Arctigenin ameliorates high-fat diet-induced metabolic disorders by reshaping gut microbiota and modulating GPR/HDAC3 and TLR4/NF-κB pathways.

BACKGROUND: Arctigenin (AG), a phenylpropanoid lignan from the medicinal and food homologous plant Arctium lappa l., is known for its anti-cancer, anti-inflammatory and antioxidant properties. However, the pharmacological effects of AG on metabolic disorders remain limited, and specific mechanisms based on gut microbiota have not been reported. PURPOSE: This study aimed to evaluate the regulation of glycolipid metabolism by AG in obese mice and investigate the potential mechanisms associated with gut microbes. METHODS: The anti-obesity efficacy of AG was evaluated in high-fat diet (HFD)-fed mice. 16S rRNA gene sequencing and GC-MS were used to detect changes in gut microbes and metabolite levels. Immunohistochemistry, immunofluorescence, and polymerase chain reaction were used to validate the molecular mechanisms of gut microbe-derived metabolites involved in the improvement of intestinal homeostasis and hepatic metabolism by AG. RESULTS: We found that AG significantly ameliorated HFD-induced glucolipid metabolism disorders, liver degeneration and the imbalance of macrophage M1/M2 polarization. In addition, AG attenuated intestinal barrier damage, inflammation and imbalance of Th17/Treg immune in HFD mice. Importantly, AG promoted short-chain fatty acid (SCFA)-producing bacteria and SCFA levels, which regulated the G protein-coupled receptor (GPR)41/43 and HDAC3 pathways to induce FOXP3 protein expression and consequently maintained intestinal Th17/Treg immunity. AG also inhibited lipopolysaccharide (LPS) production leading to attenuation of TLR4/NF-κB-mediated intestinal inflammation. Furthermore, AG upregulated intestinal MCT1 protein levels to promote absorption of SCFA and activated the hepatic GPR41/43/109a-AMPK pathway to regulate lipid metabolism, and thus reduced lipid accumulation. CONCLUSION: This study first demonstrated that AG could modulate the gut microbiota and derived metabolites to repair intestinal damage and regulate hepatic metabolic pathways, thereby ameliorating metabolic disorders induced by HFD. These findings support the great potential of AG as a novel prebiotic to fight obesity and chronic metabolic diseases by targeting the gut microbiota.

Mining of adverse event signals associated with inclisiran: a post-marketing analysis based on FAERS.

BACKGROUND: This study analyzed adverse events (AEs) associated with inclisiran using the FDA's Adverse Event Reporting System (FAERS) to detect and characterize relevant safety signals. METHODS: We retrospectively extracted AE reports from the FAERS database spanning Q1 2022 to Q2 2024. Four disproportionality analysis algorithms were employed to identify AE signals for inclisiran, with subsequent comparisons made to PCSK9 monoclonal antibodies (alirocumab/evolocumab). Additionally, we examined the characteristics and onset timing of inclisiran-related AE. RESULTS: A total of 4,122 reports of inclisiran as the 'primary suspected'. Compared with all other drugs, the most significant system organ class (SOC) was 'musculoskeletal and connective tissue disorders' (ROR = 3.64, PRR = 3.19) and the most common SOC was 'general disorders and administration site conditions' (n = 2,769). These two SOCs were more strongly with inclisiran than evolocumab. At the preferred term level, strong signals were detected for cellulitis gangrenous (ROR = 101.29, PRR = 101.27, IC = 6.54, EBGM = 92.91) and bladder discomfort (ROR = 12.61, PRR = 12.61, IC = 3.64, EBGM = 12.48). The median onset time for inclisiran-related AEs was 43 days (interquartile range: 7-99 days). CONCLUSIONS: This study enhanced our understanding of AEs to inclisiran. Future research on its long-term real-world use will offer insights into its safety.

A Strongly Coupled Metal/Hydroxide Heterostructure Cascades Carbon Dioxide and Nitrate Reduction Reactions toward Efficient Urea Electrosynthesis.

