Effects of climate change and anthropogenic activity on ranges of vertebrate species endemic to the Qinghai - Tibet Plateau over 40 years

Over the past 40 years, the climate has been changing and human disturbance has increased in the vast Qinghai¿Tibet Plateau (QTP). These 2 factors are expected to affect the distribution of a large number of endemic vertebrate species. However, quantitative relationships between range shifts and climate change and human disturbance of these species in the QTP have rarely been evaluated. We used occurrence records of 19 terrestrial vertebrate species (birds, mammals, amphibians, and reptiles) occurring in the QTP from 1980 to 2020 to quantify the effects of climate change and anthropogenic impacts on the distribution of these 4 taxonomic groups and estimated species range changes in each species. The trend in distribution changes differed among the taxonomic groups, although, generally, ranges shifted to central QTP. Climate change contributed more to range variation than human disturbance (the sum of the 4 climatic variables contributed more than the sum of the 4 human disturbance variables for all 4 taxonomic groups). Suitable geographic range increased for most mammals, amphibians, and reptiles (+27.6%, +18.4%, and +27.8% on average, respectively), whereas for birds range decreased on average by 0.9%. Quantitative evidence for climate change and human disturbance associations with range changes for endemic vertebrate species in the QTP can provide useful insights into biodiversity conservation under changing environments.This project was supported by the Second Tibetan Plateau Scientific Expedition and Research Program (STEP) (2019QZKK0501); the Strategic Priority Research Program of Chinese Academy of Sciences (CAS) (XDB31000000); the National Natural Science Foundation of China (32070410; 32100396); the Youth Innovation Promotion Association of CAS (2021370); and the Sichuan Science and Technology Program (2023NSFSC0197)INTRODUCTION METHODS Species distribution data Statistical analyses RESULTS DISCUSSION ACKNOWLEDGMENT

Characteristics, risk management and GMP standards of pharmaceutical companies in China

The Good Manufacturing Practice (GMP) is one of the gold standards by which governments worldwide judge modern pharmaceutical companies’ production processes and product-safety standards. However, in all the nations, it is di cult to obtain real data about GMP inspection results, so conducting the related research is impossible. Taking advantage of a rare chance to obtain the on-site GMP inspection results in China, we have been able to initiate an empirical analysis of how company characteristics and risk management aWeb of Science11art. no. 110355

Acute osimertinib exposure induces electrocardiac changes by synchronously inhibiting the currents of cardiac ion channels

Introduction: As the third generation of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), osimertinib has demonstrated more significant cardiotoxicity than previous generations of EGFR-TKIs. Investigating the mechanism of osimertinib cardiotoxicity can provide a reference for a comprehensive understanding of osimertinib-induced cardiotoxicity and the safety of the usage of this drug in clinical practice.Methods: Multichannel electrical mapping with synchronous ECG recording was used to investigate the effects of varying osimertinib concentrations on electrophysiological indicators in isolated Langendorff-perfused hearts of guinea pigs. Additionally, a whole-cell patch clamp was used to detect the impact of osimertinib on the currents of hERG channels transfected into HEK293 cells and the Nav1.5 channel transfected into Chinese hamster ovary cells and acute isolated ventricular myocytes from SD rats.Results: Acute exposure to varying osimertinib concentrations produced prolongation in the PR interval, QT interval, and QRS complex in isolated hearts of guinea pigs. Meanwhile, this exposure could concentration-dependently increase the conduction time in the left atrium, left ventricle, and atrioventricular without affecting the left ventricle conduction velocity. Osimertinib inhibited the hERG channel in a concentration-dependent manner, with an IC50 of 2.21 ± 1.29 μM. Osimertinib also inhibited the Nav1.5 channel in a concentration-dependent manner, with IC50 values in the absence of inactivation, 20% inactivation, and 50% inactivation of 15.58 ± 0.83 μM, 3.24 ± 0.09 μM, and 2.03 ± 0.57 μM, respectively. Osimertinib slightly inhibited the currents of L-type Ca2+ channels in a concentration-dependent manner in acutely isolated rat ventricular myocytes.Discussion: Osimertinib could prolong the QT interval; PR interval; QRS complex; left atrium, left ventricle, and atrioventricular conduction time in isolated guinea pig hearts. Furthermore, osimertinib could block the hERG, Nav1.5, and L-type Ca2+ channels in concentration-dependent manners. Therefore, these findings might be the leading cause of the cardiotoxicity effects, such as QT prolongation and decreased left ventricular ejection fraction

Acetate suppresses myocardial contraction via the short-chain fatty acid receptor GPR43

