Morphological and phylogenetic analyses reveal a new species of Anthracophyllum (Omphalotaceae, Agaricales) in Zhejiang Province, China.

During the investigations of macrofungi resources in Zhejiang Province, China, an interesting wood rot fungus was collected. Based on morphological and molecular phylogenetic studies, it is described as a new species, Anthracophyllum sinense. A. sinense is characterized by its sessile, charcoal black and pleurotoid pileus, sparse lamellae occasionally branching, clavate basidia with long sterigmata [(3-)6-7(-8) µm], and non-heteromorphous cystidia. A. sinense establishes a separate lineage close to A. archeri and A. lateritium in the phylogenetic tree.

Design, synthesis and biological evaluation of novel 2,4-diaminopyrimidine cinnamyl derivatives as inhibitors of FAK with potent anti-gastric cancer activities.

In this study, twenty-one novel 2,4-diaminopyrimidine cinnamyl derivatives as inhibitors targeting FAK were designed and synthesized based on the structure of TAE-226, and the inhibitory effects of these compounds on both the FAK enzyme and three cancer cell lines (MGC-803, HCT-116, and KYSE30) were investigated. Among them, compound 12s displayed potent inhibitory potency on FAK (IC50 = 47 nM), and demonstrated more significant antiproliferative activities in MGC-803, HCT-116 and KYSE30 cells (IC50 values were 0.24, 0.45 and 0.44 µM, respectively) compared to TAE-226. Furthermore, compound 12s significantly inhibited FAK activation leading to the negative regulation of FAK-related signaling pathways such as AKT/mTOR and MAPK signaling pathways. Molecular docking study suggested that compound 12s could well occupy the ATP-binding pocket site of FAK similar to TAE-226. In addition, compound 12s also efficiently inhibited the proliferation, induced apoptosis and cellular senescence in MGC-803 cells. In conclusion, compound 12s emerges a potent FAK inhibitor that could exert potent inhibitory activity against gastric cancer cells.

Visible Light-Induced Cascade Sulfonylation/Cyclization to Produce Quinoline-2,4-Diones under Metal-Free Conditions.

A general visible light-induced sulfonylation/cyclization to produce quinoline-2,4-diones was achieved under photocatalyst-free conditions. The reactions were performed at room temperature, and various substituents (halogen, alkyl, aryl) and substituted products were obtained with 29 examples within 2 h. Large-scale synthesis and derivatization study via carbonyl reduction to produce easily modified hydroxyl groups and convenient N-Ts deprotection showed the potential utility of this strategy.

Multivalent Metal Ion Cross-Linked Lignocellulosic Nanopaper with Excellent Water Resistance and Optical Performance.

Cellulose nanopaper is an attractive film material exhibiting huge potential in various fields, while its terrible water stability greatly hinders practical applications. Previous efforts on addressing this issue usually sacrifice the sustainability or material performance of film. In this study, we report a high-performing lignocellulosic nanopaper with superior water resistance and excellent optical properties. The strategy involves preparing a lignin-containing cellulose nanopaper (LCNP) first, and then infiltrating metal ions into the film to build cross-linking interactions within the fiber networks. Owing to the coordination bonds formed between metal ions and lignocellulosic components, the resulting metal ions cross-linked LCNP (M+-LCNP) displays outstanding water resistance, including the highest wet mechanical strength of ∼52 MPa after immersing in water for 24 h, which retains nearly 47% of the dry mechanical strength of the film. The ultralow water uptake ratio of ∼35% also confirms it possesses a superior wet dimensional stability. Moreover, these nanopapers also showcase the desired optical performances, including both high visible transmittance (>85%) and total ultraviolet-blocking efficiency (>91%, only transmitting a little of UVA). Overall, this fully degradable film is a promising alternative to replacing conventional plastics that are applied in multiple areas.

Exercise interventions on patients with end-stage renal disease: a systematic review.

