The epithelial Na+ channel (ENaC) in ovarian granulosa cells modulates Ca2+ mobilization and gonadotrophin signaling for estrogen homeostasis and female fertility.

Ovarian granulosa cells are essential to gonadotrophin-regulated estrogen production, female cycle maintenance and fertility. The epithelial Na+ channel (ENaC) is associated with female fertility; however, whether and how it plays a role in ovarian cell function(s) remained unexplored. Here, we report patch-clamp and Na+ imaging detection of ENaC expression and channel activity in both human and mouse ovarian granulosa cells, which are promoted by pituitary gonadotrophins, follicle stimulating hormone (FSH) or luteinizing hormone (LH). Cre-recombinase- and CRISPR-Cas9-based granulosa-specific knockout of ENaC α subunit (Scnn1a) in mice resulted in failed estrogen elevation at early estrus, reduced number of corpus luteum, abnormally extended estrus phase, reduced litter size and subfertility in adult female mice. Further analysis using technologies including RNA sequencing and Ca2+ imaging revealed that pharmacological inhibition, shRNA-based knockdown or the knockout of ENaC diminished spontaneous or stimulated Ca2+ oscillations, lowered the capacity of intracellular Ca2+ stores and impaired FSH/LH-stimulated transcriptome changes for estrogen production in mouse and/or human granulosa cells. Together, these results have revealed a previously undefined role of ENaC in modulating gonadotrophin signaling in granulosa cells for estrogen homeostasis and thus female fertility.

A Prognostic Model for Survival in Patients with Gastric Signet Ring Cell Carcinoma.

INTRODUCTION: The objective of our study was to develop a nomogram to predict overall survival (OS) and cancer-specific survival (CSS) in patients with gastric signet ring cell carcinoma (GSRCC). METHODS: A total of 3,408 GSRCC patients between 1975 and 2017 were screened from the Surveillance, Epidemiology, and End Results (SEER) database and randomly divided into training and validation cohorts. Univariate and multivariate Cox analyses were conducted to identify independent prognostic factors for the construction of a nomogram. The performance of the model was then assessed by the concordance index (C-index), calibration plot, and area under the receiver operating characteristic curve (AUC). Then, the novel nomogram was further assessed by 64 GSRCC patients from our hospital as the external cohort. RESULTS: We identified age, tumor lymph node metastasis (TNM) staging system, surgery, and chemotherapy as significant independent elements of prognosis. On this basis, a nomogram was constructed, with a C-index of OS in the training and validation cohorts of 0.763 (95% CI: 0.751-0.774) and 0.766 (95% CI: 0.748-0.784) and a C-index of CSS of 0.765 (95% CI: 0.753-0.777) and 0.773 (95% CI: 0.755-0.791), respectively. The AUCs of the nomogram for predicting 2- and 5-year OS were 0.848 and 0.885, respectively, and those for predicting CSS were 0.854 and 0.899, respectively, demonstrating the excellent predictive value of the constructed nomogram compared to the traditional AJCC staging system. Similar results were also observed in both the internal and external validation sets. CONCLUSION: The nomogram provided an accurate tool to predict OS and CSS in patients with GSRCC, which can assist clinicians in making predictions about individual patient survival.

Calycosin activates Nrf2/Keap1 signaling to ameliorate hydrogen peroxide-induced spinal cord neuron death and mitochondrial dysfunction.

Oxidative stress is a hallmark of secondary injury of spinal cord injuries. Controlling oxidative stress is crucial for mitigating secondary injury and promoting functional recovery after spinal cord injuries. Calycosin is an O-methylated isoflavone with antioxidant activity. To evaluate the effect of calycosin on spinal cord neurons under oxidative stress and clarify the molecular mechanism underlying the effect, we tested the neuroprotective activity of calycosin in a primary spinal cord neuron culture model. We found that calycosin protected neurons from H2O2-induced neuronal death in a dose-dependent manner. Further experiments revealed that calycosin decreased H2O2-induced mitochondrial fragmentation and mitochondrial membrane potential loss, and subsequently reduced H2O2-triggered release of mitochondrial cytochrome c into the cytoplasm. In addition, calycosin inhibited H2O2-induced reactive oxygen species generation and activation of NF-κB signaling in spinal cord neurons. Furthermore, the expression of several antioxidant enzymes such as HO-1, NQO1, GCLC, GCLM, TrxR1, and Trx1 was significantly promoted by calycosin. More importantly, we revealed that the Nrf2/Keap1 signal is crucial for the effect of calycosin, because calycosin increased the amount of nuclear Nrf2 while decreasing the amount of cytoplasmic Nrf2. Nrf2 knockdown with siRNA transfection abolished the neuroprotective effect of calycosin. Taken together, this study disclosed a novel mechanism by which calycosin combats oxidative stress. Our study thus sheds light on the potential clinical application of calycosin in SCI treatment.

