Cold hypersensitivity in the hands and feet is associated with erectile dysfunction in young Taiwanese men.

Cold hypersensitivity in the hands and feet (CHHF) is a protective or predisposing factor for many diseases; however, the relationship between CHHF and erectile dysfunction (ED) remains unclear. We aimed to investigate associations between CHHF and ED among young men of Southeast Asian origin. In this cross-sectional study, sexually active Taiwanese men aged 20-40 years were enrolled via an online questionnaire comprising general demographic information, comorbidities, subjective thermal sensations of their hands and feet in the past 6 months, and their erectile function using the International Index of Erectile Function-5 (IIEF-5). Participants who reported cold sensation of hands and feet were classified to have CHHF; those with IIEF-5 score ≤ 21 were considered to have ED. Total 54.2% and 27.9% of participants had ED and CHHF, respectively. Men with CHHF were significantly younger, had lower body mass index and IIEF-5 scores (p < 0.001), and a lower prevalence of diabetes mellitus (p = 0.033) along with higher prevalence of ED, psychiatric disorders, and insomnia (p < 0.001). After adjusting for predisposing factors of ED, CHHF (odds ratio 1.410, 95% confidence interval 1.159-1.714; p = 0.001) remained an independent predictor of ED. Thus, CHHF is independently associated with ED, affecting more than a quarter of young Taiwanese men. Autonomic dysregulation and subclinical endothelial dysfunction may be common pathophysiologies of CHHF and ED.

Lower serum uric acid and impairment of right cerebral hemisphere structural brain networks are related to depressive symptoms in cerebral small vessel disease: A cross-sectional study.

Cerebral small vessel disease (SVD) may be associated with an increased risk of depressive symptoms. Serum uric acid (SUA), an antioxidant, may be involved in the occurrence and development of depressive symptoms, but the mechanism remains unknown. Moreover, the relationship between structural brain networks and SUA has not been explored. This study examined the relationship between SUA and depressive symptoms in patients with SVD using graph theory analysis. We recruited 208 SVD inpatients and collected fasting blood samples upon admission. Depressive symptoms were assessed using the 24-item Hamilton Depression Rating Scale (HAMD-24). Magnetic resonance imaging was used to evaluate SVD, and diffusion tensor images were used to analyze structural brain networks using graph theory. Patients with depressive symptoms (n = 34, 25.76%) compared to those without (334.53 vs 381.28 µmol/L, p = 0.017) had lower SUA levels. Graph theoretical analyses showed a positive association of SUA with betweenness centrality, nodal efficiency, and clustering coefficients and a negative correlation with the shortest path length in SVD with depressive symptoms group. HAMD scores were significantly associated with nodal network metrics in the right cerebral hemisphere. Our findings suggested that lower SUA levels are significantly associated with disrupted structural brain networks in the right cerebral hemisphere of patients with SVD who have depressive symptoms.

Cerebral Perfusion Characteristics and Dynamic Brain Structural Changes in Stroke-Prone Renovascular Hypertensive Rats: A Preclinical Model for Cerebral Small Vessel Disease.

Hypertension is a leading cause of cerebral small vessel disease (CSVD) and vascular dementia in elderly individuals. We aimed to assess cerebral perfusion and dynamic changes in brain structure in stroke-prone renovascular hypertensive rats (RHRSPs) with different durations of hypertension and to investigate whether they have pathophysiological features similar to those of humans with CSVD. The RHRSP model was established using the two-kidney, two-clip (2k2c) method, and the Morris water maze (MWM) test, MRI, immunohistochemistry, and biochemical analysis were performed at multiple time points for up to six months following the 2k2c operation. Systolic blood pressure was significantly greater in the RHRSP group than in the sham-operated group at week 4 post-surgery and continued to increase over time, leading to cognitive decline by week 20. Arterial spin labeling revealed cerebral hypoperfusion in the RHRSP group at 8 weeks, accompanied by vascular remodeling and decreased vessel density. Diffusion tensor imaging and Luxol fast blue staining indicated that white matter disintegration and demyelination gradually progressed in the corpus callosum and that myelin basic protein levels decreased. Eight weeks after surgery, blood-brain barrier (BBB) leakage into the corpus callosum was observed. The albumin leakage area was negatively correlated with the myelin sheath area (r=-0.88, p<0.001). RNA-seq analysis revealed downregulation of most angiogenic genes and upregulation of antiangiogenic genes in the corpus callosum of RHRSPs 24 weeks after surgery. RHRSPs developed cerebral hypoperfusion, BBB disruption, spontaneous white matter damage, and cognitive impairment as the duration of hypertension increased. RHRSPs share behavioral and neuropathological characteristics with CSVD patients, making them suitable animal models for preclinical trials related to CSVD.

