Variation in a Poaceae-conserved fatty acid metabolic gene cluster controls rice yield by regulating male fertility.

A wide variety of metabolic gene clusters exist in eukaryotic genomes, but fatty acid metabolic gene clusters have not been discovered. Here, combining with metabolic and phenotypic genome-wide association studies, we identify a major locus containing a six-gene fatty acid metabolic gene cluster on chromosome 3 (FGC3) that controls the cutin monomer hydroxymonoacylglycerols (HMGs) contents and rice yield, possibly through variation in the transcription of FGC3 members. We show that HMGs are sequentially synthesized in the endoplasmic reticulum by OsFAR2, OsKCS11, OsGPAT6, OsCYP704B2 and subsequently transported to the apoplast by OsABCG22 and OsLTPL82. Mutation of FGC3 members reduces HMGs, leading to defective male reproductive development and a significant decrease in yield. OsMADS6 and OsMADS17 directly regulate FGC3 and thus influence male reproduction and yield. FGC3 is conserved in Poaceae and likely formed prior to the divergence of Pharus latifolius. The eukaryotic fatty acid and plant primary metabolic gene cluster we identified show a significant impact on the origin and evolution of Poaceae and has potential for application in hybrid crop breeding.

Research on the mechanism of Ursolic acid for treating Parkinson's disease by network pharmacology and experimental verification.

The objective of this study was to investigate the potential targets and mechanisms of UA in the treatment of PD. The efficacy of UA in PD was assessed through network pharmacology, molecular docking, and experimental methods. Common target protein-protein interaction (PPI) networks were constructed and visualized using Cytoscape. As a result, 9 key genes, namely CASP3, IL6, IL1B, PTGS2, CREB1, TNF, MAPK3, JUN, and CASP8, were selected. Molecular docking simulations were performed using Discovery Studio 2019 to validate the correlation between UA and the core targets. The results demonstrated a favorable binding affinity between UA and CASP8, IL1B, CASP3, TNF, MAPK3 and IL6. In vivo studies showed UA ameliorated motor dysfunction, and UA can significantly increase the protein expression of tyrosine hydroxylase (TH) in PD mice model. In addition, in vitro experiments confirmed that UA effectively reduced the protein expression of CASP8, CASP3 and MAPK3 in PD cell models and suppressed the gene expression of TNF-α, IL-6, and IL-1ß. These findings indicate that the therapeutic effects of UA on PD could be due to its influence on various targets within both the apoptosis and neuroinflammatory signaling pathways. Consequently, this study provides a methodological and theoretical foundation for further elucidating the pharmacological mechanism of UA.

Intrinsic or Nonintrinsic End-stage Liver Disease and Its Association With Thromboelastography-based Coagulation States in Patients Undergoing Liver Transplantation: A Retrospective Cohort Study.

OBJECTIVES: Perioperative coagulation management in liver transplantation recipients is challenging. Viscoelastic testing with rotational thromboelastography (TEG) can help quantify hemostatic profiles. The current work aimed to investigate whether the etiology of end-stage liver disease, pretransplant disease severity, or pretransplant thrombotic or bleeding complications are associated with specific TEG patterns. DESIGN: Retrospective cohort study. SETTING: Single quaternary care hospital. PARTICIPANTS: A total of 1,078 adult liver transplant patients. INTERVENTIONS: The primary exposure was the etiology of end-stage liver disease classified as either intrinsic or nonintrinsic (eg, biliary obstruction or cardiovascular). Secondary exposures were patients' preoperative Model for End-Stage Liver Disease (MELD) score, Child-Pugh class, presence of major preoperative thrombotic complications, and major bleeding complications. MEASUREMENTS AND MAIN RESULTS: Patients with intrinsic liver disease (84%) showed higher odds of hypocoagulable (odds ratio [OR]: 3.70, 95% confidence interval [CI]: 1.94-7.07, p < 0.0001) and mixed TEG patterns (OR: 4.59, 95% CI: 2.07-10.16, p = 0.0002) compared with those with nonintrinsic disease. Increasing MELD scores correlated with higher odds of hypocoagulable (OR: 1.14, 95% CI: 1.08-1.19, p < 0.0001) and mixed TEG patterns (OR: 1.08, 95% CI: 1.03-1.14, p = 0.0036). Child-Pugh class C was associated with higher odds of hypocoagulable (OR: 8.55, 95% CI: 3.26-22.42, p < 0.0001) and mixed patterns (OR: 12.48, 95% CI: 3.89-40.03, p < 0.0001). Major preoperative thrombotic complications were not associated with specific TEG patterns, although an interaction with liver disease severity was observed. CONCLUSIONS: Liver transplantation candidates with intrinsic liver disease tend to exhibit hypocoagulable TEG patterns, while nonintrinsic disease is associated with hypercoagulability. Increasing end-stage liver disease severity, as evidenced by increasing MELD scores and higher Child-Pugh classification, was also associated with hypocoagulable TEG patterns.