Small-molecule caspase-1 inhibitor CZL80 terminates refractory status epilepticus via inhibition of glutamatergic transmission.

Status epilepticus (SE), a serious and often life-threatening medical emergency, is characterized by abnormally prolonged seizures. It is not effectively managed by present first-line anti-seizure medications and could readily develop into drug resistance without timely treatment. In this study, we highlight the therapeutic potential of CZL80, a small molecule that inhibits caspase-1, in SE termination and its related mechanisms. We found that delayed treatment of diazepam (0.5 h) easily induces resistance in kainic acid (KA)-induced SE. CZL80 dose-dependently terminated diazepam-resistant SE, extending the therapeutic time window to 3 h following SE, and also protected against neuronal damage. Interestingly, the effect of CZL80 on SE termination was model-dependent, as evidenced by ineffectiveness in the pilocarpine-induced SE. Further, we found that CZL80 did not terminate KA-induced SE in Caspase-1-/- mice but partially terminated SE in IL1R1-/- mice, suggesting the SE termination effect of CZL80 was dependent on the caspase-1, but not entirely through the downstream IL-1ß pathway. Furthermore, in vivo calcium fiber photometry revealed that CZL80 completely reversed the neuroinflammation-augmented glutamatergic transmission in SE. Together, our results demonstrate that caspase-1 inhibitor CZL80 terminates diazepam-resistant SE by blocking glutamatergic transmission. This may be of great therapeutic significance for the clinical treatment of refractory SE.

Effects of major air pollutants on angina hospitalizations: a correlation study.

BACKGROUND: Angina is a crucial risk signal for cardiovascular disease. However, few studies have evaluated the effects of ambient air pollution exposure on angina. OBJECTIVE: We aimed to explore the short-term effects of air pollution on hospitalization for angina and its lag effects. METHODS: We collected data on air pollutant concentrations and angina hospitalizations from 2013 to 2020. Distributed lag nonlinear model (DLNM) was used to evaluate the short-term effects of air pollutants on angina hospitalization under different lag structures. Stratified analysis by sex, age and season was obtained. RESULTS: A total of 39,110 cases of angina hospitalization were included in the study. The results showed a significant positive correlation between PM2.5, SO2, NO2, and CO and angina hospitalization. Their maximum harmful effects were observed at lag0-7 (RR = 1.042; 95% CI: 1.017, 1.068), lag0-3 (RR = 1.067; 95% CI: 1.005, 1.133), lag0-6 (RR = 1.078; 95% CI: 1.041, 1.117), and lag0-6 (RR = 1.244; 95% CI: 1.109, 1.397), respectively. PM10 did not have an overall risk effect on angina hospitalization, but it did have a risk effect on women and the elderly. O3 was significantly negatively correlated with angina hospitalization, with the most pronounced effect observed at lag0-6 (RR = 0.960; 95% CI: 0.940, 0.982). Stratified analysis results showed that women and the elderly were more susceptible to pollutants, and the adverse effects of pollutants were stronger in the cold season. CONCLUSION: Short-term exposure to PM2.5, SO2, NO2, and CO increases the risk of hospitalization for angina.

The correlation between daily temperature, diurnal temperature range, and asthma hospital admissions in Lanzhou city, 2013-2020.

