Association of hospital-treated infectious diseases and infection burden with cardiovascular diseases and life expectancy.

BACKGROUND: The association of a broad spectrum of infectious diseases with cardiovascular outcomes remains unclear. OBJECTIVES: We aim to provide the cardiovascular risk profiles associated with a wide range of infectious diseases and explore the extent to which infections reduce life expectancy. METHODS: We ascertained exposure to 900+ infectious diseases before cardiovascular disease (CVD) onset in 453,102 participants from the UK Biobank study. Time-varying Cox proportional hazard models were used. Life table was used to estimate the life expectancy of individuals aged ≥50 with different levels of infection burden (defined as the number of infection episodes over time and the number of co-occurring infections). RESULTS: Infectious diseases were associated with a greater risk of CVD events (adjusted HR [aHR] 1.79 [95% confidence interval {CI} 1.74-1.83]). For type-specific analysis, bacterial infection with sepsis had the strongest risk of CVD events [aHR 4.76 (4.35-5.20)]. For site-specific analysis, heart and circulation infections posed the greatest risk of CVD events [aHR 4.95 (95% CI 3.77-6.50)], whereas noncardiac infections also showed excess risk [1.77 (1.72-1.81)]. Synergistic interactions were observed between infections and genetic risk score. A dose-response relationship was found between infection burden and CVD risks (p-trend <0.001). Infection burden >1 led to a CVD-related life loss at age 50 by 9.3 years [95% CI 8.6-10.3]) for men and 6.6 years [5.5-7.8] for women. CONCLUSIONS: The magnitude of the infection-CVD association showed specificity in sex, pathogen type, infection burden, and infection site. High genetic risk and infection synergistically increased the CVD risk.

Hospital-treated infectious diseases, infection burden and risk of Parkinson disease: An observational and Mendelian randomization study.

BACKGROUND: Experimental and cross-sectional evidence has suggested a potential role of infection in the ethology of Parkinson's disease (PD). We aim to examine the longitudinal association of infections with the incidence of PD and to explore whether the increased risk is limited to specific infection type rather than infection burden. METHODS: Based on the UK Biobank, hospital-treated infectious diseases and incident PD were ascertained through record linkage to national hospital inpatient registers. Infection burden was defined as the sum of the number of infection episodes over time and the number of co-occurring infections. The polygenic risk score (PRS) for PD was calculated. The genome-wide association studies (GWAS) used in two-sample Mendelian Randomization (MR) were obtained from observational cohort participants of mostly European ancestry. RESULTS: Hospital-treated infectious diseases were associated with an increased risk of PD (adjusted HR [aHR] 1.35 [95 % CI 1.20-1.52]). This relationship persisted when analyzing new PD cases occurring more than 10 years post-infection (aHR 1.22 [95 % CI 1.04-1.43]). The greatest PD risk was observed in neurological/eye infection (aHR 1.72 [95 % CI 1.32-2.34]), with lower respiratory tract infection (aHR 1.43 [95 % CI 1.02-1.99]) ranked the second. A dose-response association was observed between infection burden and PD risk within each PD-PRS tertile (p-trend < 0.001). Multivariable MR showed that bacterial and viral infections increase the PD risk. CONCLUSIONS: Both observational and genetic analysis suggested a causal association between infections and the risk of developing PD. A dose-response relationship between infection burden and incident PD was revealed.

Channel HCN4 mutation R666Q associated with sporadic arrhythmia decreases channel electrophysiological function and increases protein degradation.

Mutations in the hyperpolarization-activated nucleotide-gated channel 4 (HCN4) are known to be associated with arrhythmias in which QT prolongation (delayed ventricular repolarization) is rare. Here, we identified a HCN4 mutation, HCN4-R666Q, in two sporadic arrhythmia patients with sinus bradycardia, QT prolongation, and short bursts of ventricular tachycardia. To determine the functional effect of the mutation, we conducted clinical, genetic, and functional analyses using whole-cell voltage-clamp, qPCR, Western blot, confocal microscopy, and co-immunoprecipitation. The mean current density of HEK293T cells transfected with HCN4-R666Q was lower in 24 to 36 h after transfection and was much lower in 36 to 48 h after transfection relative to cells transfected with wildtype HCN4. Additionally, we determined that the HCN4-R666Q mutant was more susceptible to ubiquitin-proteasome system-mediated protein degradation than wildtype HCN4. This decreased current density for HCN4-R666Q could be partly rescued by treatment with a proteasome inhibitor. Therefore, we conclude that HCN4-R666Q had an effect on HCN4 function in two aspects, including decreasing the current density of the channel as a biophysical effect and weakening its protein stability. Our findings provide new insights into the pathogenesis of the HCN4-R666Q mutation.