The direct coupling of nitrate ions and carbon dioxide for urea synthesis presents an appealing alternative to the Bosch-Meiser process in industry. The simultaneous activation of carbon dioxide and nitrate, however, as well as efficient C-N coupling on single active site, poses significant challenges. Here, we propose a novel metal/hydroxide heterostructure strategy based on synthesizing an Ag-CuNi(OH)2 composite to cascade carbon dioxide and nitrate reduction reactions for urea electrosynthesis. The strongly coupled metal/hydroxide heterostructure interface integrates two distinct sites for carbon dioxide and nitrate activation, and facilitates the coupling of *CO (on silver, where * denotes an active site) and *NH2 (on hydroxide) for urea formation. Moreover, the strongly coupled interface optimizes the water splitting process and facilitates the supply of active hydrogen atoms, thereby expediting the deoxyreduction processes essential for urea formation. Consequently, our Ag-CuNi(OH)2 composite delivers a high urea yield rate of 25.6 mmol gcat.-1 h-1 and high urea Faradaic efficiency of 46.1%, as well as excellent cycling stability. This work provides new insights into the design of dual-site catalysts for C-N coupling, considering their role on the interface.

A nomogram with Ki-67 in the prediction of postoperative recurrence and death for glioma.

This study examined to evaluate the predictive value of a nomogram with Ki-67 in overall and disease-free survival in glioma patients, a total of 76 patients diagnosed with glioma by pathology in Tengzhou Central People's Hospital were enrolled. The baseline data and follow ups were retrospectively collected from medical records. The associations between Ki-67 and survival status were examined using log-rank test, univariate and multivariate Cox proportional hazard regression models. Calibrations were performed to validate the established nomograms. Ki-67 negative group showed of a longer OS survival time and a longer PFS survival time with log-rank test (x2 = 16.101, P < 0.001 and x2 = 16.961, P < 0.001). Age older than 50 years (HR = 2.074, 95% CI 1.097-3.923), abnormal treatment (HR = 2.932, 95% CI 1.343-6.403) and Ki-67 positive (HR = 2.722, 95% CI 1.097-6.755) were the independent predictive factors of death. High grade pathology (HR = 2.453, 95% CI 1.010-5.956) and Ki-67 positive (HR = 2.200, 95% CI 1.043-4.639) were the independent predictive factors of recurrence. The C-index for the nomogram of OS and PFS were 0.745 and 0.723, respectively. The calibration results showed that the nomogram could predict the overall and disease-free 1-year survival of glioma patients. In conclusion, the nomograms with Ki-67 as independent risk factor for OS and PFS could provide clinical consultation in the treatment and follow-up of malignant glioma.

Association of life's essential 8 and asthma: mediating effect of inflammation and oxidative stress.

BACKGROUND: The association of cardiovascular health (CVH) with asthma risk in U.S. adults remains unclear. This study aimed to explore the association of Life's Essential 8 (LE8), a measurement of CVH, with asthma and investigate the potential mediating effect of inflammation and oxidative stress. METHODS: The data was obtained from the National Health and Nutrition Examination Survey (NHANES) in 2005-2018. LE8 score (range 0 ∼ 100) was measured and categorized as low (<50), moderate (50 ∼ <80), and high (≥80) CVH. Survey-weighted logistic regression and restricted cubic spline model were employed to explore the association between LE8 score and asthma. Mediation analyses were conducted to identify the mediating effects of inflammation and oxidative stress biomarkers. RESULTS: This study included 10,932 participants aged ≥ 20 years, among whom 890 (8.14%) reported prevalent asthma. After adjusting for all covariates, the odd ratios (OR) for asthma were 0.67 (95% confidence interval (CI): 0.48, 0.94) in the moderate CVH group and 0.52 (95% CI: 0.34, 0.79) in the high CVH group compared with the low CVH group, respectively. The OR for asthma was 0.85 (95% CI: 0.78, 0.93) for every 10 score increase in LE8 score, and linear dose-response relationship was observed (p = 0.0642). Mediation analyses showed that inflammation and oxidative stress mediated 15.97% and 11.50% of the association between LE8 score and asthma, respectively (all p < 0.05). CONCLUSIONS: LE8 score was negatively associated with asthma, and inflammation and oxidative stress partially mediated this association. It is recommended that maintaining optimal CVH may prevent asthma.