BACKGROUND: With the backdrop of global climate change, the impact of climate change on respiratory diseases like asthma is receiving increasing attention. However, the effects of temperature and diurnal temperature range (DTR) on asthma are complex, and understanding these effects across different seasons, age groups, and sex is of utmost importance. METHODS: This study utilized asthma hospitalization data from Lanzhou, China, and implemented a distributed lag nonlinear model (DLNM) to investigate the relationship between temperature and DTR and asthma hospitalizations. It considered differences in the effects across various seasons and population subgroups. RESULTS: The study revealed that low temperatures immediately increase the risk of asthma hospitalization (RR = 1.2010, 95% CI: 1.1464, 1.2580), and this risk persists for a period of time. Meanwhile, both high and low DTR were associated with an increased risk of asthma hospitalization. Lower temperatures (RR = 2.9798, 95% CI: 1.1154, 7.9606) were associated with higher asthma risk in the warm season, while in the cold season, the risk significantly rose for the general population (RR = 3.6867, 95% CI: 1.7494, 7.7696), females (RR = 7.2417, 95% CI: 2.7171, 19.3003), and older individuals (RR = 18.5425, 95% CI: 5.1436, 66.8458). In the warm season, low DTR conditions exhibited a significant association with asthma hospitalization risk in males (RR = 7.2547, 95% CI: 1.2612, 41.7295) and adults aged 15-64 (RR = 9.9494, 95% CI: 2.2723, 43.5643). Children also exhibited noticeable risk within specific DTR ranges. In the cold season, lower DTR increases the risk of asthma hospitalization for the general population (RR = 3.1257, 95% CI: 1.4004, 6.9767). High DTR significantly increases the risk of asthma hospitalization in adults (RR = 5.2563, 95% CI: 2.4131, 11.4498). CONCLUSION: This study provides crucial insights into the complex relationship between temperature, DTR, and asthma hospitalization, highlighting the variations in asthma risk across different seasons and population subgroups.

Effect of social participation on the trajectories of activities of daily living disability among community-dwelling older adults: a 7-year community-based cohort.

INTRODUCTION: Studies examining the effects of social participation on activities of daily living (ADL) disability are still scarce. AIM: To assess the reciprocal relationship between ADL disability trajectories and social participation among older Chinese people aged ≥ 60 years. METHODS: This study included 2976 participants aged ≥ 60 years in six waves of a community-based survey from 2015 to 2022. Basic activities of daily living (BADL) and instrumental activities of daily living (IADL) were used to assess the ADL disability in each survey. Social participation was assessed by involvement in four social activities and an extensive social participation score. Group-based trajectory modeling was used to identify potential heterogeneity in longitudinal changes over 7 years and explore associations between baseline predictors of group membership and these trajectories. RESULTS: Two BADL disability trajectories were identified: stable (94.8%) and increase (5.2%). Additionally, three IADL disability trajectories were distinguished: stable (73.2%), moderate (20.2%), and increase (6.6%). After controlling for the potential covariates, each point increase in the extensive social participation score correlated with a 17% decrease in the odds of older individuals belonging to the increase BADL trajectory group (OR = 0.83, 95% CI = 0.68-1.00). For IADL, it decreased the odds of being assigned to the moderate trajectory group by 16% (OR = 0.84, 95% CI = 0.75-0.95) and to the increase trajectory group by 23% (OR = 0.77, 95% CI = 0.64-0.93). CONCLUSIONS: Higher levels of social participation among older individuals were more likely to be classified as stable trajectories in both BADL and IADL. Increased participation in social activities by community-dwelling elderly adults may promote healthy aging.

Heavy metal contamination impacts the structure and co-occurrence patterns of bacterial communities in agricultural soils.