A novel score to predict progression in anterior circulation single subcortical infarction patients.

OBJECTIVE: Progressive infarction (PI) has a negative effect on functional prognosis. Our study aimed to develop and validate a risk score for predicting PI in patients with anterior circulation single subcortical infarction (ACSSI). METHODS: Between January 2020 and October 2022, we retrospectively enrolled 638 eligible patients with ACSSI. Two-thirds of the eligible patients were randomly allocated to the training cohort (n = 425). Another resampling sample was formed through the bootstrap method and was used as the validation group (n = 425). Multivariate logistic regression analysis was used to identify the independent factors associated with PI. Each factor was then point assigned based on ß-coefficient and a risk scoring system was developed. This scoring system was internally validated through 1000-bootstrap resamplings. The C-statistic and Hosmer-Lemeshow test were used to assess model discrimination and calibration. RESULTS: PI occurred in 121 patients, accounting for 19.0% of the total patients. A 7-point NTS score system based on the initial NIHSS score, triglyceride-glucose index, and the number of infarct slices on axial diffusion-weighted imaging was developed. The NTS score showed good discrimination and calibration in the training cohort (C-statistic = 0.686; p value of Hosmer-Lemeshow test = 0.797) and validation cohort (C-statistic = 0.681; p value of Hosmer-Lemeshow test = 0.451). The three risk levels for predicting PI in the training and validation cohorts based on NTS score were as follows: low (0-2, 9.6% vs. 9.3%), intermediate (3-5, 28.2% vs. 26.7%), and high risk (6-7, 60.2% vs. 57.4%). INTERPRETATION: The NTS score is a valid and convenient risk score for predicting PI in ACSSI patients.

Long-term complications and outcomes of augmentation cystoplasty in children with neurogenic bladder.

Augmentation cystoplasty (AC) is an effective surgical procedure for patients with neurogenic bladder whenever conservative treatments have failed. The present study aimed to determine the risks of metabolic complications, malignancy, long-term outcomes and histopathologic changes of native bladder and the augmented intestine after AC in children with neurogenic bladder. Pediatric patients < 18 years who underwent AC between 2000 and 2020 were enrolled. Early postoperative complications, long-term outcomes and histopathologic changes in mucosal biopsies of native bladder and the augmented intestine after AC were reviewed. Twenty-two patients with a mean age of 7.6 ± 4.4 years were included. The ileum was used in 19 patients and the sigmoid colon in 3 patients. The length of hospital stay was 14.8 ± 6.8 days. Post-operatively, the urinary continence rate improved from 22.7 to 81.8% (p < 0.001). Hydronephrosis resolved in 17 of 19 patients. Vesicoureteral reflux resolved in 16 (64.0%) of the refluxing ureter units and was downgraded in 7 (28.0%). Grades of hydronephrosis and reflux significantly improved following AC (p < 0.001). The estimated glomerular filtration rate also significantly increased (p = 0.012). Formation of urinary tract stones was the most frequent late complication (in 8 patients, 36.4%). Life-threatening spontaneous bladder perforation occurred in 1 patient. After a mean follow-up of 13.4 ± 5.9 years, there were no cases of mortality, new-onset symptomatic metabolic acidosis, or changes in serum electrolytes. Of the 17 patients who were followed for > 10 years, no cases of malignancy or metaplastic changes were identified in the native bladder or augmented bowel epithelium. AC is a safe and effective procedure with low surgical and metabolic complication rates. In addition, AC provides a satisfactory continence rate and long-term protection of renal function, increases functional capacity, and regresses reflux and hydronephrosis. Individualized surveillance is recommended for the early identification of urolithiasis and metabolic disturbances.

Disparity in risk factors of ischemic stroke in four coastal-area hospitals in China.