OBJECTIVE:: This study aimed to conduct an up-to-date systematic review of the literature to evaluate the effects of exercise on fatigue, anxiety, depression, physical activity, and quality of life (QOL) in patients with end-stage renal disease. DATA SOURCES:: We searched PubMed (October 2018), Embase (from 1966 to October 2018), Web of Science (from 1900 to October 2018), The Cochrane Library (October 2018), and references of papers. METHODS:: This study includes randomized controlled trials that analyzed the combined effects of exercise intervention on patients with end-stage renal disease. Two reviewers independently screened the retrieved records, extracted data, and assessed the risk of bias for inclusion in the study. The effects of exercise intervention were conducted in the meta-analysis using RevMan 5.3 software. RESULTS:: A total of 614 participants were included in 13 randomized controlled studies. The study revealed that exercise can improve fatigue, anxiety, depression, physical activity, and QOL. The effect value results were as follows: (1) fatigue, -0.97 (95% confidence interval (CI) -1.32 to -0.62, P < 0.00001); (2) anxiety, -0.78 (95% CI -1.17 to -0.39, P < 0.0001); (3) depression, -0.85 (95% CI -1.13 to -0.56, P < 0.00001) (4) physical activity, 38.15 (95% CI 21.20 to 55.10, P < 0.0001); (5) QOL, the physical component of the 36-item Short-Form Health Survey (SF-36), 4.73 (95% CI 1.92 to 7.54, P = 0.0010); and (6) the mental component of the SF-36, 3.42 (95% CI 0.27 to 6.56, P = 0.03). CONCLUSION:: Exercise intervention is more effective in fatigue, anxiety, depression, physical activity, and QOL. However, large-scale randomized controlled trials are needed to confirm the appropriate types of exercise and optimal time for patients with end-stage renal disease.

An asymmetric naphthalimide derivative for n-channel organic field-effect transistors.

A new naphthalene diimide (NDI) derivative with an asymmetric aromatic backbone of 2-tetradecylbenzo[lmn]benzo[4,5]imidazo[2,1-b][3,8]phenanthroline-1,3,6(2H)-trione (IZ0) was designed and synthesized. Low LUMO level, large energy gap, and high thermal stability are characterized for this IZ0 compound. The OFET devices based on an IZ0 semiconductor exhibit typical n-type behavior. Through continuously optimizing the fabrication conditions, high performance n-channel OFETs were fabricated based on IZ0 films and single crystals, with the highest carrier mobility of 0.072 cm(2) V(-1) s(-1) and 0.22 cm(2) V(-1) s(-1), respectively.

A novel electrochemical DNA biosensor construction based on layered CuS-graphene composite and Au nanoparticles.

A novel CuS-graphene (CuS-Gr) composite was synthesized to achieve excellent electrochemical properties for application as a DNA electrochemical biosensor. CuS-Gr composite was prepared by a hydrothermal method, in which two-dimensional graphene served as a two-dimensional conductive skeleton to support CuS nanoparticles. A sensitive electrochemical DNA biosensor was fabricated by immobilizing single-stranded DNA (ss-DNA) labeled at the 5' end using 6-mercapto-1-hexane (HS-ssDNA) on the surface of Au nanoparticles (AuNPs) to form ssDNA-S-AuNPs/CuS-Gr, and hybridization sensing was done in phosphate buffer. Cyclic voltammetry and electrochemical impedance spectroscopy were performed for the characterization of the modified electrodes. Differential pulse voltammetry was applied to monitor the DNA hybridization using an [Fe(CN)6](3-/4-) solution as a probe. Under optimum conditions, the biosensor developed exhibited a good linear relationship between the current and the logarithm of the target DNA concentration ranging from 0.001 to 1 nM, with a low detection limit of 0.1 pM (3σ/S). The biosensor exhibited high selectivity to differentiate one-base-mismatched DNA and three-base-mismatched DNA. The results indicated that the sensing platform based on CuS-Gr provides a stable and conductive interface for electrochemical detection of DNA hybridization, and could easily be extended to the detection of other nucleic acids.

[Sensitive determination of Bi3+ by spectrofluorimetry based on graphene oxide-methylene blue system].

