Application of multiple strategies to enhance oleanolic acid biosynthesis by engineered Saccharomyces cerevisiae.

Oleanolic acid and its derivatives are widely used in the pharmaceutical, agricultural, cosmetic and food industries. Previous studies have shown that oleanolic acid production levels in engineered cell factories are low, which is why oleanolic acid is still widely extracted from traditional medicinal plants. To construct a highly efficient oleanolic acid production strain, rate-limiting steps were regulated by inducible promoters and the expression of key genes in the oleanolic acid synthetic pathway was enhanced. Subsequently, precursor pool expansion, pathway refactoring and diploid construction were considered to harmonize cell growth and oleanolic acid production. The multi-strategy combination promoted oleanolic acid production of up to 4.07 g/L in a 100 L bioreactor, which was the highest level reported.

Effects of dietary selenized glucose on intestinal microbiota and tryptophan metabolism in rats: Assessing skatole reduction potential.

3-Methylindole (Skatole), a degradation product of tryptophan produced by intestinal microbial activity, significantly contributes to odor nuisance. Its adverse effects on animal welfare, human health, and environmental pollution have been noted. However, it is still unclear whether the intestinal microbiota mediates the impact of selenium (Se) on skatole production and what the underlying mechanisms remain elusive. A selenized glucose (SeGlu) derivative is a novel organic selenium compound. In this study, a diverse range of dietary SeGlu-treated levels, including SeGlu-deficient (CK), SeGlu-adequate (0.15 mg Se per L), and SeGlu-supranutritional (0.4 mg Se per L) conditions, were used to investigate the complex interaction of SeGlu on intestinal microbiome and serum metabolome changes in male Sprague-Dawley (SD) rats. The study showed that SeGlu supplementation enhanced the antioxidant ability in rats, significantly manifested in the increases of the activity of catalase (CAT) and glutathione peroxidase (GSH-Px), while no change in the level of malonaldehyde (MDA). Metagenomic sequencing analysis verified that the SeGlu treatment group significantly increased the abundance of beneficial microorganisms such as Clostridium, Ruminococcus, Faecalibacterium, Lactobacillus, and Alloprevotella while reducing the abundance of opportunistic pathogens such as Bacteroides and Alistipes significantly. Further metabolomic analysis revealed phenylalanine, tyrosine, and tryptophan biosynthesis changes in the SeGlu treatment group. Notably, the biosynthesis of indole, a critical pathway, was affected by SeGlu treatment, with several crucial enzymes implicated. Correlation analysis demonstrated strong associations between specific bacterial species - Treponema, Bacteroides, and Ruminococcus, and changes in indole and derivative concentrations. Moreover, the efficacy of SeGlu-treated fecal microbiota was confirmed through fecal microbiota transplantation, leading to a decrease in the concentration of skatole in rats. Collectively, the analysis of microbiota and metabolome response to diverse SeGlu levels suggests that SeGlu is a promising dietary additive in modulating intestinal microbiota and reducing odor nuisance in the livestock and poultry industry.

Self-controlled in silico gene knockdown strategies to enhance the sustainable production of heterologous terpenoid by Saccharomyces cerevisiae.