Background: Currently, ischemic stroke is the leading cause of death in China. To compare regional differences of ischemic stroke, we analyzed the clinical characteristics of patients with ischemic stroke in four regionally representative hospitals in China. Methods: We conducted a retrospective study at four tertiary hospitals in east China, with regionally representative patients. The associated factors include hypertension, diabetes mellitus, coronary heart disease, hyperlipidemia and a combination of these factors. The standardized ratio (SR), estimated as the observed number divided by the expected number, computed as the sum of predicted probabilities from a multivariable logistic regression model derived using data from all other cities, was used to compare to average levels. Results: A total of 34,707 patients were included. The number of patients increased with age in all four hospitals and patients were predominantly male. The number of ischemic stroke cases with related factors increased with age, except for hyperlipidemia. There was no significant gender difference when multiple related factors existed simultaneously. Coronary heart disease had a more significant impact on ischemic stroke in Qingdao Municipal Hospital and the First Hospital of Qinhuangdao, while hyperlipidemia had a significant influence on ischemic stroke in the First Hospital of Qinhuangdao. Conclusions: At four hospitals in east China, with the increase of age, the risk factors associated with ischemic stroke increased, and the distribution of ischemic stroke-related factors showed regional differences.

Certification of stroke centers at primary hospitals and the improvement of thrombolysis in South China during 2020-2022.

INTRODUCTION: IVT use declined globally in 2020 due to the Corona Virus Disease 2019 (COVID-19) pandemic, but it increased in South China. This study was conducted to evaluate the association of establishing Stroke Prevention Centers (SPCs) at primary hospitals with IVT increase in South China. MATERIALS AND METHODS: We conducted a longitudinal observational study across 336 hospitals in 114 areas in South China during 2020-2022. Data regarding certified stroke centers, IVT volumes, and IVT rates were collected. Correlations between IVT rates and the number or density of stroke centers were accessed. IVT use was compared among areas with different levels of stroke centers or on different certification process. RESULTS: During 2020-2022, there were 83, 125, and 152 stroke centers, with 26, 65, and 92 SPCs, respectively. IVT therapies were 12,795, 17,266, and 20,411, representing a 29.8% increase/year (all p < 0.001). IVT rates increased from 7.2% in 2020 to 8.8% and 10.4% in 2021 and 2022, demonstrating a 22.2% increase/year (all p < 0.001). IVT rates correlated with the number and density of SPCs (all p < 0.05). IVT rates were higher in areas equipped with SPCs than in those without stroke centers (all p < 0.05). IVT rates consistently increased during the SPC certification process from 1 year before through the certification and subsequent maintenance (both p < 0.05). DISCUSSION AND CONCLUSION: Well-organised SPCs and IVT therapy demonstrated substantial increase during the 3-year period. Certification of SPCs at primary hospitals is associated with improved IVT therapy in South China even with city lockdown during COVID-19 pandemic.

Identification of potential pathogenic hepatic super-enhancers regulatory network in high-fat diet induced hyperlipidemia.

Hyperlipidemia (HLP) is a prevalent metabolic disorder and a significant risk factor for cardiovascular disease. According to recent discoveries, super-enhancers (SEs) play a role in the increased expression of genes that encode important regulators of both cellular identity and the progression of diseases. However, the underlying function of SEs in the development of HLP is still unknown. We performed an integrative analysis of data on H3K27ac ChIP-seq and RNA sequencing obtained from liver tissues of mice under a low-fat diet (LFD) and high-fat diet (HFD) from GEO database. The rank ordering of super enhancers algorithm was employed for the computation and identification of SEs. A total of 1,877 and 1,847 SEs were identified in the LFD and HFD groups, respectively. The SE inhibitor JQ1 was able to potently reverse lipid deposition and the increased intracellular triglyceride and total cholesterol induced by oleic acid, indicating that SEs are involved in regulating lipid accumulation. Two hundred seventy-eight were considered as HFD-specific SEs (HSEs). GO and KEGG pathway enrichment analysis of the upregulated HSEs-associated genes revealed that they were mainly involved in lipid metabolic pathway. Four hub genes, namely Cd36, Pex11a, Ech1, and Cidec, were identified in the HSEs-associated protein-protein interaction network, and validated with two other datasets. Finally, we constructed a HSEs-specific regulatory network with Cidec and Cd36 as the core through the prediction and verification of transcription factors. Our study constructed a HSEs-associated regulatory network in the pathogenesis of HLP, providing new ideas for the underlying mechanisms and therapeutic targets of HLP.