The Causal Effect of 179 Plasma Lipid Groups on Immune Thrombocytopenia: A Mendelian Randomized Study.

OBJECTIVE: Immune thrombocytopenia (ITP) is a common bleeding disorder. Although global lipidomic analyses have identified a potential role for lipid species in platelet function, there is currently no evidence to support a causal relationship between plasma lipids and ITP. To investigate this further, we conducted a two-sample Mendelian randomization analysis to determine whether there is a genetically predicted causal relationship between 179 plasma lipid groups and ITP. METHODS: Genome-wide association data from 179 plasma lipid species from 7,174 Finnish subjects were used in a preliminary analysis of ITP GWAS data from the GWAS catalogue database (GCST90018865, case=675, control=488,749). Causal analyses were performed using random inverse variance weighting (IVW) with MR-Egger and weighted median as complementary analyses. Sensitivity analyses were conducted using the MR-Egger intercept test, MR-PRESSO, and leave-one-out analysis. To assess the association of lipid metabolites with the risk of developing ITP, multivariate MR analysis was performed. Significant correlations were found. The final identification of lipid metabolites was further evaluated using the Steiger test for chain imbalance. RESULTS: The results of this study showed that six plasma lipid species, sterol esters (27:1/20:2) (SE) (odds ratio [OR]: 1.30, 95% confidence interval [CI]: 1.06-1.60, p=0.013), phosphatidylethanolamine (18:0_0:0) (PE) (OR: 1. 46, 95% CI: 1.10-1.95, p=0.009), phosphatidylcholine (16:0_18:3) (PC) (OR: 1.51, 95% CI: 1.12-2.02, p=0.006), phosphatidylcholine-ether (O-16:0_16:0) (PCO) (OR: 0.64, 95% CI: 0. 47-0.88, p = 0.005), phosphatidylethanolamine-ether (O-18:2_20:4) (PEO) (OR: 0.71, 95% CI: 0.55-0.93, p=0.013), triacylglycerol (49:1) (TAG) (OR: 1.65, 95% CI: 1.21-2.24, p=0.001), and ITP were all significantly correlated. MVMR analysis showed that genetically predicted phosphatidylcholine ethers may independently influence ITP without dependence on other metabolites. Triacylglycerol may be affected by other plasma liposomal metabolites and is a risk factor for the development of ITP. CONCLUSION: The current work provides evidence for a causal role of six plasma lipids in ITP and provides new perspectives for combining genomics and metabolomics to explore the biological mechanisms of ITP. These findings may contribute to the screening, prevention, and treatment of ITP.

Targeted proteomics profiling reveals valuable biomarkers in the diagnosis of primary immune thrombocytopaenia.

The lack of biomarkers for accurate diagnosis and prognosis is a major clinical challenge of primary immune thrombocytopaenia (ITP). Using an Olink proteomics platform with a 92 immune response-related human protein panel, we analysed plasma samples from ITP patients (ITP, n = 40), patients with thrombocytopaenia secondary to other causes (Non-ITP, n = 19) and healthy controls (NC, n = 18), of a discovery cohort as well as a validation cohort (ITP, n = 36; NC, n = 20). A total of 10 differentially expressed proteins (DEPs) were identified in the ITP group compared with the non-ITP and NC groups of the discovery cohort. These include CXCL11, GZMH, ARG1, TGF-ß1, ANGPT1, CXCL12, CD40-L, PDGF subunit B, IL4 and TNFSF14. Furthermore, least absolute shrinkage and selection operator regression analysis showed some of these DEPs, such as CXCL11, TGF-ß1, ARG1 and GZMH to be significant in differentiating between patients with ITP and healthy controls (validation area under the curve = 0.87). The analysis demonstrated that the ITP group has a specific proteomic profile relative to non-ITP and NC groups. In summary, we report for the first time that Olink precision proteomics can specifically detect up-regulated inflammatory proteins as potential diagnostic biomarkers for ITP.