Graphene oxide was prepared by the modified Hummers method and characterized by field emission scanning electron microscopy. The interaction of graphene with methylene blue was studied by UV absorption, the intensity of two main absorption peaks of methylene blue decreased significantly after the fluorescence was quenched, and the energy transfer didn't occur because the overlap of the absorption spectrum of GO and the emission spectrum of MB is too small. Therefore, the fluorescence quenching of MB and GO was static. When adding a certain amount of Bi3+ in the graphene-methylene blue system, Bi3+ replaces the methylene blue from the graphene-methylene blue complexes because Bi3+ has the smaller volume and is more positively charged. The methylene blue therefore dissociates from the GO-MB complexes, resulting in the recovery of fluorescence of the system. Furthermore, the fluorescence of the system increases with the increase in the amount of Bi3+ due to the enhanced amount of MB in the system. A novel spectrofluorimetric method was therefore developed for the sensitive determination of Bi3+. Some parameters including the concentration of methylene blue, the amount of graphene oxide, the amount of nitric acid and the sequence of reagent adding were optimized to obtain higher sensitivity. The fluorescence of the system was detected at an emission wavelength of 667 nm with excitation at 690 nm. Under the optimized conditions, the concentration of Bi3+ showed good linear relationships with the fluorescence intensity in the range of 0.5-100 micromol x L(-1), with correlation coefficients of r = 0.9955. The limits of detection for Bi3+ was 1.0 x 10(-8) mol x L(-1) (S/N=3). The selectivity of the proposed method was evaluated and the results showed that 1000-fold K+, Ca+, Na+, Mg2+, Cu2+; 100-fold Fe3+, Be2+, SiO2- Al3+, Ni2+, Sb3+, NO3-, Cl-, F-, and 20-fold Pb2+, Hg2+, Cd2+ had negligible interference with the determination of Bi3+. The method has advantages of sensitivity, rapidness and low cost. It was used for the determination of Bi3+ in environmental water samples inclu- ding pond water, rain water and sewage water with recoveries of 93.4%-105.2%.

METTL3 aggravates cell damage induced by Streptococcus pneumoniae via the NEAT1/CTCF/MUC19 axis.

Disruption of the alveolar barrier can trigger acute lung injury. This study elucidated the association of methyltransferase-like 3 (METTL3) with Streptococcus pneumoniae (SP)-induced apoptosis and inflammatory injury of alveolar epithelial cells (AECs). AECs were cultured and then infected with SP. Furthermore, the expression of METTL3, interleukin (IL)-10, IL-6, tumor necrosis factor-alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1), long noncoding RNA nuclear paraspeckle assembly transcript 1 (NEAT1), mucin 19 (MUC19), N6-methyladenosine (m6A), and NEAT1 after m6A modification were detected by qRT-PCR, Western blot, and enzyme-linked immunosorbent, m6A quantification, and methylated RNA immunoprecipitation-qPCR analyses, respectively. Moreover, the subcellular localization of NEAT1 was analyzed by nuclear/cytosol fractionation assay, and the binding between NEAT1 and CCCTC-binding factor (CTCF) was also analyzed. The results of this investigation revealed that SP-induced apoptosis and inflammatory injury in AECs and upregulated METTL3 expression. In addition, the downregulation of METTL3 alleviated apoptosis and inflammatory injury in AECs. METTL3-mediated m6A modification increased NEAT1 and promoted its binding with CTCF to facilitate MUC19 transcription. NEAT1 or MUC19 overexpression disrupted their protective role of silencing METTL3 in AECs, thereby increasing apoptosis and inflammatory injury. In conclusion, this is the first study to suggest that METTL3 aggravates SP-induced cell damage via the NEAT1/CTCF/MUC19 axis.

Long-term exposure to PM2.5 chemical constituents and diabesity: evidence from a multi-center cohort study in China.

