PASTICCINO2 interacting with Golgi Anti-Apoptotic Proteins resists endoplasmic reticulum stress dependent on very long-chain fatty acids.

The endoplasmic reticulum (ER) is crucial for maintaining cell homeostasis because it is the primary site for synthesizing secreted and transmembrane proteins and lipids. The unfolded protein response (UPR) is activated to restore ER homeostasis under ER stress. However, the relationship between lipids and the ER stress response in plants is not well understood. Arabidopsis Golgi anti-apoptotic proteins (GAAPs) are involved in resisting ER stress. To elucidate the function of GAAPs, PASTICCINO2 (PAS2), involved in very long-chain fatty acid (VLCFA) synthesis, was found to interact with GAAPs and IRE1. Single pas2 and gaap1/gaap2pas2 double mutants exhibited increased seedling damage and impaired UPR response under chronic ER stress. Site mutation combined with genetic analysis revealed that the role of PAS2 in resisting ER stress depended on its VLCFA synthesis domain. VLCFA contents were upregulated under ER stress, which required GAAPs. Exogenous VLCFAs partially restored the defect in UPR upregulation caused by PAS2 or GAAP mutations under chronic ER stress. These findings demonstrate that the association of PAS2 with GAAPs confers plant resistance to ER stress by regulating VLCFA synthesis and the UPR. This provides a basis for further studies on the connection between lipids and cell fate decisions under stress.

[Water Quality Prediction Model for the Pearl River Estuary Based on BiLSTM Improved with Attention Mechanism].

To improve the accuracy and stability of water quality prediction in the Pearl River Estuary, a water quality prediction model was proposed based on BiLSTM improved with an attention mechanism. The feature attention mechanism was introduced to enhance the ability of the model to capture important features, and the temporal attention mechanism was added to improve the mining ability of time series correlation information and water quality fluctuation details. The new model was applied to the water quality prediction of eight estuaries of the Pearl River, and the prediction performance test, generalization ability test, and characteristic parameter expansion test were carried out. The results showed that:① The new model achieved high prediction accuracy in the water quality prediction of the Zhuhaidaqiao section. The root-mean-square error (RMSE) between the predicted value and the measured value was 0.004 1 mg·L-1, and the coefficient of determination (R2) was 98.3 %. Compared with that of Multi-BiLSTM, Multi-LSTM, BiLSTM, and LSTM, the results showed that the new model had the highest prediction accuracy, which verified the accuracy of the model. ② Both the number of training samples and the number of forecasting steps affected the prediction accuracy of the model, and the prediction accuracy of the model increased with the increase of the training samples. When predicting the total phosphorus of the Zhuhaidaqiao section, more than 240 training samples could obtain higher prediction accuracy. Increasing the number of prediction steps caused the prediction accuracy of the model to decline rapidly, and the reliability of the model prediction could not be guaranteed when the number of prediction steps was greater than 5. ③ When the new model was applied to the prediction of different water quality indexes in eight estuaries of the Pearl River, the prediction results had high precision and the model had strong generalization ability. The input data of upstream water quality, rainfall, and other characteristic parameters associated with the section prediction index of the object could improve the prediction accuracy of the model. Through many tests, the results showed that the new model could meet the requirements of precision, applicability, and expansibility of water quality prediction in the Pearl River Estuary and thus is a new exploration method for high-precision prediction of water quality in complex hydrodynamic environments.

Evaluating the effectiveness of echocardiographic guidance in diminishing postoperative wound complications for left atrial appendage closure: A clinical retrospective study.

Echocardiographic guidance in left atrial appendage (LAA) closure procedures is increasingly recognized for its potential to enhance patient outcomes in atrial fibrillation (AF). This retrospective study assesses its impact on hospital stay duration, readmission rates and surgical site wound complications in 200 AF patients. Divided equally into an echocardiographically guided group (Group E) and a non-guided group (Group N), the analysis focused on detailed patient data encompassing hospital stay, 30-day readmission and wound complications. Findings revealed that Group E experienced a significantly shorter average hospital stay of 3.5 days, compared with 6.5 days in Group N, along with a lower 30-day readmission rate (5% vs. 18% in Group N). Furthermore, Group E showed a considerable reduction in surgical site wound complications, such as infections and hematomas. The study concludes that echocardiographic guidance in LAA closure procedures markedly improves postoperative wound outcomes, underscoring its potential as a standard practice in cardiac surgeries for AF patients. This approach not only optimizes patient safety and postoperative recovery but also enhances healthcare resource utilization.