Bidentate Coordination Enables Anions-Regulated Solvation Structure for Advanced Aqueous Zinc Metal Batteries.

Rechargeable aqueous Zn metal batteries (AZMBs) are attractive for stationary energy storage due to their low cost and high safety. However, their practical application is hindered by the excessive use of zinc anodes and poor high-temperature performance, caused by severe side reactions and dendritic growth issues. Here, an electrolyte design strategy is reported based on bidentate coordination of Zn2+ and solvent to tailor the solvation structure. The triethylene glycol (TEG) co-solvent with two-oxygen coordination sites is demonstrated to facilitate the formation of an anions-involved solvation shell, greatly reducing the activity of coordinated H2O molecules. The sequential reduction of OTF- anions and TEG to form an organic-inorganic bilayer SEI (hydrophobic organic layer and high ion conductivity inorganic layer), protecting Zn anodes from side reaction and dendrite growth, thus ensuring an unprecedented Zn reversibility (99.95% over 5000 cycles at 0.5 mA cm-2). More importantly, the full cells of Zn||V2O5 exhibit a record-high cumulative capacity (2552 mAh cm-2) under a lean electrolyte condition (E/C ratio = 15 µL mAh-1), a limited Zn supply (N/P ratio = 1.9) and a high areal capacity (3.0 mAh cm-2).

Identification of novel mitophagy-related biomarkers for Kawasaki disease by integrated bioinformatics and machine-learning algorithms.

Background: Kawasaki disease (KD) is a systemic vasculitis primarily affecting the coronary arteries in children. Despite growing attention to its symptoms and pathogenesis, the exact mechanisms of KD remain unclear. Mitophagy plays a critical role in inflammation regulation, however, its significance in KD has only been minimally explored. This study sought to identify crucial mitophagy-related biomarkers and their mechanisms in KD, focusing on their association with immune cells in peripheral blood. Methods: This research used four datasets from the Gene Expression Omnibus (GEO) database that were categorized as the merged and validation datasets. Screening for differentially expressed mitophagy-related genes (DE-MRGs) was conducted, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. A weighted gene co-expression network analysis (WGCNA) identified the hub module, while machine-learning algorithms [random forest-recursive feature elimination (RF-RFE) and support vector machine-recursive feature elimination (SVM-RFE)] pinpointed the hub genes. Receiver operating characteristic (ROC) curves were generated for these genes. Additionally, the CIBERSORT algorithm was used to assess the infiltration of 22 immune cell types to explore their correlations with hub genes. Interactions between transcription factors (TFs), genes, and Gene-microRNAs (miRNAs) of hub genes were mapped using the NetworkAnalyst platform. The expression difference of the hub genes was validated using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Results: Initially, 306 DE-MRGs were identified between the KD patients and healthy controls. The enrichment analysis linked these MRGs to autophagy, mitochondrial function, and inflammation. The WGCNA revealed a hub module of 47 KD-associated DE-MRGs. The machine-learning algorithms identified cytoskeleton-associated protein 4 (CKAP4) and serine-arginine protein kinase 1 (SRPK1) as critical hub genes. In the merged dataset, the area under the curve (AUC) values for CKAP4 and SRPK1 were 0.933 [95% confidence interval (CI): 0.901 to 0.964] and 0.936 (95% CI: 0.906 to 0.966), respectively, indicating high diagnostic potential. The validation dataset results corroborated these findings with AUC values of 0.872 (95% CI: 0.741 to 1.000) for CKAP4 and 0.878 (95% CI: 0.750 to 1.000) for SRPK1. The CIBERSORT analysis connected CKAP4 and SRPK1 with specific immune cells, including activated cluster of differentiation 4 (CD4) memory T cells. TFs such as MAZ, SAP30, PHF8, KDM5B, miRNAs like hsa-mir-7-5p play essential roles in regulating these hub genes. The qRT-PCR results confirmed the differential expression of these genes between the KD patients and healthy controls. Conclusions: CKAP4 and SRPK1 emerged as promising diagnostic biomarkers for KD. These genes potentially influence the progression of KD through mitophagy regulation.