Association of regular glucosamine use with incident dementia: evidence from a longitudinal cohort and Mendelian randomization study.

BACKGROUND: Emerging data suggests the neuroprotective and anti-neuroinflammatory effects of glucosamine. We aimed to examine the association between regular glucosamine use and risk of incident dementia, including dementia subtypes. METHODS: We conducted large-scale observational and two-sample Mendelian randomization (MR) analyses. Participants in UK Biobank having accessible data for dementia incidence and who did not have dementia at baseline were included in the prospective cohort. Through the Cox proportional hazard model, we examined the risks of incident all-cause dementia, Alzheimer's disease (AD), and vascular dementia among glucosamine users and non-users. To further test the causal association between glucosamine use and dementia, we conducted a 2-sample MR utilizing summary statistics from genome-wide association studies (GWAS). The GWAS data were obtained from observational cohort participants of mostly European ancestry. RESULTS: During a median follow-up of 8.9 years, there were 2458 cases of all-cause dementia, 924 cases of AD, and 491 cases of vascular dementia. In multivariable analysis, the hazard ratios (HR) of glucosamine users for all-cause dementia, AD, and vascular dementia were 0.84 (95% CI 0.75-0.93), 0.83 (95% CI 0.71-0.98), and 0.74 (95% CI 0.58-0.95), respectively. The inverse associations between glucosamine use and AD appeared to be stronger among participants aged below 60 years than those aged above 60 years (p = 0.04 for interaction). The APOE genotype did not modify this association (p > 0.05 for interaction). Single-variable MR suggested a causal relationship between glucosamine use and lower dementia risk. Multivariable MR showed that taking glucosamine continued to protect against dementia after controlling for vitamin, chondroitin supplement use and osteoarthritis (all-cause dementia HR 0.88, 95% CI 0.81-0.95; AD HR 0.78, 95% CI 0.72-0.85; vascular dementia HR 0.73, 95% CI 0.57-0.94). Single and multivariable inverse variance weighted (MV-IVW) and MR-Egger sensitivity analyses produced similar results for these estimations. CONCLUSIONS: The findings of this large-scale cohort and MR analysis provide evidence for potential causal associations between the glucosamine use and lower risk for dementia. These findings require further validation through randomized controlled trials.

Blood levels of MCP-1 modulate the genetic risks of Alzheimer's disease mediated by HLA-DRB1 and APOE for Alzheimer's disease.

INTRODUCTION: C-Reactive protein (CRP) and monocyte chemoattractant protein-1 (MCP-1) are both implicated in the peripheral proinflammatory cascade and blood-brain barrier (BBB) disruption. Since the blood CRP level increases Alzheimer's disease (AD) risk depending on the apolipoprotein E (APOE) genotype, we hypothesized that the blood MCP-1 level exerts different effects on the AD risk depending on the genotypes. METHODS: Using multiple regression analyses, data from the Framingham Heart Study (n = 2884) and Alzheimer's Disease Neuroimaging Initiative study (n = 231) were analyzed. RESULTS: An elevated blood MCP-1 level was associated with AD risk in major histocompatibility complex, Class II, DR beta 1 (HLA-DRB1) rs9271192-AC/CC (hazard ratio [HR] = 3.07, 95% confidence interval [CI] = 1.50-6.28, p = 0.002) and in APOE ε4 carriers (HR = 3.22, 95% CI = 1.59-6.53, p = 0.001). In contrast, among HLA-DRB1 rs9271192-AA and APOE ε4 noncarriers, blood MCP-1 levels were not associated with these phenotypes. DISCUSSION: Since HLA-DRB1 and APOE are expressed in the BBB, blood MCP-1 released in the peripheral inflammatory cascade may function as a mediator of the effects of HLA-DRB1 rs9271192-AC/CC and APOE ε4 genotypes on AD pathogenesis in the brain via the BBB pathways.