Discontinuity of deep medullary veins in SWI is associated with deep white matter hyperintensity volume and cognitive impairment in cerebral small vessel disease.

BACKGROUND: Discontinuation of the deep medullary veins (DMVs) may be an early imaging marker for identifying cognitive impairment caused by cerebral small vessel disease (CSVD). However, this method lacks mechanistic exploration. We aimed to investigate whether the DMV score is related to CSVD imaging markers and cognitive impairment in patients with CSVD. METHODS: This retrospective study included patients with CSVD who completed DMV score and cognition (e.g., MMSE, MoCA) assessments, and underwent MRI scanning (T2-FLAIR for white matter hyperintensities (WMH) volume, T1-weighted MRI for brain parenchymal fractions (BPF) analysis, and SWI for assessment of DMV score). The CSVD imaging markers were quantitatively assessed using the AccuBrain® system. We assessed the diagnostic value of neuroimaging biomarkers for detecting CSVD-related cognitive impairment. In addition, we explored the relationship between the DMV score, CSVD imaging markers, and cognition using mediation analysis. RESULTS: Ninety-four patients with CSVD were divided into a cognitive impairment group (n = 39) and a non-cognitive impairment group (n = 55). Higher DMV scores, larger WMH volumes, and smaller BPF were observed in the cognitive impairment group than those in the non-cognitive impairment group. Receiver operating characteristics (ROC) analysis revealed that the discovery value of the integration of patient age, BPF, whole WMH volume, and DMV score for cognitive impairment was 0.742, with a sensitivity and specificity of 79.5 % and 61.5 %, respectively. Mediation analysis showed mediation by WMH and BPF in the relationship between DMV score and cognitive impairment (all P < 0.05). LIMITATIONS: This study did not evaluate the DMV score in subregions according to DMV anatomy. CONCLUSIONS: The DMV score is significantly associated with cognitive impairment in patients with CSVD, and this association is mediated through WMH and BPF.

Loss of SARM1 ameliorates secondary thalamic neurodegeneration after cerebral infarction.

Ischemic stroke causes secondary neurodegeneration in the thalamus ipsilateral to the infarction site and impedes neurological recovery. Axonal degeneration of thalamocortical fibers and autophagy overactivation are involved in thalamic neurodegeneration after ischemic stroke. However, the molecular mechanisms underlying thalamic neurodegeneration remain unclear. Sterile /Armadillo/Toll-Interleukin receptor homology domain protein (SARM1) can induce Wallerian degeneration. Herein, we aimed to investigate the role of SARM1 in thalamic neurodegeneration and autophagy activation after photothrombotic infarction. Neurological deficits measured using modified neurological severity scores and adhesive-removal test were ameliorated in Sarm1-/- mice after photothrombotic infarction. Compared with wild-type mice, Sarm1-/- mice exhibited unaltered infarct volume; however, there were markedly reduced neuronal death and gliosis in the ipsilateral thalamus. In parallel, autophagy activation was attenuated in the thalamus of Sarm1-/- mice after cerebral infarction. Thalamic Sarm1 re-expression in Sarm1-/- mice increased thalamic neurodegeneration and promoted autophagy activation. Auotophagic inhibitor 3-methyladenine partially alleviated thalamic damage induced by SARM1. Moreover, autophagic initiation through rapamycin treatment aggravated post-stroke neuronal death and gliosis in Sarm1-/- mice. Taken together, SARM1 contributes to secondary thalamic neurodegeneration after cerebral infarction, at least partly through autophagy inhibition. SARM1 deficiency is a potential therapeutic strategy for secondary thalamic neurodegeneration and functional deficits after stroke.

Pillar-Layered Porous Metal-Organic Frameworks with Co2N2O8 Clusters and Tetragonal Ligands for CO2 Conversion.

