Development and validation of a predictive nomogram for the risk of MAFLD in postmenopausal women.

Background and aim: Metabolic-associated fatty liver disease (MAFLD) has gradually become one of the main health concerns regarding liver diseases. Postmenopausal women represent a high-risk group for MAFLD; therefore, it is of great importance to identify and intervene with patients at risk at an early stage. This study established a predictive nomogram model of MAFLD in postmenopausal women and to enhance the clinical utility of the new model, the researchers limited variables to simple clinical and laboratory indicators that are readily obtainable. Methods: Data of 942 postmenopausal women from January 2023 to October 2023 were retrospectively collected and divided into two groups according to the collection time: the training group (676 cases) and the validation group (226 cases). Significant indicators independently related to MAFLD were identified through univariate logistic regression and stepwise regression, and the MAFLD prediction nomogram was established. The C-index and calibration curve were used to quantify the nomogram performance, and the model was evaluated by measuring the area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA). Results: Of 37 variables, 11 predictors were identified, including occupation (worker), body mass index, waist-to-hip ratio, number of abortions, anxiety, hypertension, hyperlipidemia, diabetes, hyperuricemia, and diet (meat and processed meat). The C-index of the training group predicting the related risk factors was 0.827 (95% confidence interval [CI] 0.794-0.860). The C-index of the validation group was 0.787 (95% CI 0.728-0.846). Calibration curves 1 and 2 (BS1000 times) were close to the diagonal, showing a good agreement between the predicted probability and the actual incidence in the two groups. The AUC of the training group was 0.827, the sensitivity was 0.784, and the specificity was 0.735. The AUC of the validation group was 0.787, the sensitivity was 0.674, and the specificity was 0.772. The DCA curve showed that the nomogram had a good net benefit in predicting MAFLD in postmenopausal women. Conclusions: A predictive nomogram for MAFLD in postmenopausal women was established and verified, which can assist clinicians in evaluating the risk of MAFLD at an early stage.

Convergent direct and indirect cortical streams shape avoidance decisions in mice via the midline thalamus.

Current concepts of corticothalamic organization in the mammalian brain are mainly based on sensory systems, with less focus on circuits for higher-order cognitive functions. In sensory systems, first-order thalamic relays are driven by subcortical inputs and modulated by cortical feedback, while higher-order relays receive strong excitatory cortical inputs. The applicability of these principles beyond sensory systems is uncertain. We investigated mouse prefronto-thalamic projections to the midline thalamus, revealing distinct top-down control. Unlike sensory systems, this pathway relies on indirect modulation via the thalamic reticular nucleus (TRN). Specifically, the prelimbic area, which influences emotional and motivated behaviors, impacts instrumental avoidance responses through direct and indirect projections to the paraventricular thalamus. Both pathways promote defensive states, but the indirect pathway via the TRN is essential for organizing avoidance decisions through disinhibition. Our findings highlight intra-thalamic circuit dynamics that integrate cortical cognitive signals and their role in shaping complex behaviors.

Correlation between inflammatory cytokines and the likelihood of developing multiple types of digestive system cancers: A Mendelian randomization study.

OBJECTIVE: Inflammatory cytokines have been linked to digestive system cancers, yet their exact causal connection remains uncertain. Consequently, we conducted a Mendelian randomization (MR) analysis to gauge how inflammatory cytokines are linked to the risk of five prevalent digestive system cancers (DSCs). METHODS: We collected genetic variation data for 41 inflammatory cytokines from genome-wide association studies (GWAS), and the results data for five common diseases from the Finnish database. Our primary analytical approach involved employing the inverse-variance weighted, residual sum (IVW) method, complemented by the MR-Egger method, the weighted median method, simple mode analysis, and weighted mode analysis as supplementary analytical techniques. Furthermore, we conducted multiple sensitivity analyses. RESULTS: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), macrophage colony-stimulating factor (M-CSF), and interleukin (IL)-18 showed a negative association with the risk of hepatocellular carcinoma. Conversely, TRAIL was inversely linked to the risk of gastric cancer, while IL-16 exhibited a positive correlation with gastric cancer risk. Stem cell factor (SCF) acted as a protective factor against pancreatic cancer. For colorectal cancer, IL-7, IL-9, IL-13, and vascular endothelial growth factor (VEGF) were identified as risk factors. Notably, our results did not indicate a significant correlation between inflammatory cytokines and the risk of esophageal cancer. CONCLUSION: Our research unveils potential connections between 41 inflammatory cytokines and the risk of five common DSCs through a MR analysis. These associations offer valuable insights that could aid in the development of diagnostic biomarkers and the identification of novel therapeutic targets for DSCs.

