-accurate probe is of great significance to chemical sensing in complex practical scenarios. Here, a self-accelerating naphthalimide-based probe with fast response and high sensitivity toward hydrogen peroxide (H2O2) is designed. By coupling with the specially selected upconversion nanoparticles (UCNPs), an ultra-accurate colorimetric-fluorescent-upconversion luminescence (UCL) tri-mode platform is constructed. Owing to the promoted reaction process, this platform demonstrates rapid response (< 1 s), an ultra-low detection limit (4.34 nM), and superb anti-interferent ability even in presence of > 21 types of oxidants, explosives, metallic salts, daily compounds, colorful or fluorescent substances. In addition, the effectiveness of this design is further verified by a sponge-based sensing chip loaded with the UCNPs/probe in recognizing trace H2O2 vapor from interferents with the three characteristic colors existing simultaneously. The proposed design of probe and tri-mode visualization detection platform is expected to open up a brand-new methodology for ultra-accurate sensing.

Exposure to organophosphate, pyrethroid, and neonicotinoid insecticides and dyslexia: Association with oxidative stress.

Organophosphates (OPPs), pyrethroids (PYRs), and neonicotinoids (NNIs) are three major classes of insecticides used worldwide. They might compromise child neurodevelopment. However, few studies have explored the association between exposure to them and dyslexia. The present study aimed to investigate the association between dyslexia and exposure to the three classes of insecticides, as well as explore the potential role of oxidative stress in the association. A total of 355 dyslexic children and 390 controls were included in this study. The exposure biomarkers were determined by liquid chromatography-tandem mass spectrometry. Specifically, the exposure biomarkers included three typical metabolites of OPPs, three of PYRs, and nine of NNIs. Additionally, three typical oxidative stress biomarkers, namely, 8-hydroxy-2'-deoxyguanosine (8-OHdG) for DNA damage, 8-hydroxyguanosine (8-OHG) for RNA damage, and 4-hydroxy-2-nonenal-mercapturic acid (HNEMA) for lipid peroxidation were measured. The detection frequencies of the urinary biomarkers ranged from 83.9% to 100%. Among the target metabolites of the insecticides, a significant association was observed between urinary 3,5,6-trichloro-2-pyridinol (TCPy, the metabolite of chlorpyrifos, an OPP insecticide) and dyslexia. After adjusting for potential confounding variables, children in the highest quartile of TCPy levels had an increased odds of dyslexia (odds ratio [OR], 1.68; 95% confidence interval [CI]: 1.03, 2.75] in comparison to those in the lowest quartile. Among the three oxidative stress biomarkers, urinary HNEMA concentration showed a significant relationship with dyslexia. Children in the highest quartile of HNEMA levels demonstrated an increased dyslexic odds in comparison to those in the lowest quartile after multiple adjustments (OR, 1.64; 95% CI: 1.01, 2.65). Mediation analysis indicated a significant effect of HNEMA in the association between urinary TCPy and dyslexia, with an estimate of 17.2% (P < 0.01). In conclusion, this study suggested the association between urinary TCPy and dyslexia. The association could be attributed to lipid peroxidation partially.

Pathophysiology and Genetic Associations of Varicose Veins: A Narrative Review.

Varicose veins (VVs) have a high prevalence worldwide and have become a major medical burden. Their pathophysiology involves a complex interplay of inflammation and tissue remodeling, and current treatment is limited by its impact on the pathophysiological mechanisms. In addition, despite clear environmental factors, family history is an important risk factor, suggesting a genetic component to the risk of developing VVs. Our understanding of the pathogenesis of these diseases has benefited greatly from the expansion of population genetic studies, from pioneering family studies to large genome-wide association studies; we now find multiple risk loci for each venous disease. This review considers the pathophysiology of VVs, highlighting the current state of genetic knowledge. We also propose future directions for research.

Hydrogen-bonded organic frameworks in solution enables continuous and high-crystalline membranes.

Hydrogen-Bonded organic frameworks (HOFs) are a type of emerging porous materials. At present, little research has been conducted on their solution state. This work demonstrates that HOFs fragment into small particles while maintaining their original assemblies upon dispersing in solvents, as confirmed by Cryo-electron microscopy coupled with 3D electron diffraction technology. 1D and 2D-Nuclear Magnetic Resonance (NMR) and zeta potential analyses indicate the HOF-based colloid solution and the isolated molecular solution have significant differences in intermolecular interactions and aggregation behavior. Such unique solution processibility allows for fabricating diverse continuous HOF membranes with high crystallinity and porosity through solution-casting approach on various substrates. Among them, HOF-BTB@AAO membranes show high C3H6 permeance (1.979 × 10-7 mol·s-1·m-2·Pa-1) and excellent separation performance toward C3H6 and C3H8 (SF = 14). This continuous membrane presents a green, low-cost, and efficient separation technology with potential applications in petroleum cracking and purification.