An atypical two-component system, AtcR/AtcK, simultaneously regulates the biosynthesis of multiple secondary metabolites in Streptomyces bingchenggensis.

Streptomyces bingchenggensis is an industrial producer of milbemycins, which are important anthelmintic and insecticidal agents. Two-component systems (TCSs), which are typically situated in the same operon and are composed of a histidine kinase and a response regulator, are the predominant signal transduction pathways involved in the regulation of secondary metabolism in Streptomyces. Here, an atypical TCS, AtcR/AtcK, in which the encoding genes (sbi_06838/sbi_06839) are organized in a head-to-head pair, was demonstrated to be indispensable for the biosynthesis of multiple secondary metabolites in S. bingchenggensis. With the null TCS mutants, the production of milbemycin and yellow compound was abolished but nanchangmycin was overproduced. Transcriptional analysis and electrophoretic mobility shift assays showed that AtcR regulated the biosynthesis of these three secondary metabolites by a MilR3-mediated cascade. First, AtcR was activated by phosphorylation from signal-triggered AtcK. Second, the activated AtcR promoted the transcription of milR3. Third, MilR3 specifically activated the transcription of downstream genes from milbemycin and yellow compound biosynthetic gene clusters (BGCs) and nanR4 from the nanchangmycin BGC. Finally, because NanR4 is a specific repressor in the nanchangmycin BGC, activation of MilR3 downstream genes led to the production of yellow compound and milbemycin but inhibited nanchangmycin production. By rewiring the regulatory cascade, two strains were obtained, the yield of nanchangmycin was improved by 45-fold to 6.08 g/L and the production of milbemycin was increased twofold to 1.34 g/L. This work has broadened our knowledge on atypical TCSs and provided practical strategies to engineer strains for the production of secondary metabolites in Streptomyces.IMPORTANCEStreptomyces bingchenggensis is an important industrial strain that produces milbemycins. Two-component systems (TCSs), which consist of a histidine kinase and a response regulator, are the predominant signal transduction pathways involved in the regulation of secondary metabolism in Streptomyces. Coupled encoding genes of TCSs are typically situated in the same operon. Here, TCSs with encoding genes situated in separate head-to-head neighbor operons were labeled atypical TCSs. It was found that the atypical TCS AtcR/AtcK played an indispensable role in the biosynthesis of milbemycin, yellow compound, and nanchangmycin in S. bingchenggensis. This atypical TCS regulated the biosynthesis of specialized metabolites in a cascade mediated via a cluster-situated regulator, MilR3. Through rewiring the regulatory pathways, strains were successfully engineered to overproduce milbemycin and nanchangmycin. To the best of our knowledge, this is the first report on atypical TCS, in which the encoding genes of RR and HK were situated in separate head-to-head neighbor operons, involved in secondary metabolism. In addition, data mining showed that atypical TCSs were widely distributed in actinobacteria.

MiR-1278 targets CALD1 and suppresses the progression of gastric cancer via the MAPK pathway.

This study aimed to investigate the interaction between miR-1278 and Caldesmon (CALD1) in gastric cancer (GC) and the regulatory mechanism. In both GC cells and tissues, the levels of CALD1, miR-1278, migration-related markers (E-cadherin, N-cadherin, and Snail), and MAPK signaling pathway-related proteins were clarified using quantitative real-time PCR and western blotting analyses. The effects of miR-1278 and CALD1 on GC cell viability and migration were analyzed using CCK-8 and Transwell assays, respectively. The targeting effect of miR-1278 on CALD1 was investigated using bioinformatics prediction and a dual luciferase reporter assay. The effect of miR-1278 on tumor growth was estimated in vivo using a tumor xenograft assay. In GC, miR-1278 expression decreased, whereas CALD1 was highly expressed. Transfecting an miR-1278 mimic into cells inhibited the viability as well as migration of GC cells, and suppressed Ras, phosphorylated (p)-P38, and p-ERK1/2 protein levels. Moreover, miR-1278 targeted and negatively regulated CALD1 expression. CALD1 overexpression promoted GC cell survival and migration and activated the MAPK pathway. Treatment with an miR-1278 mimic partially rescued the changes caused by CALD1 overexpression. Overall, our study revealed that miR-1278 suppresses the malignant behavior of GC cells by targeting CALD1 and regulating the MAPK pathway.