The pivotal role of dysregulated autophagy in the progression of non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is a clinicopathologic syndrome characterized by excessive fat deposition in hepatocytes and a major cause of end-stage liver disease. Autophagy is a metabolic pathway responsible for degrading cytoplasmic products and damaged organelles, playing a pivotal role in maintaining the homeostasis and functionality of hepatocytes. Recent studies have shown that pharmacological intervention to activate or restore autophagy provides benefits for liver function recovery by promoting the clearance of lipid droplets (LDs) in hepatocytes, decreasing the production of pro-inflammatory factors, and inhibiting activated hepatic stellate cells (HSCs), thus improving liver fibrosis and slowing down the progression of NAFLD. This article summarizes the physiological process of autophagy, elucidates the close relationship between NAFLD and autophagy, and discusses the effects of drugs on autophagy and signaling pathways from the perspectives of hepatocytes, kupffer cells (KCs), and HSCs to provide assistance in the clinical management of NAFLD.

Exploring the possible therapeutic mechanism of Danzhixiaoyao pills in depression and MAFLD based on "Homotherapy for heteropathy": A network pharmacology and molecular docking.

Objective: Danzhixiaoyao pills (DXP) is a traditional Chinese medicine formula that has been effectively used in clinical practice to treat depression and metabolic associated fatty liver disease (MAFLD), but its therapeutic mechanism is not yet clear. The purpose of this study is to explore the possible mechanisms of DXP in treating depression and MAFLD using network pharmacology and molecular docking techniques based on existing literature reports. Methods: By combining TCMSP, Swiss ADME, Swiss TargetPrediction, and UniProt databases, the active ingredients and potential targets of DXP were screened and obtained. By searching for relevant disease targets through Gene Cards, OMIM, and TTD databases, intersection targets between drugs and diseases were obtained. The network of "Disease - Potential targets - Active ingredients - Traditional Chinese medicine - Prescriptions" was constructed using Cytoscape 3.9.1 software, and the PPI network was constructed using STRING 12.0 database. The core targets were obtained through topology analysis. GO function enrichment and KEGG pathway enrichment analysis were conducted based on DAVID. The above results were validated by molecular docking using PyMol 2.5 and AutoDock Tool 1.5.7 software, and their possible therapeutic mechanisms were discussed. Results: Network pharmacology analysis obtained 130 main active ingredients of drugs, 173 intersection targets between drugs and diseases, and 37 core targets. Enrichment analysis obtained 1390 GO functional enrichment results, of which 922 were related to biological process, 107 were related to cellular component, 174 were related to molecular function, and obtained 180 KEGG pathways. Molecular docking has confirmed the good binding ability between relevant components and targets, and the literature discussion has preliminarily verified the above results. Conclusion: DXP can act on targets such as TNF, AKT1, ALB, IL1B, TP53 through active ingredients such as kaempferol, quercetin, naringenin, isorhamnetin, glyuranolide, etc, and by regulating signaling pathways such as pathways in cancer, MAPK signaling pathway, lipid and atherosclerosis, to exert its effect of "homotherapy for heteropathy" on depression and MAFLD. In addition, glyuranolide showed the strongest affinity with TNF (-7.88 kcal/mol), suggesting that it may play a key role in the treatment process. The research results provide a theoretical basis for elucidating the scientific connotation and mechanism of action of traditional Chinese medicine compound DXP, and provide new directions for its clinical application.

The short- and mid-term efficacy and safety of elagolix in the management of pain associated with endometriosis: A systematic review and meta-analysis.