Heavy metal (HM) contamination caused by mining and smelting activities can be harmful to soil microbiota, which are highly sensitive to HM stress. Here, we explore the effects of HM contamination on the taxonomic composition, predicted function, and co-occurrence patterns of soil bacterial communities in two agricultural fields with contrasting levels of soil HMs (i.e., contaminated and uncontaminated natural areas). Our results indicate that HM contamination does not significantly influence soil bacterial α diversity but changes the bacterial community composition by enriching the phyla Gemmatimonadetes, Planctomycetes, and Parcubacteria and reducing the relative abundance of Actinobacteria. Our results further demonstrate that HM contamination can strengthen the complexity and modularity of the bacterial co-occurrence network but weaken positive interactions between keystone taxa, leading to the gradual disappearance of some taxa that originally played an important role in healthy soil, thereby possibly reducing the resistance of bacterial communities to HM toxicity. The predicted functions of bacterial communities are related to membrane transport, amino acid metabolism, energy metabolism, and carbohydrate metabolism. Among these, functions related to HM detoxification and antioxidation are enriched in uncontaminated soils, while HM contamination enriches functions related to metal resistance. This study demonstrated that microorganisms adapt to the stress of HM pollution by adjusting their composition and enhancing their network complexity and potential ecological functions.

Short-term association between air pollution and daily genitourinary disorder admissions in Lanzhou, China.

The aim of this study was to determine the relationship between short-term exposure to ambient air pollution and the number of daily hospital admissions for genitourinary disorders in Lanzhou. Hospital admission data and air pollutants, including PM2.5, PM10, SO2, NO2, O38h and CO, were obtained from the period 2013 to 2020. A generalized additive model (GAM) combined with distribution lag nonlinear model (DLNM) based on quasi-Poisson distribution was used by the controlling for trends, weather, weekdays and holidays. Short-term exposure to PM2.5, NO2 and CO increased the risk of genitourinary disorder admissions with RR of 1.0096 (95% CI 1.0002-1.0190), 1.0255 (95% CI 1.0123-1.0389) and 1.0686 (95% CI 1.0083-1.1326), respectively. PM10, O38h and SO2 have no significant effect on genitourinary disorders. PM2.5 and NO2 are more strongly correlated in female and ≥ 65 years patients. CO is more strongly correlated in male and < 65 years patients. PM2.5, NO2 and CO are risk factors for genitourinary morbidity, and public health interventions should be strengthened to protect vulnerable populations.

Online mindfulness-based stress reduction improves anxiety and depression status and quality of life in caregivers of patients with severe mental disorders. / ç½‘ç»œæ­£å¿µå‡åŽ‹ç–—æ³•å¯æ”¹å–„ä¸¥é‡ç²¾ç¥žéšœç¢æ‚£è€ ç §æ–™è€ ç„¦è™‘æŠ‘éƒçŠ¶æ€åŠå ¶ç”Ÿæ´»è´¨é‡.

OBJECTIVES: To explore the effects of online mindfulness-based stress reduction (MBSR) on the anxiety and depression status, and quality of life in the caregivers of patients with severe mental disorders. METHODS: Ninety-three caregivers for patients with schizophrenia or bipolar disorder, who were hospitalized in Yunnan Provincial Mental Hospital in March 2021, were enrolled and randomly divided into control group (n=47) and MBSR intervention group (n=46). Both groups received basic health education and rehabilitation skill training, while the intervention group received additional online MBSR for 8 weeks. The anxiety and depression status, and the quality of life of the caregivers were evaluated by Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS) and the 36-item Short Form Health Survey (SF-36) before and 8 weeks after intervention, respectively. RESULTS: Thirteen caregivers dropped out of the study, and 80 subjects (40 in each group) were included in the final analysis. At the baseline, there were no significant differences in SAS, SDS and SF-36 scores between two groups (all P>0.05). Compared with the baseline, SAS and SDS scores in the intervention group significantly decreased after 8 weeks of intervention (both P<0.01) and were significantly lower than those in the control group (both P<0.01). There were no significant changes in the control group (all P>0.05). Except the physiological function dimension, the total score and the scores of each dimension of SF-36 in the intervention group were significantly increased after 8-week intervention (all P<0.05), and were significantly higher than those in the control group (all P<0.01). There were no significant changes in the control group before and after intervention (all P>0.05). CONCLUSIONS: Online MBSR can reduce the anxiety and depression levels, improve the quality of life in the caregivers of patients with severe mental disorders.

Downregulation of DDIT4 ameliorates abnormal behaviors in autism by inhibiting ferroptosis via the PI3K/Akt pathway.