Microbial bioengineering is a growing field for producing plant natural products (PNPs) in recent decades, using heterologous metabolic pathways in host cells. Once heterologous metabolic pathways have been introduced into host cells, traditional metabolic engineering techniques are employed to enhance the productivity and yield of PNP biosynthetic routes, as well as to manage competing pathways. The advent of computational biology has marked the beginning of a novel epoch in strain design through in silico methods. These methods utilize genome-scale metabolic models (GEMs) and flux optimization algorithms to facilitate rational design across the entire cellular metabolic network. However, the implementation of in silico strategies can often result in an uneven distribution of metabolic fluxes due to the rigid knocking out of endogenous genes, which can impede cell growth and ultimately impact the accumulation of target products. In this study, we creatively utilized synthetic biology to refine in silico strain design for efficient PNPs production. OptKnock simulation was performed on the GEM of Saccharomyces cerevisiae OA07, an engineered strain for oleanolic acid (OA) bioproduction that has been reported previously. The simulation predicted that the single deletion of fol1, fol2, fol3, abz1, and abz2, or a combined knockout of hfd1, ald2 and ald3 could improve its OA production. Consequently, strains EK1∼EK7 were constructed and cultivated. EK3 (OA07△fol3), EK5 (OA07△abz1), and EK6 (OA07△abz2) had significantly higher OA titers in a batch cultivation compared to the original strain OA07. However, these increases were less pronounced in the fed-batch mode, indicating that gene deletion did not support sustainable OA production. To address this, we designed a negative feedback circuit regulated by malonyl-CoA, a growth-associated intermediate whose synthesis served as a bypass to OA synthesis, at fol3, abz1, abz2, and at acetyl-CoA carboxylase-encoding gene acc1, to dynamically and autonomously regulate the expression of these genes in OA07. The constructed strains R_3A, R_5A and R_6A had significantly higher OA titers than the initial strain and the responding gene-knockout mutants in either batch or fed-batch culture modes. Among them, strain R_3A stand out with the highest OA titer reported to date. Its OA titer doubled that of the initial strain in the flask-level fed-batch cultivation, and achieved at 1.23 ± 0.04 g L-1 in 96 h in the fermenter-level fed-batch mode. This indicated that the integration of optimization algorithm and synthetic biology approaches was efficiently rational for PNP-producing strain design.

Clinical-radiomics nomogram for the risk prediction of esophageal fistula in patients with esophageal squamous cell carcinoma treated with intensity-modulated radiation therapy or volumetric-modulated arc therapy.

Background: Esophageal fistula (EF) is a serious adverse event as a result of radiotherapy in patients with esophageal cancer (EC). We aimed to identify the predictive factors and establish a prediction model of EF in patients with esophageal squamous cell carcinoma (ESCC) who underwent intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT). Methods: Patients with ESCC treated with IMRT or VMAT from January 2013 to December 2020 at Xijing Hospital were retrospectively analyzed. Ultimately, 43 patients with EF and 129 patients without EF were included in the analysis and propensity-score matched in a 1:3 ratio. The clinical characteristics and radiomics features were extracted. Univariate and multivariate stepwise logistic regression analyses were used to determine the risk factors associated with EF. Results: The median follow-up time was 24.0 months (range, 1.3-104.9 months), and the median overall survival (OS) was 13.1 months in patients with EF. A total of 1,158 radiomics features were extracted, and eight radiomics features were selected for inclusion into a model for predicting EF, with an area under the receiver operating characteristic curve (AUC) value of 0.794. Multivariate analysis showed that tumor length, tumor volume, T stage, lymphocyte rate (LR), and grade IV esophagus stenosis were related to EF, and the AUC value of clinical model for predicting EF was 0.849. The clinical-radiomics model had the best performance in predicting EF with an AUC value of 0.896. Conclusions: The clinical-radiomics nomogram can predict the risk of EF in ESCC patients and is helpful for the individualized treatment of EC.

Comparative transcriptome and metabolome analysis revealed diversity in the response of resistant and susceptible rose (Rosa hybrida) varieties to Marssonina rosae.