Background: Long-term exposure to PM2.5 is known to increase the risks for diabetes and obesity, but its effects on their coexistence, termed diabesity, remain uncertain. This study aimed to investigate the associations of long-term exposure to PM2.5 and its chemical constituents with the risks for diabesity, diabetes, and obesity. Methods: This cross-sectional study used the baseline data of a multi-center cohort, consisting of three provincially representative cohorts comprising a total of 134,403 participants from the eastern (Fujian Province), central (Hubei Province), and western (Yunnan Province) regions of China. Obesity and diabetes, and diabesity were identified by a body mass index (BMI) ≥28 kg/m2 and fasting plasma glucose (FPG) ≥126 mg/dL. The average concentrations of PM2.5 and five chemical constituents (NO3 -, SO4 2-, NH4 +, organic matter, and black carbon) over participants' residence during the past three years were estimated using machine learning models. Logistic regression models with double robust estimators, Bayesian kernel machine regression, and weighted quantile sum regression were employed to estimate independent and joint effects of PM2.5 chemical constituents on the risks for diabesity, diabetes, and obesity, as well as the differences from the effects on obesity. Stratified analyses were performed to examine effect modification of sociodemographic and lifestyle factors. Findings: There were 129,244 participants with a mean age of 54.1 ± 13.8 years included in the study. Each interquartile range increase in PM2.5 concentration (8.53 µg/m3) was associated with an increased risk for diabesity (OR = 1.23 [1.17, 1.30]), diabetes only (OR = 1.16 [1.13, 1.19]), and obesity only (OR = 1.03 [1.00, 1.05]). Long-term exposure to each PM2.5 chemical constituent was associated with an increased risk for diabesity, where organic matter exposure, with maximum weight (48%), was associated with a higher risk for diabesity (OR = 1.21 [1.16, 1.27]). Among those with obesity, black carbon contributed most (68%) to the joint effect of PM2.5 chemical constituents on diabesity (OR = 1.16 [1.11, 1.22]). Physical activity reduced adverse effects of PM2.5 on diabesity. Also, additive rather than multiplicative effects of obesity on the PM2.5-diabetes association were observed. Interpretation: Long-term exposure to PM2.5 and its chemical constituents was associated with an increased risk for diabesity, stronger than associations for diabetes and obesity alone. The main constituents associated with diabesity and obesity were black carbon and organic matter. Funding: National Natural Science Foundation of China (42271433, 723B2017), National Key R&D Program of China (2023YFC3604702), Fundamental Research Funds for the Central Universities (2042023kfyq04, 2042024kf1024), the Science and Technology Major Project of Tibetan Autonomous Region of China (XZ202201ZD0001G), Science and technology project of Tibet Autonomous Region（XZ202303ZY0007G), Key R&D Project of Sichuan Province (2023YFS0251), Renmin Hospital of Wuhan University (JCRCYG-2022-003), Jiangxi Provincial 03 Special Foundation and 5G Program (20224ABC03A05), Wuhan University Specific Fund for Major School-level Internationalization Initiatives (WHU-GJZDZX-PT07).

Annual review of PROTAC degraders as anticancer agents in 2022.

Following nearly two decades of development, significant advancements have been achieved in PROTAC technology. As of the end of 2022, more than 20 drugs have entered clinical trials, with ARV-471 targeting estrogen receptor (ER) showing remarkable progress by entering phase III clinical studies. In 2022, significant progress has been made on multiple targets. The first reversible covalent degrader designed to target the KRASG12C mutant protein, based on cyclopropionamide, has been reported. Additionally, the activity HDCA1 degrader surpassed submicromolar levels during the same year. A novel FEM1B covalent ligand called EN106 was also discovered, expanding the range of available ligands. Furthermore, the first PROTAC drug targeting SOS1 was reported. Additionally, the first-in-class degraders that specifically target BRD4 isoforms (BRD4 L and BRD4 S) have recently been reported, providing a valuable tool for further investigating the biological functions of these isoforms. Lastly, a breakthrough was also achieved with the first degrader targeting both CDK9 and Cyclin T1. In this review, we aimed to update the PROTAC degraders as potential anticancer agents covering articles published in 2022. The design strategies, degradation effects, and anticancer activities were highlighted, which might provide an updated sight to develop novel PROTAC degraders with great potential as anticancer agents as well as favorable drug-like properties.

Design, synthesis and biological evaluation of 1,2,3-triazole benzothiazole derivatives as tubulin polymerization inhibitors with potent anti-esophageal cancer activities.

In this work, we utilized the molecular hybridization strategy to design and synthesize novel 1,2,3-triazole benzothiazole derivatives K1-26. The antiproliferative activities against MGC-803, Kyse30 and HCT-116 cells were explored, and their structure-activity relationship were preliminarily conducted and summarized. Among them, compound K18, exhibited the strongest proliferation inhibitory activity, with esophageal cancer cells Kyse30 and EC-109 being the most sensitive to its effects (IC50 values were 0.042 and 0.038 µM, respectively). Compound K18 effectively inhibited tubulin polymerization (IC50 = 0.446 µM), thereby hindering tubulin polymerize into filamentous microtubules in Kyse30 and EC-109 cells. Additionally, compound K18 induced the degradation of oncogenic protein YAP via the UPS pathway. Based on these dual molecular-level effects, compound K18 could induce G2/M phase arrest and cell apoptosis in Kyse30 and EC-109 cells, as well as regulate the expression levels of cell cycle and apoptosis-related proteins. In summary, our findings highlight a novel 1,2,3-triazole benzothiazole derivative K18, which possesses significant potential for treating esophageal cancers.

