Explore the vast range of titles available.

Prolonged exposure to negative stressors could be harmful if a subject cannot respond appropriately. Strategies evolved to respond to stress, including repetitive displacement behaviours, are important in maintaining behavioural homoeostasis. In rodents, self-grooming is a frequently observed repetitive behaviour believed to contribute to post-stress de-arousal with adaptive value. Here we identified a rat limbic di-synaptic circuit that regulates stress-induced self-grooming with positive affective valence. This circuit links hippocampal ventral subiculum to ventral lateral septum (LSv) and then lateral hypothalamus tuberal nucleus. Optogenetic activation of this circuit triggers delayed but robust excessive grooming with patterns closely resembling those evoked by emotional stress. Consistently, the neural activity of LSv reaches a peak before emotional stress-induced grooming while inhibition of this circuit significantly suppresses grooming triggered by emotional stress. Our results uncover a previously unknown limbic circuitry involved in regulating stress-induced self-grooming and pinpoint a critical role of LSv in this ethologically important behaviour. Self-grooming is a frequently observed repetitive behaviour in rodents that is believed to contribute to post-stress de-arousal. The authors identified a previously unknown limbic circuit that includes the ventral lateral septum in rats and is involved in regulating stress-induced self-grooming.

Background Early identification of populations at high cardiovascular disease (CVD) risk and improvement of risk factors can significantly decrease the probability of CVD development and improve outcomes. Insulin resistance (IR) is a CVD risk factor. The triglyceride glucose (TyG) index is a simple and reliable index for evaluating IR. However, no clinical studies on the prognostic value of the TyG index in a high risk CVD population have been conducted. This study evaluated the relationship between the TyG index and prognosis in a high risk CVD population. Methods This study enrolled 35,455 participants aged 35–75 years who were at high CVD risk and visited selected health centers and community service centers between 2017 and 2021. Their general clinical characteristics and baseline blood biochemical indicators were recorded. The TyG index was calculated as ln[fasting triglyceride (mg/dl)× fasting blood glucose (mg/dl)/2]. The endpoints were all-cause death and cardiovascular death during follow-up. Cox proportional hazard models and restricted cubic spline (RCS) analysis were used to evaluate the correlation between the TyG index and endpoints. Results In the overall study population, the mean age of all participants was 57.9 ± 9.6 years, 40.7% were male, and the mean TyG index was 8.9 ± 0.6. All participants were divided into two groups based on the results of the RCS analysis, with a cut-off value of 9.83. There were 551 all-cause deaths and 180 cardiovascular deaths during a median follow-up time of 3.4 years. In the multivariate Cox proportional hazard model, participants with a TyG index ≥ 9.83 had a higher risk of all-cause death (Hazard ratio [HR] 1.86, 95% Confdence intervals [CI] 1.37–2.51, P <0.001) and cardiovascular death (HR 2.41, 95%CI 1.47–3.96, P  = 0.001) than those with a TyG index < 9.83. Subgroup analysis revealed that there was no interaction between the TyG index and variables in all subgroup analyses. Conclusions The high TyG index was associated with an increased risk of all-cause death and cardiovascular death in people at high risk of CVD. This finding demonstrates the value of the TyG index in the primary prevention of CVD. Trial registration retrospectively registered, the registration number is K2022-01-005 and the date is 2022.01.30.

The left ventricular global longitudinal strain (LVGLS) is a crucial prognostic indicator. However, inconsistencies in measurements due to the speckle tracking algorithm and manual adjustments have hindered its standardization and democratization. To solve this issue, we proposed a fully automated strain measurement by artificial intelligence-assisted LV segmentation contours. The LV segmentation model was trained from echocardiograms of 368 adults (11,125 frames). We compared the registration-like effects of dynamic time warping (DTW) with speckle tracking on a synthetic echocardiographic dataset in experiment-1. In experiment-2, we enrolled 80 patients to compare the DTW method with commercially available software. In experiment-3, we combined the segmentation model and DTW method to create the artificial intelligence (AI)-DTW method, which was then tested on 40 patients with general LV morphology, 20 with dilated cardiomyopathy (DCMP), and 20 with transthyretin-associated cardiac amyloidosis (ATTR-CA), 20 with severe aortic stenosis (AS), and 20 with severe mitral regurgitation (MR). Experiments-1 and -2 revealed that the DTW method is consistent with dedicated software. In experiment-3, the AI-DTW strain method showed comparable results for general LV morphology (bias − 0.137 ± 0.398%), DCMP (− 0.397 ± 0.607%), ATTR-CA (0.095 ± 0.581%), AS (0.334 ± 0.358%), and MR (0.237 ± 0.490%). Moreover, the strain curves showed a high correlation in their characteristics, with R-squared values of 0.8879–0.9452 for those LV morphology in experiment-3. Measuring LVGLS through dynamic warping of segmentation contour is a feasible method compared to traditional tracking techniques. This approach has the potential to decrease the need for manual demarcation and make LVGLS measurements more efficient and user-friendly for daily practice.

