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Abstract Background As neuropeptide Y is associated with endothelial dysfunction, this study explored the relationship between neuropeptide Y and acute myocardial infarction. Methods We included 128 acute myocardial infarction cases and 62 controls. Using the SYNTAX scoring system, the acute myocardial infarction group was sub-grouped into “SYNTAX ≤ 22,” “SYNTAX = 23–32,” and “SYNTAX ≥ 33.” Plasma neuropeptide Y, endothelin, endothelial nitric oxide synthase, and thromboxane A2 levels were measured. Results The acute myocardial infarction group had higher plasma neuropeptide Y, endothelin, and thromboxane A2 levels than controls ([58.76 ± 17.63 vs. 37.48 ± 11.36 ng/ml, P = 0.000], [36.16 ± 10.04 vs. 27.80 ± 7.18 pg/ml, P = 0.000], and [27.69 ± 6.91 vs. 24.32 ± 7.28 pg/ml, P = 0.002], respectively). The acute myocardial infarction group also had lower plasma endothelial nitric oxide synthase levels than controls (3.00 ± 0.94 vs. 4.05 ± 1.44 ng/ml, P = 0.000). Additionally, the receiver operating characteristic curve analysis showed that a neuropeptide Y value of 49.94 ng/ml could help diagnose acute myocardial infarction (sensitivity: 70.9%; specificity: 91.9%). The SYNTAX scores, smoking, plasma endothelin, thromboxane A2, and neuropeptide Y levels were positively correlated, whereas plasma endothelial nitric oxide synthase and neuropeptide Y levels were negatively correlated. Lastly, plasma neuropeptide Y levels were different among subgroups (P

Background: Dermatoscopy is a noninvasive method of examining skin lesions under high magnification, gradually replacing the need for invasive biopsies. Training is required to gain clinical competency. Gamification employs game-like elements to enhance education engagement and is an engaging means of delivering medical education. We sought to use gamification and a mobile-based platform to deliver dermatoscopy education to physicians. Methods: We developed SKIN@GoPRIME, an interactive smartphone platform. Thirty physician participants were randomly assigned to watch an online dermatoscopy lecture or to use SKIN@GoPRIME. Twenty-eight participants completed prelearning and postlearning quizzes and provided feedback on SKIN@GoPRIME. Results: Users of SKIN@GoPRIME demonstrated a significant 1.71-point mean score improvement (P = .0018). The group that watched the online dermatoscopy lecture had a higher 2.36-point mean score improvement (P = .00021). Both family medicine and internal medicine physicians demonstrated a significant mean score increase of 1.29 (P = .049) and 2.14 (P = .023), respectively, after using SKIN@GoPRIME. Based on feedback, 83% believed that SKIN@GoPRIME can be used to acquire the applied competencies required for their job scope. Discussion and Conclusion: SKIN@GoPRIME, a novel learning tool via gamification effectively delivers dermatoscopy education, although it is not shown to be more effective than lectures. Larger studies are required to further validate the effectiveness of gamified learning techniques in dermatoscopy education. Future studies should involve the optimization of SKIN@GoPRIME to more effectively deliver dermatoscopy education.