Omni-dimensional dynamic convolution feature coordinate attention network for pneumonia classification.

Pneumonia is a serious disease that can be fatal, particularly among children and the elderly. The accuracy of pneumonia diagnosis can be improved by combining artificial-intelligence technology with X-ray imaging. This study proposes X-ODFCANet, which addresses the issues of low accuracy and excessive parameters in existing deep-learning-based pneumonia-classification methods. This network incorporates a feature coordination attention module and an omni-dimensional dynamic convolution (ODConv) module, leveraging the residual module for feature extraction from X-ray images. The feature coordination attention module utilizes two one-dimensional feature encoding processes to aggregate feature information from different spatial directions. Additionally, the ODConv module extracts and fuses feature information in four dimensions: the spatial dimension of the convolution kernel, input and output channel quantities, and convolution kernel quantity. The experimental results demonstrate that the proposed method can effectively improve the accuracy of pneumonia classification, which is 3.77% higher than that of ResNet18. The model parameters are 4.45M, which was reduced by approximately 2.5 times. The code is available at https://github.com/limuni/X-ODFCANET .

Impact of Nurse Residency Program on Time-to-Fill Nurse Vacancies at the Veterans Health Administration.

BACKGROUND: The Department of Veterans Affairs (VA) offers a 1-year Post-Baccalaureate-Registered Nurse Residency (PB-RNR) Program. The impact of the PB-RNR program on local RN recruitment was unknown. OBJECTIVES: We aimed to evaluate the effect of the size of the PB-RNR program at a VA facility on its time-to-fill RN vacancies. PROJECT DESIGN: We used an instrumental variable approach with a 2-stage residual inclusion specification. SUBJECTS: We included RN filled vacancies in the VA that were posted nationwide between 2020 and 2021. MEASURES: Our independent variable was the facility-year level number of PB-RNR program allocations. The 3 binary outcomes were whether the RN vacancy was filled within 90, 60, or 30 days. RESULTS: An increase of one training allocation was significantly associated with a 5.60 percentage point (PP) (95% CI: 2.74-8.46) higher likelihood of filling a vacancy within 90 days, 7.34 PP (95% CI: 4.66-10.03) higher likelihood of filling a vacancy within 60 days, and 5.32 PP (95% CI: 3.18-7.46) higher likelihood of filling a vacancy within 30 days. The impact was significant in both 2020 and 2021 positions, and in facilities located in areas with lower social deprivation scores, higher-quality public schools, or with either no or partial primary care physician shortages. CONCLUSIONS: We found favorable impacts of the size of the PB-RNR program at a VA facility on filling RN vacancies.

A novel mutation alters GNE bifunctional enzyme activity and leads to familial inherited GNE diseases.

Distal myopathies are a group of rare heterogeneous diseases that are mostly caused by genetic factors. At least 20 genes have been associated with distal myopathies. We performed whole-exome sequencing to identify the genetic cause of disease in a family with distal myopathy. Following the American College of Medical Genetics and Genomics (ACMG) guidelines, we analyzed the sequencing results and screened suspicious mutations based on mutation frequency, functional impact, and disease inheritance pattern. The harmfulness of the mutations was predicted using bioinformatics methods, and the pathogenic mutations were determined. We identified a novel amino acid mutation (NP_005467.1:p.S663L) on the GNE gene that may cause familial distal myopathy. This mutation is the result of the simultaneous mutation of two adjacent nucleotides (c.1988C > T, c.1989C > A) in the codon. First, we measured the mRNA and protein expression of the GNE gene in the lymphoblastoid cell lines (LCLs) of the probands and their family members. Second, GNE vectors carrying the novel mutation, two other known pathogenic mutations, and the wild-type gene were constructed and transfected into HEK293T cells. The enzymatic activity of these GNE variants was investigated and showed that the p.S663L mutation significantly reduced the activity of the bifunctional GNE enzyme without altering the expression level of the GNE protein. Furthermore, the mutation may also alter the immunogenicity of the 3' end of the GNE protein, potentially affecting its oligomer formation. In this study, a novel GNE gene mutation that may cause distal myopathy was identified, expanding the spectrum of genetic mutations associated with this disease.