Aim： Targeting the VEGF/VEGF receptor （VEGFR） pathway has proved to be an effective antiangiogenic approach for cancer treatment. Here, we identified 6-（（2-（（3-acetamidophenyl）amino）pyrimidin-4-yl）oxy）-N-phenyl-l-naphthamide （designated herein as DW10075） as a novel and highly selective inhibitor of VEGFRs. Methods： In vitro tyrosine kinase activity was measured using ELISA, and intracellular signaling pathway proteins were detected by Western blot analysis. Endothelial cell proliferation was examined with CCK-8 assays, and tumor cell proliferation was determined with SRB assays. Cell,migration, tube formation and rat aortic ring assays were used to detect antiangiogenic activity. Antitumor efficacy was further evaluated in U87-MG human glioblastoma xenograft tumors in nude mice receiving DW10075 （500 mg.kg-1.d-1, po） for two weeks. Results： Among a panel of 21 kinases tested, DW10075 selectively inhibited VEGFR-1, VEGFR-2 and VEGFR-3 （the IC50 values were 6.4, 0.69 and 5.5 nmol/L, respectively）, but did not affect 18 other kinases including FGFR and PDGFR at 10 pmol/L. DW10075 significantly blocked VEGF-induced activation of VEGFR and its downstream signaling transduction in primary human umbilical vein endothelial cells （HUVECs）, thus inhibited VEGF-induced HUVEC proliferation. DW10075 （1-100 nmol/L） dose-dependently inhibited VEGF-induced HUVEC migration and tube formation and suppressed angiogenesis in both the rat aortic ring model and the chicken chorioallantoic membrane model. Furthermore, DW10075 exhibited anti-proliferative activity against 22 different human cancer cell lines with IC5o values ranging from 2.2 pmol/L （for U87-MG human glioblastoma cells） to 22.2 pmol/L （for A375 melanoma cells）. In U87-MG xenograft tumors in nude mice, oral administration of DW10075 significantly suppressed tumor growth, and reduced the expression of CD31 and Ki67 in the tumor tissues. Conclusion： DW10075 is a potent and highly selective inhibitor of VEGFR that deserves further development.Aim： Targeting the VEGF/VEGF receptor （VEGFR） pathway has proved to be an effective antiangiogenic approach for cancer treatment. Here, we identified 6-（（2-（（3-acetamidophenyl）amino）pyrimidin-4-yl）oxy）-N-phenyl-l-naphthamide （designated herein as DW10075） as a novel and highly selective inhibitor of VEGFRs. Methods： In vitro tyrosine kinase activity was measured using ELISA, and intracellular signaling pathway proteins were detected by Western blot analysis. Endothelial cell proliferation was examined with CCK-8 assays, and tumor cell proliferation was determined with SRB assays. Cell,migration, tube formation and rat aortic ring assays were used to detect antiangiogenic activity. Antitumor efficacy was further evaluated in U87-MG human glioblastoma xenograft tumors in nude mice receiving DW10075 （500 mg.kg-1.d-1, pc） for two weeks. Results： Among a panel of 21 kinases tested, DW10075 selectively inhibited VEGFR-1, VEGFR-2 and VEGFR-3 （the ICso values were 6.4, 0.69 and 5.5 nmol/L, respectively）, but did not affect 18 other kinases including FGFR and PDGFR at 10 pmol/L. DW10075 significantly blocked VEGF-induced activation of VEGFR and its downstream signaling transduction in primary human umbilica vein endothelial cells （HUVECs）, thus inhibited VEGF-induced HUVEC proliferation. DW10075 （1-100 nmol/L） dose-dependently inhibited VEGF-induced HUVEC migration and tube formation and suppressed angiogenesis in both the rat aortic ring model and the chicken chorioallantoic membrane model. Furthermore, DW10075 exhibited anti-proliferative activity against 22 different human cancer cell lines with IC5o values ranging from 2.2 pmol/L （for U87-MG human glioblastoma cells） to 22.2 pmol/L （for A375 melanoma cells）. In U87-MG xenograft tumors in nude mice, oral administration of DW10075 significantly suppressed tumor growth, and reduced the expression of CD31 and Ki67 in the tumor tissues. Conclusion： DW10075 is a potent and highly selective inhibitor of VEGFR that deserves further development.