Autism spectrum disorder (ASD) is a complex disease with unclear etiology. Studies have shown that ferroptosis is also related to ASD progression, but the specific mechanism is still unclear. Valproic acid (VPA) induced neuronal ferroptosis in vitro. Mechanistic studies showed that both VPA and ferroptosis inducers promoted the expression of DDIT4 in neurons, thereby inhibiting the activation of the PI3K/Akt pathway. DDIT4 increased the accumulation of ROS, MDA and Fe2+, inhibited neuronal viability and downregulated GPX4 expression by inactivating the PI3K/Akt pathway. Ferroptosis inhibitors reversed the anti-survival effect of DDIT4, indicating that DDIT4 enhances ferroptosis through the PI3K/Akt pathway, thereby inhibiting neuronal viability. Further in vivo experiments found that autistic mice had high levels of ROS, MDA and Fe2+, increased DDIT4 expression, and downregulated expression levels of GPX4, p-PI3K and p-Akt; after downregulation of DDIT4 expression, the accumulation of ROS, MDA and Fe2+ was significantly reduced, while the expression levels of GPX4, p-PI3K and p-Akt were upregulated, indicating that DDIT4 knockdown reduces ferroptosis in autistic mice. In addition, DDIT4 downregulation, PI3K/Akt pathway activation, and ferroptosis inhibitors all improved social behavior deficits, repetitive stereotyped and compulsive behaviors, anxiety and exploratory behaviors in autistic mice, but PI3K/Akt pathway inhibitors significantly blocked the rescue of abnormal behaviors by DDIT4 downregulation in autistic mice. Therefore, downregulation of DDIT4 expression ameliorates abnormal behaviors in autism by inhibiting ferroptosis via the PI3K/Akt pathway, indicating that DDIT4, the PI3K/Akt pathway and ferroptosis have key roles in autism.

Association Between Air Pollution and Coronary Heart Disease Hospitalizations in Lanzhou City, 2013-2020: a Time Series Analysis.

Coronary heart disease (CHD) is one of the most serious public health problems. However, few studies have focused on the effects of exposure to particulate matter and gaseous air pollutants on CHD. This study aimed to explore the relationship between air pollutants and the number of hospitalized patients with CHD in Lanzhou, and we collected daily data on the number of hospitalized patients with CHD, daily air pollutants, and meteorological factors from 2013 to 2020. A distributed lag nonlinear model (DLNM) combined with a quasi-Poisson regression model was applied to evaluate the relationship between air pollutants and the number of hospitalized patients with CHD. The results indicated that the hysteresis effect of all pollutants except O38h reached its maximum at lag3, and the relative risk of coronary heart disease admission was 1.0014 (95%CI: 1.0004, 1.0023), 1.0003 (95%CI: 1.0000, 1.0006), 1.0020 (95%CI: 1.0004, 1.0035), and 1.0053 (95%CI: 1.0026, 1.0080) when PM2.5, PM10, NO2, and SO2 concentrations were increased by 10 µg/m3, respectively. Each 1 mg/m3 increase in CO concentration was associated with a relative risk of coronary heart disease; hospitalization risk was 1.1076 (95%CI: 1.0530, 1.1650). We observed a relative risk of 0.9991 (95%CI: 0.9986, 0.9999) for each 10 µg/m3 increase in O38h for coronary heart disease admission at lag1. Women and elderly were more susceptible to the impact of air pollution, and the impact was greater during cold seasons. Our results indicate that air pollution increased the risk of hospitalization for CHD in a short term. The research findings can provide strategic insights into the impact of current and future air pollution on CHD.

Chemogenetic inhibition of subicular seizure-activated neurons alleviates cognitive deficit in male mouse epilepsy model.