Converting CO2 to valuable chemicals and fuels is a viable method to establish a carbon-neutral energy cycle in the environment. Metal-organic frameworks (MOFs), characterized by dispersed active sites, high porosity, etc., have displayed a great application prospect in the electrochemical/chemical CO2 reduction reaction (CO2RR) process. Herein, we proposed a one-step production to establish a series of pillar-layered porous MOFs, [Co2(L)(bimb)]n (MOF 1) and [Co4(L)2(bidpe)2]n (MOF 2) [H4L = 5'-(4-carboxyphenyl)-(1,1':2',1″-terphenyl)-4,4',4″-tricarboxylic, bimb = 1,4-bis(imidazol-1-yl)-butane, bidpe = 4'-bis(imidazolyl) diphenyl ether], for preferential conversion of CO2 via ligand adjustment and increase of active sites' density. According to single-crystal X-ray diffraction studies, [Co2(L)(bimb)]n exhibits pillar-layered binuclear 3D frameworks with a 2,4,6-linked 3-nodes new topology structure, while [Co4(L)2(bidpe)2]n displays pillar-layered tetranuclear interspersed networks with a 4,6-linked 2-nodes fsc topology structure through a ligand adjustment strategy. Meanwhile, the pillar-layered structure of the MOFs with abundant active sites is conducive to mass diffusion and benefits the conversion of CO2. MOFs 1-2 exhibit good electrocatalytic activity for CO2RR in 0.5 M KHCO3 solution. Especially, the current density of MOF 2 generated at -0.90 V (vs. RHE) reaches -81.6 mA·cm-2, which is 3.1 times higher than that under an Ar atmosphere. In addition, MOFs 1-2 can be used as a heterogeneous catalyst for chemical conversion of CO2. The results are expected to provide inspiration for rational design to develop stable and high-efficiency MOF-based electrocatalysts for CO2RR.

Impact of type D personality and depressive symptoms on premature ejaculation in young adult males.

Background: Premature ejaculation (PE) is one of the most common male sexual dysfunctions with prominent psychological consequences. Type D personality (TDP) is also associated with multiple psychological disorders, such as depression and anxiety. However, the correlation between PE and TDP remains unknown. Aim: The study sought to investigate the relationships between depressive symptoms, TDP, and PE. Methods: Adult males in Taiwan who were 20 to 40 years of age and who had sexual intercourse in the past 6 months were recruited to complete online questionnaires composed of general demographics, the Premature Ejaculation Diagnostic Tool (PEDT), 5-item International Index of Erectile Function (IIEF-5), Type D Scale-14, and Depression and Somatic Symptom Scale (DSSS). Chi-square test and independent Student's t test were used to compare the parameters between the TDP and non-TDP groups. Univariate and multivariate logistic regression analyses were conducted to evaluate factors related to PE. Outcomes: Outcomes were the prevalence of PE and TDP in young Taiwanese men, the associations between depressive symptoms and PE and TDP, and the predictive factors of PE. Results: In total, 2558 men with a mean age of 31.3 ± 5.3 years were included in the present study. Among them, 315 (12.3%) and 767 (30.1%) participants were classified as having PE and moderate-to-severe erectile dysfunction (ED), respectively. In total, 1249 (48.8%) participants met the criteria for TDP. The PEDT, IIEF-5, and DSSS, including the total scores and depression and somatic subscales, were significantly higher in men with TDP (all P < .001). PE prevalence was significantly greater in men with TDP than in those without TDP (16.2% vs 8.6%; P < .001). Most parameters, including age, moderate-to-severe ED, the Type D Scale-14 subscales, and the DSSS somatic and depressive subscales, were significantly associated with PE in the univariate analysis. Only the depressive subscale of the DSSS and moderate-to-severe ED (IIEF-5 ≤16) were the independent predictors of PE in the multivariate analysis. Clinical Implications: The results suggest that it is important to consider the psychological effects of PE in young men, and the study has provided a biopsychosocial aspect to manage patients with PE. Strengths and Limitations: This is the first study to evaluate the association between PE, TDP, and depression in a large population of young adult males. However, the cross-sectional design may have limited the investigation of causality, and selection bias may be present. Conclusion: Men with TDP tended to have higher PEDT scores and a prevalence of PE and ED. Moderate-to-severe ED and depressive symptoms are the independent predictive factors of PE.

Influence of preoperative body mass index on prognosis for patients with upper urinary tract urothelial carcinoma treated with radical nephroureterectomy.