Rare correlation of somatic PRKACA mutations with pregnancy-associated aldosterone- and cortisol-producing adenomas: a case report and literature review.

BACKGROUND: Somatic mutations have been observed to induce aldosterone-producing adenomas (APAs). These may be accelerated during pregnancy. Somatic PRKACA mutations are common in cortisol-producing adenomas (CPAs). However, their role in APAs, particularly aldosterone- and cortisol-producing adenomas (A/CPAs), is not well understood. This study aims to investigate the association between PRKACA mutations and the accelerated development of A/CPAs during pregnancy. CASE PRESENTATION: A patient with primary aldosteronism (PA) associated with severe Cushing's syndrome (CS) underwent surgical resection of an adrenal tumor one year after delivery. Pathologic examination revealed an adrenocortical adenoma characterized primarily by zona glomerulosa hyperplasia. Somatic mutation analysis revealed the presence of the somatic PRKACA mutation, which was validated as a deleterious mutation by various computational databases. Immunohistochemical results showed positive staining for cytochrome P450 family 11 subfamily B member 1 (CYP11B1), cytochrome P450 family 11 subfamily B member 2 (CYP11B2), and luteinizing hormone/chorionic gonadotropin receptor (LHCGR). Our study included a review of 20 previously documented cases of aldosterone- and cortisol-producing adenomas (A/CPAs), two of which were concurrently positive for both CYP11B1 and CYP11B2, consistent with our findings. CONCLUSION: Somatic mutations in PRKACA may correlate with the upregulation of LHCGR, which synergistically drives the accelerated growth of co-secretion tumors during pregnancy, thereby exacerbating disease progression.

Medical training program size and clinical staff productivity and turnover.

OBJECTIVE: The objective of this analysis was to evaluate the effect of resident program training size on clinician productivity and turnover in the Veterans Health Administration (VHA), the largest education and training platform for medical professionals in the United States. DATA SOURCES: We retrieved administrative data on training programs and training facilities from the VA Office of Academic Affiliations and the VHA Corporate Data Warehouse. Data on primary care physician shortage areas were retrieved from the Health Resources and Services Administration. STUDY DESIGN: We used a quasi-experimental instrumental variables 2SLS design and constructed an exogenous predicted training allocation treatment variable as a function of the total national training program allocation. The outcome was clinical staff productivity and turnover. Secondary analyses stratified results using Health Professional Shortage Areas data (HPSA). DATA COLLECTION/EXTRACTION METHODS: Data were obtained for a national dataset of 141 VHA medical facilities and 26 specialties that hosted training programs across 11 years from 2011 to 2021 (N = 132,177). PRINCIPAL FINDINGS: Instrumental variables results showed that on average, an increase of one training slot in a specialty leads to a decrease of 0.039 visits per standardized clinic day (p < 0.001) and a 0.02 percentage point increase in turnover (p < 0.001). The direction of this association varied by specialty: while psychiatry and psychology specialties saw a decline in productivity, fields such as primary care and cardiology experienced an increase in productivity. HPSA stratified results indicate that negative effects on productivity and turnover are driven by areas with little to no primary care physician shortage, whereas shortage areas experienced a small increase in productivity and no effect on turnover. CONCLUSIONS: This quasi-experimental evaluation indicates that resident training program size is associated with reduced productivity and increased turnover in specialties such as psychiatry and in facilities with high baseline productivity. However, in specialties like primary care and cardiology, as well as areas with shortages of primary care, larger training programs are associated with increased productivity.

Topological regularization of networks in temporal lobe epilepsy: a structural MRI study.