Type 2 diabetes (T2D) is a chronic, multifactorial, and metabolic disorder accounting for 90% diabetes cases worldwide. Among them, almost half of T2D have hypertension, which is responsible for cardiovascular disease, morbidity, and mortality in these patients. The Chinese herbal medicine (CHM) prescription patterns of hypertension individuals among T2D patients have yet to be characterized. This study, therefore, aimed to determine their prescription patterns and evaluate the CHM effect. A cohort of one million randomly sampled cases from the National Health Insurance Research Database (NHIRD) was used to investigate the overall survival rate of CHM users, and prescription patterns. After matching CHM and non-CHM users for age, gender and date of diagnosis of hypertension, 980 subjects for each group were selected. The CHM users were characterized with slightly longer duration time from diabetes to hypertension, and more cases for hyperlipidaemia. The cumulative survival probabilities were higher in CHM users than in non-CHM users. Among these top 12 herbs, Liu-Wei-Di-Huang-Wan, Jia-Wei-Xiao-Yao-San, Dan-Shen, and Ge-Gen were the most common herbs and inhibited in vitro smooth muscle cell contractility. Our study also provides a CHM comprehensive list that may be useful in future investigation of the safety and efficacy for individuals with hypertension among type 2 diabetes patients.

Kawasaki disease (KD) is an acute, inflammatory and self-limited vasculitis affecting infants and young children. Coronary artery aneurysm (CAA) formation is the major complication of KD and the leading cause of acquired cardiovascular disease among children. To identify susceptible loci that might predispose patients with KD to CAA formation, a genome-wide association screen was performed in a Taiwanese KD cohort. Patients with both KD and CAA had longer fever duration and delayed intravenous immunoglobulin treatment time. After adjusting for these factors, 100 susceptibility loci were identified. Four genes were identified from a single cluster of 35 using the Ingenuity Pathway Analysis (IPA) Knowledge Base. Silencing KCNQ5 , PLCB1 , PLCB4 and PLCL1 inhibited the effect of lipopolysaccharide-induced endothelial cell inflammation with varying degrees of proinflammatory cytokine expression. PLCB1 showed the most significant inhibition. Endothelial cell inflammation was also inhibited by using a phospholipase C (PLC) inhibitor. The single nucleotide polymorphism rs6140791 was identified between PLCB4 and PLCB1 . Plasma PLC levels were higher in patients with KD and CC+CG rs6140791genotypes and these genotypes were more prevalent in patients with KD who also had CAA. Our results suggest that polymorphism of the PLCB4/B1 genes might be involved in the CAA pathogenesis of KD.

Renal cell cancer (RCC) is the most lethal of all the common urologic cancers and constitutes 2.2% of all malignancy diagnoses. The incidence of RCC has been steadily increasing in recent decades. The classic risk factors of RCC include smoking, hypertension, obesity, genetics, and genetic mutations. Recent studies also revealed that RCC was an immunogenic tumor and affected by host immune status. Among the pan‐cance, RCC presented with the highest degree of immune infiltration, indicating RCC patients might benefit from immunotherapy. A new immune classification of RCC has been developed by Su et al. based on tumor‐infiltrating lymphocytes to guide clinical practice. However, these studies mainly focus on biomarkers derived from tumor microenvironment (TME), the biomarkers based on peripheral blood samples to RCC have rarely been described. We collected peripheral blood samples from RCC patients and their matched healthy controls and detected the number of IL‐2 and IFN‐γ producing cells by implementing an enzyme‐linked immunospot (ELISPOT) assay. This is the first study to report blood‐based immune biomarkers for RCC using an ELISPOT assay. Our results suggested the frequency of IFN‐γ producing cells but not IL‐2 producing cells was associated with RCC risk. These findings warrant further validation in larger prospective studies.