Biological Role and Related Natural Products of SIRT1 in Nonalcoholic Fatty Liver.

Non-alcoholic fatty liver disease(NAFLD) is an umbrella term for a range of diseases ranging from hepatic fat accumulation and steatosis to non-alcoholic steatohepatitis (NASH) in the absence of excessive alcohol consumption and other definite liver damage factors. The incidence of NAFLD has increased significantly in recent years and will continue to grow in the coming decades. NAFLD has become a huge health problem and economic burden. SIRT1 is a member of Sirtuins, a group of highly conserved histone deacetylases regulated by NAD+, and plays a vital role in regulating cholesterol and lipid metabolism, improving oxidative stress, inflammation, and insulin resistance through deacetylating some downstream transcription factors and thus improving NAFLD. Although there are no currently approved drugs for treating NAFLD and some unresolved limitations in developing SIRT1 activators, SIRT1 holds promise as a proper therapeutic target for NAFLD and other metabolic diseases. In recent years, natural products have played an increasingly important role in drug development due to their safety and efficacy. It has been discovered that some natural products may be able to prevent and treat NAFLD by targeting SIRT1 and its related pathways. This paper reviews the mechanism of SIRT1 in the improvement of NALFD and the natural products that regulate NAFLD through SIRT1 and its associated pathways, and discusses the potential of SIRT1 as a therapeutic target for treating NAFLD and the effectiveness of these related natural products as clinical drugs or dietary supplements. These works may provide some new ideas and directions for finding new therapeutic targets for NAFLD and the development of anti-NAFLD drugs with good pharmacodynamic properties.

[Diosgenin alleviates NAFLD induced by a high-fat diet in rats via mTOR/SREBP-1c/HSP60/MCAD/SCAD signaling pathway].

This study aims to observe the effects of diosgenin on the expression of mammalian target of rapamycin(mTOR), sterol regulatory element-binding protein-1c(SREBP-1c), heat shock protein 60(HSP60), medium-chain acyl-CoA dehydrogenase(MCAD), and short-chain acyl-CoA dehydrogenase(SCAD) in the liver tissue of the rat model of non-alcoholic fatty liver disease(NAFLD) and explore the mechanism of diosgenin in alleviating NAFLD. Forty male SD rats were randomized into five groups: a control group, a model group, low-(150 mg·kg~(-1)·d~(-1)) and high-dose(300 mg·kg~(-1)·d~(-1)) diosgenin groups, and a simvastatin(4 mg·kg~(-1)·d~(-1)) group. The rats in the control group were fed with a normal diet, while those in the other four groups were fed with a high-fat diet. After feeding for 8 weeks, the body weight of rats in the high-fat diet groups increased significantly. After that, the rats were administrated with the corresponding dose of diosgenin or simvastatin by gavage every day for 8 weeks. The levels of triglyceride(TG), total cholesterol(TC), alanine transaminase(ALT), and aspartate transaminase(AST) in the serum were determined by the biochemical method. The levels of TG and TC in the liver were measured by the enzyme method. Oil-red O staining was employed to detect the lipid accumulation, and hematoxylin-eosin(HE) staining to detect the pathological changes in the liver tissue. The mRNA and protein levels of mTOR, SREBP-1c, HSP60, MCAD, and SCAD in the liver tissue of rats were determined by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR) and Western blot, respectively. Compared with the control group, the model group showed increased body weight, food uptake, liver index, TG, TC, ALT, and AST levels in the serum, TG and TC levels in the liver, lipid deposition in the liver, obvious hepatic steatosis, up-regulated mRNA and protein expression levels of mTOR and SREBP-1c, and down-regulated mRNA and protein expression levels of HSP60, MCAD, and SCAD. Compared with the model group, the rats in each treatment group showed obviously decreased body weight, food uptake, liver index, TG, TC, ALT, and AST levels in the serum, TG and TC levels in the liver, lessened lipid deposition in the liver, ameliorated hepatic steatosis, down-regulated mRNA and protein le-vels of mTOR and SREBP-1c, and up-regulated mRNA and protein levels of HSP60, MCAD, and SCAD. The high-dose diosgenin outperformed the low-dose diosgenin and simvastatin. Diosgenin may prevent and treat NAFLD by inhibiting the expression of mTOR and SREBP-1c and promoting the expression of HSP60, MCAD, and SCAD to reduce lipid synthesis, improving mitochondrial function, and promoting fatty acid ß oxidation in the liver.

