The role of MAPK/NF-κB-associated microglial activation in T-2 toxin-induced mouse learning and memory impairment.

T-2 toxin is a mycotoxin with multiple toxic effects and has emerged as an important food pollutant. Microglia play a significant role in the toxicity of various neurotoxins. However, whether they participate in the neurotoxicity of T-2 toxin has not been reported. To clarify this point, an in vivo mouse model of T-2 toxin (4 mg/kg) poisoning was established. The results of Morris water maze and open-field showed that T-2 toxin induced learning and memory impairment and locomotor inhibition. Meanwhile, T-2 toxin induced microglial activation, while inhibiting microglia activation by minocycline (50 mg/kg) suppressed the toxic effect of the T-2 toxin. To further unveil the potential mechanisms involved in T-2 toxin-induced microglial activation, an in vitro model of T-2 toxin (0, 2.5, 5, 10 ng/mL) poisoning was established using BV-2 cells. Transcriptomic sequencing revealed lots of differentially expressed genes related to MAPK/NF-κB pathway. Western blotting results further confirmed that T-2 toxin (5 ng/mL) induced the activation of MAPKs and their downstream NF-κB. Moreover, the addition of inhibitors of NF-κB and MAPKs reversed the microglial activation induced by T-2 toxin. Overall, microglial activation may contribute a considerable role in T-2 toxin-induced behavioral abnormalities, which could be MAPK/NF-κB pathway dependent.

Association between ambient carbon monoxide levels and hospitalization costs of patients with myocardial infarction: Potential effect modification by ABO blood group.

Previous researches have reported the association between air pollution and various diseases. However, few researches have investigated whether air pollutants are associated with the economic loss resulting from patients' hospitalization, especially the economic loss of hospitalization due to acute cardiovascular events. The purpose of our research was to explore the association between the levels of carbon monoxide (CO), taken as an index of pollution, and the hospitalization costs of myocardial infarction (MI), and the potential effect modification by the ABO blood group. A total of 3237 MI inpatients were included in this study. A multiple linear regression model was used to evaluate the association between ambient CO levels and hospitalization costs of MI patients. Moreover, we performed stratified analyses by age, gender, body mass index (BMI), season, hypertension, and ABO blood types. There was a positive association between the levels of CO in the air and the costs of hospitalization caused by MI. Furthermore, such association was stronger in males, BMI ≥25, <65 years, with hypertension, and non-O blood group. Interestingly, we found the association was particularly significant in patients with blood group B. Overall, our study first found that ambient CO levels could have an impact on the hospitalization costs for MI patients, and those with blood group B can be more sensitive.

The association between short-term ambient sulfur dioxide exposure and hospitalization costs of ischemic stroke: a hospital-based study in Chongqing, China.

Evidence of the short-term effects of ambient sulfur dioxide (SO2) exposure on the economic burden of ischemic stroke is limited. This study aimed to explore the association between short-term ambient SO2 exposure and hospitalization costs for ischemic stroke in Chongqing, the most populous city in China. The hospital-based study included 7271 ischemic stroke inpatients. Multiple linear regression models were used to estimate the association between SO2 concentration and hospitalization costs. Propensity score matching was used to compare the patients' characteristics when exposed to SO2 concentrations above and below 20 µg/m3. It is found that short-term SO2 exposure was positively correlated with the hospitalization costs of ischemic stroke. The association was more evident in males, people younger than 65, and people hospitalized in the cool seasons. Besides, among the components of hospitalization costs, medicine costs were most significantly associated with SO2. More interesting, the lower concentration of SO2, the higher costs associated with 1 µg/m3 SO2 change. Above all, SO2 was positively associated with hospitalization costs of ischemic stroke, even at its low levels. The measures to reduce the level of SO2 can help reduce the burden of ischemic stroke.

Association between short-term ambient nitrogen dioxide and type 2 diabetes outpatient visits: A large hospital-based study.