Rose black spot disease caused by Marssonina rosae is among the most destructive diseases that affects the outdoor cultivation and production of roses; however, the molecular mechanisms underlying the defensive response of roses to M. rosae have not been clarified. To investigate the diversity of response to M. rosae in resistant and susceptible rose varieties, we performed transcriptome and metabolome analyses of resistant (KT) and susceptible (FG) rose varieties and identified differentially expressed genes (DEGs) and differentially accumulated metabolites (DAMs) in response to M. rosae at different time points. In response to M. rosae, DEGs and DAMs were mainly upregulated compared to the control and transcription factors were concentrated in the WRKY and AP2/ERF families. Gene Ontology analysis showed that the DEGs of FG were mainly enriched in biological processes, such as the abscisic acid-activated signaling pathway, cell wall, and defense response, whereas the DEGs of KT were mainly enriched in Golgi-mediated vesicle transport processes. Kyoto Encyclopedia of Genes and Genomes analysis showed that the DEGs of both varieties were concentrated in plant-pathogen interactions, plant hormone signal transduction, and mitogen-activated protein kinase signaling pathways, with the greatest number of DEGs associated with brassinosteroid (BR) in the plant hormone signal transduction pathway. The reliability of the transcriptome results was verified by qRT-PCR. DAMs of KT were significantly enriched in the butanoate metabolism pathway, whereas DAMs of FG were significantly enriched in BR biosynthesis, glucosinolate biosynthesis, and tryptophan metabolism. Moreover, the DAMs in these pathways were significantly positively correlated with the DEGs. Disease symptoms were aggravated when FG leaves were inoculated with M. rosae after 24-epibrassinolide treatment, indicating that the response of FG to M. rosae involves the BR signaling pathway. Our results provide new insights into the molecular mechanisms underlying rose response to M. rosae and lay a theoretical foundation for formulating rose black spot prevention and control strategies and cultivating resistant varieties.

The Efficacy and Safety of Nirmatrelvir/Ritonavir Against COVID-19 in Elderly Patients.

Objective: To assess the key factors influencing the effectiveness of nirmatrelvir/ritonavir in treating elderly patients with COVID-19. Methods: This study was conducted on patients aged ≥60 who were admitted to the Second Affiliated Hospital of Soochow University for COVID-19 infection and were treated with nirmatrelvir/ritonavir. Clinical information was collected from patients and steady-state blood concentrations of nirmatrelvir and ritonavir were measured. Factors associated with treatment effects were searched by univariate and multivariate analysis. Results: A total of 68 (51 males and 17 females) patients had a median age of 80 (73.0-84.8) years were enrolled in this study. The blood concentration measurements (trough concentrations) of nirmatrelvir and ritonavir were 5.1 (2.6-7.1) and 0.4 (0.2-0.9) µg/mL, respectively. Adverse drug reaction was reported in 4 (5.9%) patients. Univariate analysis showed that age, clinical classification, APACHE II score, total bilirubin (TBil), aspartate transaminase (AST), lactate dehydrogenase (LDH), and total cholesterol (TC) were significantly associated with the effectiveness of treatment (P value <0.05). Concentration of nirmatrelvir was also associated with treatment outcome (P value <0.1). Based on the results of univariate analysis, the above factors were introduced into the multiple linear regression equation as independent variables, and the results showed that clinical classification was included in the regression equation model and was the most important factor affecting the treatment outcome. By receiver operating characteristic curve analysis, the area under curve of age + biochemical indicators + APACHE II score + clinical classification was 0.968 (95% CI = 0.919-1.000; P <0.0001). Among the 68 patients included in the study, 4 cases experienced adverse drug reactions. Conclusion: Age, clinical classification, APACHE II score, TBil, AST, LDH, and TC were significantly associated with the effectiveness of treatment in elderly patients with COVID-19.

GLIM criteria represent a more suitable tool to evaluate the nutritional status and predict postoperative motor functional recovery of older patients with hip fracture: A retrospective study.

Early recognition of malnutrition is essential to improve the prognosis of older patients with hip fracture. The Nutritional Risk Screening 2002 (NRS-2002), the Short-Form Mini Nutritional Assessment (MNA-SF) and the Global Leadership Initiative on Malnutrition (GLIM) are widely used in malnutrition diagnosis. However, criteria for predicting postoperative hip joint motor function in older patients with hip fractures are still necessary. The objective of this study was to select the most appropriate criteria from the NRS-2002, the MNA-SF and the GLIM in predicting the postoperative hip joint motor function recovery 1 year after surgery. This retrospective observational study included 161 patients aged ≥ 65 years with hip fractures. The nutritional status of patients was determined by the NRS-2002, MNA-SF and GLIM. The Harris hip joint score (HHS), the primary outcome of this study, was used to evaluate hip joint motor function. HHS was classified as excellent (HHS > 75) or non-excellent outcomes (HHS ≤ 75). Logistic regression models for hip joint motor function recovery were constructed. Both the receiver operating characteristic curve and the decision curve analysis were used to select the most predictive criteria. The overall mean age of the 161 patients was 77.90 ±â€…8.17. As a result, NRS-2002 (OR:0.06, 95%CI [0.01, 0.17]), MNA-SF (OR:0.05, 95%CI [0.00, 0.23]) and GLIM (OR of moderate: 0.03, 95%CI [0.01, 0.11]; OR of severe: 0.02 [0.00, 0.07]) were predictive for recovery of hip joint motor function. Additionally, both the area under curve of the receiver operating characteristic curve (NRS-2002: 81.2 [73.8, 88.6], MNA-SF: 76.3 [68.5, 84.2], GLIM: 86.2 [79.6,92.8]) and the decision curve analysis showed the GLIM was better than others. Compared with NRS-2002 and MNA-SF, GLIM was a more suitable nutritional assessment criteria to predict the postoperative recovery of hip joint motor function for older patients with hip fracture 1 year after surgery.