Objective: Patients with temporal lobe epilepsy (TLE) often exhibit neurocognitive disorders; however, we still know very little about the pathogenesis of cognitive impairment in patients with TLE. Therefore, our aim is to detect changes in the structural connectivity networks (SCN) of patients with TLE. Methods: Thirty-five patients with TLE were compared with 47 normal controls (NC) matched according to age, gender, handedness, and education level. All subjects underwent thin-slice T1WI scanning of the brain using a 3.0 T MRI. Then, a large-scale structural covariance network was constructed based on the gray matter volume extracted from the structural MRI. Graph theory was then used to determine the topological changes in the structural covariance network of TLE patients. Results: Although small-world networks were retained, the structural covariance network of TLE patients exhibited topological irregularities in regular architecture as evidenced by an increase in the small world properties (p < 0.001), normalized clustering coefficient (p < 0.001), and a decrease in the transfer coefficient (p < 0.001) compared with the NC group. Locally, TLE patients showed a decrease in nodal betweenness and degree in the left lingual gyrus, right middle occipital gyrus and right thalamus compared with the NC group (p < 0.05, uncorrected). The degree of structural networks in both TLE (Temporal Lobe Epilepsy) and control groups was distributed exponentially in truncated power law. In addition, the stability of random faults in the structural covariance network of TLE patients was stronger (p = 0.01), but its fault tolerance was lower (p = 0.03). Conclusion: The objective of this study is to investigate the potential neurobiological mechanisms associated with temporal lobe epilepsy through graph theoretical analysis, and to examine the topological characteristics and robustness of gray matter structural networks at the network level.

Design of inductive electrostatic boom spray system based on embedded closed electrode structure and droplet distribution test in soybean field.

The large water demand, insufficient deposition on the back of the leaf and the uneven distribution of droplets are the problems of traditional agricultural ground plant protection machinery, which leads to low agricultural control efficiency. Combined with the advantages of electrostatic spray technology and the characteristics of high working efficiency and low probability of droplets drift of ground sprayer, an inductive electrostatic boom spray system based on embedded electrode structure is designed and mounted on a large self-propelled boom sprayer for field testing. Based on the working characteristics of the fan nozzle and the analysis of the theory of charge, the inductive electrostatic spray device is designed. The performance of the device is tested and the rationality of the system design is verified by COMSOL numerical simulations, charge-to-mass ratio, and particle size distribution measurements. The spray deposition scanning software and the Box-Behnken experimental design method are used to analyze the spray droplet deposition rate and coverage density of the sprayer on the front and back of the target leaves. The results show that the embedded closed electrode structure designed in this paper can avoid the problem of electrode wetting, and the electric field generated by it is mainly concentrated in the spray liquid film area, and the intensity reaches 6~7 V/m. At the conventional application height (500 mm), the maximum charge-to-mass ratio is 2.91 mC/kg, and the average particle size is 168.22 µm, which is 12.87% lower than that of ordinary spray, when the spray pressure is 0.3 MPa and the electrostatic voltage is 12 kV. The results of field experiments show that the optimum combination of the working parameters with the spray speed is 8.40 m/s, the spray pressure is 0.35 MPa, the charging voltage is 11.50 kV, the amount of droplet deposition in the lower dorsal area of the blade is 1.44 µL·cm-2. This study can provide a certain basis for the application of electrostatic spray technology in ground sprayers.

Biodegradation of polystyrene (PS) and polypropylene (PP) by deep-sea psychrophilic bacteria of Pseudoalteromonas in accompany with simultaneous release of microplastics and nanoplastics.

Plastics dumped in the environment are fragmented into microplastics by various factors (UV, weathering, mechanical abrasion, animal chewing, etc.). However, little is known about plastic fragmentation and degradation mediated by deep-sea microflora. To obtain deep-sea bacteria that can degrade plastics, we enriched in situ for 1 year in the Western Pacific using PS as a carbon source. Subsequently, two deep-sea prevalent bacteria of the genus Pseudoalteromonas (Pseudoalteromonas lipolytica and Pseudoalteromonas tetraodonis) were isolated after 6 months enrichment in the laboratory under low temperature (15 °C). Both showed the ability to degrade polystyrene (PS) and polypropylene (PP), and biodegradation accelerated the generation of micro- and nanoplastics. Plastic biodegradation was evidenced by the formation of carboxyl and carboxylic acid groups, heat resistance decrease and plastic weight loss. After 80 days incubation at 15 °C, the microplastic concentration of PS and PP could be up to 1.94 × 107/L and 5.83 × 107/L, respectively, and the proportion of nanoplastics (< 1 µm) could be up to 65.8 % and 73.6 %. The film weight loss were 5.4 % and 4.5 % of the PS films, and 2.3 % and 1.8 % of the PP films by P. lipolytica and P. tetraodonis, respectively; thus after discounting the weight loss of microplastics, the only 3.9 % and 2.8 % of the PS films, and 1.3 % and 0.7 % of the PP films, respectively, were truly degraded by the two bacteria respectively after 80 days of incubation. This study highlights the role of Pseudoalteromonas in fragmentation and degradation of plastics in cold dark pelagic deep sea.