The heart has high energy requirements, with an estimated 40%–60% of myocardial ATP production derived from the oxidation of fatty acids under physiological conditions. However, the effect of short-chain fatty acids on myocardial contraction remains controversial, warranting further research. The present study sought to investigate the effects and mechanisms of acetate, a short-chain fatty acid, on myocardial contraction in rat ventricular myocytes. Echocardiography and Langendorff heart perfusion were used to evaluate cardiac function. Cell shortening and calcium transient were measured in isolated cardiomyocytes. The patch-clamp method determined the action potential and L-type Ca2+ current in cardiomyocytes. Moreover, the expression of GPR43, a type of short-chain fatty acid receptors in cardiomyocytes was examined by immunofluorescent staining and Western blot. We demonstrated that acetate transiently reduced left ventricular developmental pressure in isolated Langendorff heart perfusion model, with no effect on stroke volume and cardiac output in vivo. In addition, acetate transiently and reversibly inhibited cardiomyocyte contraction and calcium transient. Acetate did not affect the action potential and L-type Ca2+ currents in cardiomyocytes. As a short-chain fatty acid receptor, GPR43 was expressed in rat cardiomyocytes. Furthermore, the GPR43 antagonist GLPG0974 prevented the acetate-induced inhibitory effect on myocardial contraction. We conclude that acetate transiently inhibits contraction via the short-chain fatty acid receptor GPR43 in cardiomyocytes

Effect of dietary Ginkgo biloba leaf on the growth performance and nonspecific immunity of red swamp crayfish Procambarus clarkii

This trial investigated the effect of dietary Ginkgo biloba leaf (GBL) on the growth performance and nonspecific immunity of red swamp crayfish Procambarus clarkii. 180 Crayfishes were randomly divided into three groups. One group was fed with basic diet, whereas the other two groups were fed with diets containing 1% and 3% GBL. After 32 days of feeding, GBL addition tended to increase the body weight gain rate compared with control. In 3% GBL group, the bodyweight gain rate of male crayfish was higher than that of female crayfish. While female crayfish were advantageous in terms of meat yield. Liver-related indexes were influenced by GBL addition and 3% GBL could reduce glutamic pyruvic transaminase and glutamic oxaloacetic transaminase as well as total cholesterol in male crayfish, showing its function in liver protection. Moreover, GBL addition effects on liver protection was better in male crayfish than female crayfish

Somatic SF3B1 hotspot mutation in prolactinomas.

The genetic basis and corresponding clinical relevance of prolactinomas remain poorly understood. Here, we perform whole genome sequencing (WGS) on 21 patients with prolactinomas to detect somatic mutations and then validate the mutations with digital polymerase chain reaction (PCR) analysis of tissue samples from 227 prolactinomas. We identify the same hotspot somatic mutation in splicing factor 3 subunit B1 (SF3B1R625H) in 19.8% of prolactinomas. These patients with mutant prolactinomas display higher prolactin (PRL) levels (p = 0.02) and shorter progression-free survival (PFS) (p = 0.02) compared to patients without the mutation. Moreover, we identify that the SF3B1R625H mutation causes aberrant splicing of estrogen related receptor gamma (ESRRG), which results in stronger binding of pituitary-specific positive transcription factor 1 (Pit-1), leading to excessive PRL secretion. Thus our study validates an important mutation and elucidates a potential mechanism underlying the pathogenesis of prolactinomas that may lead to the development of targeted therapeutics

Efficacy and safety of Lianhua Qingwen granule in the treatment of non-influenza viral pneumonia: a randomized, double-blind, placebo-controlled, multicenter clinical study

ObjectiveTo observe the effectiveness and safety of Lianhua Qingwen granule in the treatment of non-influenza viral pneumonia.MethodsThis study was a multicenter, randomized, double-blind, placebo-controlled trial. Subjects who met the inclusion and exclusion criteria and were clinically diagnosed with viral pneumonia (negative for influenza virus) were randomly divided into the Lianhua Qingwen granule trial group and placebo control group. Patients in the trial group was given Lianhua Qingwen granule, 2 bags at a time, 3 times a day, and the controls were given placebo, with a treatment course of 7 days. Patients’ clinical symptoms and signs, and treatment-associated adverse events were observed. Subjects should be included in the full analysis set (FAS) as long as they were all given the medication and had an effectiveness test performed after randomization. Subjects should be included in the Per Protocol Set (PPS),a subset of the total analysis set, which should contain those with strong compliance, no protocol violations, and complete baseline values for the primary indicators.ResultsA total of 169 subjects were enrolled in 12 subcenters, including 151 (76 in the trial group and 75 in the control group) in the FAS and 140 (68 in the trial group and 72 in the control group) in the PPS. After 7 days of treatment, the clinical symptom relief rates were 82.98% (FAS) and 87.12% (PPS) in the trial group, and 75.11% (FAS) and 76.02% (PPS) in the control group, respectively. The clinical symptom relief rates in the trial group were significantly higher than those in the control group (p < 0.001). Significant improvements in single symptoms of cough and expectoration in the trial group were observed compared with the control group (p < 0.05). There were no statistical differences in fever, sputum color change, chest pain, muscle pain, dyspnea, chills, and thirst between the two groups (p > 0.05).SafetyThere were no significant differences in body weight, vital signs, blood routine, urine routine, stool routine, and blood biochemical indicators (CK, AST, ALT, Cr, and Bun) between the two groups before and after treatment (p > 0.05). During treatment, there were no significant differences in the incidence of adverse events and serious adverse events between the two groups (p > 0.05).ConclusionLianhua Qingwen granules improved the clinical symptoms of patients with non-influenza virus pneumonia, especially ameliorating cough and expectoration. Lianhua Qingwen granules were associated with good safety