Environmental determinants of childhood obesity: a meta-analysis.

BACKGROUND: The increasing prevalence of childhood obesity has contributed to the growing global burden of chronic diseases over the life course, which has been largely attributed to obesogenic environments. This giant-scale review was done to translate existing obesogenic environmental studies into evidence-based governance for fighting childhood obesity and promoting life-course health. METHODS: Following a standard strategy of literature search and inclusion, all obesogenic environmental studies, published since the inception of the electronic databases, were reviewed to identify the evidence on associations with childhood obesity of 16 obesogenic environmental factors, including 10 built environmental factors or indices (ie, land-use mix, street connectivity, residential density, speed limit, urban sprawl, and access to green space, public transport, bike lanes, sidewalks, and neighbourhood aesthetics) and six food environmental factors (ie, access to convenience stores, supermarkets, grocery stores, full-service restaurants, fast-food restaurants, and fruit and vegetable markets). A meta-analysis was conducted to quantify the influence of each factor with sufficient studies on childhood obesity. FINDINGS: A total of 24 155 search results were found and filtered, with 457 studies included in the analysis. All built environmental factors, except speed limit and urban sprawl, were negatively associated with childhood obesity by encouraging physical activity while discouraging sedentary behaviours; the access to all food venues, except convenience stores and fast-food restaurants, was negatively associated with childhood obesity by encouraging their healthy eating behaviours. There were some globally consistent associations, such as between greater access to fast-food restaurants in the neighbourhood and more fast-food consumption, between better access to bike lanes and more physical activity, between better access to sidewalks and reduced sedentary behaviours, and between greater access to green space and more physical activity and less TV or computer screen time. INTERPRETATION: Findings have formed the unprecedentedly inclusive evidence for policy making and the establishment of the future research agenda regarding the obesogenic environment. FUNDING: National Natural Science Foundation of China, Chengdu Technological Innovation R&D Project, Sichuan Provincial Key R&D Program, and Wuhan University Specific Fund for Major School-level Internationalization Initiatives.

DNA-Functionalized Porphyrinic Metal-Organic Framework-Based Drug Delivery System for Targeted Bimodal Cancer Therapy.

A DNA-functionalized porphyrinic MOF (porMOF) drug delivery system was successfully constructed. porMOF as a photosensitizer and drug delivery carrier can integrate photodynamic therapy (PDT) and chemotherapy. Via the strong coordination interaction between the zirconium cluster of porMOF and the terminal phosphate group of DNA, the stable modification of the DNA layer on the porMOF surface is achieved. Meanwhile, the introduction of C/G-rich base pairs into the DNA double-stranded structure provides more binding sites of chemotherapeutic drug doxorubicin (DOX). AS1411, an aptamer of nucleolin proteins that are overexpressed by cancer cells, is introduced in the double-stranded terminal, which can endow the nanosystem with the ability to selectively recognize cancer cells. C-rich sequences in DNA double strands form an i-motif structure under acidic conditions to promote the highly efficient release of DOX in cancer cells. In vitro and in vivo experiments demonstrate that the synergistic PDT/chemotherapy modality achieves highly efficient cancer cell killing and tumor ablation without undesirable side effects.

Real-world tobacco cessation practice in China: findings from the prospective, nationwide multicenter China National Tobacco Cessation Cohort Study (CNTCCS).