A water quality prediction model based on signal decomposition and ensemble deep learning techniques.

Accurate water quality predictions are critical for water resource protection, and dissolved oxygen (DO) reflects overall river water quality and ecosystem health. This study proposes a hybrid model based on the fusion of signal decomposition and deep learning for predicting river water quality. Initially, complete ensemble empirical mode decomposition with adaptive noise (CEEMDAN) is employed to split the internal series of DO into numerous internal mode functions (IMFs). Subsequently, we employed multi-scale fuzzy entropy (MFE) to compute the entropy values for each IMF component. Time-varying filtered empirical mode decomposition (TVFEMD) is used to further extract features in high-frequency subsequences after linearly aggregating the high-frequency sequences. Finally, support vector machine (SVM) and long short-term memory (LSTM) neural networks are used to predict low- and high-frequency subsequences. Moreover, by comparing it with single models, models based on 'single layer decomposition-prediction-ensemble' and combination models using different methods, the feasibility of the proposed model in predicting water quality data for the Xinlian section of Fuhe River and the Chucha section of Ganjiang River was verified. As a result, the combined prediction approach developed in this work has improved generalizability and prediction accuracy, and it may be used to forecast water quality in complicated waters.

TriTag: an integrative tool to correlate chromatin dynamics and gene expression in living cells.

A wealth of single-cell imaging studies have contributed novel insights into chromatin organization and gene regulation. However, a comprehensive understanding of spatiotemporal gene regulation requires developing tools to combine multiple monitoring systems in a single study. Here, we report a versatile tag, termed TriTag, which integrates the functional capabilities of CRISPR-Tag (DNA labeling), MS2 aptamer (RNA imaging) and fluorescent protein (protein tracking). Using this tag, we correlate changes in chromatin dynamics with the progression of endogenous gene expression, by recording both transcriptional bursting and protein production. This strategy allows precise measurements of gene expression at single-allele resolution across the cell cycle or in response to stress. TriTag enables capturing an integrated picture of gene expression, thus providing a powerful tool to study transcriptional heterogeneity and regulation.

Patients who do not fulfill criteria for hypertrophic cardiomyopathy but have unexplained giant T-wave inversion: a cardiovascular magnetic resonance mid-term follow-up study.

BACKGROUND: Patients who have unexplained giant T-wave inversions but do not meet criteria for hypertrophic cardiomyopathy (HCM) (left ventricular (LV) wall thickness < 1.5 cm) demonstrate LV apical morphological features that differ from healthy subjects. Currently, it remains unknown how the abnormal LV apical morphology in this patient population changes over time. The purpose of this study was to investigate LV morphological and functional changes in these patients using a mid-term cardiovascular magnetic resonance (CMR) exam. METHODS: Seventy-one patients with unexplained giant T-wave inversion who did not fulfill HCM criteria were studied. The mean interval time of the follow-up CMR was 24.4 ± 8.3 months. The LV wall thickness was measured in each LV segment according to the American Heart Association 17-segmented model. The apical angle (ApA) was also measured. A receiver operating curve (ROC) was used to identify the predictive values of the CMR variables. RESULTS: Of 71 patients, 16 (22.5%) progressed to typical apical HCM, while 55 (77.5%) did not progress to HCM criteria. The mean apical wall thickness was significantly different between the two groups at both baseline and follow-up, with the apical HCM group having greater wall thickness at both time points (all p < 0.001). There was a significant difference between the two groups in the change of ApA (- 1.5 ± 2.7°/yr vs. - 0.7 ± 2.0°/yr, p < 0.001) over time. The combination of mean apical wall thickness and ApA proved to be the best predictor for fulfilling criteria for apical HCM with a threshold value of 8.1 mm and 90° (sensitivity 93.8%, specificity 85.5%). CONCLUSIONS: CMR metrics identify predictors for progression to HCM in patients with unexplained giant T-wave inversion.