Cognitive deficit is a common comorbidity in temporal lobe epilepsy (TLE) and is not well controlled by current therapeutics. How epileptic seizure affects cognitive performance remains largely unclear. In this study we investigated the role of subicular seizure-activated neurons in cognitive impairment in TLE. A bipolar electrode was implanted into hippocampal CA3 in male mice for kindling stimulation and EEG recording; a special promoter with enhanced synaptic activity-responsive element (E-SARE) was used to label seizure-activated neurons in the subiculum; the activity of subicular seizure-activated neurons was manipulated using chemogenetic approach; cognitive function was assessed in object location memory (OLM) and novel object recognition (NOR) tasks. We showed that chemogenetic inhibition of subicular seizure-activated neurons (mainly CaMKIIα+ glutamatergic neurons) alleviated seizure generalization and improved cognitive performance, but inhibition of seizure-activated GABAergic interneurons had no effect on seizure and cognition. For comparison, inhibition of the whole subicular CaMKIIα+ neuron impaired cognitive function in naïve mice in basal condition. Notably, chemogenetic inhibition of subicular seizure-activated neurons enhanced the recruitment of cognition-responsive c-fos+ neurons via increasing neural excitability during cognition tasks. Our results demonstrate that subicular seizure-activated neurons contribute to cognitive impairment in TLE, suggesting seizure-activated neurons as the potential therapeutic target to alleviate cognitive impairment in TLE.

Short-term effects of air pollution on hospitalization for acute lower respiratory infections in children: a time-series analysis study from Lanzhou, China.

BACKGROUND: Short-term exposure to air pollution is associated with acute lower respiratory infections (ALRI) in children. We investigated the relationship between hospitalization for ALRI in children and air pollutant concentrations from January 1, 2014 to December 31, 2020 in Lanzhou City. METHODS: We collected data on air pollutant concentrations and children's hospitalization data during the study period. A time series regression analysis was used to assess the short-term effects of air pollutants on ALRI in children, and subgroup analyses and sensitivity analyses were performed. RESULTS: A total of 51,206 children with ALRI were studied, including 40,126 cases of pneumonia and 11,080 cases of bronchiolitis. The results of the study revealed that PM2.5, PM10, SO2 and NO2 were significantly associated with hospitalization for ALRI in children aged 0-14 years. For each 10 µg/m3 increase in air pollutant concentration in lag0-7, the relative risk of ALRI hospitalization in children due to PM2.5, PM10, SO2 and NO2 increased by 1.089 (95%CI:1.075, 1.103), 1.018 (95%CI:1.014, 1.021), 1.186 (95%CI:1.154. 1.219) and 1.149 (95%CI:1.130, 1.168), respectively. CONCLUSIONS: PM2.5, PM10, SO2 and NO2 short-term exposures were positively associated with ALRI, pneumonia and bronchiolitis hospitalizations in Lanzhou, China. Local governments should make efforts to improve urban ambient air quality conditions to reduce hospitalization rates for childhood respiratory diseases.

CFTR Modulates Hypothalamic Neuron Excitability to Maintain Female Cycle.

Cystic fibrosis transmembrane conductance regulator (CFTR), known as an epithelial Cl- channel, is increasingly noted to be expressed in the nervous system, although whether and how it plays a role in neuronal excitability is unclear. Given the association of CFTR with fertility, we tested here possible involvement of CFTR in regulating hypothalamic neuron excitability. Patch-clamp and Ca2+ imaging showed that pharmacological inhibition of CFTR evoked electrical pulses and Ca2+ spikes in primary rat hypothalamic neurons, which was dependent on extracellular Cl-. Hypothalamic neurons in brain-slice preparations from adult female mice with CFTR mutation (DF508) exhibited significantly reduced electrical pulses as compared to the wild-type controls. Removal of extracellular Cl- eliminated hypothalamic electrical pulses in the wild-type brain slices, which was reversible by subsequent addition of Cl-. In adult female mice, Ca2+ indicator (GCaMP6s)-based fiber-photometry showed that hypothalamic Ca2+ activities in vivo were enhanced at the proestrus/estrus phase as compared to the diestrus phase of the female cycle. Such estrus-associated hypothalamic activities were largely diminished in DF508 female mice, together with delayed puberty and disturbed female cycles. Therefore, these findings suggest a critical role of CFTR in modulating hypothalamic neuron excitability, which may account for the disturbed female cycles and reduced female fertility associated with CFTR mutations.

Extraction, Purification, Structural Characteristics, Health Benefits, and Application of the Polysaccharides from Lonicera japonica Thunb.: A Review.