Background: Tobacco cessation is proven to be the most effective and cost-effective strategy for smokers to reduce their risk of smoking-related disease and premature death. Providing effective, efficient, safe, and patient-centred tobacco cessation treatment to reach those who need them is a significant challenge. To date, only a few nationwide studies in China have assessed the overall clinical care practice and treatment outcome of tobacco cessation. Methods: This a prospective, nationwide, multicenter, cohort study covering all Eastern China, Northwest China, Central China, North China, Southwest China, Northeast China, and South China. Participants who were current smokers aged 18-85 years attending clinic for smoking cessation were included. All the participants were treated with 3-month cessation treatment and followed up for 3 months. Data were collected prospectively using online system. The primary outcome was 7-day point abstinence rate at 24 weeks, validated biochemically by an expired carbon monoxide level of less than 10 ppm. The participants lost to follow-up or not providing validation were included as non-abstainers. Findings: A representative sample of 3557 participants were recruited and 2943 participants were included into this analysis. These participants had mean age of 53.05 years, and 94.8% were males, with 75.8% showing symptoms of tobacco dependence. A total of 965 (32.8%) participants were treated with Bupropion + behavioural counselling, followed by 935 (31.8%) with behavioural counselling, 778 (26.4%) with Varenicline + behavioural counselling, 135 (4.6%) with alternative treatments + behavioural counselling, and 130 (4.4%) with nicotine replacement therapy (NRT) + behavioural counselling. After 3-month treatment and 3-month follow-up, 21.74% of the participants quit smoking at 24 weeks. In the multivariable-adjusted analyses, quitting smoking was significantly associated with female, higher socioeconomic status, poor health condition, different treatment received, and less smoking intensity. The tobacco cessation treatment varied widely across different areas of China. In particular, the areas with higher usage of cessation medication were associated with better cessation treatment outcome. Interpretation: The CNTCCS is the first large-scale nationwide cohort study of smoking cessation in China. Rich data collected from this prospective cohort study provided the opportunity to evaluate the clinical practice of tobacco cessation treatment in China. Funding: Chinese Academy of Medical Sciences (CAMS) Initiative for Innovative Medicine (CAMS 2021-I2M-1-010), Heilongjiang Provincial Science and Technology Key Program (2022ZXJ03C02), and National Key R&D Program of China (grant no. 2017YFC1309400).

Large-Scale Preparation of Micro-Nanofibrous and Fluffy Propylene-Based Elastomer/Polyurethane@Graphene Nanoplatelet Membranes with Breathable and Flexible Characteristics for Wearable Stretchy Heaters.

Effective personal thermal management is crucial for protecting human health during cold weather. Therefore, wearable heaters based on electric-heating membranes are one of the most promising devices to become essential appliances in our daily lives. The main challenge toward this goal is the development of electric-heating membranes with adequate breathable, flexible, and stretchable characteristics. In the work presented here, micro-nanofibrous fluffy electric-heating membranes were prepared by coating polyurethane/graphene nanoplatelet (PU@GNP) films onto melt-blown propylene-based elastomer (PBE) micro-nanofibrous membranes via a facile, cheap, and large-scale method consisting of a coating-compressing cyclic process. Investigation of the resulting PBE/PU@GNP membranes showed that the PU@GNP films were uniformly deposited onto the PBE micro-nanofiber surfaces, forming fluffy interconnected conducting channels. By applying a voltage of 36 V to the prepared PBE/PU@GNP membranes, the temperature increased to 69.7 °C, confirming excellent electric-heating features. Moreover, the porosity of the fabricated membrane could be tailored readily by adjusting the coating-compressing cycles. Benefiting from the conducting channels, the PBE/PU@GNP membranes exhibited efficiently regulated air permeability ranging from 212 to 60.2 mm/s, a prominent softness score of 53.8, and an excellent elastic recovery rate of 85.5%. These findings demonstrate that PBE/PU@GNP micro-nanofibrous fluffy membranes may well be suitable for application in electric-heating clothing. The cyclic coating-compressing preparation process may be attractive in industrial manufacturing.

Associations and pathways between residential greenness and metabolic syndromes in Fujian Province.