The protective effect of social support on all-cause and cardio-cerebrovascular mortality among middle-aged and older adults in the US.

The relationship between social support and mortality, especially cardio-cerebrovascular mortality, still has some limitations in the assessment of social support, sample selection bias, and short follow-up time. We used the data from 2005 to 2008 National Health and Nutrition Examination Survey to examine this relationship. The study analyzed a total of 6776 participants, divided into Group 1, Group 2, and Group 3 according to the social support score (0-1; 2-3; 4-5). Multivariable adjusted COX regression analyses of our study showed that Group 3 and Group 2 had a reduced risk of all-cause and cardio-cerebrovascular mortality (Group 3 vs 1, HR: 0.55, P < 0.001; HR: 0.4, P < 0.001; Group 2 vs 1, HR: 0.77, P = 0.017; HR: 0.58, P = 0.014) compared with Group 1. The same results were observed after excluding those who died in a relatively short time. Additionally, having more close friends, being married or living as married, and enough attending religious services were significantly related to a lower risk of mortality after adjustment. In brief, adequate social support is beneficial in reducing the risk of all-cause mortality and cardio-cerebrovascular mortality in middle-aged and older adults, especially in terms of attending religious services frequency, the number of close friends, and marital status.

Can the allocation of primary health care system resources affect efficiency? A spatial Dubin model study in China.

BACKGROUND: The primary health care (PHC) system plays an important role in China's health care system, but there are challenges such as irrational allocation of health resources and inefficient operation, which need to be improved. The purpose of this study was to explore the impact of resource allocation on the efficiency of the PHC system in China. METHODS: The data in 31 provinces were collected from the China Statistical Yearbook 2017-2021 and the China Health Statistical Yearbook 2017-2021. The comprehensive health resource density index (CHRDI) was constructed based on the entropy method and the health resource density index (HRDI), which was used to analyze the allocation of primary health resources in each province. The adjusted efficiency of the PHC system in each province was calculated by the bootstrap data envelopment analysis (DEA). Finally, the spatial Dubin model was used to explore the effect of the CHRDI on efficiency. RESULTS: From 2016 to 2020, the allocation of primary health resources in 31 provinces showed an increasing trend, and the average efficiency after correction showed a decreasing state year by year. The spatial direct effect and spatial spillover effect coefficients of CHRDI were 0.820 and 1.471, which positively affect the efficiency. Per capita Gross Domestic Product (GDP), urbanization rate, and the proportion of the elderly were the factors affecting the efficiency of the PHC system. CONCLUSIONS: The allocation of primary health resources in all provinces in China has improved each year, but there are still great differences, and efficiency must be further improved. Pay attention to the spatial spillover effect of the level of resource allocation and formulate differentiated measures for different regions. Attention should also be paid to the impact of population aging and economic development on the utilization of primary health resources by increasing health needs and choices.

A conserved ion channel function of STING mediates noncanonical autophagy and cell death.