The pharmacology and mechanisms of platycodin D, an active triterpenoid saponin from Platycodon grandiflorus.

Chinese doctors widely prescribed Platycodon grandiflorus A. DC. (PG) to treat lung carbuncles in ancient China. Modern clinical experiences have demonstrated that PG plays a crucial role in treating chronic pharyngitis, plum pneumonia, pneumoconiosis, acute and chronic laryngitis, and so forth. Additionally, PG is a food with a long history in China, Japan, and Korea. Furthermore, Platycodin D (PLD), an oleanane-type triterpenoid saponin, is one of the active substances in PG. PLD has been revealed to have anti-inflammatory, anti-viral, anti-oxidation, anti-obesity, anticoagulant, spermicidal, anti-tumor etc., activities. And the mechanism of the effects draws lots of attention, with various signaling pathways involved in these processes. Additionally, research on PLD's pharmacokinetics and extraction processes is under study. The bioavailability of PLD could be improved by being prescribed with Glycyrrhiza uralensis Fisch. or by creating a new dosage form. PLD has been recently considered to have the potential to be a solubilizer or an immunologic adjuvant. Meanwhile, PLD was discovered to have hemolytic activity correlated. PLD has broad application prospects and reveals practical pharmacological activities in pre-clinical research. The authors believe that these activities of PLD contribute to the efficacy of PG. What is apparent is that the clinical translation of PLD still has a long way to go. With the help of modern technology, the scope of clinical applications of PLD is probable to be expanded from traditional applications to new fields.

Clinical effects of Chemotherapy combined with Immunotherapy in patients with advanced NSCLC and the effect on their nutritional status and immune function.

Objectives: To evaluate the clinical effects of chemotherapy combined with immunotherapy in patients with advanced non-small-cell lung cancer (NSCLC) and the effect on their nutritional status and immune function. Methods: Total 120 patients with advanced NSCLC admitted to Affiliated Hospital of Hebei University from May 2019 to October 2021 were randomly divided into two groups (n= 60, respectively). Patients in the control group were treated by chemotherapy with cisplatin-paclitaxel (TP) alone: 120 mg/m2 paclitaxel was used on d1; and 25mg/m2 cisplatin (CDDP) was used for more than two hour, once every 14 days, for three consecutive three cycles. Patients in the study group were additionally given 200 mg sindilizumab by intravenous drip, once every three weeks. The contrastive analysis of clinical effects, the incidence of adverse reactions, improvement of the nutrient index and the changes in levels of CD3+, CD4+, CD8+, and CD4+/CD8+ in T-lymphocyte subsets was performed between the two groups. Result: The overall response rate (ORR) was 80% and 61% in the study group and the control group, respectively; and the difference was statistically significant (p=0.03); the contrast analysis of the incidence of post-treatment adverse drug reactions (ADRs) in patients in the two groups suggested that the incidence of adverse reactions was 33.3% and 45% in the study group and the control group, respectively; and the difference was not statistically significant (p=0.19). After the treatment, the improvement of hemoglobin, albumin, serum iron and ferritin levels in the study group was more significant than that in the control group; and the difference was statistically significant (p < 0.05). After the treatment, the levels of CD3+, CD4+ and CD4+/CD8+ in the study group were much higher than those in the control group; and the difference was statistically significant (p < 0.05). Conclusion: Chemotherapy combined with immunotherapy is effective in treating patients with advanced NSCLC without increasing the incidence of adverse reactions, and can significantly improve their nutritional status and T-lymphocyte function. This therapeutic regimen is of much higher clinical value than the chemotherapy-only regimen.

Targeting neuroinflammation in Alzheimer's disease: from mechanisms to clinical applications.

Alzheimer's disease is characterized by sustained neuroinflammation leading to memory loss and cognitive decline. The past decade has witnessed tremendous efforts in Alzheimer's disease research; however, no effective treatment is available to prevent disease progression. An increasing body of evidence suggests that neuroinflammation plays an important role in Alzheimer's disease pathogenesis, alongside the classical pathological hallmarks such as misfolded and aggregated proteins (e.g., amyloid-beta and tau). Firstly, this review summarized the clinical and pathological characteristics of Alzheimer's disease. Secondly, we outlined key aspects of glial cell-associated inflammation in Alzheimer's disease pathogenesis and provided the latest evidence on the roles of microglia and astrocytes in Alzheimer's disease pathology. Then, we revealed the double-edged nature of inflammatory cytokines and inflammasomes in Alzheimer's disease. In addition, the potential therapeutic roles of innate immunity and neuroinflammation for Alzheimer's disease were also discussed through these mechanisms. In the final section, the remaining key problems according to the current research status were discussed.