Background: Greenness exposure is beneficial to human health, but its potential mechanisms through which the risk for metabolic syndrome (MetS) could be reduced have been poorly studied. We aimed to estimate the greenness-MetS association in southeast China and investigate the independent and joint mediation effects of physical activity (PA), body mass index (BMI), and air pollutants on the association. Methods: A cross-sectional study was conducted among the 38,288 adults based on the Fujian Behavior and Disease Surveillance (FBDS), established in 2018. MetS was defined as the presence of three or more of the five components: abdominal obesity, elevated triglyceride, reduced high-density lipoprotein cholesterol (HDL-C), high blood pressure, and elevated fasting glucose. The residential greenness exposure was measured as the 3-year mean values of the normalized difference vegetation index (NDVI) and enhanced vegetation index (EVI) within the 250, 500, and 1,000 meters (m) buffer zones around the residential address of each participant. Logistic regression models were used to estimate the greenness-MetS association. The causal mediation analysis was used to estimate the independent and joint mediation effects of PA, BMI, particulate matter with an aerodynamic diameter of 2.5 µm (PM2.5), particulate matter with an aerodynamic diameter ≤ 10 µm (PM10), nitrogen dioxide (NO2), and sulfur dioxide (SO2). Results: Each interquartile range (IQR) increase in greenness was associated with a decrease of 13% (OR = 0.87 [95%CI: 0.83, 0.92] for NDVI500m and OR = 0.87 [95%CI: 0.82, 0.91] for EVI500m) in MetS risk after adjusting for covariates. This association was stronger in those aged < 60 years (e.g., OR = 0.86 [95%CI: 0.81, 0.92] for NDVI500m), males (e.g., OR = 0.73 [95%CI: 0.67, 0.80] for NDVI500m), having an educational level of primary school or above (OR = 0.81 [95%CI: 0.74, 0.89] for NDVI500m), married/cohabitation (OR = 0.86 [95%CI: 0.81, 0.91] for NDVI500m), businessman (OR = 0.82 [95%CI: 0.68, 0.99] for NDVI500m), other laborers (OR = 0.77 [95%CI: 0.68, 0.88] for NDVI500m), and non-smokers (OR = 0.77 [95%CI: 0.70, 0.85] for NDVI500m). The joint effect of all six mediators mediated about 48.1% and 44.6% of the total effect of NDVI500m and EVI500m on the MetS risk, respectively. Among them, BMI showed the strongest independent mediation effect (25.0% for NDVI500m), followed by NO2 and PM10. Conclusion: Exposure to residential greenness was associated with a decreased risk for MetS. PA, BMI, and the four air pollutants jointly interpreted nearly half of the mediation effects on the greenness-MetS association.

Chaetoglobosin E inhibits tumor growth and promotes the anti-tumor efficacy of cytotoxic drugs in esophageal squamous cell carcinoma by targeting PLK1.

Background: Currently, there is no satisfactory treatment available for esophageal squamous cell carcinoma (ESCC), and thus, there is a pressing need to develop effective drugs. Chaetoglobosin E, a cytochalasan alkaloid derived from metabolites of Chaetomium madrasense 375, is a chaetoglobosin with intense anti-tumor activity. Therefore, revealing its anti-tumor mechanism for the application of cytochalasans is crucial. Methods: The cytotoxic effect of chaetoglobosin E and cisplatin on esophageal cancer KYSE-30, KYSE-150, and TE-1 cells was detected using cell viability or colony formation assays. The cell cycle, apoptosis, autophagy, invasion, and metastasis were assayed by flow cytometry or western blot. The potential target of chaetoglobosin E was assayed by RNA sequencing (RNA-seq) and large loop prediction software analysis and was assessed by western blot and real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). The effect of its target on cell pyroptosis was assayed using overexpression and silence experiments. Results: Chaetoglobosin E significantly inhibited the proliferation of KYSE-30, KYSE-150, and TE-1 cells, especially KYSE-30 cells. Our results showed that chaetoglobosin E induced the G2/M phase arrest of KYSE-30 cells, followed by the down-regulation of cyclinB1, CDC2, and p-CDC2, and up-regulation of p21. Moreover, chaetoglobosin E also decreased the anti-apoptotic protein expression of Bcl-2, increased apoptotic expression of Bax, increased autophagy protein expressions of beclin1 and LC3, decreased invasion and metastasis protein expression of E-cadherin, and increased expression of vimentin. The RNA-seq and large loop prediction software analysis results indicated that its potential target might be polo-like kinase 1 (PLK1). Moreover, results also showed that chaetoglobosin E can reverse the PLK1 overexpression plasmid-induced up-regulation of the PLK1 protein. Furthermore, we found that chaetoglobosin E induced pyroptosis via the activation of the gasdermin E (GSDME) protein. Further studies showed that the high expression of PLK1 inactivated the GSDME protein, while the knockdown of PLK1 expression activated the GSDME protein, indicating that chaetoglobosin E induced cell pyroptosis by inhibiting PLK1. Conclusions: This study suggested that chaetoglobosin E may be a novel lead compound to the treatment of ESCC patients by targeting PLK1, and elucidated for the first time that PLK1 was involved in a new pyroptosis mechanism.