Objectives The accurate prediction of post-hepatectomy early recurrence in patients with hepatocellular carcinoma (HCC) is crucial for decision-making regarding postoperative adjuvant treatment and monitoring. We aimed to explore the feasibility of deep learning (DL) features derived from gadoxetate disodium (Gd-EOB-DTPA) MRI, qualitative features, and clinical variables for predicting early recurrence. Methods In this bicentric study, 285 patients with HCC who underwent Gd-EOB-DTPA MRI before resection were divided into training ( n  = 195) and validation ( n  = 90) sets. DL features were extracted from contrast-enhanced MRI images using VGGNet-19. Three feature selection methods and five classification methods were combined for DL signature construction. Subsequently, an mp-MR DL signature fused with multiphase DL signatures of contrast-enhanced images was constructed. Univariate and multivariate logistic regression analyses were used to identify early recurrence risk factors including mp-MR DL signature, microvascular invasion (MVI), and tumor number. A DL nomogram was built by incorporating deep features and significant clinical variables to achieve early recurrence prediction. Results MVI ( p  = 0.039), tumor number ( p  = 0.001), and mp-MR DL signature ( p  < 0.001) were independent risk factors for early recurrence. The DL nomogram outperformed the clinical nomogram in the training set (AUC: 0.949 vs. 0.751; p  < 0.001) and validation set (AUC: 0.909 vs. 0.715; p  = 0.002). Excellent DL nomogram calibration was achieved in both training and validation sets. Decision curve analysis confirmed the clinical usefulness of DL nomogram. Conclusion The proposed DL nomogram was superior to the clinical nomogram in predicting early recurrence for HCC patients after hepatectomy. Key Points • Deep learning signature based on Gd-EOB-DTPA MRI was the predominant independent predictor of early recurrence for hepatocellular carcinoma (HCC) after hepatectomy. • Deep learning nomogram based on clinical factors and Gd-EOB-DTPA MRI features is promising for predicting early recurrence of HCC. • Deep learning nomogram outperformed the conventional clinical nomogram in predicting early recurrence.

Gallstone disease (GSD) and kidney stone disease (KSD) may share metabolic pathways, however their association remains unclear. This study aimed to explore their relationship using cross-sectional and longitudinal analyses. The cross-sectional analysis included 121,550 participants in the Taiwan Biobank, and the association between self-reported GSD and KSD was examined using logistic regression. The longitudinal analysis included 25,208 participants without prior KSD, and the risk of incident KSD was assessed using Kaplan-Meier survival analysis and Cox proportional hazards models, adjusting for demographics, metabolic factors, lifestyle factors, and laboratory data. In the cross-sectional cohort, the prevalence of KSD was higher in the participants with GSD (11% vs. 6%, p < 0.001). In adjusted analysis, GSD was associated with a 51% increased risk of KSD (odds ratio: 1.51, 95% CI: 1.38-1.65, p < 0.001). In the longitudinal analysis, the participants with GSD had a higher incidence of KSD (5% vs. 2%, p < 0.001), with an adjusted hazard ratio of 1.80 (95% CI: 1.36-2.38, p < 0.001). Subgroup analyses showed a significant interaction by sex but not by age, indicating a stronger association in women. Our results showed that GSD was an independent risk factor for KSD, suggesting shared metabolic mechanisms. Future studies should explore preventive strategies targeting the pathways underlying these mechanisms.

Semiconductor-superconductor hybrid nanowires are a leading material platform for the realization of Majorana zero modes. The semiconductors in previous studies are dominantly InAs or InSb. In this work, we show the induced superconductivity in a PbTe nanowire epitaxially coupled to a superconductor Pb. The Josephson junction device based on this hybrid reveals a gate-tunable supercurrent in the open regime and a hard superconducting gap in the tunneling regime. By demonstrating the superconducting proximity effect, our result can enable Majorana searches and other applications like gate-tunable qubits in a new semiconductor system.