Atmospheric organic aerosols consist of both gas-phase organic compounds and particle-phase organic compounds. The components of aerosol particles (solid or liquid droplets) can undergo exchange or chemical reactions with gas-phase components, influencing atmospheric physical and chemical processes and potentially impacting atmospheric environment, climate, and human health. Methods for detecting organic compounds in aerosol particle phase are classified into offline and online detection. Offline detection methods involve collecting aerosol samples for analysis using chromatography-mass spectrometry, which is time-consuming and limited sensitivity. Online detection methods involve enriching aerosols through aerodynamic lens and then detecting them using laser ablation or electron impact ionization techniques. However, these methods usually generate a large number of ion fragments, making mass spectrum analysis difficult. Therefore, it is necessary to develop an online detection method for aerosol particle-phase organic compounds with soft ionization and high sampling efficiency. In the present work, a set of aerodynamic lens sampling systems was designed and developed for online detection and analysis of organic compounds in aerosol particle phase. This sampling system consists of a gas-phase stripping module for removing gas-phase organic compounds, an aerodynamic lens module for particle focusing and enrichment, and a thermal desorption module for extracting particle-phase organic compounds. The efficiency of gas-phase organic compound removal and the particle transmission rate of the gas-phase stripping module were firstly investigated. The results showed that gas-phase stripping module achieves a removal efficiency of 98.89% for gas-phase organic compounds, and the particle transmission rate ranges from 75.16% to 91.15% for particles with the diameters between 295 and 375 nm. Subsequently, the effectiveness of the aerodynamic lens was studied through theoretical simulations. The simulation results indicated that the transmission rate of particles in the diameters of 0.36-6.0 μm is above 90% in the designed aerodynamic lens. Finally, The designed aerodynamic lens sampling system with a homemade proton transfer reaction mass spectrometer (PTR-MS) was integrated to develop an aerodynamic lens-PTR-MS device. This device was tested by detecting simulated aerosol samples containing reaction products of α-pinene and ozone. The mass spectrometry results demonstrated that the intensity changes of the examined ten ions are closely related to the presence of α-pinene, confirming that the device can achieve online detection of organic compounds in aerosols ranging from submicron to several micrometers.

Abstract Most cancer cells reprogram their glucose metabolic pathway from oxidative phosphorylation to aerobic glycolysis for energy production. By reducing enzyme activity of pyruvate kinase M2 (PKM2), cancer cells attain a greater fraction of glycolytic metabolites for macromolecule synthesis needed for rapid proliferation. Here we demonstrate that hydrogen sulfide (H2S) destabilizes the PKM2 tetramer into monomer/dimer through sulfhydration at cysteines, notably at C326, leading to reduced PKM2 enzyme activity and increased PKM2-mediated transcriptional activation. Blocking PKM2 sulfhydration at C326 through amino acid mutation stabilizes the PKM2 tetramer and crystal structure further revealing the tetramer organization of PKM2-C326S. The PKM2-C326S mutant in cancer cells rewires glucose metabolism to mitochondrial respiration, significantly inhibiting tumor growth. In this work, we demonstrate that PKM2 sulfhydration by H2S inactivates PKM2 activity to promote tumorigenesis and inhibiting this process could be a potential therapeutic approach for targeting cancer metabolism.

Abstract The genetic contribution of protein-coding variants to immune-mediated diseases (IMDs) remains underexplored. Through whole exome sequencing of 40 IMDs in 350,770 UK Biobank participants, we identified 162 unique genes in 35 IMDs, among which 124 were novel genes. Several genes, including FLG which is associated with atopic dermatitis and asthma, showed converging evidence from both rare and common variants. 91 genes exerted significant effects on longitudinal outcomes (interquartile range of Hazard Ratio: 1.12-5.89). Mendelian randomization identified five causal genes, of which four were approved drug targets (CDSN, DDR1, LTA, and IL18BP). Proteomic analysis indicated that mutations associated with specific IMDs might also affect protein expression in other IMDs. For example, DXO (celiac disease-related gene) and PSMB9 (alopecia areata-related gene) could modulate CDSN (autoimmune hypothyroidism-, psoriasis-, asthma-, and Graves’ disease-related gene) expression. Identified genes predominantly impact immune and biochemical processes, and can be clustered into pathways of immune-related, urate metabolism, and antigen processing. Our findings identified protein-coding variants which are the key to IMDs pathogenesis and provided new insights into tailored innovative therapies.

Given the large hysteresis in the material outlet temperature of the heating furnace, a differential evolution algorithm with adaptive adjustment factors (AAFDE)-radial basis function (RBF)-proportional integral derivative (PID)-PI cascade is proposed. First, we introduce an adaptive mutation factor into the differential evolution (DE) algorithm and define the individual merit coefficient to incorporate a self-adaptive crossover probability factor. Second, the initial parameters of RBF are optimized by the AFFDE algorithm, and RBF neural network model is established. Then, we obtain gradient information by RBF online identification. Finally, we perform online adjustments to the three parameters of PID based on the gradient information. The three parameters are applied to the adjustment of the main controller, while the sub-controller employs PI control. Experimental results show that the anti-disturbance performance of the AFFDE-RBF-PID-PI cascade control outperforms the improved differential evolution (IDE)-RBF-PID-PI cascade control, generalized opposition-based differential evolution (GODE)-RBF-PID-PI cascade control, and MCOBDE-RBF-PID-PI cascade control respectively by 16%, 11%, and 7%, with the response speed improving by 18%, 12%, and 9%, and the stability improving by 19%, 13%, and 8%. These results show that AFFDE-RBF-PID-PI cascade control exhibits enhanced anti-disturbance performance, faster response speed, improved stability, and superior control effect.

