Sodium-glucose cotransporter-2 inhibitors and abnormal serum potassium: a real-world, pharmacovigilance study.

BACKGROUND: New trials indicated a potential of sodium-glucose cotransporter-2 inhibitors (SGLT2i) to reduce hyperkalemia, which might have important clinical implications, but real-world data are limited. Therefore, we examined the effect of SGLT2i on hyper- and hypokalemia occurrence using the FDA adverse event reporting system (FAERS). METHODS: The FAERS database was retrospectively queried from 2004q1 to 2021q3. Disproportionality analyses were performed based on the reporting odds ratio (ROR) and 95% confidence interval (CI). RESULTS: There were 84 601 adverse event reports for SGLT2i and 1 321 186 reports for other glucose-lowering medications. The hyperkalemia reporting incidence was significantly lower with SGLT2i than with other glucose-lowering medications (ROR, 0.83; 95% CI, 0.79-0.86). Reductions in hyperkalemia reports did not change across a series of sensitivity analyses. Compared with that with renin-angiotensin-aldosterone system inhibitors (RAASi) alone (ROR, 4.40; 95% CI, 4.31-4.49), the hyperkalemia reporting incidence was disproportionally lower among individuals using RAASi with SGLT2i (ROR, 3.25; 95% CI, 3.06-3.45). Compared with that with mineralocorticoid receptor antagonists (MRAs) alone, the hyperkalemia reporting incidence was also slightly lower among individuals using MRAs with SGLT-2i. The reporting incidence of hypokalemia was lower with SGLT2i than with other antihyperglycemic agents (ROR, 0.79; 95% CI, 0.75-0.83). CONCLUSION: In a real-world setting, hyperkalemia and hypokalemia were robustly and consistently reported less frequently with SGLT2i than with other diabetes medications. There were disproportionally fewer hyperkalemia reports among those using SGLT-2is with RAASi or MRAs than among those using RAASi or MRAs alone.

WGCNA reveals a biomarker for cancer-associated fibroblasts to predict prognosis in cervical cancer.

BACKGROUND: Cancer-associated fibroblasts (CAFs) are crucial components of the cervical cancer tumor microenvironment, playing a significant role in cervical cancer progression, treatment resistance, and immune evasion, but whether the expression of CAF-related genes can predict clinical outcomes in cervical cancer is still unknown. In this study, we sought to analyze genes associated with CAFs through weighted gene co-expression network analysis (WGCNA) and to create a predictive model for CAFs in cervical cancer. METHODS: We acquired transcriptome sequencing data and clinical information on cervical cancer patients from the TCGA and GEO databases. Weighted gene co-expression network analysis was conducted to identify genes related to CAFs. We developed a prognostic model based on CAF genes in cervical cancer using LASSO Cox regression analysis. Single-cell sequencing data analysis and in vivo experiments for validation of hub genes in CAFs. RESULTS: A prognostic model for cervical cancer was developed based on CAF genes including COL4A1, LAMC1, RAMP3, POSTN, and SERPINF1. Cervical cancer patients were divided into low and high risk groups based on the optimal cutoff value. Patients in the high risk group had significantly worse prognosis. Single-cell RNA sequencing data revealed that hub genes in the CAFs risk model were expressed mainly in fibroblasts. The real-time fluorescence quantitative PCR results revealed a significant difference in the expression levels of COL4A1, LAMC1, POSTN, and SERPINF1 between the cancer group and the normal group (p < 0.05). Consistently, the results of the immunohistochemical tests exhibited notable variations in COL4A1, LAMC1, RAMP3, POSTN, and SERPINF1 expression between the cancer and normal groups (p < 0.001). CONCLUSION: The CAF risk model for cervical cancer constructed in this study can be used to predict prognosis, while the CAF hub genes can be utilized as crucial markers for cervical cancer prognosis.

Integrated Information for Pathogenicity and Treatment of Spiroplasma.

Spiroplasma, belonging to the class Mollicutes, is a small, helical, motile bacterium lacking a cell wall. Its host range includes insects, plants, and aquatic crustaceans. Recently, a few human cases of Spiroplasma infection have been reported. The diseases caused by Spiroplasma have brought about serious economic losses and hindered the healthy development of agriculture. The pathogenesis of Spiroplasma involves the ability to adhere, such as through the terminal structure of Spiroplasma, colonization, and invasive enzymes. However, the exact pathogenic mechanism of Spiroplasma remains a mystery. Therefore, we systematically summarize all the information about Spiroplasma in this review article. This provides a reference for future studies on virulence factors and treatment strategies of Spiroplasma.