BACKGROUND: Elagolix, an approved non-peptide GnRH antagonist, shows promise in relieving endometriosis-related pain, but its short- and mid-term efficacy and potential side effects are still under investigation. OBJECTIVE: The aim is to provide data for therapeutic applications by methodically evaluating elagolix's safety and effectiveness in treating endometriosis-related pain. METHODS: Databases such as PubMed, Embase, Cochrane Library, Web of Science, ClinicalTrials.gov, and others were thoroughly searched. The search time was from the establishment date to September 2023. The study included randomized controlled trials (RCTs) that compared the efficacy of elagolix versus placebo in treating endometriosis-associated pain. After data extraction and literature scanning, quality assessment was carried out using Quality evaluation was carried out using the bias risk assessment tool suggested by the Cochrane Reviewers' Handbook 5.1.0 after literature screening and data extraction. Stata 15.0 was used to do the meta-analysis. RESULTS: In total, five RCTs involving 2056 patients were included in the analysis. The meta-analysis demonstrated a significant superiority of elagolix over placebo in the management of endometriosis-related pain, specifically in endometriosis pain [WMD=-0.77, 95% CI (-1.00, -0.53), P<0.001], as well as in non-menstrual pelvic pain, daily assessment of dysmenorrhea (DYS), and dyspareunia (DYSP), all of which are associated with endometriosis. Regarding safety, no discernible variation was observed in the incidence of serious adverse responses between the elagolix and placebo groups [RR=0.90, 95% CI (0.58, 1.40), P=0.643]. Conversely, the elagolix group exhibited a significantly higher incidence rate of general adverse responses [RR = 1.34, 95% CI (1.18, 1.52), P<0.001] compared to the control group. CONCLUSIONS: The efficacy of elagolix in reducing pain in premenopausal women with endometriosis has been demonstrated over the short- to mid-term. However, careful monitoring for potential adverse effects is essential throughout the treatment duration.

Neuroprotective Effects of Metformin on Cerebral Ischemia-Reperfusion Injury: Modulation of JNK and p38 MAP Kinase Signaling Pathways.

Cerebral ischemia-reperfusion injury (CIRI) is a significant pathological process in stroke, characterized by neuronal cell death and neurological dysfunction. Metformin, commonly used for diabetes management, has been noted for its neuroprotective properties, though its effects on CIRI and the mechanisms involved remain unclear. This study explored the neuroprotective impact of metformin on CIRI, focusing on its potential to modulate the c-Jun N-terminal kinase (JNK) and p38 MAP kinase (p38) signaling pathways. Using in vitro models of oxygen-glucose deprivation/reperfusion (OGD/R) in neuronal cells and in vivo mouse models of middle cerebral artery occlusion (MCAO), the effects of metformin were assessed. Cell viability was measured with Cell Counting Kit-8 (CCK-8), protein expression via Western Blot (WB), and apoptosis through flow cytometry. The extent of brain injury in mice was evaluated using 2,3,5-triphenyltetrazolium chloride (TTC) staining, while JNK and p38 activation statuses were detected through WB and phospho-JNK (p-JNK) immunofluorescence staining. Results showed that metformin significantly improved the viability of HT22 cells post-OGD/R, reduced apoptosis, and decreased OGD/R-induced phosphorylation of JNK and p38 in vitro. In vivo, metformin treatment notably reduced brain infarct volume in MCAO mice, inhibited p-p38 and p-JNK expression, and enhanced neurological function. These findings suggest that metformin exerts neuroprotective effects against CIRI by modulating the JNK/p38 signaling pathway, highlighting its potential therapeutic value in treating cerebral ischemia-reperfusion injury and paving the way for clinical applications.

Inhibition of inflammation and apoptosis through the cyclic GMP-AMP synthase-stimulator of interferon genes pathway by stress granules after ALKBH5 demethylase activation during diabetic myocardial ischaemia-reperfusion injury.