Abstract Alcohol consumption is a heritable behavior seriously endangers human health. However, genetic studies on alcohol consumption primarily focuses on common variants, while insights from rare coding variants are lacking. Here we leverage whole exome sequencing data across 304,119 white British individuals from UK Biobank to identify protein-coding variants associated with alcohol consumption. Twenty-five variants are associated with alcohol consumption through single variant analysis and thirteen genes through gene-based analysis, ten of which have not been reported previously. Notably, the two unreported alcohol consumption-related genes GIGYF1 and ANKRD12 show enrichment in brain function-related pathways including glial cell differentiation and are strongly expressed in the cerebellum. Phenome-wide association analyses reveal that alcohol consumption-related genes are associated with brain white matter integrity and risk of digestive and neuropsychiatric diseases. In summary, this study enhances the comprehension of the genetic architecture of alcohol consumption and implies biological mechanisms underlying alcohol-related adverse outcomes.

In this study, the bactericidal activity and mechanism of slightly acidic electrolyzed water (SAEW) against Campylobacter jejuni were examined. The effect of available chlorine concentration (ACC), treatment time and protein addition on the bactericidal activity of SAEW were investigated. In addition, the killing effect of SAEW on multi-generational cultures of C. jejuni was analyzed. The bactericidal mechanism was explored based on the changes in cell membrane integrity, morphology, and contents. The results showed that the inactivation of C. jejuni by SAEW was positively correlated with ACC and treatment time. Exogenous protein significantly weakened the bactericidal efficacy of SAEW. C. jejuni did not develop resistance to SAEW within ten passages. SAEW could destroy the integrity of the cell membrane. After treatment with SAEW, the cell surface was sunken, wrinkled and broken, and nucleic acid, protein and ATP leaked out from the cells, indicating that cell membrane damage may be the major reason for SAEW to inactivate C. jejuni.

Abstract Previous genetic studies of venous thromboembolism (VTE) have been largely limited to common variants, leaving the genetic determinants relatively incomplete. We performed an exome-wide association study of VTE among 14,723 cases and 334,315 controls. Fourteen known and four novel genes (SRSF6, PHPT1, CGN, and MAP3K2) were identified through protein-coding variants, with broad replication in the FinnGen cohort. Most genes we discovered exhibited the potential to predict future VTE events in longitudinal analysis. Notably, we provide evidence for the additive contribution of rare coding variants to known genome-wide polygenic risk in shaping VTE risk. The identified genes were enriched in pathways affecting coagulation and platelet activation, along with liver-specific expression. The pleiotropic effects of these genes indicated the potential involvement of coagulation factors, blood cell traits, liver function, and immunometabolic processes in VTE pathogenesis. In conclusion, our study unveils the valuable contribution of protein-coding variants in VTE etiology and sheds new light on its risk stratification.

Objective. Bariatric surgery effectively treats non-alcoholic fatty liver disease (NAFLD). The glutamate-serine-glycine (GSG) index has emerged as a non-invasive diagnostic marker for NAFLD, but its ability to monitor treatment response remains unclear. This study investigates the GSG index's ability to monitor NAFLD's response to bariatric surgery. Methodology. Ten NAFLD participants were studied at baseline and 6 months post-bariatric surgery. Blood samples were collected for serum biomarkers and metabolomic profiling. Hepatic steatosis [proton density fat fraction (PDFF)] and fibroinflammation (cT1) were quantified with multiparametric magnetic resonance imaging (mpMRI), and hepatic stiffness with magnetic resonance elastography (MRE). Amino acids and acylcarnitines were measured with mass spectrometry. Statistical analyses included paired Student’s t-test, Wilcoxon-signed rank test, and Pearson’s correlation. Results. Eight participants provided complete data. At baseline, all had hepatic steatosis (BMI 39.3 ± 5.6 kg/m2, PDFF ≥ 5%). Post-surgery reductions in PDFF (from 12.4 ± 6.7% to 6.2 ± 2.8%, p = 0.013) and cT1 (from 823.3 ± 85.4ms to 757.5 ± 41.6ms, p = 0.039) were significant, along with the GSG index (from 0.272 ± 0.03 to 0.157 ± 0.05, p = 0.001). Conclusion. The GSG index can potentially be developed as a marker for monitoring the response of patients with NAFLD to bariatric surgery.