First-Principles Calculations of TiB4 and TiB5 as Anodes with High Capacity for Na-Ion Batteries.

The electrochemical properties of TiB4 and TiB5 monolayers in Na-ion batteries (NIBs) were studied by using the first-principles calculation method based on density functional theory. The TiB4/TiB5 monolayer showed excellent Na storage capacity, capable of adsorbing two layers of Na with theoretical capacities of 1176.77 and 1052.05 mA g-1, respectively. The average operating voltages of the TiB4 and TiB5 monolayers are 0.073 and 0.042 eV, respectively, indicating that they can be used as anode materials for NIBs. More interestingly, the exposed B surface not only brings a high theoretical capacity but also provides a relatively small diffusion barrier of 0.16 (for TiB4) and 0.33 eV (for TiB5), enhancing their rate capability in NIBs.

Mitochondrial Targeted Cerium Oxide Nanoclusters for Radiation Protection and Promoting Hematopoiesis.

Purpose: Mitochondrial oxidative stress is an important factor in cell apoptosis. Cerium oxide nanomaterials show great potential for scavenging free radicals and simulating superoxide dismutase (SOD) and catalase (CAT) activities. To solve the problem of poor targeting of cerium oxide nanomaterials, we designed albumin-cerium oxide nanoclusters (TPP-PCNLs) that target the modification of mitochondria with triphenyl phosphate (TPP). TPP-PCNLs are expected to simulate the activity of superoxide dismutase, continuously remove reactive oxygen species, and play a lasting role in radiation protection. Methods: First, cerium dioxide nanoclusters (CNLs), polyethylene glycol cerium dioxide nanoclusters (PCNLs), and TPP-PCNLs were characterized in terms of their morphology and size, ultraviolet spectrum, dispersion stability and cellular uptake, and colocalization Subsequently, the anti-radiation effects of TPP-PCNLs were investigated using in vitro and in vivo experiments including cell viability, apoptosis, comet assays, histopathology, and dose reduction factor (DRF). Results: TPP-PCNLs exhibited good stability and biocompatibility. In vitro experiments indicated that TPP-PCNLs could not only target mitochondria excellently but also regulate reactive oxygen species (ROS)levels in whole cells. More importantly, TPP-PCNLs improved the integrity and functionality of mitochondria in irradiated L-02 cells, thereby indirectly eliminating the continuous damage to nuclear DNA caused by mitochondrial oxidative stress. TPP-PCNLs are mainly targeted to the liver, spleen, and other extramedullary hematopoietic organs with a radiation dose reduction factor of 1.30. In vivo experiments showed that TPP-PCNLs effectively improved the survival rate, weight change, hematopoietic function of irradiated animals. Western blot experiments have confirmed that TPP-PCNLs play a role in radiation protection by regulating the mitochondrial apoptotic pathway. Conclusion: TPP-PCNLs play a radiologically protective role by targeting extramedullary hematopoietic organ-liver cells and mitochondria to continuously clear ROS.

[Quercetin Alleviates H2O2-Induced Oxidative Stress Damage to Human Endometrial Stromal Cells by Inhibiting the p38 MAPK/NOX4 Signaling Pathway]. / æ§²çš®ç´ é€šè¿‡æŠ‘åˆ¶p38 MAPK/NOX4信号通路减轻H2O2è¯±å¯¼çš„äººå­å®«å† è†œåŸºè´¨ç»†èƒžæ°§åŒ–åº”æ¿€æŸä¼¤.