Type 2 diabetes (T2DM) as a non-communicable disease imposes heavy disease burdens on society. Limited studies have been conducted to assess the effects of short-term air pollution exposure on T2DM, especially in Asian regions. Our research aimed to determine the association between short-term exposure to ambient nitrogen dioxide (NO2) and outpatient visits for T2DM in Chongqing, the largest city in western China, based on the data collected from November 28, 2013 to December 31, 2019. A generalized additive model (GAM) was applied, and stratified analyses were performed to investigate the potential modifying effects by age, gender, and season. Meanwhile, the disease burden was revealed from attributable risk. Positive associations between short-term NO2 and daily T2DM outpatient visits were observed. The strongest association was observed at lag 04, with per 10 µg/m3 increase of NO2 corresponded to increased T2DM outpatient visits at 1.57% [95% confidence interval (CI): 0.48%, 2.65%]. Stronger associations were presented in middle-aged group (35-64 years old), male group, and cool seasons (October to March). Moreover, there were 1.553% (8664.535 cases) of T2DM outpatient visits attributable to NO2. Middle-aged adults, males, and patients who visited in cool seasons suffered heavier burdens. Conclusively, short-term exposure to NO2 was associated with increased outpatient visits for T2DM. Attention should be paid to the impact of NO2 on the burden of T2DM, especially for those vulnerable groups.

Predictive Factors for Adjacent Vertebral Fractures After Percutaneous Kyphoplasty in Patients With Osteoporotic Vertebral Compression Fracture.

BACKGROUND: Adjacent vertebral fracture (AVF) seemed to be a frequent and severe complication in osteoporotic vertebral compression fracture (OVCF) patients receiving percutaneous vertebroplasty  or percutaneous kyphoplasty (PKP), resulting in poor long-term outcome and recurrence of pain-related symptoms. Nonetheless, its mechanism remains unclear. OBJECTIVES: To investigate the potential predictor of AVF after PKP and figure out whether the intervertebral disc plays a role during the process of AVF. STUDY DESIGN: Retrospective study. SETTING: Department of Orthopedic, an affiliated hospital of a medical university. METHODS: Clinical data of OVCF patients receiving PKP were reviewed in our hospital from January 2016 to December 2020. Four hundred and forty-five patients were recruited who met the abovementioned criteria in this study. The clinical data, including age, gender, bone mineral density (BMD), vertebral height, vertebral kyphosis angle, cement volume, cement distribution, as well as adjacent disc degeneration extent, were recorded for each patient. Independent-sample t tests and chi-squared tests were performed to compare these indexes. Bivariate correlation tests and multiple linear regression analyses were performed among potential predictors. Receiver operator characteristic (ROC) analysis and Kaplan-Meier plotter were applied to evaluate the diagnostic efficiency of parameters for predicting the occurrence of AVF. RESULTS: Patients in both groups gained obvious improvements in symptomatic and radiographic indexes after first PKP. Statistically significant difference (P < 0.05) was only found between 2 groups with respect to BMD, kyphosis angle at last follow-up before second PKP, cement distribution, and disc degeneration grade. The ROC analysis showed that BMD = 15.5° was highly predictive of AVF after PKP (sensitivity, 92.2%; specificity, 24.6%; area under curve, 0.569, P = 0.109). Statistically significant difference of AVF incidence amongst patients with different cement distribution (P = 0.018) and similar trend was also found amongst patients with different disc degeneration (P = 0.000). Statistically significant difference was noted in terms of disc degeneration grade between 2 adjacent discs in AVF group. LIMITATIONS: The main limitation is the retrospective nature of this study. CONCLUSIONS: The risk of AVF should be focused, especially when OVCF patients with the following predictors: (1) BMD < -3.45; (2) kyphosis angle at last follow-up > 15.5°; (3) I or II cement distribution; and (4) IV or V disc degeneration. More prophylactic treatment should be prescribed for these patients to avoid the occurrence of AVF.

The relationship between short-term PM2.5 exposure and outpatient visits for acne vulgaris in Chongqing, China: a time-series study.

Many researches have reported the air pollution impacts, either long term or short term, on inflammatory skin diseases, but there are few studies on the relation between PM2.5 and acne vulgaris. To determine the correlation between short-term PM2.5 exposure and acne outpatient visits, data for 120,842 acne vulgaris outpatient visits between December 2013 and December 2019 were obtained from three large hospitals in Chongqing, China. Both single-pollutant models and two-pollutant models were established to explore the relationship between PM2.5 exposure and acne outpatient visits. The stratified analyses were conducted through two-sample z-tests to investigate the possible gender (male or female) and age (< 25 years or ≥ 25 years) differences in PM2.5 effects. The results demonstrated positive correlations between PM2.5 concentrations and acne outpatient visits. A 10 µg/m3 increase in PM2.5 concentration was associated with a 1.71% (95% CI: 1.06-2.36%) increase in acne outpatient visits at lag 0-7 day. Stratified analyses showed that PM2.5 effects were greater in individuals aged ≥ 25 years than those aged < 25 years, but no gender difference was found. In conclusion, short-term PM2.5 exposure was positively associated with the risk of acne outpatient visits, especially for people ≥ 25 years old.