AIM: Post-transcriptional modifications and their specific mechanisms are the focus of research on the regulation of myocardial damage. Stress granules (SGs) can inhibit the inflammatory response by inhibiting the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway. This study investigated whether alkylation repair homologue protein 5 (ALKBH5) could affect myocardial inflammation and apoptosis during diabetic myocardial ischaemia-reperfusion injury (IRI) through the cGAS-STING pathway via SGs. METHODS: A diabetes ischaemia-reperfusion rat model and a high glucose hypoxia/reoxygenation cell model were established. Adeno-associated virus (AAV) and lentivirus (LV) were used to overexpress ALKBH5, while the SG agonist arsenite (Ars) and the SG inhibitor anisomycin were used as interventions. Then, the levels of apoptosis and related indicators in the cell and rat models were measured. RESULTS: In the in vivo experiment, compared with the normal sham group, the degree of myocardial tissue damage, creatine kinase-MB and cardiac troponin I in serum, and myocardial apoptosis, the infarcted area of myocardium, and the level of B-cell lymphoma 2 associated X protein, cGAS-STING pathway and inflammatory factors in the diabetes ischaemia-reperfusion group were significantly increased. However, the expression of SGs and the levels of ALKBH5, rat sarcoma-GTPase-activating protein-binding protein 1, T-cell intracellular antigen-1 and Bcl2 were significantly decreased. After AAV-ALKBH5 intervention, the degree of myocardial tissue damage, degree of myocardial apoptosis, and extent of myocardial infarction in myocardial tissue were significantly decreased. In the in vitro experiment, compared with those in the normal control group, the levels of lactate dehydrogenase, inflammation and apoptosis were significantly greater, and cell viability and the levels of ALKBH5 and SGs were decreased in the high glucose and hypoxia/reoxygenation groups. In the high glucose hypoxia/reoxygenation cell model, the degree of cell damage, inflammation, and apoptosis was greater than those in the high glucose and hypoxia/reoxygenation models, and the levels of ALKBH5 and SGs were further decreased. LV-ALKBH5 and Ars alleviated the degree of cell damage and inhibited inflammation and cell apoptosis. The inhibition of SGs could partly reverse the protective effect of LV-ALKBH5. The cGAS agonist G140 antagonized the inhibitory effects of the SG agonist Ars on cardiomyocyte apoptosis, inflammation and the cGAS-STING pathway. CONCLUSION: Both ALKBH5 and SGs inhibited myocardial inflammation and apoptosis during diabetic myocardial ischaemia-reperfusion. Mechanistically, ALKBH5 might inhibit the apoptosis of cardiomyocytes by promoting the expression of SGs through the cGAS-STING pathway.

Development of Bio-Voltage Operated Humidity-Sensory Neurons Comprising Self-Assembled Peptide Memristors.

Biomimetic humidity sensors offer a low-power approach for respiratory monitoring in early lung-disease diagnosis. However, balancing miniaturization and energy efficiency remains challenging. This study addresses this issue by introducing a bioinspired humidity-sensing neuron comprising a self-assembled peptide nanowire (NW) memristor with unique proton-coupled ion transport. The proposed neuron shows a low Ag+ activation energy owing to the NW and redox activity of the tyrosine (Tyr)-rich peptide in the system, facilitating ultralow electric-field-driven threshold switching and a high energy efficiency. Additionally, Ag+ migration in the system can be controlled by a proton source owing to the hydrophilic nature of the phenolic hydroxyl group in Tyr, enabling the humidity-based control of the conductance state of the memristor. Furthermore, a memristor-based neuromorphic perception neuron that can encode humidity signals into spikes is proposed. The spiking characteristics of this neuron can be modulated to emulate the strength-modulated spike-frequency characteristics of biological neurons. A three-layer spiking neural network with input neurons comprising these highly tunable humidity perception neurons shows an accuracy of 92.68% in lung-disease diagnosis. This study paves the way for developing bioinspired self-assembly strategies to construct neuromorphic perception systems, bridging the gap between artificial and biological sensing and processing paradigms.

Mapping of spastic muscle activity after stroke: difference between passive stretch and active contraction.

BACKGROUND: Investigating the spatial distribution of muscle activity would facilitate understanding the underlying mechanism of spasticity. The purpose of this study is to investigate the characteristics of spastic muscles during passive stretch and active contraction by high-density surface electromyography (HD-sEMG). METHODS: Fourteen spastic hemiparetic subjects and ten healthy subjects were recruited. The biceps brachii (BB) muscle activity of each subject was recorded by HD-sEMG during passive stretch at four stretch velocities (10, 60, 120, 180˚/s) and active contraction at three submaximal contraction levels (20, 50, 80%MVC). The intensity and spatial distribution of the BB activity were compared by the means of two-way analysis of variance, independent sample t-test, and paired sample t-test. RESULTS: Compared with healthy subjects, spastic hemiparetic subjects showed significantly higher intensity with velocity-dependent heterogeneous activation during passive stretch and more lateral and proximal activation distribution during active contraction. In addition, spastic hemiparetic subjects displayed almost non-overlapping activation areas during passive stretch and active contraction. The activation distribution of passive stretch was more distal when compared with the active contraction. CONCLUSIONS: These alterations of the BB activity could be the consequence of deficits in the descending central control after stroke. The complementary spatial distribution of spastic BB activity reflected their opposite motor units (MUs) recruitment patterns between passive stretch and active contraction. This HD-sEMG study provides new neurophysiological evidence for the spatial relationship of spastic BB activity between passive stretch and active contraction, advancing our knowledge on the mechanism of spasticity. TRIAL REGISTRATION: ChiCTR2000032245.

Association between diabetes mellitus and primary biliary cholangitis: a two-sample Mendelian randomization study.