Objective: This study aims to systematically evaluate the protective role of quercetin (QCT), a naturally occurring flavonoid, against oxidative damage in human endometrial stromal cells (HESCs) induced by hydrogen peroxide (H2O2). Oxidative stress, such as that induced by H2O2, is known to contribute significantly to cellular damage and has been implicated in various reproductive health issues. The study is focused on investigating how QCT interacts with specific molecular pathways to mitigate this damage. Special attention was given to the p38 MAPK/NOX4 signaling pathway, which is crucial to the regulation of oxidative stress responses in cellular systems. By elucidating these mechanisms, the study seeks to confirm the potential of QCT not only as a protective agent against oxidative stress but also as a therapeutic agent that could be integrated in treatments of conditions characterized by heightened oxidative stress in endometrial cells. Methods: I n vitro cultures of HESCs were treated with QCT at different concentrations (0, 10, 20, and 40 µmol/L) for 24 h to verify the non-toxic effects of QCT on normal endometrial cells. Subsequently, 250 µmol/L H2O2 was used to incubate the cells for 12 h to establish an H2O2-induced HESCs injury model. HESCs were pretreated with QCT for 24 h, which was followed by stimulation with H2O2. Then, CCK-8 assay was performed to examine the cell viability and to screen for the effective intervention concentration. HESCs were divided into 3 groups, the control group, the H2O2 model group, and the H2O2+QCT group. Intracellular levels of reactive oxygen species (ROS) were precisely quantified using the DCFH-DA fluorescence assay, a method known for its accuracy in detecting and quantifying oxidative changes within the cell. The mitochondrial membrane potential was determined by JC-1 staining. Annexin Ⅴ/PI double staining and flow cytometry were performed to determine the effect of QCT on H2O2-induced apoptosis of HESCs. Furthermore, to delve deeper into the cellular mechanisms underlying the observed effects, Western blot analysis was conducted to measure the expression levels of the critical proteins involved in oxidative stress response, including NADPH oxidase 4 (NOX4), p38 mitogen-activated protein kinase (p38 MAPK), and phosphorylated p38 MAPK (p-p38 MAPK). This analysis helps increase understanding of the specific intracellular signaling pathways affected by QCT treatment, giving special attention to its potential for modulation of the p38 MAPK/NOX4 pathway, which plays a significant role in cellular defense mechanisms against oxidative stress. Results: In this study, we started off by assessing the toxicity of QCT on normal endometrial cells. Our findings revealed that QCT at various concentrations (0, 10, 20, and 40 µmol/L) did not exhibit any cytotoxic effects, which laid the foundation for further investigation into its protective roles. In the H2O2-induced HESCs injury model, a significant reduction in cell viability was observed, which was linked to the generation of ROS and the resultant oxidative damage. However, pretreatment with QCT (10 µmol/L and 20 µmol/L) significantly enhanced cell viability after 24 h (P<0.05), with the 20 µmol/L concentration showing the most substantial effect. This suggests that QCT can effectively reverse the cellular damage caused by H2O2. Furthermore, the apoptosis assays demonstrated a significant increase in the apoptosis rates in the H2O2 model group compared to those in the control group (P<0.01). However, co-treatment with QCT significantly reversed this trend (P<0.05), indicating QCT's potential protective role in mitigating cell apoptosis. ROS assays showed that, compared to that in the control group, the average fluorescence intensity of ROS in the H2O2 model group significantly increased (P<0.01). QCT treatment significantly reduced the ROS fluorescence intensity in the H2O2+QCT group compared to the that in the H2O2 model group, suggesting an effective alleviation of oxidative damage (P<0.05). JC-1 staining for mitochondrial membrane potential changes revealed that compared to that in the control, the proportion of cells with decreased mitochondrial membrane potential significantly increased in the H2O2 model group (P<0.01). However, this proportion was significantly reduced in the QCT-treated group compared to that of the H2O2 model group (P<0.05). Finally, Western blot analysis indicated that the expression levels of NOX4 and p-p38 MAPK proteins were elevated in the H2O2 model group compared to those of the control group (P<0.05). Following QCT treatment, these protein levels significantly decreased compared to those of the H2O2 model group (P<0.05). These results suggest that QCT may exert its protective effects against oxidative stress by modulating the p38 MAPK/NOX4 signaling pathway. Conclusion: QCT has demonstrated significant protective effects against H2O2-induced oxidative damage in HESCs. This protection is primarily achieved through the effective reduction of ROS accumulation and the inhibition of critical signaling pathways involved in the oxidative stress response, notably the p38 MAPK/NOX4 pathway. The results of this study reveal that QCT's ability to modulate these pathways plays a key role in alleviating cellular damage associated with oxidative stress conditions. This indicates not only its potential as a protective agent against cellular oxidative stress, but also highlights its potential for therapeutic applications in treating conditions characterized by increased oxidative stress in the endometrium, thereby offering the prospect of enhancing reproductive health. Future studies should explore the long-term effects of QCT and its clinical efficacy in vivo, thereby providing a clear path toward its integration into therapeutic protocols.

Obesity is associated with lower levels of negative emotions in polycystic ovary syndrome in clinical and animal studies.