Different Short-Chain Fatty Acids Unequally Modulate Intestinal Homeostasis and Reverse Obesity-Related Symptoms in Lead-Exposed High-Fat Diet Mice.

Our previous study showed that heavy metal lead (Pb) exposure exacerbates high-fat-diet (HFD)-induced metabolic damage and significantly depletes the gut microbiota-derived metabolite short-chain fatty acid (SCFA) levels. However, it remains unclear whether SCFA is a key metabolite involved in accelerating adverse consequences after Pb exposure. In this study, we explored the effects of exogenous supplementation of acetate, propionate, and butyrate on a metabolic disorder model in Pb-exposed HFD mice. We found that three SCFA interventions attenuated glycolipid metabolism disorders and liver damage, with butyrate performing the best effects in improving obesity-related symptoms. All three SCFA promoted the abundance of Muribaculaceae and Muribaculum, acetate specifically enriched Christensenellaceae, Blautia, and Ruminococcus, and butyrate specifically enriched Parasutterella, Rikenella, Prevotellaceae_UCG-001, and Bacteroides, which contributed to the positive promotion of SCFA production forming a virtuous cycle. Besides, butyrate inhibited Gram-negative bacteria Escherichia-Shigella. All of these events alleviated the intestinal Th17/Treg imbalance and inflammatory response through crosstalk between the G protein-coupled receptor (GPR)/histone deacetylase 3 (HDAC3) and lipopolysaccharide (LPS)/toll-like receptors 4 (TLR4)/nuclear factor κ-B (NF-κB) pathways and ultimately improved the intestinal barrier function. SCFA further upregulated the monocarboxylate transporter 1 (MCT1) and GPR43/adenosine 5'-monophosphate-activated protein kinase (AMPK) pathways to inhibit hepatic lipid accumulation. Overall, SCFA, especially butyrate, is an effective modulator to improve metabolic disorders in obese individuals exposed to heavy metals by targeting gut microecology.

Suboptimal reporting of randomized controlled trials on non-pharmacological therapies in Chinese medicine.

With the successive release of the CONSORT extensions for acupuncture, moxibustion, cupping, and Tuina/massage, this review aims to assess the reporting characteristics and quality of randomized controlled trials (RCTs) based on these specific guidelines. A comprehensive review was conducted by searching multiple databases, including Embase, Ovid MEDLINE(R), All EBM Reviews, AMED, CNKI, VIP Chinese Medical Journal Database, and Wanfang Data, for publications from January 1 to December 31, 2022. Two reviewers independently evaluated the eligibility of the records, extracted predetermined information, and assessed the reporting based on the STRICTA, STRICTOM, STRICTOC, and STRICTOTM checklists. Among the included 387 studies (acupuncture, 213; Tuina/massage, 85; moxibustion, 73; cupping, 16), the overall reporting compliance averaged 56.0%, with acupuncture leading at 62.6%, followed by cupping (60.2%), moxibustion (53.1%), and Tuina/massage (47.9%). About half of the evaluated items showed poor reporting (compliance rate < 65%). Notably, international journals demonstrated significantly higher reporting quality than Chinese journals (P < 0.05). Although acupuncture trials had relatively higher compliance rates, deficiencies persist in reporting non-pharmacological therapies of Chinese medicine, particularly in areas like treatment environment details and provider background information.

Inference of forensic body fluids/tissues based on mitochondrial DNA copy number: a preliminary study.