More obvious association between short-term ambient nitrogen dioxide and atrial fibrillation outpatient visits in cool seasons: A hospital-based study in northwestern China.

Atrial fibrillation (AF) is the most common sustained heart rhythm disorder associated with high mortality and morbidity. Limited studies have been conducted to assess the relationship between short-term exposure to ambient air pollution and AF attacks. This study aimed to explore the association between short-term ambient nitrogen dioxide (NO2) exposure and outpatient visits for AF in Xi'an, China. Data on daily AF outpatient visits and air pollutants from 2013 to 2019 (2555 days) were obtained. A time-series approach using over-dispersed Poisson generalized additive model (GAM) was employed, and stratified analyses were performed to investigate the potential modifying effects by season, age, and gender. A total of 8307 outpatient visits for AF were recorded. Increased levels of NO2 were associated with increased AF outpatient visits, and the most significant effect estimates were observed at lag 03: A 10 µg/m3 increase of NO2 at lag 03 was related to an elevation of 5.59% (95% CI: 2.67%, 8.51%) in daily outpatient visits for AF. Stratified analyses showed that there were no gender and age difference in the effect of NO2, while more obvious association was observed in cool seasons (October to March) than in warm seasons (April to September). In summary, short-term ambient NO2 exposure can be positively associated with daily outpatient visits for AF, especially in cool seasons. This work provided novel data that the association between air pollutants and AF can vary by seasons, further supporting that the prevention of cardiovascular health effects should be strengthened in winter.

The association between short-term exposure to ambient carbon monoxide and hospitalization costs for bronchitis patients: A hospital-based study.

Ambient carbon monoxide (CO) is associated with bronchitis morbidity, but there is no evidence concerning its correlation with hospitalization costs for bronchitis patients. This study aimed to investigate the relationship between short-term ambient CO exposure and hospitalization costs for bronchitis patients in Chongqing, China. Baseline data for 3162 hospitalized bronchitis patients from November 2013 to December 2019 were collected. Multiple linear regression analysis was used to determine the association, delayed and cumulative, between short-term CO exposure and hospitalization costs. Additionally, subgroup analyses were performed by gender, age, season, and comorbidity. Positive association between CO and hospitalization costs for bronchitis patients was observed. The strongest association was observed at lag 015 days, with per 1 mg/m3 increase of CO concentrations corresponded to 5834.40 Chinese Yuan (CNY) (95% CI: 2318.71, 9350.08; P < 0.001) (845.97 US dollars) increment in hospitalization costs. Stratified analysis results showed that the association was more obvious among those males, elderly, with comorbidities, and in warm seasons. More importantly, there was strongest correlation between CO and bronchitis patients with coronary heart disease. In summary, short-term exposure to ambient CO, even lower than Chinese and WHO standards, can be associated with increased hospitalization costs for bronchitis. Controlling CO exposure can be helpful to reduce medical burden associated with bronchitis patients. The results also suggest that when setting air quality standards and formulating preventive measures, susceptible subpopulations ought to be considered.

Clinical features and prognostic factors of patients with metastatic renal cell carcinoma stratified by age.

This study compared the clinicopathological characteristics and survival of patients with metastatic renal cell carcinoma (mRCC) stratified by age to identify clinical features and prognostic factors. Patients with renal cell carcinoma (RCC) between 2010 and 2015 were identified from the Surveillance, Epidemiology and End Results database. Age was an independent prognostic factor for patients with RCC, mRCC, mRCC of clear cell renal cell carcinoma and lung-related metastases. There were many significant differences between the younger and older groups, including differences in marital status, race, sex, year of diagnosis, histology grade, laterality, T stage, N stage, tumor size, type of treatment, including surgery, radiation or chemotherapy, and pattern of organic metastasis to the liver, lung, or brain (P<0.05). Moreover, different natural metastasis patterns and poorer overall survival were observed in the older group compared with the younger group (P<0.05). Parameters, including marital status, sex, year of diagnosis, histological grade, N stage, surgery, chemotherapy, lung metastasis and liver metastasis, were independent prognostic factors for elderly patients (P<0.05). Age plays a significant role in mRCC, and elderly patients with mRCC are a special group of individuals whose clinical characteristics and prognostic factors are different from those of younger patients; therefore, these patients require special attention.