BACKGROUND: Polycystic ovary syndrome (PCOS) is one of the most common endocrine and metabolic disorders in women of reproductive age. It is frequently comorbid with obesity and negative emotions. Currently, there are few reports on the relationship between obesity and negative emotions in patients with PCOS. Here we performed both basic and clinical studies to study the relationship between obesity and negative emotions in PCOS. METHODS: We performed a cross-sectional study including 608 patients with PCOS and 184 healthy participants to assess the mental health status of people with different body mass indices (BMI). Self-rated anxiety, depression, and perceived stress scales were used for subjective mood evaluations. Rat PCOS models fed 45 and 60% high-fat diets were used to confirm the results of the clinical study. Elevated plus maze and open field tests were used to assess anxiety- and depression-like behaviors in rats. RESULTS: We observed overweight/obesity, increased depression, anxiety, and perceived stress in women with PCOS, and found that anxiety and depression were negatively correlated with BMI in patients with severe obesity and PCOS. Similar results were confirmed in the animal study; the elevated plus maze test and open field test demonstrated that only 60% of high fat diet-induced obesity partly reversed anxiety- and depression-like behaviors in PCOS rats. A high-fat diet also modulated rat hypothalamic and hippocampal luteinizing hormone and testosterone levels. CONCLUSION: These results reveal a potential relationship between obesity and negative emotions in PCOS and prompt further investigation. The interactions between various symptoms of PCOS may be targeted to improve the overall well-being of patients.

Obesity was negatively correlated with negative emotions in patients with PCOS.Obesity may affect the downregulation of LH and testosterone and participate in the regulation of emotions.Increased BMI may be beneficial for patients with PCOS in terms of the psychological aspects.

The coagulation status in women of endometriosis with stage IV.

BACKGROUND: Endometriosis is considered as a systemic disease with the presence of proinflammatory cytokines in the circulation, which drives hypercoagulable state of endometriosis. Currently, endometriosis is classified into four stages: I (minimal), II (mild), III (moderate) and IV (severe). The aim of this study is to investigate the correlations between inflammatory markers and coagulation factors in patients diagnosed of endometriosis with stage IV. METHODS: This retrospective case-control study included 171 endometriosis patients with stage IV and 184 controls. Continuous data were expressed by mean ± standard deviation. Mann-Whitney U and χ2 tests were used to compare the medians and frequencies among the groups. Spearman analysis was conducted to determine the correlation among the measured parameters. The diagnostic values of the parameters differentiating endometriomas were tested by receiver operating characteristic (ROC) curve. RESULTS: The time of activated partial thromboplastin time (APTT) was decreased and the concentration of fibrinogen (FIB) and neutrophil-to-lymphocyte ratio (NLR) were increased in women of endometriosis with stage IV. The APTT were negatively correlated with NLR while the concentrations of FIB were positively correlated with NLR. The ROC analysis showed that the Area under the curve (AUC) of FIB was 0.766 (95% confidence interval:0.717-0.814) with sensitivity and specificity reaching 86.5 and 60.9%, respectively. The AUC of CA125 and CA199 was 0.638 (95% confidence interval: 0.578-0.697), 0.71 (95% confidence interval: 0.656-0.763) with sensitivity and specificity reaching 40.9 and 91.8%, 80.7 and 56.5% respectively. The combination of these factors showed the highest AUC of 0.895 (0.862-0.927) with sensitivity of 88.9% and specificity of 77.7%. CONCLUSION: In the present study, we found that inflammatory factors showed significant correlation with APTT or FIB in endometriosis with stage IV. Moreover, the coagulation factors combined with CA125 and CA199 were more reliable for identifying the endometriosis with stage IV.

Co-administration of GnRH-agonist and hCG (double trigger) for final oocyte maturation increases the number of top-quality embryos in patients undergoing IVF/ICSI cycles.