The cGAS/STING pathway triggers inflammation upon diverse cellular stresses such as infection, cellular damage, aging, and diseases. STING also triggers noncanonical autophagy, involving LC3 lipidation on STING vesicles through the V-ATPase-ATG16L1 axis, as well as induces cell death. Although the proton pump V-ATPase senses organelle deacidification in other contexts, it is unclear how STING activates V-ATPase for noncanonical autophagy. Here we report a conserved channel function of STING in proton efflux and vesicle deacidification. STING activation induces an electron-sparse pore in its transmembrane domain, which mediates proton flux in vitro and the deacidification of post-Golgi STING vesicles in cells. A chemical ligand of STING, C53, which binds to and blocks its channel, strongly inhibits STING-mediated proton flux in vitro. C53 fully blocks STING trafficking from the ER to the Golgi, but adding C53 after STING arrives at the Golgi allows for selective inhibition of STING-dependent vesicle deacidification, LC3 lipidation, and cell death, without affecting trafficking. The discovery of STING as a channel opens new opportunities for selective targeting of canonical and noncanonical STING functions.

Associations between Serum Mineral Nutrients, Gut Microbiota, and Risk of Neurological, Psychiatric, and Metabolic Diseases: A Comprehensive Mendelian Randomization Study.

Recent observational studies have reported associations between serum mineral nutrient levels, gut microbiota composition, and neurological, psychiatric, and metabolic diseases. However, the causal effects of mineral nutrients on gut microbiota and their causal associations with diseases remain unclear and require further investigation. This study aimed to identify the associations between serum mineral nutrients, gut microbiota, and risk of neurological, psychiatric, and metabolic diseases using Mendelian randomization (MR). We conducted an MR study using the large-scale genome-wide association study (GWAS) summary statistics of 5 serum mineral nutrients, 196 gut microbes at the phylum, order, family, and genus levels, and a variety of common neurological, psychiatric, and metabolic diseases. Initially, the independent causal associations of mineral nutrients and gut microbiota with diseases were examined by MR. Subsequently, the causal effect of mineral nutrients on gut microbiota was estimated to investigate whether specific gut microbes mediated the association between mineral nutrients and diseases. Finally, we performed sensitivity analyses to assess the robustness of the study results. After correcting for multiple testing, we identified a total of 33 causal relationships among mineral nutrients, gut microbiota, and diseases. Specifically, we found 4 causal relationships between 3 mineral nutrition traits and 3 disease traits, 15 causal associations between 14 gut microbiota traits and 6 disease traits, and 14 causal associations involving 4 mineral nutrition traits and 15 gut microbiota traits. Meanwhile, 118 suggestive associations were identified. The current study reveals multiple causal associations between serum mineral nutrients, gut microbiota, risk of neurological, psychiatric, and metabolic diseases, and potentially provides valuable insights for subsequent nutritional therapies.

Influence of Cry1Ab protein on growth and development of a predatory spider, Pardosa pseudoannulata, from protective perspectives.

The expression of Cry proteins in genetically modified rice varieties safeguards the crop from lepidopteran pests. These proteins have the potential to be transferred through the food chain to arthropods like planthoppers and predatory spiders, triggering defensive responses in these unintended organisms. Hence, we hypothesized that Cry protein might influence the growth and development of spiders by altering protective enzyme activities. The results showed that Cry1Ab protein could accumulate in tissues and subcellular organelles of Pardosa pseudoannulata from Nilaparvata lugens. Cry1Ab protein exposure prolonged the developmental duration in the 5th and 7th instar spiderlings but induced no alterations of other growth indicators, such as body length, median ocular area, and survival rate. In addition, Cry1Ab protein exerted no adverse impacts on several detoxifying enzymes (i.e., superoxide dismutase, catalase, glutathione peroxidase, and acetylcholine esterase) in muscle, midgut, ganglia, and hemolymph at subcellular components (i.e., microsome and cytoplasm). To further explore the effects of Cry1Ab protein on the spiderlings, we performed an integrated transcriptome analysis on spiderlings exposed to Cry1Ab protein. The results showed that Cry1Ab protein might prolong the development duration of P. pseudoannulata via the altered cuticle metabolism (e.g., chitin metabolic process and structural constituent of cuticle). In addition, the gene expression profile associated with detoxifying enzymes and three stress-responsive pathways (JAK/STAT, JNK/SAPK, and Hippo pathways) also displayed no significant alterations under Cry1Ab exposure. Collectively, this integrated analysis generates multidimensional insights to assess the effects of Cry1Ab protein on non-target spiders and demonstrates that Cry1Ab protein exerts no toxicity in P. pseudoannulata.