The inference of body fluids and tissues is critical in reconstructing crime scenes and inferring criminal behaviors. Nevertheless, present methods are incompatible with conventional DNA genotyping, and additional testing might result in excessive consumption of forensic scene materials. This study aims to investigate the feasibility of distinguishing common body fluids/tissues through the difference in mitochondrial DNA copy number (mtDNAcn). Four types of body fluids/tissues were analyzed in this study - hair, saliva, semen, and skeletal muscle. MtDNAcn was estimated by dividing the read counts of mitochondrial DNA to that of nuclear DNA (RRmt/nu). Results indicated that there were significant differences in RRmt/nu between different body fluids/tissues. Specifically, hair samples exhibited the highest RRmt/nu (log10RRmt/nu: 4.3 ± 0.28), while semen samples showed the lowest RRmt/nu (log10RRmt/nu: -0.1 ± 0.28). RRmt/nu values for DNA samples without extraction were notably higher (approximately 2.9 times) than those obtained after extraction. However, no significant difference in RRmt/nu was observed between various age and gender groups. Hierarchical clustering and Kmeans clustering analyses showed that body fluids/tissues of the same type clustered closely to each other and could be inferred with high accuracy. In conclusion, this study demonstrated that the simultaneous detection of nuclear and mitochondrial DNA made it possible to perform conventional DNA analyses and body fluid/tissue inference at the same time, thus killing two birds with one stone. Furthermore, mtDNAcn has the potential to serve as a novel and promising biomarker for the identification of body fluids/tissues.

[Efficiency of different large language models in China in response to consultations about PCa-related perioperative nursing and health education].

OBJECTIVE: To evaluate the efficiency of the four domestic language models, ERNIE Bot, ChatGLM2, Spark Desk and Qwen-14B-Chat, all with a massive user base and significant social attention, in response to consultations about PCa-related perioperative nursing and health education. METHODS: We designed a questionnaire that includes 15 questions commonly concerned by patients undergoing radical prostatectomy and 2 common nursing cases, and inputted the questions into each of the four language models for simulation consultation. Three nursing experts assessed the model responses based on a pre-designed Likert 5-point scale in terms of accuracy, comprehensiveness, understandability, humanistic care, and case analysis. We evaluated and compared the performance of the four models using visualization tools and statistical analyses. RESULTS: All the models generated high-quality texts with no misleading information and exhibited satisfactory performance. Qwen-14B-Chat scored the highest in all aspects and showed relatively stable outputs in multiple tests compared with ChatGLM2. Spark Desk performed well in terms of understandability but lacked comprehensiveness and humanistic care. Both Qwen-14B-Chat and ChatGLM2 demonstrated excellent performance in case analysis. The overall performance of ERNIE Bot was slightly inferior. All things considered, Qwen-14B-Chat was superior to the other three models in consultations about PCa-related perioperative nursing and health education. CONCLUSION: In PCa-related perioperative nursing, large language models represented by Qwen-14B-Chat are expected to become powerful auxiliary tools to provide patients with more medical expertise and information support, so as to improve the patient compliance and the quality of clinical treatment and nursing.

Spectrally Stable and Bright Red Perovskite Light-Emitting Diodes.

Mixing iodide and bromide in three-dimensional metal-halide perovskites is a facile strategy for achieving red light-emitting diodes (LEDs). However, these devices often face challenges such as instability in electroluminescence spectra and low brightness due to phase segregation in mixed-halide perovskites. Here, we demonstrate spectrally stable and bright red perovskite LEDs by substituting some of the halide ions with pseudohalogen thiocyanate ions (SCN-). We find that SCN- can occupy halogen vacancies, thereby releasing microstrain and passivating defects in the perovskite crystals. This leads to the suppression of mixed-halide phase segregation under electrical bias. As a result, the red perovskite LEDs exhibit a high brightness of >35 000 cd m-2 with stable Commission Internationale de l'Eclairage (CIE) coordinates of (0.713, 0.282). This brightness surpasses that of the best-performing red perovskite LEDs, showing great promise for advancing perovskite LEDs in display and lighting applications.