Corrigendum: Association between GSDMB gene polymorphism and cervical cancer in the Northeast Chinese Han population.

[This corrects the article DOI: 10.3389/fgene.2022.860727.].

Exploration of the B3 transcription factor superfamily in Aquilaria sinensis reveal their involvement in seed recalcitrance and agarwood formation.

The endangered tree species of the Aquilaria genus produce agarwood, a high value material produced only after wounding; however, conservation of Aquilaria seeds is difficult. The B3 transcription factor family has diverse important functions in plant development, especially in seed development, although their functions in other areas, such as stress responses, remain to be revealed. Here germination tests proved that the seeds of A. sinensis were recalcitrant seeds. To provide insights into the B3 superfamily, the members were identified and characterized by bioinformatic approaches and classified by phylogenetic analysis and domain structure. In total, 71 members were identified and classified into four subfamilies. Each subfamily not only had similar domains, but also had conserved motifs in their B3 domains. For the seed-related LAV subfamily, the B3 domain of AsLAV3 was identical to that of AsVALs but lacked a typical zf-CW domain such as VALs. AsLAV5 lacks a typical PHD-L domain present in Arabidopsis VALs. qRT-PCR expression analysis showed that the LEC2 ortholog AsLAV4 was not expressed in seeds. RAVs and REMs induced after wound treatment were also identified. These findings provide insights into the functions of B3 genes and seed recalcitrance of A. sinensis and indicate the role of B3 genes in wound response and agarwood formation.This is the first work to investigate the B3 family in A. sinensis and to provide insights of the molecular mechanism of seed recalcitrance.This will be a valuable guidance for studies of B3 genes in stress responses, secondary metabolite biosynthesis, and seed development.

Ultrasound Molecular Imaging of Bladder Cancer via Extradomain B Fibronectin-Targeted Biosynthetic GVs.

Purpose: Ultrasound molecular imaging (UMI) has proven promising to diagnose the onset and progression of diseases such as angiogenesis, inflammation, and thrombosis. However, microbubble-based acoustic probes are confined to intravascular targets due to their relatively large particle size, greatly reducing the application value of UMI, especially for extravascular targets. Extradomain B fibronectin (ED-B FN) is an important glycoprotein associated with tumor genesis and development and highly expressed in many types of tumors. Here, we developed a gas vesicles (GVs)-based nanoscale acoustic probe (ZD2-GVs) through conjugating ZD2 peptides which can specially target to ED-B FN to the biosynthetic GVs. Materials and Methods: ED-B FN expression was evaluated in normal liver and tumor tissues with immunofluorescence and Western blot. ZD2-GVs were prepared by conjugating ZD2 to the surface of GVs by amide reaction. The inverted microscope was used to analyze the targeted binding capacity of ZD2-GVs to MB49 cells (bladder cancer cell line). The contrast-enhanced imaging features of GVs, non-targeted control GVs (CTR-GVs), and targeted GVs (ZD2-GVs) were compared in three MB49 tumor mice. The penetration ability of ZD2-GVs in tumor tissues was assessed by fluorescence immunohistochemistry. The biosafety of GVs was evaluated by CCK8, blood biochemistry, and HE staining. Results: Strong ED-B FN expression was observed in tumor tissues while little expression in normal liver tissues. The resulting ZD2-GVs had only 267.73 ± 2.86 nm particle size and exhibited excellent binding capability to the MB49 tumor cells. The in vivo UMI experiments showed that ZD2-GVs produced stronger and longer retention in the BC tumors than that of the non-targeted CTR-GVs and GVs. Fluorescence immunohistochemistry confirmed that ZD2-GVs could penetrate the tumor vascular into the interstitial space of the tumors. Biosafety analysis revealed there was no significant cytotoxicity to these tested mice. Conclusion: Thus, ZD2-GVs can function as a potential UMI probe for the early diagnosis of bladder cancer.

Impact of CD40 gene polymorphisms on the risk of cervical squamous cell carcinoma: a case-control study.