PURPOSE: The impact of body mass index (BMI) on patients with upper urinary tract urothelial carcinoma (UTUC) undergoing radical nephroureterectomy (RNU) is controversial. Increasing evidence suggests an age-dependent relationship between obesity and outcomes for some solid organ tumors. Herein, we aimed to assess the prognostic value of preoperative BMI in UTUC patients treated with RNU in Taiwan. METHODS: This was a retrospective single-center study of 468 UTUC patients undergoing RNU during January 2010-December 2017, with preoperative BMI classification and subgroup analysis based on ages of < or ≥ 70 years. All UTUC patients underwent RNU and bladder cuff excision. Overall survival (OS), cancer-specific survival, and disease-free survival (DFS) were analyzed. Fisher's exact test, Mann-Whitney U test, Kaplan-Meier method, and Cox regression model were used for data analysis. RESULTS: The median follow-up duration was 36 months. Patients with higher versus lower BMI (cutoff: 25 kg/m2) showed no differences in OS; older patients had poor OS (hazard ratio [HR] 1.74; 95% confidence interval [CI] 1.24-2.40; p < 0.001). Older age was an independent predictor of poor OS in multivariate Cox regression analysis (p = 0.001). Younger patients with higher BMI (p = 0.02) had better DFS than older patients with no BMI-related survival differences. Higher BMI was an independent predictor of favorable DFS in younger patients in multivariate Cox regression analysis (HR, 0.53; 95% CI 0.28-0.99; p = 0.043). CONCLUSION: Younger UTUC patients with higher BMI were independently associated with a favorable DFS.

Nurses' Willingness and Demand for Internet+Home Care Services and the Associated Factors in Municipal Hospitals in China: Cross-Sectional Survey.

BACKGROUND: Developing Internet+home care (IHC) services is a promising way to address the problems related to population aging, which is an important global issue. However, IHC services are in their infancy in China. Limited studies have investigated the willingness and demand of nurses in municipal hospitals to provide IHC services. OBJECTIVE: This study aims to investigate the willingness and demand of nurses in municipal hospitals in China to provide IHC services and analyze the factors to promote IHC development in China. METHODS: This cross-sectional study used multistage sampling to recruit 9405 nurses from 10 hospitals in 5 regions of China. A self-designed questionnaire with good reliability and validity was used to measure nurses' willingness and demand for providing IHC services. Data analysis used the chi-square test, Welch t test, binary logistic regression analysis, and multiple linear regression analysis. RESULTS: Nurses were highly willing to provide IHC services and preferred service distances of <5 km and times from 8 AM to 6 PM. An individual share >60% was the expected service pay sharing. Job title, educational level, monthly income, and marital status were associated with nurses' willingness to provide IHC services in binary logistic regression analysis. Supervising nurses were 1.177 times more likely to express a willingness to provide IHC services than senior nurses. Nurses with a bachelor's degree had a 1.167 times higher likelihood of expressing willingness to provide IHC services than those with a junior college education or lower. Married nurses were 1.075 times more likely to express a willingness than unmarried nurses. A monthly income >¥10,000 increased the likelihood of nurses' willingness to provide IHC services, by 1.187 times, compared with an income <¥5000. Nurses' total mean demand score for IHC services was 17.38 (SD 3.67), with the highest demand being privacy protection. Multiple linear regression analysis showed that job title, monthly income, and educational level were associated with nurses' demand for IHC services. Supervising nurses (B=1.058, P<.001) and co-chief nurses or those with higher positions (B=2.574, P<.001) reported higher demand scores than senior nurses. Monthly incomes of ¥5000 to ¥10,000 (B=0.894, P<.001) and >¥10,000 (B=1.335, P<.001), as well as a bachelor's degree (B=0.484, P=.002) and at least a master's degree (B=1.224, P=.02), were associated with higher demand scores compared with a monthly income <¥5000 and junior college education or lower, respectively. CONCLUSIONS: Nurses in municipal hospitals showed a high willingness and demand to provide IHC services, with differences in willingness and demand by demographic characteristics. Accordingly, government and hospitals should regulate the service period, service distance, and other characteristics according to nurses' willingness and demand and establish relevant laws and regulations to ensure the steady and orderly development of IHC services.

Characterization of uropathogenic Escherichia coli phylogroups associated with antimicrobial resistance, virulence factor distribution, and virulence-related phenotypes.