MRI T1 Mapping in Hypertrophic Cardiomyopathy: Evaluation in Patients Without Late Gadolinium Enhancement and Hemodynamic Obstruction.

Background The value of native myocardial T1 mapping and extracellular volume (ECV) fraction in patients who have hypertrophic cardiomyopathy (HCM) but no late gadolinium enhancement (LGE) and no hemodynamic obstruction are currently unknown. Purpose To evaluate myocardial fibrosis in patients with nonobstructive HCM and no LGE by using native myocardial T1 mapping and ECV fraction and to study their relationships to left ventricular (LV) function and LV hypertrophy. Materials and Methods Patients with HCM who underwent cardiac MRI between 2012 and 2015 were retrospectively evaluated. Patients were included if they had no LGE at MRI, LV ejection fraction greater than or equal to 45%, and no LV outflow tract obstruction. Healthy participants had similar age and sex distribution. Native myocardial T1 and ECV were measured with MRI. Results A total of 258 patients with HCM (mean age ± standard deviation, 49 years ± 15; 74% men) and 122 healthy participants (mean age, 50 years ± 14; 76% men) were evaluated. Native myocardial T1 was longer and ECV fraction was higher in the patients with HCM relative to the healthy participants (mean native T1, 950 msec ± 48 vs 913 msec ± 46; mean ECV, 24.5% ± 2.8 vs 23.0% ± 2.7; both P < .001). Maximum T1 and ECV values correlated strongly with LV mass index for the entire patient cohort with HCM (both r = 0.86; P < .001) and for the subgroups (r = 0.86 and 0.85 for interventricular septal group and r = 0.88 and 0.86 for apical group; all P < .001). Conclusion Prolonged myocardial T1 and elevated extracellular volume in hypertrophic cardiomyopathy suggests diffuse myocardial fibrosis, even in the absence of regionally apparent late gadolinium enhancement and hemodynamic obstruction, and is associated with left ventricular hypertrophy. © RSNA, 2019 See also the editorial by Bluemke and Lima in this issue.

Contribution of Electrocardiogram in the Differentiation of Cardiac Amyloidosis and Nonobstructive Hypertrophic Cardiomyopathy.

UNLABELLED: Due to similar manifestations of hypertensive ventricular walls and abnormal ventricular compliance, it is difficult to differentiate cardiac amyloidosis (CA) and nonobstructive hypertrophic cardiomyopathy (NOHCM) clinically. The purpose of the study was to investigate the value of electrocardiography (ECG) in the differentiation of the two diseases. METHODS: We enrolled 46 consecutive patients with CA and 64 patients with NOHCM and compared their ECG characteristics.Compared with NOHCM patients, the ECG of CA patients showed more low voltage on limb leads (50% versus 1.6%), atrioventricular block (21.7% versus 4.7%), pseudo-infarct pattern (84.8% versus 39.1%), and longer QRS duration (104 ± 25 versus 98 ± 14 ms) (all P < 0.05). The QRS complex voltage of avR demonstrated the highest diagnostic performance (sensitivity 89%, specificity 94%, cut-off value 0.45mV) as assessed by ROC analysis. The combination of the R wave voltage of I and avR reached a sensitivity of 95% and a specificity of 87% for the diagnosis of amyloidosis.Compared with NOHCM patients, CA patients showed more ECG characteristics of low voltage on limb leads, pseudo-infarct pattern, atrioventricular block, and longer QRS duration. The combination of the R wave voltage of I, avR, and QRS was of diagnostic value in the differentiation of CA from NOHCM.

[Role of cardiac magnetic resonance on predicting outcome in patients with hypertrophic obstructive cardiomyopathy undergoing percutaneous transluminal septal myocardial ablation].