[Mechanism of Puerariae Lobatae Radix against lung cancer by inhibiting histone demethylase LSD1].

Histone lysine-specific demethylase 1(LSD1) has become a promising molecular target for lung cancer therapy. Upon the screening platform for LSD1 activity, some Chinese herbal extracts were screened for LSD1 activity inhibition, and the underlying mechanism was preliminarily investigated at both molecular and cellular levels. The results of LSD1 inhibition showed that Puerariae Lobatae Radix extract can effectively reduce LSD1 expression to elevate the expression of H3 K4 me2 and H3 K9 me2 substrates in H1975 and H1299 cells. Furthermore, Puerariae Lobatae Radix was evaluated for its anti-lung cancer activity. It had a potent inhibitory ability against the proliferation and colony formation of both H1975 and H1299 cells. Flow cytometry and DAPI staining assays indicated that Puerariae Lobatae Radix can induce the apoptosis of lung cancer cells. In addition, it can significantly suppress the migration and reverse the epithelial-mesenchymal transition(EMT) process of lung cancer cells by activating E-cadherin and suppressing the expression of N-cadherin, slug and vimentin. To sum up, Puerariae Lobatae Radix displayed a robust inhibitory activity against lung cancer, and the mechanism may be related to the down-regulation of LSD1 expression to induce the cell apoptosis and suppress the cell migration and EMT process. These findings will provide new insights into the action of Puerariae Lobatae Radix as an anti-lung cancer agent and offer new ideas for the study on the anti-cancer action of Chinese medicine based on the epigenetic modification.

Comparison of the prevalence of sarcopenia in geriatric patients in Xining based on three different diagnostic criteria.

BACKGROUND: Sarcopenia is an age-related decline in skeletal muscle mass, which depends on an assessment of muscle strength and muscle mass. The diagnostic definition of sarcopenia varies by region. AIM: To determine the optimal diagnostic criteria for sarcopenia in a plateau population. Cut off values for the components of diagnostic algorithms for sarcopenia in plateau populations should consider altitude. METHODS: One hundred and fifty subjects aged > 60 years attending a tertiary comprehensive hospital in the city of Xining (elevation: 2260 m) between October and December 2018 were enrolled. Handgrip strength, muscle mass, and physical performance were measured. Sarcopenia was diagnosed according to the Asian Working Group for Sarcopenia (AWGS) 2019 criteria, Beijing criteria, and Lasha criteria. RESULTS: Across diagnostic criteria, there were significant differences in the prevalence of sarcopenia in the overall population and stratified by gender. The prevalence of sarcopenia measured by the AWGS 2019 or Lasha criteria was significantly higher in female compared to male subjects. In males, the prevalence of sarcopenia measured by the Beijing criteria was significantly higher in subjects who identified as Han compared to Minority. In females, there were no significant differences in the prevalence of sarcopenia by ethnicity according to any criteria. CONCLUSION: The Lasha criteria provided a lower prevalence of sarcopenia (males, 8.7%; females, 22.41%; overall, 14%) and were able to differentiate between males and females. The Lasha criteria are likely most appropriate for detection of sarcopenia in this plateau population. We recommend the Lasha criteria for detection of sarcopenia in Xining.

The effect of chronoradiotherapy on cervical cancer patients: A multicenter randomized controlled study.