BACKGROUND: The utilization of a double trigger, involving the co-administration of gonadotropin-releasing hormone agonist (GnRH-a) and human chorionic gonadotropin (hCG) for final oocyte maturation, is emerging as a novel approach in gonadotropin-releasing hormone antagonist (GnRH-ant) protocols during controlled ovarian hyperstimulation (COH). This protocol involves administering GnRH-a and hCG 40 and 34 h prior to ovum pick-up (OPU), respectively. This treatment modality has been implemented in patients with low/poor oocytes yield. This study aimed to determine whether the double trigger could improve the number of top-quality embryos (TQEs) in patients with fewer than three TQEs. METHODS: The stimulation characteristics of 35 in vitro fertilization (IVF) cycles were analyzed. These cycles were triggered by the combination of hCG and GnRHa (double trigger cycles) and compared to the same patients' previous IVF attempt, which utilized the hCG trigger (hCG trigger control cycles). The analysis involved cases who were admitted to our reproductive center between January 2018 and December 2022. In the hCG trigger control cycles, all 35 patients had fewer than three TQEs. RESULTS: Patients who received the double trigger cycles yielded a significantly higher number of 2PN cleavage embryos (3.54 ± 3.37 vs. 2.11 ± 2.15, P = 0.025), TQEs ( 2.23 ± 2.05 vs. 0.89 ± 0.99, P < 0.001), and a simultaneously higher proportion of the number of cleavage stage embryos (53.87% ± 31.38% vs. 39.80% ± 29.60%, P = 0.043), 2PN cleavage stage embryos (43.89% ± 33.01% vs. 27.22% ± 27.13%, P = 0.014), and TQEs (27.05% ± 26.26% vs. 14.19% ± 19.76%, P = 0.019) to the number of oocytes retrieved compared with the hCG trigger control cycles, respectively. The double trigger cycles achieved higher rates of cumulative clinical pregnancy (20.00% vs. 2.86%, P = 0.031), cumulative persistent pregnancy (14.29% vs. 0%, P < 0.001), and cumulative live birth (14.29% vs. 0%, P < 0.001) per stimulation cycle compared with the hCG trigger control cycles. CONCLUSION: Co-administration of GnRH-agonist and hCG for final oocyte maturation, 40 and 34 h prior to OPU, respectively (double trigger) may be suggested as a valuable new regimen for treating patients with low TQE yield in previous hCG trigger IVF/intracytoplasmic sperm injection (ICSI) cycles.

Human CD56+CD39+ dNK cells support fetal survival through controlling trophoblastic cell fate: immune mechanisms of recurrent early pregnancy loss.

Decidual natural killer (dNK) cells are the most abundant immune cells at the maternal-fetal interface during early pregnancy in both mice and humans, and emerging single-cell transcriptomic studies have uncovered various human dNK subsets that are disrupted in patients experiencing recurrent early pregnancy loss (RPL) at early gestational stage, suggesting a connection between abnormal proportions or characteristics of dNK subsets and RPL pathogenesis. However, the functional mechanisms underlying this association remain unclear. Here, we established a mouse model by adoptively transferring human dNK cells into pregnant NOG (NOD/Shi-scid/IL-2Rγnull) mice, where human dNK cells predominantly homed into the uteri of recipients. Using this model, we observed a strong correlation between the properties of human dNK cells and pregnancy outcome. The transfer of dNK cells from RPL patients (dNK-RPL) remarkably worsened early pregnancy loss and impaired placental trophoblast cell differentiation in the recipients. These adverse effects were effectively reversed by transferring CD56+CD39+ dNK cells. Mechanistic studies revealed that CD56+CD39+ dNK subset facilitates early differentiation of mouse trophoblast stem cells (mTSCs) towards both invasive and syncytial pathways through secreting macrophage colony-stimulating factor (M-CSF). Administration of recombinant M-CSF to NOG mice transferred with dNK-RPL efficiently rescued the exacerbated pregnancy outcomes and fetal/placental development. Collectively, this study established a novel humanized mouse model featuring functional human dNK cells homing into the uteri of recipients and uncovered the pivotal role of M-CSF in fetal-supporting function of CD56+CD39+ dNK cells during early pregnancy, highlighting that M-CSF may be a previously unappreciated therapeutic target for intervening RPL.

Machine learning-based nomogram: integrating MRI radiomics and clinical indicators for prognostic assessment in acute ischemic stroke.