OBJECTIVE: To investigate the predictive value of cardiac magnetic resonance (CMR) on outcome of patients with hypertrophic obstructive cardiomyopathy (HOCM) undergoing percutaneous transluminal septal myocardial ablation (PTSMA). METHODS: A total of 38 consecutive HOCM patients underwent CMR imaging before PTSMA in Fuwai hospital From March 2010 to September 2012 were included in this retrospective study. The efficacy was defined as >30 mmHg (1 mmHg = 0.133 kPa) reduction of echocardiography derived left ventricular outflow tract gradient (LVOTG) at 6 months post operation. The relationship between CMR imaging derived parameters and effect of PTSMA was analyzed. Receiver operating curve (ROC) was applied to assess the predicting effectiveness of related CMR parameters. RESULTS: The effective rate of PTSMA was 65.8% (25/38). The thickness of basal anterior wall (r = 0.505, P = 0.001), basal anteroseptal wall (0.500, P = 0.001) and the sum of the two segments (r = 0.656, P < 0.001) was positively correlated to the post-procedure reduction of LVOTG. The area under the ROC curve of the thickness of basal anterior wall, basal anteroseptal wall and the sum of the two segments was 0.806, 0.675 and 0.834, respectively. The sensitivity was 84.6% and specificity was 84.0% to predict the efficacy of PTSMA using the sum of left ventricular basal anterior wall and basal anteroseptal wall thickness 49.6 mm as cut-off value. CONCLUSIONS: LVOTG reduction post PTSMA positively correlates to pre-procedure left ventricular basal anterior wall, basal anteroseptal wall and the total thickness of these two segments in patients with HOCM. The total thickness of these two segments is a superior parameter for predicting efficacy of PTSMA in HOCM patients.

Hospital-treated infectious diseases, genetic susceptibility and risk of type 2 diabetes: A population-based longitudinal study.

BACKGROUND: The longitudinal association between infectious diseases and the risk of type 2 diabetes (T2D) remains unclear. METHODS: Based on the UK Biobank, the prospective cohort study included a total of 396,080 participants without diabetes at baseline. We determined the types and sites of infectious diseases and incident T2D using the International Classification of Diseases 10th Revision codes (ICD-10). Time-varying Cox proportional hazard model was used to assess the association. Infection burden was defined as the number of infection episodes over time and the number of co-occurring infections. Genetic risk score (GRS) for T2D consisted of 424 single nucleotide polymorphisms. RESULTS: During a median of 9.04 [IQR, 8.3-9.7] years of follow-up, hospital-treated infectious diseases were associated with a greater risk of T2D (adjusted HR [aHR] 1.54 [95 % CI 1.46-1.61]), with risk difference per 10,000 individuals equal to 154.1 [95 % CI 140.7-168.2]. The heightened risk persisted after 5 years following the index infection. Bacterial infection with sepsis had the strongest risk of T2D (aHR 2.95 [95 % CI 2.53-3.44]) among different infection types. For site-specific analysis, bloodstream infections posed the greatest risk (3.01 [95 % CI 2.60-3.48]). A dose-response association was observed between infection burden and T2D risk within each GRS tertile (p-trend <0.001). High genetic risk and infection synergistically increased the T2D risk. CONCLUSION: Infectious diseases were associated with an increased risk of subsequent T2D. The risk showed specificity according to types, sites, severity of infection and the period since infection occurred. A potential accumulative effect of infection was revealed.

Does increasing forest age lead to greater trade-offs in ecosystem services? A study of a Robinia pseudoacacia artificial forest on the Loess Plateau, China.

Artificial forest ecosystems offer various ecosystem services (ES) and help mitigate climate change effects. Trade-offs or synergies exist among ES in artificial forests. Although forest age influences ES and ecosystem processes, the long-term dynamics of trade-offs among ES in artificial forests and during vegetation restorations remain unclear, complicating vegetation and sustainable management. We studied a Robinia pseudoacacia plantation on the Loess Plateau, China, with a restoration time of 10-44 years. The entropy weight method was used to assess five ES (carbon sequestration, water conservation, soil conservation, understory plant diversity, and runoff and sediment reduction) and investigate how ES change with forest age. The root mean square deviation (RMSD) was used to quantify the trade-offs among ES, and redundancy analysis (RDA) analysis was used to identify the key factors influencing the ES and trade-offs. The results showed that (1) as forest age increased, ES scores initially increased and then decreased. The optimal range for ES values was observed during the middle-aged to mature stages of the forest. (2) Before reaching maturity, the planted forests primarily delivered services related to water conservation and runoff and sediment reduction. (3) In young forests, ES showed a synergistic relationship (RMSD = 0.06), whereas trade-offs occurred in forests at other ages. The largest trade-off was observed in middle-aged forests. (4) The ES pairs with the dominant trade-offs in planted forests differed at different forest age stages. The largest trade-off occurred between carbon sequestration and water conservation (RMSD = 0.28). RDA analysis showed that understory vegetation coverage had a positive correlation with all ES. The ES indicators that significantly (P < 0.001) affected the water­carbon trade-off were tree carbon storage, soil organic carbon storage, soil total nitrogen, and soil total phosphorus. Thus, the water and carbon relationship must be balanced, and the key factors affecting ES trade-offs in forest management must be regulated to support ES multifunctionality.