Objectives: To investigate the short-term efficacy and radiotoxicity 3.543of chronoradiotherapy in patients with cervical cancer. We also examined the overall symptom score and quality of life (QOL) of patients who underwent morning radiotherapy and evening radiotherapy. Methods: We conducted a multicenter randomized controlled trial to compare the effects of morning radiotherapy (9:00-11:00 AM) with evening radiotherapy (7:00-9:00 PM) in cervical cancer patients receiving radiotherapy. From November 2021 to June 2022, 114 cervical cancer patients admitted to eight cancer center hospitals in Tianjin, Chongqing, Hubei, Shanxi, Shandong, Shaanxi, Hebei, and Cangzhou were randomly divided into the morning radiotherapy group (MG; N = 61) and the evening radiotherapy group (EG; N = 53). The short-term efficacy of radiotherapy on cervical cancer patients at different time points and the occurrence of radiotoxicity were explored after patients had undergone radiotherapy. Results: The total effective response (partial remission [PR] + complete remission [CR]) rate was similar across the two groups (93.5% vs. 96.3%, p > 0.05). However, the incidence of bone marrow suppression and intestinal reaction in the two groups were significantly different (p < 0.05). The patients in the MG had significantly higher Anderson symptom scores than patients in the EG (21.64 ± 7.916 vs. 18.53 ± 4.098, p < 0.05). In terms of physical activity, functional status, and overall QOL, the MG had significantly lower scores than the EG (p < 0.05). No other measures showed a significant difference between the groups. Conclusion: The radiotherapy effect of the MG was consistent with that of the EG. The incidence of radiation enteritis and radiation diarrhea in the MG was significantly higher than that in the EG; however, bone marrow suppression and blood toxicity in the EG were more serious than in the MG. Because of the small sample size of the study, we only examined the short-term efficacy of radiotherapy. Therefore, further clinical trials are needed to verify the efficacy and side effects of chronoradiotherapy. Clinical Trial Registration: http://www.chictr.org.cn/searchproj.aspx, Registration Number: ChiCTR2100047140.

Analysis of pathogenesis and drug treatment of chronic obstructive pulmonary disease complicated with cardiovascular disease.

Chronic obstructive pulmonary disease (COPD) is a disease characterized by persistent airflow limitation, and is associated with abnormal inflammatory responses in the lungs to cigarette smoke and toxic and harmful gases. Due to the existence of common risk factors, COPD is prone to multiple complications, among which cardiovascular disease (CVD) is the most common. It is currently established that cardiovascular comorbidities increase the risk of exacerbations and mortality from COPD. COPD is also an independent risk factor for CVD, and its specific mechanism is still unclear, which may be related to chronic systemic inflammation, oxidative stress, and vascular dysfunction. There is evidence that chronic inflammation of the airways can lead to destruction of the lung parenchyma and decreased lung function. Inflammatory cells in the airways also generate reactive oxygen species in the lungs, and reactive oxygen species further promote lung inflammation through signal transduction and other pathways. Inflammatory mediators circulate from the lungs to the whole body, causing intravascular dysfunction, promoting the formation and rupture of atherosclerotic plaques, and ultimately leading to the occurrence and development of CVD. This article reviews the pathophysiological mechanisms of COPD complicated by CVD and the effects of common cardiovascular drugs on COPD.

Biofilm Alterations on the Stepwise Acquisition of Fluconazole-resistant Candida Albicans Isolates.

By assessing and comparing the phenotypic changes on the stepwise acquisition of fluconazole resistant Candida albicans isolates, we could find and describe the relationship between drug resistance and biofilm formation ability in a series of clonal strains. Methods: We performed antifungal susceptibility of five drugs (fluconazole, itraconazole, voriconazole, caspofungin and amphotericin B) to further verify the antifungal activity of the six isolates in vitro. Then we combined hyphal formation assay, cell surface hydrophobicity test positively related to adherence ability, and biofilm assays in vitro to observe and compare the phenotypic characteristics of our six clonal strains. Results: Biofilm capability is enhanced for four drug- intermediate strains, whereas the initial susceptible strain and the final resistant strain are both poor in adherence, hyphal growth and biofilm formation. Conclusions: It was suggested that the biofilm formation ability were not absolutely related to the degree of fluconazole resistance.

[Preparation and in vitro evaluation of quercetin nanosuspension stabilized by gypenosides].

This study was designed to explore the potential of gypenosides as a novel natural stabilizer for the production of nanosuspensions. The gypenosides-stabilized quercetin nanosuspensions(QUE-NS) were prepared using the high-speed shearing and high-pressure homogenization method with quercetin as a model drug, followed by their in vitro evaluation.Based on the measured mean particle size and polydispersity index(PDI) of QUE-NS,the single factor experiment was conducted to optimize the preparation process parameters.The freeze-drying method was used to transform QUE-NS into freeze-dried powders, whose storage stability and saturation solubility were then studied.Moreover, the effects of pH and ionic strength on the physical stability of the nanosuspension system were examined.According to the results, the optimized process parameters were listed as follows: shear rate 13 000 r·min~(-1),shear time 2 min, homogenization pressure 100 MPa, and homogenization frequency 12 times.The mean particle size of QUE-NS prepared under the optimum process conditions was(461.9±2.4) nm, and the PDI was 0.059±0.016.During the two months of storage at room temperature, the freeze-dried QUE-NS powders remained stable.The saturation solubility of freeze-dried QUE-NS powders was proved higher than those of quercetin and the physical mixture.The results of stability testing demonstrated that QUE-NS stabilized with gypenosides exhibited good stability within the pH range of 6 to 8,while coalescence was prone to occur in the presence of salt.Overall, gypenosides is expected to become a new natural stabilizer for the preparation of nanosuspensions.