Wheat (Triticum aestivum L.) is one of the world's most important staple crops, whose production is critical to feed the expanding population worldwide. The 90-kDa Heat Shock Protein 90 (HSP90) is a highly abundant chaperone protein involved in multiple cellular processes. It facilitates the folding of nascent preproteins for their maturation and functioning. This data described HSP90.2 clients identified from the whole genome of wheat. The HSP90.2 chaperome contains over 1500 proteins, most detected by the C terminus and full-length of HSP90.2. Over 60 % of the clients reside in the cytosol, nucleus, and chloroplasts. Cytoskeleton-related proteins are enriched in the chaperome of the N terminus of HSP90.2. The clients of the middle part of HSP90.2 contains several factors involved in ethylene biosynthesis and extracellular vesicle or organelle-related activities. Some clients related to plant hypersensitive response are induced by stripe rust. The presented dataset could isolate proteins regulated by HSP90.2 at the post-translational level.

Abstract Background There are a variety of determinants that are key to functional disability of older adults. However, little is known regarding the relationship between cognitive frailty and disability among older people. The aims of this study were to examine the associations between cognitive frailty and its six components with instrumental activities of daily living (IADL) functioning in community-dwelling older adults. Methods A total of 313 community-dwelling older adults (aged ≥ 65 years) were recruited from eight community centers in central China. Cognitive frailty was operationalized using the Mini-Mental State Examination for the evaluation of cognitive status and the Fried criteria for the evaluation of physical frailty. The outcome was functional disability assessed by the IADL scale. The association between cognitive frailty, as well as its components, and IADL limitations was identified by conducting binary logistic regression analysis. Results The prevalence of cognitive frailty was 8.9% in this study. The results showed that cognitive frailty (OR = 22.86) and frailty without cognitive impairment (OR = 8.15) were associated with IADL limitations. Subdimensions of cognitive frailty, exhaustion, weakness, low physical activity and cognitive impairment components were independently associated with IADL limitations. Conclusion Cognitive frailty was associated with a higher prevalence of disability. Interventions for improving cognitive frailty should be developed to prevent IADL disability among community-dwelling older adults in China.

Abstract Background Blood-based biomarkers for dementia are gaining attention due to their non-invasive nature and feasibility in regular healthcare settings. Here, we explored the associations between 249 metabolites with all-cause dementia (ACD), Alzheimer’s disease (AD), and vascular dementia (VaD) and assessed their predictive potential. Methods This study included 274,160 participants from the UK Biobank. Cox proportional hazard models were employed to investigate longitudinal associations between metabolites and dementia. The importance of these metabolites was quantified using machine learning algorithms, and a metabolic risk score (MetRS) was subsequently developed for each dementia type. We further investigated how MetRS stratified the risk of dementia onset and assessed its predictive performance, both alone and in combination with demographic and cognitive predictors. Results During a median follow-up of 14.01 years, 5274 participants developed dementia. Of the 249 metabolites examined, 143 were significantly associated with incident ACD, 130 with AD, and 140 with VaD. Among metabolites significantly associated with dementia, lipoprotein lipid concentrations, linoleic acid, sphingomyelin, glucose, and branched-chain amino acids ranked top in importance. Individuals within the top tertile of MetRS faced a significantly greater risk of developing dementia than those in the lowest tertile. When MetRS was combined with demographic and cognitive predictors, the model yielded the area under the receiver operating characteristic curve (AUC) values of 0.857 for ACD, 0.861 for AD, and 0.873 for VaD. Conclusions We conducted the largest metabolome investigation of dementia to date, for the first time revealed the metabolite importance ranking, and highlighted the contribution of plasma metabolites for dementia prediction.