The association between circulating CD34+CD133+ endothelial progenitor cells and reduced risk of Alzheimer's disease in the Framingham Heart Study.

Aim: Endothelial dysfunction has been associated with both cerebrovascular pathology and Alzheimer's disease (AD). However, the connection between circulating endothelial cells and the risk of AD remains uncertain. The objective was to leverage data from the Framingham Heart Study to investigate various circulating endothelial subtypes and their potential correlations with the risk of AD. Methods: The study conducted data analyses using Cox proportional hazard regression and linear regression methods. Additionally, genome-wide association study (GWAS) was carried out to further explore the data. Results: Among the eleven distinct circulating endothelial subtypes, only circulating endothelial progenitor cells (EPCs) expressing CD34+CD133+ were found to be negatively and dose-dependently associated with reduced AD risk. This association persisted even after adjusting for age, sex, years of education, apolipoprotein E (APOE) ε4 status, and various vascular diseases. Particularly noteworthy was the significant association observed in individuals with hypertension and cerebral microbleeds. Consistently, positive associations were identified between CD34+CD133+ EPCs and specific brain regions, such as higher proportions of circulating CD34+CD133+ cells correlating with increased volumes of white matter and the hippocampus. Additionally, a GWAS study unveiled that CD34+CD133+ cells influenced AD risk specifically in individuals with homozygous genotypes for variants in two stem cell-related genes: kirre like nephrin family adhesion molecule 3 (KIRREL3, rs580382 CC and rs4144611 TT) and exocyst complex component 6B (EXOC6B, rs61619102 CC). Conclusions: The findings suggest that circulating CD34+CD133+ EPCs possess a protective effect and may offer a new therapeutic avenue for AD, especially in individuals with vascular pathology and those carrying specific genotypes of KIRREL3 and EXOC6B genes.

Heterogeneous Graph Convolutional Neural Network via Hodge-Laplacian for Brain Functional Data.

This study proposes a novel heterogeneous graph convolutional neural network (HGCNN) to handle complex brain fMRI data at regional and across-region levels. We introduce a generic formulation of spectral filters on heterogeneous graphs by introducing the k-th Hodge-Laplacian (HL) operator. In particular, we propose Laguerre polynomial approximations of HL spectral filters and prove that their spatial localization on graphs is related to the polynomial order. Furthermore, based on the bijection property of boundary operators on simplex graphs, we introduce a generic topological graph pooling (TGPool) method that can be used at any dimensional simplices. This study designs HL-node, HL-edge, and HL-HGCNN neural networks to learn signal representation at a graph node, edge levels, and both, respectively. Our experiments employ fMRI from the Adolescent Brain Cognitive Development (ABCD; n=7693) to predict general intelligence. Our results demonstrate the advantage of the HL-edge network over the HL-node network when functional brain connectivity is considered as features. The HL-HGCNN outperforms the state-of-the-art graph neural networks (GNNs) approaches, such as GAT, BrainGNN, dGCN, BrainNetCNN, and Hypergraph NN. The functional connectivity features learned from the HL-HGCNN are meaningful in interpreting neural circuits related to general intelligence.

Pyroptosis-based risk score predicts prognosis and drug sensitivity in lung adenocarcinoma.