BACKGROUND: Cervical cancer is the fourth most common cancer among women worldwide. Genome-wide association studies have revealed multiple susceptible genes and their polymorphisms for cervical cancer risk. Therefore, we aimed to investigate the correlation between single nucleotide polymorphisms (SNPs) of the CD40 gene and susceptibility to cervical squamous cell carcinoma (CSCC) in a population from the northeastern Han Chinese population. METHODS: The three SNPs (rs1800686, rs3765459, and rs4810485) of the CD40 gene were analyzed by multiplex polymerase chain reaction (PCR) combined with next-generation sequencing methods in 421 patients with CSCC, 594 patients with high-grade squamous intraepithelial lesions (HSIL), and 504 healthy females. Multivariate logistic regression analysis was used to analyze the potential relationship between CD40 gene polymorphisms and CSCC, or HSIL. RESULTS: Our research results showed the AA genotype of rs1800686 had a protective effect on CSCC in comparison to the GG genotype and AG+GG genotypes (AA vs. GG: p = 0.0389 and AA vs. AG+GG: p = 0.0280, respectively). After FDR correction, the results were still statistically significant (p = 0.0389 and p = 0.0389, respectively). Similarly, rs3765459 showed a reduced risk association for CSCC in the codominant and recessive models (AA vs. GG: p = 0.0286 and AA vs. AG+GG: p = 0.0222, respectively). Significant differences remained after FDR correction (p = 0.0286 and p = 0.0286, respectively). However, these differences were no longer significant after the Bonferroni correction. In addition, the genotypes for the rs4810485 polymorphisms were associated with parity of the patients with CSCC. The genotypes for the rs3765459 polymorphisms were significantly correlated with the D-dimer of the patients with CSCC. The 3 SNPs genotypes of the CD40 gene were closely related to the squamous cell carcinoma antigen (SCC) of the patients with HSIL. CONCLUSIONS: The CD40 gene may play a role in the occurrence and development of CSCC.

Association between urinary 2-hydroxyethyl mercapturic acid and dyslexia among school-aged children.

Ethylene oxide is commonly used in industrial synthesis and medical disinfection. It is a known human carcinogen and has neurotoxicity. However, the association between ethylene oxide exposure and neurodevelopmental disorders remains unclear. This study aimed to evaluate the association between urinary concentrations of 2-hydroxyethyl mercapturic acid (HEMA; metabolite of ethylene oxide) and dyslexia among school-aged children. A total of 355 dyslexic children and 390 controls from three cities in China were enrolled in this case-control study from November 2017 to December 2020. Urinary HEMA was detected in 100% of the urine samples, suggesting widespread exposure to ethylene oxide in the children. Notably, the children with dyslexia had higher concentrations of urinary HEMA compared to the controls (geometric mean: 2.92 vs. 2.47 ng/mL) (P = 0.004). In the multivariable-adjusted model, urinary concentrations of HEMA were significantly associated with dyslexia risk. The individuals within the highest HEMA concentration demonstrated a 1.97-fold increased odds of dyslexia compared to those within the lowest quartile (95% confidence interval: 1.20-3.23). Thus, these findings suggested the possible link between HEMA levels and the risk of dyslexia. Further studies are warranted to validate this finding and illustrate the underlying mechanism.

Effects of PM2.5 and high-fat diet interaction on blood glucose metabolism in adolescent male Wistar rats: A serum metabolomics analysis based on ultra-high performance liquid chromatography/mass spectrometry.