Background: Previous observational studies have demonstrated a link between diabetes mellitus(DM) and primary biliary cholangitis (PBC). Nevertheless, since these relationships might be confused, whether there is any causal connection or in which direction it exists is unclear. Our investigation aimed to identify the causal associations between DM and PBC. Methods: We acquired genome-wide association study (GWAS) datasets for PBC, Type 1 diabetes(T1DM), and Type 2 diabetes(T2DM) from published GWASs. Inverse variance-weighted (IVW), MR-Egger, weighted median (WM), Simple mode, and weighted mode methods were used to determine the causal relationships between DM(T1DM or T2DM) and PBC. Sensitivity analyses were also carried out to ensure the results were robust. To determine the causal relationship between PBC and DM(T1DM or T2DM), we also used reverse MR analysis. Results: T1DM was associated with a higher risk of PBC (OR 1.1525; 95% CI 1.0612-1.2517; p = 0.0007) in the IVW method, but no evidence of a causal effect T2DM on PBC was found (OR 0.9905; 95% CI 0.8446-1.1616; p = 0.9071) in IVW. Results of the reverse MR analysis suggested genetic susceptibility that PBC was associated with an increased risk of T1DM (IVW: OR 1.1991; 95% CI 1.12-1.2838; p = 1.81E-07), but no evidence of a causal effect PBC on T2DM was found (IVW: OR 1.0101; 95% CI 0.9892-1.0315; p = 0.3420). Conclusion: The current study indicated that T1DM increased the risk of developing PBC and vice versa. There was no proof of a causal connection between PBC probability and T2DM. Our results require confirmation through additional replication in larger populations.

DJ-1 preserves ischemic postconditioning-induced cardioprotection in STZ-induced type 1 diabetic rats: role of PTEN and DJ-1 subcellular translocation.

BACKGROUND: Ischemic postconditioning (IPostC) has been reported as a promising method for protecting against myocardial ischemia-reperfusion (MI/R) injury. Our previous study found that the infarct-limiting effect of IPostC is abolished in the heart of diabetes whose cardiac expression of DJ-1 (also called PARK7, Parkinsonism associated deglycase) is reduced. However, the role and in particular the underlying mechanism of DJ-1 in the loss of sensitivity to IPostC-induced cardioprotection in diabetic hearts remains unclear. METHODS: Streptozotocin-induced type 1 diabetic rats were subjected to MI/R injury by occluding the left anterior descending artery (LAD) and followed by reperfusion. IPostC was induced by three cycles of 10s of reperfusion and ischemia at the onset of reperfusion. AAV9-CMV-DJ-1, AAV9-CMV-C106S-DJ-1 or AAV9-DJ-1 siRNA were injected via tail vein to either over-express or knock-down DJ-1 three weeks before inducing MI/R. RESULTS: Diabetic rats subjected to MI/R exhibited larger infarct area, more severe oxidative injury concomitant with significantly reduced cardiac DJ-1 expression and increased PTEN expression as compared to non-diabetic rats. AAV9-mediated cardiac DJ-1 overexpression, but not the cardiac overexpression of DJ-1 mutant C106S, restored IPostC-induced cardioprotection and this effect was accompanied by increased cytoplasmic DJ-1 translocation toward nuclear and mitochondrial, reduced PTEN expression, and increased Nrf-2/HO-1 transcription. Our further study showed that AAV9-mediated targeted DJ-1 gene knockdown aggravated MI/R injury in diabetic hearts, and this exacerbation of MI/R injury was partially reversed by IPostC in the presence of PTEN inhibition or Nrf-2 activation. CONCLUSIONS: These findings suggest that DJ-1 preserves the cardioprotective effect of IPostC against MI/R injury in diabetic rats through nuclear and mitochondrial DJ-1 translocation and that inhibition of cardiac PTEN and activation of Nrf-2/HO-1 may represent the major downstream mechanisms whereby DJ-1 preserves the cardioprotective effect of IPostC in diabetes.

The intervention of curcumin on rodent models of hepatic fibrosis: A systematic review and meta-analysis.