Background: Acute Ischemic Stroke (AIS) remains a leading cause of mortality and disability worldwide. Rapid and precise prognostication of AIS is crucial for optimizing treatment strategies and improving patient outcomes. This study explores the integration of machine learning-derived radiomics signatures from multi-parametric MRI with clinical factors to forecast AIS prognosis. Objective: To develop and validate a nomogram that combines a multi-MRI radiomics signature with clinical factors for predicting the prognosis of AIS. Methods: This retrospective study involved 506 AIS patients from two centers, divided into training (n = 277) and validation (n = 229) cohorts. 4,682 radiomic features were extracted from T1-weighted, T2-weighted, and diffusion-weighted imaging. Logistic regression analysis identified significant clinical risk factors, which, alongside radiomics features, were used to construct a predictive clinical-radiomics nomogram. The model's predictive accuracy was evaluated using calibration and ROC curves, focusing on distinguishing between favorable (mRS ≤ 2) and unfavorable (mRS > 2) outcomes. Results: Key findings highlight coronary heart disease, platelet-to-lymphocyte ratio, uric acid, glucose levels, homocysteine, and radiomics features as independent predictors of AIS outcomes. The clinical-radiomics model achieved a ROC-AUC of 0.940 (95% CI: 0.912-0.969) in the training set and 0.854 (95% CI: 0.781-0.926) in the validation set, underscoring its predictive reliability and clinical utility. Conclusion: The study underscores the efficacy of the clinical-radiomics model in forecasting AIS prognosis, showcasing the pivotal role of artificial intelligence in fostering personalized treatment plans and enhancing patient care. This innovative approach promises to revolutionize AIS management, offering a significant leap toward more individualized and effective healthcare solutions.

Osteoking prevents bone loss and enhances osteoblastic bone formation by modulating the AGEs/IGF-1/ß-catenin/OPG pathway in type 2 diabetic db/db mice.

Type 2 diabetic osteoporosis (T2DOP) is a skeletal metabolic syndrome characterized by impaired bone remodeling due to type 2 diabetes mellitus, and there are drawbacks in the present treatment. Osteoking (OK) is widely used for treating fractures and femoral head necrosis. However, OK is seldom reported in the field of T2DOP, and its role and mechanism of action need to be elucidated. Consequently, this study investigated whether OK improves bone remodeling and the mechanisms of diabetes-induced injury. We used db/db mice as a T2DOP model and stimulated MC3T3-E1 cells (osteoblast cell line) with high glucose (HG, 50 mM) and advanced glycation end products (AGEs, 100 µg/mL), respectively. The effect of OK on T2DOP was assessed using a combined 3-point mechanical bending test, hematoxylin and eosin staining, and enzyme-linked immunosorbent assay. The effect of OK on enhancing MC3T3-E1 cell differentiation and mineralization under HG and AGEs conditions was assessed by an alkaline phosphatase activity assay and alizarin red S staining. The AGEs/insulin-like growth factor-1(IGF-1)/ß-catenin/osteoprotegerin (OPG) pathway-associated protein levels were assayed by western blot analysis and immunohistochemical staining. We found that OK reduced hyperglycemia, attenuated bone damage, repaired bone remodeling, increased tibial and femoral IGF-1, ß-catenin, and OPG expression, and decreased receptor activator of nuclear kappa B ligand and receptor activator of nuclear kappa B expression in db/db mice. Moreover, OK promoted the differentiation and mineralization of MC3T3-E1 cells under HG and AGEs conditions, respectively, and regulated the levels of AGEs/IGF-1/ß-catenin/OPG pathway-associated proteins. In conclusion, our results suggest that OK may lower blood glucose, alleviate bone damage, and attenuate T2DOP, in part through activation of the AGEs/IGF-1/ß-catenin/OPG pathway.

Factors influencing fatigue, mental workload and burnout among Chinese health care workers during public emergencies: an online cross-sectional study.

OBJECTIVES: The purpose of this study was to investigate fatigue, mental workload, and burnout among health care workers (HCWs) and explore the possible underlying factors. MATERIALS AND METHODS: An online cross-sectional survey design was used to collect data from HCWs in Chongqing, China. The online survey included the Fatigue Severity Scale, NASA Task Load Index, and Chinese version of the Maslach Burnout Inventory-General Survey to assess fatigue, mental workload, and burnout, respectively, and was conducted from February 1 to March 1, 2023. RESULTS: In this study, the incidence of fatigue and burnout among HCWs was 76.40% and 89.14%, respectively, and the incidence of moderate to intolerable mental workloads was 90.26%. Work-family conflict, current symptoms, number of days of COVID-19 positivity, mental workload, burnout and reduced personal accomplishment were significantly associated with fatigue. Mental workload was affected by fatigue and reduced personal accomplishment. Furthermore, burnout was influenced by marital status and fatigue. Moreover, there was a correlation among mental workload, fatigue, and burnout. CONCLUSIONS: Fatigue, mental workload and burnout had a high incidence and were influenced by multiple factors during COVID-19 public emergencies in China.