Lonicera japonica Thunb. is a widely distributed plant with ornamental, economic, edible, and medicinal values. L. japonica is a phytoantibiotic with broad-spectrum antibacterial activity and a potent therapeutic effect on various infectious diseases. The anti-diabetic, anti-Alzheimer's disease, anti-depression, antioxidative, immunoregulatory, anti-tumor, anti-inflammatory, anti-allergic, anti-gout, and anti-alcohol-addiction effects of L. japonica can also be explained by bioactive polysaccharides isolated from this plant. Several researchers have determined the molecular weight, chemical structure, and monosaccharide composition and ratio of L. japonica polysaccharides by water extraction and alcohol precipitation, enzyme-assisted extraction (EAE) and chromatography. This article searched in the Chinese Pharmacopoeia, Flora of China, Web of Science, PubMed, and CNKI databases within the last 12 years, using "Lonicera. japonica polysaccharides", "Lonicera. japonica Thunb. polysaccharides", and "Honeysuckle polysaccharides" as the key word, systematically reviewed the extraction and purification methods, structural characteristics, structure-activity relationship, and health benefits of L. japonica polysaccharides to provide insights for future studies. Further, we elaborated on the potential applications of L. japonica polysaccharides in the food, medicine, and daily chemical industry, such as using L. japonica as raw material to make lozenges, soy sauce and toothpaste, etc. This review will be a useful reference for the further optimization of functional products developed from L. japonica polysaccharides.

Acute effects of air pollution on type II diabetes mellitus hospitalization in Lanzhou, China.

Studies on the effects of short-term air pollution exposure on hospitalization for type 2 diabetes mellitus (T2DM) are relatively scarce in developing regions. The time-series study was used to explore the acute effects of air pollutants on hospitalization for T2DM in Lanzhou, China. A distribution lag nonlinear model based on the generalized additive model was used to analyze the hospitalization impact of air pollution on T2DM. Stratified analysis by gender, age and season was obtained. The results were indicated as the relative risk (RR) with 95% confidence interval (CI) for single-day lags (from lag0 to lag7) and cumulative lag days (from lag0-1 to lag0-7). The strongest correlations (RR, 95% CI) of hospitalization for T2DM and PM10 (RR = 1.003, 95% CI 1.000, 1.001) at lag7 and NO2 (RR = 1.022, 95% CI 1.000, 1.045) at lag0-4 were observed for an increase of 10 µg/m3 in the concentrations and CO (RR = 1.091, 95% CI 1.017, 1.170) at lag0-4 for an increase of 1 mg/m3 in the concentration. The hazardous impacts of PM10, NO2 and CO were greater for females, people aged ≥ 65 years and in the cold season. However, there was no significant association between PM2.5, SO2 and O38h and the number of hospitalizations for T2DM.

[Effect of Diurnal Temperature Range on the Number of Residents Hospitalized Due to Stroke in Lanzhou].

Objective To analyze the relationship between diurnal temperature range (DTR) and the hospitalization of stroke in Lanzhou,so as to provide a scientific basis for probing into the mechanism of temperature changes in inducing stroke and formulating comprehensive prevention and control measures for stroke by relevant departments.Methods The information of the patients hospitalized due to stroke in Lanzhou during January 2014 to December 2019 and the air pollutants (PM10,SO2,and NO2) and meteorological data in the same period were collected for statistical analysis.Spearman rank correlation analysis was performed to analyze the correlations between air pollutants and meteorological factors.The distributed lag nonlinear model was adopted to fit the relationship between DTR and the number of stroke inpatients,and three-dimensional diagrams and the correlation diagrams of DTR against stroke risk were established.The stratified analysis was performed according to gender and age (< 65 years and ≥65 years).Results From 2014 to 2019,a total of 92 812 stroke patients were hospitalized in Lanzhou,with a male-to-female ratio of 1.35:1.There was a nonlinear relationship between DTR and the number of stroke inpatients in Lanzhou,which presented a lag effect.The low DTR at 4.5 ℃ had the largest RR value of 1.25 (95%CI=1.16-1.35) for stroke inpatients at a cumulative lag of 18 d.The effect of high DTR (18.5 ℃) on the hospitalization of stroke patients peaked at a cumulative lag of 21 d,with an RR value of 1.09 (95%CI=1.01-1.18).The stratified analysis results suggested that low levels of DTR had greater effects on the hospitalization of male stroke patients and stroke patients <65 years.Conclusions Short-term exposure to different levels of DTR had an impact on the number of stroke inpatients,and low levels of DTR had a slightly greater impact on stroke inpatients than high levels of DTR.Importance should be attached to the protection of males and people aged <65 years at low levels of DTR.