Prognostic value and immune infiltration of the NEK family in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is a fatal urological malignancy. Members of the never-in mitosis gene A (NIMA)-related kinase (NEK) family have been found to participate in the progression of several cancers and could be used as target genes to treat corresponding diseases. Nonetheless, the prognostic value and immune infiltration levels of NEK family genes in ccRCC remain unknown. The GSCA, TIMER, and GEPIA databases were utilized to examine the differential expression of NEK family members in ccRCC, and the Kaplan-Meier plotter was utilized to analyze the prognosis. The STRING database was used to construct a protein-protein interaction network. Analysis of function was performed by the Sangerbox tool. In addition, the relationship between NEK family genes and immune cells was explored using the TIMER and TISIDB databases. Finally, we used quantitative real-time PCR (qPCR) and immunohistochemistry (IHC) for experimental verification. Transcriptional levels of NEK2, NEK3, NEK5, NEK6, and NEK11 significantly differed between ccRCC and normal tissues. Moreover, there was a significant correlation between NEK1, NEK2, NEK4, NEK8, NEK9, and NEK10 and their clinicopathological stages in patients with ccRCC. Based on survival analysis, ccRCC patients with high transcriptional levels of NEK2, NEK3, NEK8, and NEK10 and low transcriptional levels of NEK1, NEK4, NEK5, NEK6, NEK7, NEK9, NEK11 had shorter survival times. Additionally, a significant relationship was observed between NEK family members and immune cell infiltration, immune cell markers, and immune subtypes. These results indicate that NEK family members are significantly differentially expressed in ccRCC, and a significant correlation exists between the NEK family and prognosis and immune infiltration. NEK family members may act as therapeutic targets and prognostic indicators in ccRCC.

Arcobacteraceae are ubiquitous mixotrophic bacteria playing important roles in carbon, nitrogen, and sulfur cycling in global oceans.

Mixotrophy is an important trophic strategy for bacterial survival in the ocean. However, the global relevance and identity of the major mixotrophic taxa remain largely elusive. Here, we combined phylogenetic, metagenomic, and metatranscriptomic analyses to characterize ubiquitous Arcobacteraceae based on our deep-sea in situ incubations and the global data. The phylogenomic tree of Arcobacteraceae is divided into three large clades, among which members of clades A and B are almost all from terrestrial environments, while those of clade C are widely distributed in various marine habitats in addition to some terrestrial origins. All clades harbor genes putatively involved in chitin degradation, sulfide oxidation, hydrogen oxidation, thiosulfate oxidation, denitrification, dissimilatory nitrate reduction to ammonium, microaerophilic respiration, and metal (iron/manganese) reduction. Additionally, in clade C, more unique pathways were retrieved, including thiosulfate disproportionation, ethanol fermentation, methane oxidation, fatty acid oxidation, cobalamin synthesis, and dissimilatory reductions of sulfate, perchlorate, and arsenate. Within this clade, two mixotrophic Candidatus genera represented by UBA6211 and CAIJNA01 harbor genes putatively involved in the reverse tricarboxylic acid pathway for carbon fixation. Moreover, the metatranscriptomic data in deep-sea in situ incubations indicated that the latter genus is a mixotroph that conducts carbon fixation by coupling sulfur oxidation and denitrification and metabolizing organic matter. Furthermore, global metatranscriptomic data confirmed the ubiquitous distribution and global relevance of Arcobacteraceae in the expression of those corresponding genes across all oceanic regions and depths. Overall, these results highlight the contribution of previously unrecognized Arcobacteraceae to carbon, nitrogen, and sulfur cycling in global oceans.IMPORTANCEMarine microorganisms exert a profound influence on global carbon cycling and ecological relationships. Mixotrophy, characterized by the simultaneous utilization of both autotrophic and heterotrophic nutrition, has a significant impact on the global carbon cycling. This report characterizes a group of uncultivated bacteria Arcobacteraceae that thrived on the "hot time" of bulky particulate organic matter and exhibited mixotrophic strategy during the in situ organic mineralization. Compared with clades A and B, more unique metabolic pathways were retrieved in clade C, including the reverse tricarboxylic acid pathway for carbon fixation, thiosulfate disproportionation, methane oxidation, and fatty acid oxidation. Global metatranscriptomic data from the Tara Oceans expeditions confirmed the ubiquitous distribution and extensive transcriptional activity of Arcobacteraceae with the expression of genes putatively involved in carbon fixation, methane oxidation, multiple sulfur compound oxidation, and denitrification across all oceanic regions and depths.