Genome-wide identification of JAZ gene family members in autotetraploid cultivated alfalfa (Medicago sativa subsp. sativa) and expression analysis under salt stress.

BACKGROUND: Jasmonate ZIM-domain (JAZ) proteins, which act as negative regulators in the jasmonic acid (JA) signalling pathway, have significant implications for plant development and response to abiotic stress. RESULTS: Through a comprehensive genome-wide analysis, a total of 20 members of the JAZ gene family specific to alfalfa were identified in its genome. Phylogenetic analysis divided these 20 MsJAZ genes into five subgroups. Gene structure analysis, protein motif analysis, and 3D protein structure analysis revealed that alfalfa JAZ genes in the same evolutionary branch share similar exon‒intron, motif, and 3D structure compositions. Eight segmental duplication events were identified among these 20 MsJAZ genes through collinearity analysis. Among the 32 chromosomes of the autotetraploid cultivated alfalfa, there were 20 MsJAZ genes distributed on 17 chromosomes. Extensive stress-related cis-acting elements were detected in the upstream sequences of MsJAZ genes, suggesting that their response to stress has an underlying function. Furthermore, the expression levels of MsJAZ genes were examined across various tissues and under the influence of salt stress conditions, revealing tissue-specific expression and regulation by salt stress. Through RT‒qPCR experiments, it was discovered that the relative expression levels of these six MsJAZ genes increased under salt stress. CONCLUSIONS: In summary, our study represents the first comprehensive identification and analysis of the JAZ gene family in alfalfa. These results provide important information for exploring the mechanism of JAZ genes in alfalfa salt tolerance and identifying candidate genes for improving the salt tolerance of autotetraploid cultivated alfalfa via genetic engineering in the future.

Preparation of novel sulfated polysaccharide-carboxymethyl-5-fluorouracil-folic acid conjugates for targeted anticancer drug delivery.

GFP1, a sulfated polysaccharide extracted from Grateloupia filicina, exhibits remarkable immunomodulatory activity. To reduce the side effects of 5-fluorouracil (5-FU), GFP1 was employed as a macromolecular carrier to synthesize of GFP1-C-5-FU by reacting with carboxymethyl-5-fluorouracil (C-5-FU). Subsequently, this new compound was reacted with folic acid (FA) through an ester bond, forming novel conjugates named GFP1-C-5-FU-FA. Nuclear magnetic resonance analysis confirmed the formation of GFP1-C-5-FU-FA. In vitro drug release studies revealed that the cumulative release rate of C-5-FU reached 46.9 % in phosphate buffer (pH 7.4) after 96 h, a rate significantly higher than that of the control groups, indicating the controlled drug release behavior of GFP1-C-5-FU-FA. Additionally, in vitro anticancer assays demonstrated the potent anticancer activity of GFP1-C-5-FU-FA conjugates, as evidenced by the reduced viability of HeLa and AGS cancer cells, along with increased levels of apoptosis and cellular uptake. Western blot analysis indicated that the GFP1-C-5-FU-FA conjugate effectively enhanced phosphorylation in cancer cells through the NF-kB and MAPK pathways, thereby promoting apoptosis. These findings highlight the potential of folate-targeted conjugates in efficiently treating HeLa and AGS cancer cells in vitro and lay a robust theoretical groundwork for future in vivo anti-cancer research involving these cells.

Research Progress on Dental Age Estimation Based on MRI Technology.

Dental age estimation is a crucial aspect and one of the ways to accomplish forensic age estimation, and imaging technology is an important technique for dental age estimation. In recent years, some studies have preliminarily confirmed the feasibility of magnetic resonance imaging (MRI) in evaluating dental development, providing a new perspective and possibility for the evaluation of dental development, suggesting that MRI is expected to be a safer and more accurate tool for dental age estimation. However, further research is essential to verify its accuracy and feasibility. This article reviews the current state, challenges and limitations of MRI in dental development and age estimation, offering reference for the research of dental age assessment based on MRI technology.

Risk factors for avascular necrosis of the femoral head after developmental hip dislocation reduction surgery and construction of Nomogram prediction model.