[Effects of Akt2-siRNA on chemotherapeutic sensitivity and drug resistance in human lung cancer cells].

OBJECTIVE: To explore the effects of oncogene protein v-akt-siRNA on the sensitivity of human lung cancer cell line NCI-H446 to cisplatin and drug resistance proteins in human lung cancer cells. METHODS: The small interfering siRNA expression vector targeting Akt2 gene (siAkt2) was constructed. And the NCI-H446 cells were transfected with negative control vector or siRNA vector. The expressions of Akt2-mRNA and lung resistance-related protein (LRP) and P-glycoprotein (P-gp) were detected by reverse transcription-polymerase chain reaction and immunocytochemistry respectively. NCI-H446 and transfected cells were treated by cisplatin for 24 h. The cell proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium (MTT) assay and cell apoptotic rate detected by flow cytometry. RESULTS: Akt2-mRNA decreased significantly in the transfected NCI-H446 cells versus the non-transfection group. And the expressions of LRP and P-gp proteins decreased significantly in the transfection group versus the control group (P < 0.01). The cell proliferation rate decreased from (60.2 ± 2.8)% to (34.7 ± 2.6)% (P < 0.01). The cell apoptotic rate increased from (19.3 ± 1.6)% to (38.8 ± 1.2)% after a therapy of cisplatin (P < 0.01). CONCLUSION: The siRNA targeting Akt2 can decrease the Akt2 expression, increase the chemotherapeutic sensitivity to cisplatin and partially reverse the cisplatin resistance of NCI-H446. The mechanism may be through the lowered expressions of LRP and P-gp.

[Levels of HMGB1 in induced sputum from patients with asthma and chronic obstructive pulmonary disease].

OBJECTIVE: To explore the relationship between the sputum levels of high mobility group protein B1 (HMGB1) and airway inflammation in bronchial asthma and chronic obstructive pulmonary disease (COPD) patients. METHODS: A total of 57 patients with persistent asthma [per Global Initiative for Asthma (GINA) guidelines], 30 patients with stable COPD [stratified by Global Initiative for COPD (GOLD) status] and 20 control subjects were recruited. After completing an asthma control questionnaire, spirometry was performed before sputum induction. The ratio of forced expiratory volume in the first second (FEV(1))/predictive value (FEV(1)%Pre) and neutrophil differential count in induced sputum were recorded. The concentrations of HMGB1 in the supernatant of sputum were measured by ELISA (enzyme-linked immunosorbent assay). RESULTS: The sputum concentrations of HMGB1 in the asthmatics and COPD patients were significantly higher than those of the control subjects [(291 ± 55) and (511 ± 39) vs (61 ± 5) ng/L, all P < 0.01]. And they were significantly negatively correlated with FEV(1)%Pre in all subjects. The levels of HMGB1 in induced sputum of COPD patients were significantly higher than those of asthmatics and healthy controls (P < 0.01). No significant difference existed in the levels of HMGB1 between patients with eosinophilic and noneosinophilic asthma [(290 ± 55) vs (292 ± 54) ng/L, P > 0.05]. The HMGB1 levels with COPD stage II and stage III were significantly higher than those with stage I [(526 ± 29) and (541 ± 29) vs (471 ± 18) ng/L]. The differences of sputum neutrophil percentage were statistically significant in mild, moderate and severe asthma [(27 ± 2)%, (36 ± 4)%, (49 ± 4)%]. And the sputum levels of HMGB1 were significantly higher in the patients with moderate and severe asthma [(312 ± 14) vs (347 ± 11) ng/L]. And the levels of HMGB1 in asthmatic and COPD patients were positively correlated with neutrophil percentage. According to the multivariate analysis, neutrophil percentage and FEV(1)%Pre were independent predictors of sputum HMGB1, but not smoking, age, gender and eosinophilic percentage. CONCLUSION: HMGB1 may contribute to airway inflammation through its higher expression in bronchial asthma and COPD patients.