Bifunctional Chiral Electrocatalysts Enable Enantioselective α-Alkylation of Aldehydes.

Herein, we describe an innovative approach to the asymmetric electrochemical α-alkylation of aldehydes facilitated by a newly designed bifunctional chiral electrocatalyst. The highly efficient bifunctional chiral electrocatalyst combines a chiral aminocatalyst with a redox mediator. It plays a dual role as a redox mediator for electrooxidation, while simultaneously providing remarkable asymmetric induction for the stereoselective α-alkylation of aldehydes. Additionally, this novel catalyst exhibits enhanced catalytic activity and excellent stereoselective control comparable to conventional catalytic systems. As a result, this strategy provides a new avenue for versatile asymmetric electrochemistry. The electrooxidation of diverse phenols enables the C-H/C-H oxidative α-alkylation of aldehydes in a highly chemo- and stereoselective fashion. Detailed mechanistic studies by control experiments and cyclic voltammetry analysis demonstrate possible reaction pathways and the origin of enantio-induction.

Plasma proteomic profiling reveals that SERPINE1 is a potential biomarker associated with coronary artery lesions in Kawasaki disease.

BACKGROUND: Kawasaki disease (KD) is the most common cause of acquired heart disease in childhood. Coronary artery lesions (CALs) are serious complications of KD that can result in stenosis and thrombosis, but the specific underlying pathogenic mechanisms have not been elucidated. Therefore, exploring biomarkers to help predict early CALs is urgently needed for clinical treatment. METHODS: Patients were recruited from three independent cohorts. In the discovery cohort, Data-Independent Acquisition Mass Spectrometry (DIA-MS) was performed to screen plasma proteins from healthy controls (HCs), KD patients prior to intravenous immunoglobulin (IVIG) treatment, and KD patients post-IVIG treatment. KD patients were further divided into KD patients without CALs (nCAL) and with CALs (CALs) groups. Bioinformatic analysis was carried out for the differentially expressed proteins (DEPs) and hub proteins. Candidate proteins were quantified by enzyme-linked immunosorbent assay (ELISA) in the validation cohort 1 and 2. Furthermore, candida albicans cell wall extract (CAWS)-induced KD vasculitis mice and cell models were established to investigate the expression of biomarkers identified in the aforementioned clinical cohort. RESULTS: According to the quantitative proteomics analysis, SERPINE1 was significantly increased in KD patients with CALs. Receiver operating characteristic curves (ROC) revealed that plasma SERPINE1 exhibited greater ability in predicting CALs (AUC = 0.824, P < 0.0001). After IVIG treatment, the concentrations of SERPINE1 in the nCALs group significantly decreased. However, the concentration of SERPINE1 remained persistently elevated in the CALs group. Moreover, the expression of SERPINE1 was significantly upregulated in the heart tissue of KD mice, KD plasma, or tumor necrosis factor-α (TNF-α)-stimulated human coronary artery endothelial cells (HCAECs). CONCLUSIONS: Overall, our results suggest that the plasma concentration of SERPINE1 might serve as a new potential predictive biomarker for CALs in KD patients.

The phosphorylation of a WD40-repeat protein negatively regulates flavonoid biosynthesis in Camellia sinensis under drought stress.