BACKGROUND: To analyze the risk factors for the development of avascular necrosis (AVN) of the femoral head after reduction surgery in children with developmental hip dysplasia (DDH), and to establish a prediction nomogram. METHODS: The clinical data of 134 children with DDH (169 hips) treated with closure reduction or open reduction from December 2016 to December 2019 were retrospectively analyzed. Independent risk factors for AVN after DDH reduction being combined with cast external immobilization were determined by univariate analysis and multivariate logistic regression and used to generate nomograms predicting the occurrence of AVN. RESULTS: A total of 169 hip joints in 134 children met the inclusion criteria, with a mean age at surgery of 10.7 ± 4.56 months (range: 4-22 months) and a mean follow-up duration of 38.32 ± 27.00 months (range: 12-94 months). AVN developed in 42 hip joints (24.9%); univariate analysis showed that the International Hip Dysplasia Institute (IHDI) grade, preoperative development of the femoral head ossification nucleus, cartilage acetabular index, femoral head to acetabular Y-shaped cartilage distance, residual acetabular dysplasia, acetabular abduction angle exceeding 60°, and the final follow-up acetabular index (AI) were associated with the development of AVN (P < 0.05). Multivariate logistic regression analysis showed that the preoperative IHDI grade, development of the femoral head ossification nucleus, acetabular abduction angle exceeding 60°, and the final follow-up AI were independent risk factors for AVN development (P < 0.05). Internal validation of the Nomogram prediction model showed a consistency index of 0.833. CONCLUSION: Preoperative IHDI grade, preoperative development of the femoral head ossification nucleus, final AI, and acetabular abduction angle exceeding 60° are risk factors for AVN development. This study successfully constructed a Nomogram prediction model for AVN after casting surgery for DDH that can predict the occurrence of AVN after casting surgery for DDH.

Morphological and molecular data reveal Cerrenacaulinicystidiata sp. nov. and Polyporusminutissimus sp. nov. in Polyporales from Asia.

Two new species of Polyporales, Cerrenacaulinicystidiata and Polyporusminutissimus, are illustrated and described on the basis of morphological studies and phylogenetic analyses from southern China and Vietnam. C.caulinicystidiata is characterized by annual, resupinate, sometimes effused-reflexed basidiocarps, greyish orange to brownish orange pore surface, irregular pores (3-8 per mm), a trimitic hyphal system, pyriform to ventricose cystidia, and subglobose basidiospores 3.2-4.5 × 2.8-3.5 µm in size. P.minutissimus is characterized by annual, solitary, fan-shaped with a depressed center or infundibuliform basidiocarps, obvious black stipe, cream to buff yellow pileal surface with glabrous, occasionally zonate and radially aligned stripes, angular pores (6-9 per mm), a dimitic hyphal system, and cylindrical basidiospores, 5-9.2 × 2.2-4 µm. Detailed descriptions and illustrations of the two new species are provided. The differences between the two new species and their morphologically similar and phylogenetically related species are discussed.

Exploring salivary metabolome alterations in people with HIV: towards early diagnostic markers.

Background: The human immunodeficiency virus (HIV) remains a critical global health issue, with a pressing need for effective diagnostic and monitoring tools. Methodology: This study explored distinctions in salivary metabolome among healthy individuals, individuals with HIV, and those receiving highly active antiretroviral therapy (HAART). Utilizing LC-MS/MS for exhaustive metabolomics profiling, we analyzed 90 oral saliva samples from individuals with HIV, categorized by CD4 count levels in the peripheral blood. Results: Orthogonal partial least squares-discriminant analysis (OPLS-DA) and other analyses underscored significant metabolic alterations in individuals with HIV, especially in energy metabolism pathways. Notably, post-HAART metabolic profiles indicated a substantial presence of exogenous metabolites and changes in amino acid pathways like arginine, proline, and lysine degradation. Key metabolites such as citric acid, L-glutamic acid, and L-histidine were identified as potential indicators of disease progression or recovery. Differential metabolite selection and functional enrichment analysis, combined with receiver operating characteristic (ROC) and random forest analyses, pinpointed potential biomarkers for different stages of HIV infection. Additionally, our research examined the interplay between oral metabolites and microorganisms such as herpes simplex virus type 1 (HSV1), bacteria, and fungi in individuals with HIV, revealing crucial interactions. Conclusion: This investigation seeks to contribute understanding into the metabolic shifts occurring in HIV infection and following the initiation of HAART, while tentatively proposing novel avenues for diagnostic and treatment monitoring through salivary metabolomics.