OBJECTIVE: This study aimed to evaluate the intervention effect of curcumin on hepatic fibrosis in rodent models through systematic review and meta-analysis, in order to provide meaningful guidance for clinical practice. METHODS: A systematic retrieval of relevant studies on curcumin intervention in rats or mice hepatic fibrosis models was conducted, and the data were extracted. The outcome indicators included liver cell structure and function related indicators, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), albumin (ALB), ratio of albumin to globulin (A/G), total bilirubin (TBIL), bax protein, bcl-2 protein and index of liver, as well as the relevant indicators for evaluating the degree of hepatic fibrosis, such as hyaluronic acid (HA), laminin (LN), type I collagen (Collagen I), type III collagen (Collagen III), type III procollagen (PCIII), type III procollagen amino terminal peptide (PIIINP), type IV collagen (IV-C), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), α-Smooth muscle actin (α-SMA), hydroxyproline (HYP), platelet derived factor-BB (PDGF-BB), connective tissue growth factor (CTGF) and transforming growth factor-ß1 (TGF-ß1), and oxidative stress-related indicators, such as superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px). These results were then analyzed by meta-analysis. Studies were evaluated for methodological quality using the syrcle's bias risk tool. RESULTS: A total of 59 studies were included in the meta-analysis, and the results showed that curcumin can reduce the levels of ALT, AST, ALP, TBIL, bax protein, and index of liver in hepatic fibrosis models. It can also reduce HA, LN, Collagen I, Collagen III, PCIII, PIIINP, IV-C, TNF-α, α-SMA, HYP, PDGF-BB, CTGF, TGF-ß1 and MDA, and increase the levels of ALB, A/G, SOD, and GSH-Px in the hepatic fibrosis models. However, the effects of curcumin on bcl-2 protein, IL-6 in hepatic fibrosis models and index of liver in mice were not statistically significant. CONCLUSION: The analysis results indicate that curcumin can reduce liver cell apoptosis by maintaining the stability of liver cell membrane, inhibit the activation and proliferation of hepatic stellate cells by reducing inflammatory response, and alleviate tissue peroxidation damage by clearing oxygen free radicals.

Schiff base functionalized dialdehyde starch for enhanced removal of Cu (II): Preparation, performances, DFT calculations.

Dialdehyde starch modified by 2-hydrazinopyridine (HYD-DAS) based on the reaction of dialdehyde starch (DAS) and 2-hydrazinopyridine was synthesized and characterized by FT-IR spectra, element analysis and SEM. HYD-DAS can efficiently adsorb Cu (II) ion to demonstrate visual color changes from yellow to dark brown in aqueous solutions. The influence on HYD-DAS to Cu (II) adsorption including pH value of solution, isotherm, kinetics, thermodynamics and possible mechanism had also been examined. Batch experiments indicate that HYD-DAS's to Cu (II) adsorption reaches equilibrium within 250 min, and its adsorption capacity and rate are 195.75 mg/g and 98.63 %, respectively. Moreover, HYD-DAS to Cu (II) adsorption remains robust and underscoring after five cycles to exhibit good selectivity and reusability. Kinetics studies suggest the absorption process follows a quasi-second-order with isotherms aligning to the Langmuir monolayer model, and thermodynamics reveals that it is a spontaneous endothermic nature of adsorption. Based on the analyses of XPS and DFT calculations, a possible mechanism for HYD-DAS to Cu (II) adsorption is that Cu (II) combined with nitrogen atoms from Schiff base and hydrazine pyridine ring in HYD-DAS.

Identification and functional analysis of the hub Ferroptosis-Related gene EZH2 in diabetic kidney disease.

BACKGROUND: Diabetic kidney disease (DKD) is a common microvascular complication and one of the main causes of death in diabetes. Ferroptosis, an iron-dependent mode of cell death characterized by lipid ROS accumulation, was found to be associated with a number of diseases and has great potential for kidney diseases. It has great value to identify potential ferroptosis-related genes and their biological mechanisms in DKD. METHODS: We obtained the GSE30122 dataset from Gene Expression Omnibus (GEO) database and ferroptosis-related genes from the Ferrdb database. After differential expression analysis, and three machine learning algorithms, the hub ferroptosis-related gene EZH2 was identified. In order to investigate the function of EZH2, Gene Set Enrichment Analysis (GSEA), Gene Set Variation Analysis (GSVA) and single cell analysis were conducted. The expression of EZH2 was validated in DKD patients, HK-2 cell models and DKD mouse models. EZH2 knockdown HK-2 cells and HK-2 cells treated with GSK126 were performed to verify whether EZH2 affected ferroptosis in DKD. CHIP assay was used to detect whether EZH2 regulated ferroptosis by suppressing SLC7A11. Molecular docking was performed to explore EZH2 and four traditional Chinese medicine (Sennoside A, Berberine, Umbelliferone, Platycodin D) related to ferroptosis in DKD treatment. RESULTS: According to the GSE30122 dataset in GEO and ferroptosis-related genes from the Ferrb database, we obtained the hub ferroptosis-related gene EZH2 in DKD via diversified machine learning methods. The increasing of EZH2 expression was shown in single cell analysis, DKD patients, DKD mouse models and high glucose induced DKD cell models. Further study showed that EZH2 knockdown and inhibition can alleviate HG-induced ferroptosis in vitro. CHIP assay showed EZH2-mediated epigenetic silencing regulated the expression of SLC7A11. Molecular docking results showed that EZH2 had strong binding stability with Sennoside A, Berberine, Umbelliferone, and Platycodin D. CONCLUSION: Overall, our data shouwed that histone H3K27 methyltransferase EZH2 could regulate the renal tubular epithelial cell ferroptosis by suppressing SLC7A11 in DKD, which may serve as a credible reliable indicator for diagnosing DKD and a potential target for treatment.