Flavonoids constitute the main nutraceuticals in the leaves of tea plants (Camellia sinensis). To date, although it is known that drought stress can negatively impact the biosynthesis of flavonoids in tea leaves, the mechanism behind this phenomenon is unclear. Herein, we report a protein phosphorylation mechanism that negatively regulates the biosynthesis of flavonoids in tea leaves in drought conditions. Transcriptional analysis revealed the downregulation of gene expression of flavonoid biosynthesis and the upregulation of CsMPK4a encoding a mitogen-activated protein kinase in leaves. Luciferase complementation and yeast two-hybrid assays disclosed that CsMPK4a interacted with CsWD40. Phosphorylation assay in vitro, specific protein immunity, and analysis of protein mass spectrometry indicated that Ser-216, Thr-221, and Ser-253 of CsWD40 were potential phosphorylation sites of CsMPK4a. Besides, the protein immunity analysis uncovered an increased phosphorylation level of CsWD40 in tea leaves under drought conditions. Mutation of the three phosphorylation sites generated dephosphorylated CsWD403A and phosphorylated CsWD403D variants, which were introduced into the Arabidopsis ttg1 mutant. Metabolic analysis showed that the anthocyanin and proanthocyanidin content was lower in ttg1:CsWD403D transgenic plants than ttg1::CsWD403A transgenic and wild type plants. The transient overexpression of CsWD403D downregulated the anthocyanidin biosynthesis in tea leaves. The dual-fluorescein protein complementation experiment showed that CsWD403D did not interact with CsMYB5a and CsAN2, two key transcription factors of procyanidins and anthocyanidins biosynthesis in tea plant. These findings indicate that the phosphorylation of CsWD40 by CsMPK4a downregulates the flavonoid biosynthesis in tea plants in drought stresses.

Combined effects of genetic predisposition and sleep quality on acceleration of biological ageing: Findings from the UK biobank cohort.

OBJECTIVE: Genetic risks can accelerate ageing, yet better quality sleep may slow down it. We thus examined the interaction and combined effects of genetic predisposition and sleep quality on the risk of accelerate aging. METHODS: This study included 407,027 participants from the UK Biobank. Sleep index of each participant was retrieved from the following seven sleep behaviors: snoring, chronotype, daytime sleepiness, sleep duration, insomnia, nap and difficulties in getting up. The biological age (PhenoAge) were estimated by corresponding algorithms based on clinical traits, and their residual discrepancies with chronological age were defined as the age accelerations (PhenoAgeaccel). We explored the interaction and combined effects of genetic risk and sleep quality on accelerated ageing by constructing a linear model. RESULTS: Compared with participants in low sleep quality group, those in medium and high sleep quality group decreased 0.727 (95%CI, 0.653 to 0.801) and 1.056 (95%CI, 0.982 to 1.130) years of PhenoAgeaccel, respectively. Compared with participants in low genetic risk group, those in medium and high genetic risk group increased 0.833 (95%CI, 0.792 to 0.874) and 1.543 (95%CI, 1.494 to 1.592) years of PhenoAgeaccel, respectively. There was interaction between the genetic risk and sleep quality (P-interaction<0.001). For combined effect, compared to the group with high sleep quality and lower genetic risk, people with low sleep quality and high genetic risk had 2.747 (95%CI, 2.602 to 2.892) years higher PhenoAgeaccel. CONCLUSION: Our findings elucidate that better sleep quality could lessen accelerated biological ageing especially among population with high genetic risk.

Superior sodiophilicity and molecule crowding of crown ether boost the electrochemical performance of all-climate sodium-ion batteries.

Sodium-ion batteries (SIBs) as one of the promising alternatives to lithium-ion batteries have achieved remarkable progress in the past. However, the all-climate performance is still very challenging for SIBs. Herein, 15-Crown-5 (15-C-5) is screened as an electrolyte additive from a number of ether molecules theoretically. The good sodiophilicity, high molecule rigidity, and bulky size enable it to reshape the solvation sheath and promote the anion engagement in the solvated structures by molecule crowding. This change also enhances Na-ion transfer, inhibits side reactions, and leads to a thin and robust solid-electrolyte interphase. Furthermore, the electrochemical stability and operating temperature windows of the electrolyte are extended. These profits improve the electrochemical performance of SIBs in all climates, much better than the case without 15-C-5. This improvement is also adopted to µ-Sn, µ-Bi, hard carbon, and MoS2. This work opens a door to prioritize the potential molecules in theory for advanced electrolytes.