Tao-Hong-Si-Wu-Tang improves thioacetamide-induced liver fibrosis by reversing ACSL4-mediated lipid accumulation and promoting mitophagy.

ETHNOPHARMACOLOGICAL RELEVANCE: Liver fibrosis is a generic fibrous scarring event resulting from accumulation of extracellular matrix (ECM) proteins, easily progressing to end-stage liver diseases. Tao-Hong-Si-Wu-Tang (THSWT) is a traditional Chinese medicine formula applied in clinics to treat gynecological and chronic liver diseases. However, the role of THSWT on thioacetamide (TAA)-induced hepatic fibrosis and the specific mechanisms remains unclear. AIM OF THE STUDY: To investigate the improving effects of THSWT on TAA-insulted hepatic fibrosis and the underlying mechanisms. MATERIALS AND METHODS: UHPLC-MS/MS was performed to explore the chemical characterization of THSWT. Mice were orally administered with THSWT once daily for 6 weeks along with TAA challenge. Liver function was reflected through serum biomarkers and histopathological staining. RNA sequencing, non-targeted metabolomics and molecular biology experiments were applied to investigate the underlying mechanisms. RESULTS: THSWT profoundly repaired lipid metabolism dysfunction and blocked collagen accumulation both in TAA-stimulated mice and in hepatocytes. Results of RNA sequencing and non-targeted metabolomics revealed that the anti-fibrotic effects of THSWT mostly relied on lipid metabolism repairment by increasing levels of acetyl-CoA, phosphatidylcholine, phosphatidylethanolamine, lysophosphatidylcholine and lysophosphatidylethanolamine, and decreasing relative abundances of acyl-CoA, total cholesterol, diacylglycerol, triacylglycerol and phosphatidylinositol. Mechanically, long-chain acyl-CoA synthetases 4 (ACSL4) was a key profibrotic target both in human and mice by disrupting lipid oxidation and metabolism in hepatic mitochondria. THSWT effectively blocked ACSL4 and promoted mitophagy to reverse above outcomes, which was verified by mitophagy depletion. CONCLUSION: THSWT may be a promising therapeutic option for treating hepatic fibrosis and its complications by modulating lipid metabolism and promoting mitophagy in livers.

Effects of different natural products in patients with non-alcoholic fatty liver disease-A network meta-analysis of randomized controlled trials.

Due to a scarcity of appropriate therapeutic approaches capable of ameliorating or eliminating non-alcoholic fatty liver disease (NAFLD), many researchers have come to focus on natural products based on traditional medicine that can be utilized to successfully treat NAFLD. In this study, we aimed to evaluate the effects exerted by seven natural products (curcumin, silymarin, resveratrol, artichoke leaf extract, berberine, catechins, and naringenin) on patients with NAFLD. For this purpose, PubMed, Embase, Cochrane Library, and Web of Science, were searched for randomized controlled trials (RCTs) exclusively. The selected studies were evaluated for methodological quality via the Cochrane bias risk assessment tool, and data analysis software was used to analyze the data accordingly. The RCTs from the earliest available date until September 2022 were collected. This process resulted in 37 RCTs with a total sample size of 2509 patients being included. The results of the network meta-analysis showed that artichoke leaf extract confers a relative advantage in reducing the aspartate aminotransferase (AST) levels (SUCRA: 99.1%), alanine aminotransferase (ALT) levels (SUCRA: 88.2%) and low-density lipoprotein cholesterol (LDL-C) levels (SUCRA: 88.9%). Naringenin conferred an advantage in reducing triglyceride (TG) levels (SUCRA: 97.3%), total cholesterol (TC) levels (SUCRA: 73.9%), and improving high-density lipoprotein cholesterol (HDL-C) levels (SUCRA: 74.9%). High-density catechins significantly reduced body mass index (BMI) levels (SUCRA: 98.5%) compared with the placebo. The Ranking Plot of the Network indicated that artichoke leaf extract and naringenin performed better than the other natural products in facilitating patient recovery. Therefore, we propose that artichoke leaf extract and naringenin may exert a better therapeutic effect on NAFLD. This study may help guide clinicians and lead to further detailed studies.