Probing the occurrence, sources and cancer risk assessment of polycyclic aromatic hydrocarbons in PM2.5 in a humid metropolitan city in China.

Fifty-two consecutive PM2.5 samples from December 2021 to February 2022 (the whole winter) were collected in the center of Chongqing, a humid metropolitan city in China. These samples were analysed for the 16 USEPA priority polycyclic aromatic hydrocarbons (16 PAHs) to explore their composition and sources, and to assess their cancer risks to humans. The total concentrations of the 16 PAHs (ng m-3) ranged from 16.45 to 174.15, with an average of 59.35 ± 21.45. Positive matrix factorization (PMF) indicated that traffic emissions were the major source (42.4%), followed by coal combustion/industrial emission (31.3%) and petroleum leakage/evaporation (26.3%). The contribution from traffic emission to the 16 PAHs increased from 40.0% in the non-episode days to as high as 46.2% in the air quality episode during the sampling period. The population attributable fraction (PAF) indicates that when the unit relative risk (URR) is 4.49, the number of lung cancer cases per million individuals under PAH exposure is 27 for adults and 38 for seniors, respectively. It was 5 for adults and 7 for seniors, when the URR is 1.3. The average incremental lifetime cancer risk (ILCR) for children, adolescents, adults and seniors was 0.25 × 10-6, 0.23 × 10-6, 0.71 × 10-6, and 1.26 × 10-6, respectively. The results of these two models complemented each other well, and both implied acceptable PAH exposure levels. Individual genetic susceptibility and exposure time were identified as the most sensitive parameters. The selection and use of parameters in risk assessment should be further deepened in subsequent studies to enhance the reliability of the assessment results.

Time-varying and speed-matched model for the evaluation of stroke-induced changes in ankle mechanics.

The ankle mechanics (stiffness and moment) are modulated continuously when interacting with the environment during human walking. However, it remains unclear how ankle mechanics vary with walking speeds, and how they are affected by stroke. This study aimed to determine time-varying ankle stiffness and moment in stroke participants during walking, comparing them with healthy participants at matched speeds. A motion capture system, surface electromyography (EMG) system and force plates were used to measure biomechanics of seven healthy participants walking at 5 controlled speeds and ten patients with stroke at self-selected speeds. The ankle moment and stiffness during the stance phase were calculated using an EMG-driven musculoskeletal model. Surface equations of ankle moment and stiffness in healthy participants, with walking speed and stance phase as variables, were proposed based on polynomial fitting. Results showed that as walking speed increased, there was an increase in the ankle stiffness and moment of healthy participants during 77 %-89 % and 63 %-91 % of stance phase, respectively. Patients with stroke had lower ankle stiffness and moment at self-selected walking speed than healthy participants at 1.04 m/s walking speed during 52 %-87 % and 52 %-91 % of stance phase, respectively. At matched walking speed, the peak values of ankle stiffness and moment in patients with stroke were significantly less than those in healthy participants (p = 0.007; p = 0.028, respectively). This study proposes a novel approach to evaluate the ankle mechanics of patients with stroke using the speed-matched model of healthy participants and may provide insights into understanding speed-dependent movement mechanisms of human walking.

Regulation of intestinal flora in patients with chronic atrophic gastritis by modified Chai Shao Liu Jun Zi decoction based on 16S rRNA sequencing.