Protein intake and risk of inflammatory bowel disease: A meta-analysis.

BACKGROUND AND OBJECTIVES: Although the association between dietary protein intake and inflammatory bowel disease (IBD) risk has been investigated, the results are inconsistent. Therefore, we conducted a meta-analysis to reassess the relationship between dietary protein intake and IBD risk. METHODS AND STUDY DESIGN: The PubMed, Web of Knowledge, and Wanfang databases were searched for pertinent studies through January 31, 2020. Relative risks (RRs) with 95% confidence intervals (CIs) were derived using a random-effect model. Subgroup analyses according to disease type, geographic location, and sex; sensitivity analysis; and publication bias analysis were performed. RESULTS: The current report includes 8 articles consisting of 12 studies with 1069 cases and 330,676 participants. The pooled RR (95% CI) of the highest vs. the lowest categories of dietary protein intake for the IBD risk was 1.561 (0.384-6.347) in cohort studies and 1.060 (0.663-1.694) in case-control studies. Evidence of heterogeneity was found both in cohort studies (I2=86.4%, p=0.007) and in case-control studies (I2=49.0%, p=0.039). However, the association was significant among Asian populations (RR=1.675, 95% CI=1.096-2.559) but not in other populations. We did not find any relationship of dietary protein intake with the risk of either Crohn's disease or ulcerative colitis. CONCLUSIONS: Based on limited information, the highest dietary protein intakes among Asians may increase the risk of IBD, undifferentiated for ulcerative colitis or Crohn's disease. This may reflect dietary patterns for which protein is a marker rather than implicate protein itself.

Discovery of polymethoxyphenyl-pyridines bearing amino side chains as tubulin colchicine-binding site inhibitors.

Nineteen TH03 analogues were designed and synthesized as tubulin colchicine-binding site inhibitors with potent antiproliferative activities. Among these compounds, 3,5-dimethoxyphenylpyridines 8j bearing a 4-methoxybenzyl aniline side-chain displayed the best antiproliferative activities against glioma (U87MG and U251). In addition, the trimethoxyphenylpyridine 8o bearing a 4-methyl-N-methyl aniline side-chain showed the best antiproliferative activities against colon carcinoma and lung cancer with the lowest IC50 value (0.09 µM < IC50 < 0.86 µM). Compared with CA-4, Compounds 8j and 8o displayed lower cytotoxicities toward normal cells but higher antiproliferative activities against RKO (IC50 = 0.15 µM and 0.09 µM respectively), NCI-H1299 (IC50 = 0.73 µM and 0.14 µM respectively), and A549 cells (IC50 = 0.86 µM and 0.37 µM respectively). Further investigations revealed that 8o shows higher tubulin polymerization inhibitory activity (IC50 = 3.1 ± 0.5 µM) than colchicine (IC50 = 8.6 ± 0.2 µM), and induced cell cycle arrest at the G2/M phase and cellular apoptosis through disrupting the microtubule network.

Health care worker occupational experiences during the COVID-19 outbreak: A cross-sectional study.