Model driven method for exploring individual and confounding effects in spontaneous adverse event reporting databases.

BACKGROUND: Spontaneous Adverse Event Reporting (SAER) databases play a crucial role in post-marketing drug surveillance. However, the traditional model-free disproportionality analysis has been challenged by the insufficiency in investigating subgroup and confounders. These issues result in significant low-precision and biases in data mining for SAER. METHODS: The Model-Driven Reporting Odds Ratio (MD-ROR) was proposed to bridge the gap between SAER database and explainable models for exploring individual and confounding effects. MD-ROR is grounded in a well-designed model, rather than a 2 × 2cross table, for estimating AE-drug signals. Consequently, individual and confounding effects can be parameterized based on these models. We employed simulation data and the FDA Adverse Event Reporting System (FAERS) database. RESULT: The simulated data indicated the subgroup effects estimated by MD-ROR were unbiased and efficient. Moreover, the adjusted-MD-ROR demonstrated greater robustness against confounding biases than the crude ROR. Applying our method to the FAERS database suggested higher occurrences of drug interactions and cardiac adverse events induced by Midazolam in females compared to males. CONCLUSION: The study underscored that MD-ROR holds promise as a method for investigating individual and confounding effects in SAER databases.

Immune and oxidative stress disorder in ovulation-dysfunction women revealed by single-cell transcriptome.

Introduction: Ovulation dysfunction is now a widespread cause of infertility around the world. Although the impact of immune cells in human reproduction has been widely investigated, systematic understanding of the changes of the immune atlas under female ovulation remain less understood. Methods: Here, we generated single cell transcriptomic profiles of 80,689 PBMCs in three representative statuses of ovulation dysfunction, i.e., polycystic ovary syndrome (PCOS), primary ovarian insufficiency (POI) and menopause (MENO), and identified totally 7 major cell types and 25 subsets of cells. Results: Our study revealed distinct cluster distributions of immune cells among individuals of ovulation disorders and health. In patients with ovulation dysfunction, we observed a significant reduction in populations of naïve CD8 T cells and effector memory CD4 T cells, whereas circulating NK cells and regulatory NK cells increased. Discussion: Our results highlight the significant contribution of cDC-mediated signaling pathways to the overall inflammatory response within ovulation disorders. Furthermore, our data demonstrated a significant upregulation of oxidative stress in patients with ovulation disorder. Overall, our study gave a deeper insight into the mechanism of PCOS, POI, and menopause, which may contribute to the better diagnosis and treatments of these ovulatory disorder.

Revealing the mechanism of quinoa on type 2 diabetes based on intestinal flora and taste pathways.

To investigate the antidiabetic effects and mechanisms of quinoa on type 2 diabetes mellitus (T2DM) mice model. In this context, we induced the T2DM mice model with a high-fat diet (HFD) combined with streptozotocin (STZ), followed by treatment with a quinoa diet. To explore the impact of quinoa on the intestinal flora, we predicted and validated its potential mechanism of hypoglycemic effect through network pharmacology, molecular docking, western blot, and immunohistochemistry (IHC). We found that quinoa could significantly improve abnormal glucolipid metabolism in T2DM mice. Further analysis showed that quinoa contributed to the improvement of gut microbiota composition positively. Moreover, it could downregulate the expression of TAS1R3 and TRPM5 in the colon. A total of 72 active components were identified by network pharmacology. Among them, TAS1R3 and TRPM5 were successfully docked with the core components of quinoa. These findings confirm that quinoa may exert hypoglycemic effects through gut microbiota and the TAS1R3/TRPM5 taste signaling pathway.

Tripartite evolutionary game study on coordination information security in prescription circulation.