Design, Synthesis, Antifungal Activity, and 3D-QSAR Study of Novel Quinoxaline-2-Oxyacetate Hydrazide.

Plant pathogenic fungi pose a major threat to global food security, ecosystem services, and human livelihoods. Effective and broad-spectrum fungicides are needed to combat these pathogens. In this study, a novel antifungal 2-oxyacetate hydrazide quinoxaline scaffold as a simple analogue was designed and synthesized. Their antifungal activities were evaluated against Botrytis cinerea (B. cinerea), Altemaria solani (A. solani), Gibberella zeae (G. zeae), Rhizoctonia solani (R. solani), Colletotrichum orbiculare (C. orbiculare), and Alternaria alternata (A. alternata). These results demonstrated that most compounds exhibited remarkable inhibitory activities and possessed better efficacy than ridylbacterin, such as compound 15 (EC50 = 0.87 µg/mL against G. zeae, EC50 = 1.01 µg/mL against C. orbiculare) and compound 1 (EC50 = 1.54 µg/mL against A. alternata, EC50 = 0.20 µg/mL against R. solani). The 3D-QSAR analysis of quinoxaline-2-oxyacetate hydrazide derivatives has provided new insights into the design and optimization of novel antifungal drug molecules based on quinoxaline.

Si-Wu-Tang alleviates metabolic dysfunction-associated fatty liver disease by inhibiting ACSL4-mediated arachidonic acid metabolism and ferroptosis in MCD diet-fed mice.

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a prevalent chronic liver disease worldwide. Si-Wu-Tang (SWT), a traditional Chinese medicine decoction has shown therapeutic effects on various liver diseases. However, the hepatoprotective effects and underlying mechanism of SWT on MAFLD remain unclear. METHODS: First, a methionine-choline-deficient (MCD) diet-fed mice model was used and lipidomic analysis and transcriptomic analysis were performed. The contents of total iron ions, ferrous ions, and lipid peroxidation were detected and Prussian blue staining was performed to confirm the protective effects of SWT against ferroptosis. Finally, chemical characterization and network pharmacological analysis were employed to identify the potential active ingredients. RESULTS: Serological and hepatic histopathological findings indicated SWT's discernible therapeutic impact on MCD diet-induced MAFLD. Lipidomic analysis revealed that SWT improved intrahepatic lipid accumulation by inhibiting TG synthesis and promoting TG transport. Transcriptomic analysis suggested that SWT ameliorated abnormal FA metabolism by inhibiting FA synthesis and promoting FA ß-oxidation. Then, ferroptosis phenotype experiments revealed that SWT could effectively impede hepatocyte ferroptosis, which was induced by long-chain acyl-CoA synthetase 4 (ACSL4)-mediated esterification of arachidonic acid (AA). Finally, chemical characterization and network pharmacological analysis identified that paeoniflorin and other active ingredients might be responsible for the regulative effects against ferroptosis and MAFLD. CONCLUSION: In conclusion, our study revealed the intricate mechanism through which SWT improved MCD diet-induced MAFLD by targeting FA metabolism and ferroptosis in hepatocytes, thus offering a novel therapeutic approach for the treatment of MAFLD and its complications.

Efficacy of endovascular embolization versus microsurgical clamping in the treatment of intracranial aneurysms: a meta-analysis.