Chai Shao Liu Jun Zi decoction (CSLJZD) is an effective Chinese medicine for the treatment of chronic atrophic gastritis (CAG). However, the effect of CSLJZD on the intestinal flora of patients with CAG remains unclear. We used 16S rRNA gene sequencing to investigate the regulatory effects of CSLJZD on intestinal microflora in patients with CAG. Eight patients with CAG were randomly selected as the model group and 8 healthy medical examiners as the control group; the treatment group comprised patients with CAG after CSLJZD treatment. High-throughput sequencing and bioinformatics analysis of the V3V4 region of the 16S rRNA gene of intestinal bacteria obtained from the intestinal isolates of fecal specimens from all participants were performed separately. A rarefaction curve, species accumulation curve, Chao1 index, and ACE index were calculated to assess the alpha diversity. Principal component analysis (PCA), non-metric multi-dimensional scaling, and the unweighted pair group method with arithmetic mean were used to examine beta diversity. The LEfSe method was used to identify the differentially expressed bacteria. Differential function analysis was performed using PCA based on KEGG function prediction. Rarefaction and species accumulation curves showed that the sequencing data were reasonable. The Chao1 and ACE indices were significantly increased in patients with CAG compared with those in the healthy group. Following CSLJZD and vitacoenzyme treatment, Chao1 and ACE indices decreased. The PCA, non-metric multi-dimensional scaling, and unweighted pair group method with arithmetic mean results showed that the CAG group was distinct from the healthy and treatment groups. The LEfSe results showed that the abundances of the genus Bilophila, family Desulfovibrionaceae, order Desulfovibrionales and genus Faecalibacterium were significantly higher in the healthy group. The abundance of genus Klebsiella, order Deltaproteobacteria, genus Gemmiger, and other genera was significantly higher in the treatment group. Treatment with CSLJZD had a therapeutic effect on the intestinal flora of patients with CAG.

Dietary supplementation with inulin improves burn-induced skeletal muscle atrophy by regulating gut microbiota disorders.

Inulin, as a prebiotic, could modulate the gut microbiota. Burn injury leads to gut microbiota disorders and skeletal muscle catabolism. Therefore, whether inulin can improve burn-induced muscle atrophy by regulating microbiota disorders remains unknown. This study aimed to clarify that inulin intake alleviates gut microbiota disorders and skeletal muscle atrophy in burned rats. Rats were divided into the sham group, burn group, prebiotic inulin intervention group, and pseudo-aseptic validation group. A 30% total body surface area (TBSA) third-degree burn wound on dorsal skin was evaluated in all groups except the sham group. Animals in the intervention group received 7 g/L inulin. Animals in the validation group received antibiotic cocktail and inulin treatment. In our study inulin intervention could significantly alleviate the burn-induced skeletal muscle mass decrease and skeletal myoblast cell apoptosis. Inulin intake increased the abundances of Firmicutes and Actinobacteria but decreased the abundance of Proteobacteria. The biosynthesis of amino acids was the most meaningful metabolic pathway distinguishing the inulin intervention group from the burn group, and further mechanistic studies have shown that inulin can promote the phosphorylation of the myogenesis-related proteins PI3K, AKT and P70S6K and activate PI3K/AKT signaling for protein synthesis. In conclusion, inulin alleviated burn induced muscle atrophy through PI3K/AKT signaling and regulated gut microbiota dysbiosis.

Ni Single-Atoms Based Memristors with Ultrafast Speed and Ultralong Data Retention.

Memristor with low-power, high density, and scalability fulfills the requirements of the applications of the new computing system beyond Moore's law. However, there are still nonideal device characteristics observed in the memristor to be solved. The important observation is that retention and speed are correlated parameters of memristor with trade off against each other. The delicately modulating distribution and trapping level of defects in electron migration-based memristor is expected to provide a compromise method to address the contradictory issue of improving both switching speed and retention capability. Here, high-performance memristor based on the structure of ITO/Ni single-atoms (NiSAs/N-C)/Polyvinyl pyrrolidone (PVP)/Au is reported. By utilizing well-distributed trapping sites , small tunneling barriers/distance and high charging energy, the memristor with an ultrafast switching speed of 100 ns, ultralong retention capability of 106  s, a low set voltage (Vset ) of ≈0.7 V, a substantial ON/OFF ration of 103 , and low spatial variation in cycle-to-cycle (500 cycles) and device-to-device characteristics (128 devices) is demonstrated. On the premise of preserving the strengths of a fast switching speed, this memristor exhibits ultralong retention capability comparable to the commercialized flash memory. Finally, a memristor ratioed logic-based combinational memristor array to realize the one-bit full adder is further implemented.