Pyroptosis is a recently identified form of programmed cell death; however, its role in lung adenocarcinoma (LUAD) remains unclear. Therefore, we set out to explore the prognostic potential of pyroptosis-related genes in LUAD. The pyroptosis-related risk score (PRRS) was developed by least absolute shrinkage and selection operator Cox regression and multivariate Cox regression. We found that PRRS was an independent prognostic factor for LUAD. LUAD patients in the high-PRRS group showed a significantly shorter overall survival (OS) and enriched in cell proliferation-related pathways. Then pathway enrichment analyses, mutation profile, tumor microenvironment, and drug sensitivity analysis were further studied in PRRS stratified LUAD patients. Tumor purity (TP) analyses revealed that L-PRRS LUAD patients had a lower TP, and patients in L-TP + L-PRRS subgroup had the most prolonged OS. Mutation analyses suggested that the L-PRRS LUAD patients had a lower tumor mutation burden (TMB), and patients in H-TMB + L-PRRS subgroup had the most prolonged OS. Drug sensitivity analyses showed that PRRS was significantly negatively correlated with the sensitivity of cisplatin, besarotene, etc., while it was significantly positively correlated with the sensitivity of kin001-135. Eventually, a nomogram was constructed based on PRRS and clinical characters of LUAD. Overall, the pyroptosis-related signature is helpful for prognostic prediction and in guiding treatment for LUAD patients.

Dietary Supplement with Tribulus terrestris L. Extract Exhibits Protective Effects on Ischemic Stroke Rats.

SCOPE: Among herbal dietary supplements, the extract of Tribulus terrestris L. (TT) has been used as a commercially registered product in multiple studies. The previous studies demonstrate the protective effect of gross saponins of TT (GSTTF) on ischemic stroke. However, the mechanism by which GSTTF protects against ischemic stroke is still unclear. METHODS AND RESULTS: The study applies molecular biology and unbiased transcriptomics to explore the pathways and targets underlying the therapeutic impact of GSTTF in treating ischemic stroke. The mRNA of brain tissues from different groups is analyzed using a transcriptomics method. The data reveal that treatment with GSTTF significantly reduces elevated CRP, IL-6, and Ca2+ levels induced by middle cerebral artery occlusion (MCAO). A total of 61 differentially expressed genes (DEGs) are identified, GSTTF is found to effectively reverse the abnormal mRNA expression levels in rat brain tissues affected by ischemic stroke models. These positive effects of GSTTF are likely achieved through the suppression of calcium ion and the MyD88/IKK/NF-κB signaling pathway. CONCLUSIONS: This study uncovers the mechanisms behind the efficacy of GSTTF in treating ischemic stroke, which not only expands its potential medicinal applications but also confirmed its potential as a dietary supplement.

Association of Diabetes Mellitus Status and Hyperglycemia With Symptomatic Knee Osteoarthritis.

OBJECTIVE: Emerging evidence indicates that hyperglycemia has an adverse impact on the knee joint which, in turn, may increase the risk of knee osteoarthritis (OA), but evidence from the real-life settings of large-scale cohort studies remains unclear. We sought to evaluate the association of glycemic control and the risk of symptomatic knee OA in a community-based cohort of older adults. METHODS: We conducted a prospective analysis of 10,730 participants without knee OA. Comprehensive blood biomarker data were obtained. Diabetes mellitus (DM) was defined mainly using a glycosylated hemoglobin (HbA1c ) level of ≥6.5%; poor glycemic control in individuals with DM was defined as an HbA1c level of ≥7%. We fit Cox regression models, stratified according to DM status. We evaluated the hazards associated with HbA1c and fasting blood glucose levels using a spline model. RESULTS: During a median follow-up of 5 years, knee OA developed in 1,089 participants (108 with DM and 971 without). Knee OA was related to DM (hazard ratio [HR] 1.29 [95% confidence interval (95% CI) 1.02-1.78]), bad glycemic regulation in DM patients (HR 1.41 [95% CI 1.05-2.09]), and long-term DM (≥5 versus <5 years; HR 1.49 [95% CI 1.02-2.17]). High levels of HbA1c (>7.7% and 61 mmoles/mole) and fasting blood glucose (>186 mg/dl) were significantly associated with higher risk of incident knee OA. CONCLUSION: DM, bad glycemic management, and long-term DM are potential risk factors of symptomatic knee OA independent of age and body mass index. Targeting blood glucose, in addition to bodyweight, may be an important avenue for prevention of knee OA.