Intracranial aneurysms (IA) can induce increased intracranial pressure, headache, and the development of nausea and vomiting if not treated in time, and failure to receive timely diagnosis and treatment can lead to disability or death. However, the efficacy and prognostic value of craniotomy and endovascular embolization in patients with IA remains a controversial topic. This meta-analysis systematically evaluated the efficacy of endovascular coiling versus cranial aneurysm clamping on the immediate postoperative outcome and prognosis of patients with IA. PubMed, EMBASE, and the Cochrane Library databases were searched for retrieval of relevant references. Literature was screened according to pre-defined inclusion and exclusion criteria, and data were extracted and assessed for quality. A total of 10 studies, including 2,654 cases, were included in the analysis. Among them, 1,313 cases underwent craniotomy clipping surgery (clip group), and 1,341 cases underwent endovascular coiling (coil group). The quality of the studies in 8 articles evaluated using the Newcastle-Ottawa Scale (NOS) was ≥6. Meta-analysis was conducted using Rev Man 5.3 and Stata 17 software. The results of meta-analysis showed that no significant difference in complete occlusion rate [OR=1.76, 95% CI (0.78, 3.96), P=0.17] when comparing the clip and coil group. Compared to the clip group, the coil group had a better clinical short-term outcome [OR=1.55, 95% CI (1.05, 2.27), P=0.03], but an increased rate of postoperative residual or recurrence [OR=0.40, 95% CI (0.17, 0.91), P=0.03]. In addition, there were no significance differences identified in terms of complications, including the rates of postoperative rebleeding [OR=1.60, 95% CI (0.97, 2.63), P=0.07], ischemic stroke [OR=1.12, 95% CI (0.45, 2.79), P=0.81], and cerebral vasospasm [OR=0.90, 95% CI (0.13, 6.03), P=0.91]. Subsequently, we conducted experimental sequence analysis for each indicator, and the results were consistent with the results of meta-analysis. According to the recent clinical prognosis, a funnel plot was constructed, showing significant asymmetry on both sides, indicating some publication bias. However, the results of Begg's test with P=0.734 and Egger's test with P=0.633 suggest no significant publication bias. In general, endovascular coiling and microsurgical clipping appear to be equally effective in achieving vascular occlusion. Endovascular coiling may be more effective in improving the short-term clinical outcomes for patients. However, this approach may increase the rate of postoperative residual issue or recurrence.

Chinese herbal medicine Shufeng Jiedu capsule for mild to moderate COVID-19: a multicenter, randomized, double-blind, placebo-controlled phase II trial.

Background: The COVID-19 pandemic has had a profound global impact, although the majority of recently infected cases have presented with mild to moderate symptoms. Previous clinical studies have demonstrated that Shufeng Jiedu (SFJD) capsule, a Chinese herbal patent medicine, effectively alleviates symptoms associated with the common cold, H1N1 influenza, and COVID-19. This study aimed to assess the efficacy and safety of SFJD capsules in managing symptoms of mild to moderate COVID-19 infection. Methods: A randomized, double-blind, placebo-controlled trial was conducted from May to December 2022 at two hospitals in China. Mild and moderate COVID-19-infected patients presenting respiratory symptoms within 3 days from onset were randomly assigned to either the SFJD or placebo groups in a 1:1 ratio. Individuals received SFJD capsules or a placebo three times daily for five consecutive days. Participants were followed up for more than 14 days after their RT-PCR nucleoid acid test for SARS-CoV-2 turned negative. The primary outcome measure was time to alleviate COVID-19 symptoms from baseline until the end of follow-up. Results: A total of 478 participants were screened; ultimately, 407 completed the trial after randomization (SFJD, n = 203; placebo, n = 204). No statistically significant difference in baseline parameters was observed between the two groups. The median time to alleviate all symptoms was 7 days in the SFJD group compared to 8 days in the placebo group (p = 0.037). Notably, the SFJD group significantly attenuated fever/chills (p = 0.04) and headache (p = 0.016) compared to the placebo group. Furthermore, the median time taken to reach normal body temperature within 24 h was reduced by 7 hours in the SFJD group compared to the placebo group (p = 0.033). No deaths or instances of serious or critical conditions occurred during this trial period; moreover, no serious adverse events were reported. Conclusion: The trial was conducted in a unique controlled hospital setting, and the 5-day treatment with SFJD capsules resulted in a 1-day reduction in overall symptoms, particularly headache and fever/chills, among COVID-19-infected participants with mild or moderate symptoms. Compared to placebo, SFJD capsules were found to be safe with fewer side effects. SFJD capsules could potentially serve as an effective treatment for alleviating mild to moderate symptoms of COVID-19. Clinical Trial Registration: https://www.isrctn.com/, identifier ISRCTN14236594.