Fine particulate matter (PM2.5) and high-fat diet (HFD) are known to contribute to blood glucose metabolic disorders. However, limited research has investigated the combined impact of PM2.5 and HFD on blood glucose metabolism. This study aimed to explore the joint effects of PM2.5 and HFD on blood glucose metabolism in rats using serum metabolomics and to identify involved metabolites and metabolic pathways. The 32 male Wistar rats were exposed to filtered air (FA) or PM2.5 (real-world inhaled, concentrated PM2.5, 8 times the ambient level, ranging from 131.42 to 773.44 µg/m3) and fed normal diet (ND) or HFD for 8 weeks. The rats were divided into four groups (n = 8/group): ND-FA, ND-PM2.5, HFD-FA and HFD-PM2.5 groups. Blood samples were collected to determine fasting glucose (FBG), plasma insulin and glucose tolerance test and HOMA Insulin Resistance (HOMA-IR) index was calculated. Finally, the serum metabolism of rats was analyzed by ultra-high performance liquid chromatography/mass spectrometry (UHPLC-MS). Then we constructed the partial least squares discriminant analysis (PLS-DA) model to screen the differential metabolites, and performed pathway analysis to screen the main metabolic pathways. Results showed that combined effect of PM2.5 and HFD caused changes in glucose tolerance, increased FBG levels and HOMA-IR in rats and there were interactions between PM2.5 and HFD in FBG and insulin. By metabonomic analysis, the serum differential metabolites pregnenolone and progesterone, which involved in steroid hormone biosynthesis, were two different metabolites in the ND groups. In the HFD groups, the serum differential metabolites were L-tyrosine and phosphorylcholine, which involved in glycerophospholipid metabolism, and phenylalanine, tyrosine, and tryptophan biosynthesis. When PM2.5 and HFD coexist, they may lead to more severe and complex effects on glucose metabolism by affecting lipid metabolism and amino acid metabolism. Therefore, reducing PM2.5 exposure and controlling dietary structure are important measures for preventing and reducing glucose metabolism disorders.

GCKR and ADIPOQ gene polymorphisms in women with gestational diabetes mellitus.

AIMS: To investigate the associations of GCKR and ADIPOQ variants with the risk of gestational diabetes mellitus (GDM) in Chinese women. METHODS: GCKR rs1260326, ADIPOQ rs266729, and rs1501299 were selected and genotyped in 519 GDM patients and 498 controls. Candidate SNPs were genotyped using multiplex polymerase chain reaction (PCR) combined with next-generation sequencing methods, and the association of these SNPs with GDM was analyzed. RESULTS: We found that GCKR rs1260326 was significantly associated with an increased risk of GDM in the allele model, the codominant model (CC vs. TT), the dominant model, the recessive model, and the genotypic model distributions (p = 0.0029, p = 0.0022, p = 0.0402, p = 0.0038, and p = 0.0028, respectively). The rs1260326 polymorphism was shown to be associated with 1 h-OGTT level and gravidity in GDM patients (CC vs. TT: p = 0.0475 and p = 0.0220, respectively). Diastolic blood pressure (DBP) was significantly higher in the GDM patients with the rs266729 GG genotype compared to those with the CC or CG genotype (p = 0.0444 and p = 0.0339, respectively). The DBP of the GDM patients with the rs1501299 GT genotype was lower than that of those with the GG genotype (p = 0.0197). There was a weak linkage disequilibrium value between the GCKR and ADIPOQ SNPs. CONCLUSIONS: The genes GCKR and ADIPOQ may be involved in the pathophysiology of GDM.

Rational Design of Electron Transfer Kineties of CdS/Zn(impim) Dots-on-Rods for Efficient Visible-Light Reduced C-X Bond.

Halogenated organic compounds are a kind of common environmental pollutants. Photocatalytic dehalogenation of C-halogen (C-X) bonds to C-H bonds can not only control environmental pollution but also realize important organic conversion reactions. However, the electron transfer kinetics of photocatalytic reduction of the C-X bond for semiconductor/MOF composites has remained unexplored. Herein, we successfully synthesized CdS/Zn(impim) (MOF) dots-on-rods composite photocatalyst under mild conditions. Zn(impim) MOF consists of Zn(µ-N)4 clusters and imidazole derivative ligands. Zn(impim), as a carrier, is beneficial to the dispersion of CdS nanoparticles and avoiding the agglomeration of CdS nanoparticles. The photocatalytic performance of CdS/Zn(impim) composites for the reduction of the C-X bond is much higher than that of pure CdS or Zn(impim). This high activity is due to the high electron separation efficiency of CdS assisted by Zn(impim). Under visible light irradiation, Zn(impim) is not excited due to its wide band gap of 3.26 eV. Through metal-to-ligand charge transfer of Zn(µ-N)4 clusters, Zn(impim) accepts excited electrons from CdS because the Fermi energy level of CdS is more negative by Kelvin probe force microscopy. Moreover, fluorescence spectrum and femtosecond transient absorption spectroscopy reveal the related electron transfer kinetics in detail. In addition, the inherent porous structure of MOFs is beneficial to the adsorption of halogenated hydrocarbons, providing a suitable environment for the dehalogenation reaction, thus improving the activity. This work can further understand the electron transfer mechanism in semiconductor/MOF composites for photocatalytic halide dehalogenation.