Exploration of the anti-insomnia mechanism of Ganoderma by central-peripheral multi-level interaction network analysis.

BACKGROUND: Ganoderma (Lingzhi in Chinese) has shown good clinical outcomes in the treatment of insomnia, restlessness, and palpitation. However, the mechanism by which Ganoderma ameliorates insomnia is unclear. We explored the mechanism of the anti-insomnia effect of Ganoderma using systems pharmacology from the perspective of central-peripheral multi-level interaction network analysis. METHODS: The active components and central active components of Ganoderma were obtained from the TCMIP and TCMSP databases, then screened to determine their pharmacokinetic properties. The potential target genes of these components were identified using the Swiss Target Prediction and TCMSP databases. The results were matched with the insomnia target genes obtained from the GeneCards, OMIM, DisGeNET, and TCMIP databases. Overlapping targets were subjected to multi-level interaction network analysis and enrichment analysis using the STRING, Metascape, and BioGPS databases. The networks analysed were protein-protein interaction (PPI), drug-component-target gene, component-target gene-organ, and target gene-extended disease; we also performed gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. RESULTS: In total, 34 sedative-hypnotic components (including 5 central active components) were identified, corresponding to 51 target genes. Multi-level interaction network analysis and enrichment analysis demonstrated that Ganoderma exerted an anti-insomnia effect via multiple central-peripheral mechanisms simultaneously, mainly by regulating cell apoptosis/survival and cytokine expression through core target genes such as TNF, CASP3, JUN, and HSP90αA1; it also affected immune regulation and apoptosis. Therefore, Ganoderma has potential as an adjuvant therapy for insomnia-related complications. CONCLUSION: Ganoderma exerts an anti-insomnia effect via complex central-peripheral multi-level interaction networks.

Airborne particulate matter (PM2.5) triggers ocular hypertension and glaucoma through pyroptosis.

BACKGROUND: Particulate matter (PM) is strongly linked to human health and has detrimental effects on the eye. Studies have, however, focused on the ocular surface, with limited research on the impact of PM2.5 on intraocular pressure (IOP). METHODS: To investigate the impact of PM2.5 on IOP and the associated mechanism, C57BL/6 mouse eyes were topically exposed to a PM2.5 suspension for 3 months, and human trabecular meshwork (HTM) cells were subjected to various PM2.5 concentrations in vitro. Cell viability, NLRP3/caspase-1, IL-1ß, and GSDMD expression, reactive oxygen species (ROS) production and cell contractility were measured by western blot, ELISA, cell counting kit-8, ROS assay kit or a cell contractility assay. ROS scavenger N-acetyl-L-cysteine (NAC) and caspase-1 inhibitor VX-765 were used to intervene in PM2.5-induced damages. RESULTS: The results revealed that the IOP increased gradually after PM2.5 exposure, and upregulations of the NLRP3 inflammasome, caspase-1, IL-1ß, and GSDMD protein levels were observed in outflow tissues. PM2.5 exposure decreased HTM cell viability and affected contraction. Furthermore, elevated ROS levels were observed as well as an activation of the NLRP3 inflammasome and downstream inflammatory factors caspase-1 and IL-1ß. NAC improved HTM cell viability, inhibited the activation of the NLRP3 inflammasome axis, and HTM cell contraction by scavenging ROS. VX-765 showed similar protection against the PM2.5 induced adverse effects. CONCLUSION: This study provides novel evidence that PM2.5 has a direct toxic effect on intraocular tissues and may contribute to the initiation and development of ocular hypertension and glaucoma. This occurs as a result of increased oxidative stress and the subsequent induction of NLRP3 inflammasome mediated pyroptosis in trabecular meshwork cells.