To further reform the medical and health care system, regulating multi-level treatment and rationalizing the use of medicine, and securing prescription circulation information, this study explores the evolutionary behavior of three players in terms of information security collaboration under the prescription circulation policy, analyzes the evolutionary paths, and examines the influence of key parameters on evolutionary outcomes by constructing a tripartite evolutionary game model consisting of hospitals, retail pharmacies, and healthcare service platforms. The study shows the following: (1) When the information security costs of prescription circulation increase, the willingness of hospitals to promote information collaboration weakens, the probability of control and regulation by healthcare platforms will be enhanced, and the incentive for retail pharmacies to undertake prescription circulation increases and then decreases. (2) The increased profitability of prescription drug sales can cause a decrease in the likelihood of both parties working together to promote information security. Increasing the collaborative space between hospitals and retail pharmacies is conducive to improving information security in the circulation of prescriptions. (3) A bi-directional constraint relationship exists between the circulation and control subjects. The shorter the technology spillover time from the healthcare service platform is, the higher the probability that hospitals and retail pharmacies will maintain the security of prescription information. (4) In the early stages of prescription circulation, the external regulatory action of the healthcare service platform is essential to improve the coordination of information security. Finally, combined with the tripartite evolutionary game model and simulation analysis results, it offers countermeasures and suggestions for the government to realize the prescription circulation information security collaboration.

Efficacy of Chinese Herbal Medicine Formula in the Treatment of Mild to Moderate Erectile Dysfunction: Study Protocol for a Multi-Center, Randomized, Double-Blinded, Placebo-Controlled Clinical Trial.

Introduction: Erectile dysfunction (ED) is a prevalent condition in urology, primarily managed with PDE5 inhibitors (PDE5Is). However, approximately 20% of patients do not experience improvement in overall sexual satisfaction (OS) after taking PDE5Is. Among these, traditional Chinese medicine (TCM) has emerged as a complementary approach, with formulas like Hongjing I granules (HJIG) showing promise in preliminary studies. This study aims to rigorously evaluate the effectiveness and safety of HJIG in mild to moderate ED cases, assessing improvement in both sexual function and TCM pattern alignment. Methods: This study is a randomized, double-blind, placebo-controlled multicentre trial. Recruitment will be conducted from patients who have a strong willingness to try using only traditional Chinese medicine treatment (This is very common in traditional Chinese medicine hospitals.). A total of 100 patients diagnosed with mild to moderate ED caused by qi deficiency and blood stasis will be recruited and randomly assigned to receive one of two treatments: HJIG (N = 50) or placebo (N = 50). Patients will receive 8 weeks of treatment and a 16-week follow-up starting from the fourth week of treatment. Outcome measures, including the International Index of Erectile Function-Erectile Function domain (IIEF-EF) score, Sexual Encounter Profile (SEP), and Traditional Chinese Medicine symptom score, will be evaluated. Discussion: The expected outcome of this trial is that the use of the herbal formula HIJG alone can improve overall sexual satisfaction (OS) in patients with mild to moderate ED, while also improving their traditional Chinese medicine symptom scores. This will provide evidence-based support for the use of Chinese medicine in the treatment of ED in China. Trial Registration: Chinese Clinical Trial Registry, ChiCTR2000041127, Registered on 19 December 2020, https://www.chictr.org.cn/showproj.html?proj=46469. Trial Status: Recruitment began in March 2021, therefore 80 patients have been recruited. It is expected to finish recruiting in December 2023.

Androgens exacerbate hepatic triglyceride accumulation in rats with polycystic ovary syndrome by downregulating MTTP expression.