BACKGROUND: Health care workers treating coronavirus disease 2019 (COVID-19) patients experience burnout and stress due to overwork and poor working conditions. AIM: To investigate the work experiences of frontline health care workers in Wuhan city and Qinghai province, China, during the COVID-19 outbreak. METHODS: In this cross-sectional descriptive study, a self-reported questionnaire was designed to evaluate work experiences of medical staff throughout the course of the COVID-19 pandemic. A total of 178 health care workers responded to the questionnaire between February 19 and 29, 2020. Higher questionnaire dimen-sional score confirmed dimensional advantage. RESULTS: Of all dimensions evaluated by this questionnaire, the occupational value dimension had the highest mean score of 2.61 (0.59), followed by the support/security dimension score of 2.30 (0.74). Occupational protection scored lowest at 1.44 (0.75), followed by work environment at 1.97 (0.81). The social relationships dimension had an intermediate score of 2.06 (0.80). Significant differences in working conditions were observed across hospital departments, with the fever ward scoring lowest. Total scores also differed significantly across workplaces; the fever outpatient department scored lowest (P < 0.01). This phenomenon was likely due to the fact that work in the fever outpatient department, where many patients present to hospital, necessitates constant contact with a large number of individuals with insufficient provision of resources (such as protective equipment and social support). Medical workers in the fever outpatient department were burdened with a fear of COVID-19 infection and a lower sense of professional value as compared to workers in other hospital departments. Medical staff in Wuhan worked longer hours (P < 0.01) as compared to elsewhere. The mean support/security dimension score was higher for tertiary hospital as compared to secondary hospital medical staff as well as for Wuhan area as compared to Qinghai region staff (P < 0.01). Staff in Wuhan had a lower mean work environment score as compared to staff in Qinghai (P < 0.05). CONCLUSION: Medical staff treating COVID-19 patients in China report poor occupational experiences strongly affected by work environment, occupational protection and social relationships. Health care managers must address the occupational needs of medical staff by ensuring a supportive and safe work environment.

Phaeohyphomycosis in China.

Background: Due to more attentions paid to melanized fungi over the past few decades and under the background of the global coronavirus disease 2019 pandemic (COVID-19) the fact that the virus itself and the immunosuppressive agents such as glucocorticoids can further increase the risk of infections of deep mycoses, the number of patients with phaeohyphomycosis (PHM) has a substantial increase. Their spectrum is broad and the early diagnosis and treatments are extremely sticky. This study aims to more comprehensively understand the clinical features of phaeohyphomycosis in China over 35 years and to establish a more applicable systematical classification and severity grades of lesions to guide treatments and prognosis. Methods: We reviewed 174 cases of proven phaeohyphomycosis reported in Chinese and English language literature from 1987 to 2021 and we also made the accurate classification definitions and detailed information about the epidemiology, species of clinical dematiaceous fungi, minimum inhibitory concentration values, clinical features, treatments, and prognosis. Results: The mortality of cerebral, disseminated and pulmonary phaeohyphomycosis are 55%, 36%, and 25%. Nearly 19% of patients had poor quality of life caused by the complications such as disability, disfigurements, and blindness. The overall misdiagnosis rate of phaeohyphomycosis was 74%. Moderate to severe rashes are accounting for 82% of subcutaneous phaeohyphomycosis. The areas of the head and face are mostly affected accounting for 16% of severe rashes. Nearly 30% of invasive infections of phaeohyphomycosis are triggered by recurrent lesions. Voriconazole, itraconazole, amphotericin B deoxycholate (AmB-DOC), and terbinafine were most commonly used but diagnosis and treatments of phaeohyphomycosis remain challenging in reality. Conclusions: Our classifications are likely to be more practical and easier to popularize, and there are still also plenty of characteristics in these non-specific lesions. There're no significant variations in cure rates, or death rates between three grades of lesions. But patients with severe rashes have longer courses and lower effective rates.

Golgi anti-apoptotic proteins redundantly counteract cell death by inhibiting production of reactive oxygen species under endoplasmic reticulum stress.

Maintaining proteostasis in the endoplasmic reticulum (ER) is critical for cell viability and plant survival under adverse conditions. The unfolded protein response (UPR) pathways interact with reactive oxygen species (ROS) to precisely trigger adaptive outputs or cell death under ER stress with varying degrees. However, little information is known about the relationship between UPR signalling and ROS regulation. Here, Arabidopsis GOLGI ANTI-APOPTOTIC PROTEIN1 (GAAP1)-GAAP4 were found to play redundant positive roles under ER stress. Genetic analysis showed that GAAP4 played a role in INOSITOL-REQUIRING ENZYME (IRE1)-dependent and -independent pathways. In addition, GAAPs played negative roles to activate the adaptive UPR under conditions of stress. Quantitative biochemical analysis showed that mutations in GAAP genes decreased the oxidised glutathione content and altered the pattern of ROS and glutathione in early ER stress. When plants were challenged with unmitigated ER stress, mutations in GAAP advanced ROS accumulation, which was associated with a decline in adaptive UPR. These data indicated that GAAPs resist cell death by regulating glutathione content to inhibit ROS accumulation and maintain UPR during ER stress. They provide a basis for further analysis of the regulation of cell fate decision under ER stress.