SARS-CoV-2 S protein:ACE2 interaction reveals novel allosteric targets.

The spike (S) protein is the main handle for SARS-CoV-2 to enter host cells via surface angiotensin-converting enzyme 2 (ACE2) receptors. How ACE2 binding activates proteolysis of S protein is unknown. Here, using amide hydrogen-deuterium exchange mass spectrometry and molecular dynamics simulations, we have mapped the S:ACE2 interaction interface and uncovered long-range allosteric propagation of ACE2 binding to sites necessary for host-mediated proteolysis of S protein, critical for viral host entry. Unexpectedly, ACE2 binding enhances dynamics at a distal S1/S2 cleavage site and flanking protease docking site ~27 Å away while dampening dynamics of the stalk hinge (central helix and heptad repeat [HR]) regions ~130 Å away. This highlights that the stalk and proteolysis sites of the S protein are dynamic hotspots in the prefusion state. Our findings provide a dynamics map of the S:ACE2 interface in solution and also offer mechanistic insights into how ACE2 binding is allosterically coupled to distal proteolytic processing sites and viral-host membrane fusion. Thus, protease docking sites flanking the S1/S2 cleavage site represent alternate allosteric hotspot targets for potential therapeutic development.

Berberine alleviates pulmonary hypertension through Trx1 and ß-catenin signaling pathways in pulmonary artery smooth muscle cells.

Pulmonary arterial hypertension (PAH) is closely associated with profound vascular remodeling, especially pulmonary arterial medial hypertrophy and muscularization, due to aberrant proliferation of pulmonary artery smooth muscle cells (PASMCs). Berberine, a drug commonly used to treat inflammation, may be a novel therapeutic option for PAH by improving pulmonary artery remodeling. The present study investigated whether berberine affected Trx1/ß-catenin expression and/or activity and whether it could reduce the development of pulmonary hypertension in an experimental rat model and proliferation in human PASMCs (HPASMCs). The results showed that increased proliferation in hypoxia-induced healthy PASMCs or PAH PASMCs was associated with a significant increase in Trx1 and ß-catenin expression. Treatment with the Trx1-specific inhibitor PX-12 significantly reduced pulmonary arterial pressure and vascular remodeling, as well as improved in vivo cardiac function and right ventricular hypertrophy, in Su/Hox-induced PAH rats. Berberine reversed right ventricular systolic pressure and right ventricular hypertrophy and decreased pulmonary vascular remodeling in the rats. Furthermore, berberine had an antiproliferative effect on hypoxia-induced HPASMC proliferation in a manner likely mediated by inhibiting Trx1 and its target gene ß-catenin expression. Our work will help elucidate novel strategies for PAH treatment involving the traditional Chinese medicine berberine, and Trx1/ß-catenin may be a promising therapeutic target.

Production of endogenous hydrogen sulfide in human gingival tissue.

OBJECTIVE: Endogenous hydrogen sulfide (H2S) has recently been shown to play an important role in inflammation, but the role of endogenous H2S in the human gingival tissue is unknown. The aim of this study was to investigate whether gingiva had enzymes for H2S synthesis, and whether the effect of these enzymes for H2S production changed with periodontal inflammation. DESIGN: Gingival tissues were collected from patients undergoing periodontal operation including gingivitis, moderate chronic periodontitis, severe chronic periodontitis and normal controls. RT-PCR and western blotting were performed to measure mRNA and protein levels of cystathionine ß-synthase (CBS) and cystathionine γ-lyase (CSE) for H2S production. Immunohistochemistry was carried out to detect the location of the enzymes. H2S levels and synthesis in gingival tissue were evaluated with modified methylene blue method. RESULTS: The mRNA and protein of CBS and CSE were both expressed in human gingiva and raised significantly in moderate and severe periodontitis compared of that in healthy control. CBS, but not CSE, increased in gingivitis (p<0.05). However, there was no significant difference of H2S level and synthesis among these groups (p>0.05). CONCLUSIONS: Both CBS and CSE were expressed in human gingival tissue. The mRNA and protein levels of CBS and CSE were up-regulated in periodontitis.

[New mobile lidar for the measurement of tropospheric aerosol new mobile lidar for the measurement of tropospheric aerosol].

A new mobile lidar system has been developed for measuring tropospheric aerosol. Its main structure and specification as well as lidar data processing method are described. The results of measurement over Hefei city show that this lidar has ability to gain profiles of tropospheric aerosol day and night, and to manifest aerosol temporal and spatial distributions with high precision.