PURPOSE: Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder, which is closely associated with insulin resistance, glucose and lipid metabolism disorders. Patients with PCOS have a significantly higher risk of non-alcoholic fatty liver disease and are associated with hyperandrogenemia (HA). However, the exact mechanism by which HA exacerbates hepatic steatosis in PCOS has not yet been fully elucidated. This work aims to investigate the effects and underlying mechanisms of androgens on hepatic triglyceride (TG) metabolism in rats with PCOS. METHODS: Twenty-four female Sprague-Dawley rats were randomly divided into four groups (6 rats/group): control, high-fat diet (HFD), PCOS, and PCOS + flutamide (Flu). Changes in the estrous cycle, liver and ovarian tissue sections, serum total testosterone, serum and liver biochemical indicators, and key enzymes involved in TG metabolism were studied. RESULTS: Hepatocyte steatosis and TG accumulation were more evident in the PCOS group than in the control and HFD groups. The PCOS group showed apparent increases in the levels of serum alanine aminotransferase, aspartate aminotransferase, TG, free fatty acid, fasting insulin, and homeostasis model assessment of insulin resistance. Hepatic VLDL and apoB-100 levels decreased in the PCOS group. After Flu was administered to block the actions of androgens, the above abnormalities had been improved. The expression of MTTP was greatly decreased in the PCOS group and significantly increased after Flu administration. CONCLUSION: Hepatic steatosis in PCOS rats was correlated with HA. Androgens may exacerbate hepatic TG accumulation by downregulating MTTP expression in PCOS.

Recovery of residual carbon from coal gasification fine slag by a combined gravity separation-flotation process.

Recovering inner residual carbon is important for fully utilizing coal gasification fine slag (CGFS) resources. In this study, we adopted a combined gravity-separation and flotation process to efficiently recover residual carbon by considering the characteristics of the CGFS and optimizing the operating factors of the process. CGFS is principally a mixture of residual carbon and ash, with low-density particles containing more of the former. Accordingly, residual carbon is preliminarily enriched by gravity separation, in which gas velocity (vg) and water velocity (vw) significantly impact separation efficiency, followed by feed volume (m). The residual carbon in the initial concentrate was preliminarily enriched (i.e., loss on ignition (LOI): 55.90%; combustible recovery (Ro): 72.36%) under appropriate operating conditions (i.e., vw = 0.04 m/s, vg = 3 m/s, m = 150 g). Moreover, the quality of the flotation concentrate was most influenced by collector dosage (mc), followed by aeration rate (η), frother dosage (mf), stirring speed (w), and grinding time (t) during flotation of the primary concentrate. The flotation concentrate exhibited LOI and Ro values of 90.95% and 50.34%, respectively, under the optimal flotation conditions (i.e., mc = 20 kg/t, mf = 15 kg/t, w = 2600 rad/min, η = 200 L/h, t = 360 s); it has a high residual carbon content and is an ideal raw material for preparing fuels or carbon materials.

Associations Among Organizational Capabilities, Organizational Performance and the Medical Alliance Implementation Effect in Community Health Centers in China: A Moderated Mediation Model.

Purpose: Community health centers (CHCs) are an important part of the healthcare system worldwide. Based on the dual process model of organizational capabilities, this study explores the relationship between organizational capabilities and the organizational performance of CHCs, as well as the role played by the medical alliance implementation effect. Methods: In this study, whole-group sampling was used to extract CHCs. All 135 CHCs in 8 of 16 districts of Beijing were selected as subjects. The organizational capabilities of the CHCs and the medical alliance implementation effect were evaluated using a questionnaire survey of 1957 managers and 3622 medical staff, respectively. A pathway analysis of the mediating role of the organizational capabilities of CHCs and the moderating role of the medical alliance implementation effect was conducted using Mplus 8.0. Results: The development capabilities had a positive impact on basic capabilities (ß = 0.878, P < 0.001), and core capabilities (ß = 0.952, P < 0.001), but had no direct impact on organizational performance. Basic capabilities positively affected organizational performance (ß = 1.163, P < 0.001), and core capabilities negatively affected organizational performance (ß =- 0.886, P = 0.004). Both basic capabilities (ß =1.022, P < 0.001) and core capabilities (ß =- 0.843, P = 0.005) played a mediating role in the relationship between development capabilities and organizational performance. The moderating role of the medical alliance implementation effect was not significant. Conclusion: This study found that strengthening the organizational capabilities of CHCs can effectively improve their performance, with the development of basic capabilities being a primary concern. The medical alliance implementation effect has not had a significant impact on organizational performance, and the cooperation between CHCs and high-level hospitals should be further promoted to give full play to the medical alliance's role and improve the organizational performance of CHCs.