In this study, we compared the characteristics of different uropathogenic Escherichia coli phylogroups. A total of 844 E. coli isolated from urine were enrolled and the antimicrobial susceptibility of E. coli to 22 antibiotics was determined by disk diffusion test. The distribution of phylogroups and 20 virulence factor genes was determined by PCR. Phenotypes associated with bacterial virulence, including motility, biofilm formation, and the production of curli and siderophore, were examined. Phylogroup B2 was dominant in our isolates (64.8%), followed by phylogroups D (8.6%), B1 (7.8%), F (6.0%), C (4.5%), A (3.1%), untypable (2.8%), E (1.8%), and clade I (0.5%). The prevalence of multidrug-resistant strains was highest in phylogroup C (86.8%), followed by E (80.0%), F (75.0%), and D (71.2%). Moreover, 23.5% of the phylogroup F E. coli were extensively drug-resistant. Phylogroup B2 E. coli had an average of the highest virulence factor genes (10.1 genes/isolate). Compared to phylogroup B2 E. coli, phylogroups F and clade I E. coli had higher motility while phylogroup C E. coli had lower motility. >60% of phylogroups A and C E. coli showed very low curli production. In contrast, 14%, 10%, and 7%, of E. coli in phylogroups F, B2, and E, produced a very high amount of curli, respectively. Surprisingly, phylogroup A E. coli showed the highest virulence to larvae, followed by phylogroups B2 and C. In summary, we first characterized and revealed that the antimicrobial resistance, virulence gene distribution, motility, and curli production, were associated with in E. coli phylogroups.

Pyrimidinergic receptor P2Y6 expression is elevated in lung adenocarcinoma and is associated with poor prognosis.

BACKGROUD: Previous in vitro studies have indicated that pyrimidinergic receptor P2Y6 (P2RY6, P2Y6 receptor) may function as a cancer-promoting factor in lung adenocarcinoma (LUAD). However, the prognostic significance of P2RY6 expression in LUAD has not been investigated. OBJECTIVE: This study aimed to assess the impact of P2RY6 expression on the survival of patients with LUAD. METHODS: First, we assessed P2RY6 mRNA and protein expression in LUAD and non-cancerous lung tissues using the online bioinformatics analysis tool GEPIA, fresh LUAD tissues, and LUAD tissue microarrays (TMAs). Second, we investigated the correlation between P2RY6 expression and clinicopathological parameters of LUAD patients based on data from The Cancer Genome Atlas (TCGA) database and TMAs. Finally, we analyzed the prognostic significance of P2RY6 expression in LUAD using the online survival analysis tool Kaplan-Meier Plotter and data from TMAs. RESULTS: We demonstrated that P2RY6 mRNA and protein expression levels in LUAD tissues were significantly higher than those in non-cancerous lung tissues. The expression of P2RY6 in LUAD was positively correlated with poor differentiation, more lymph node metastasis, and more advanced clinical stage. Higher P2RY6 expression level was correlated with shorter survival of the LUAD patients. Univariate and multivariate Cox regression analyses indicated that higher P2RY6 tumor expression was an independent unfavorable prognostic factor for LUAD patients. CONCLUSIONS: P2RY6 expression was elevated in LUAD and correlated with poor prognosis.

Stable Co(II)-based coordination polymer as fluorescence sensor for the discriminative sensing of biomarker methylmalonic acid.

Three novel Co-based coordination polymers including {[Co(L)(µ3-O)1/3]2}n (1), {[Co(L)(bimb)]}n (2) and {[Co(L)(bimmb)1/2]}n (3) (H2L = 2,6-di(4-carboxylphenyl)-4-(4-(triazol-1-ylphenyl))pyridine), bimb = 1,4-bis(lmidazol) butane, bimmb = 1,4-bis(imidazole-1-ylmethyl)benzene) were successfully prepared under solvothermal conditions and characterized. Single-crystal X-ray diffraction analyses revealed that 1 possesses a 3D architecture composed of a trinuclear cluster [Co3N3(CO2)6(µ3-O)], 2 exhibits a 2D new topological framework with the point symbol (84·122)(8)2, whereas 3 shows a unique six-fold interpenetrated 3D framework with a (63·82·10)2(63)2(8) topology. Impressively, all of them can function as a highly selective and sensitive fluorescent sensor for the biomarker methylmalonic acid (MMA) via fluorescence quenching. The low detection limit, reusability and high anti-interference performance together make 1-3 become promising sensors for the practical detection of MMA. Furthermore, the successful application of MMA detection in urine sample was demonstrated, which may be a potential candidate for the further development of clinical diagnostic tools.

TAK1 Improves Cognitive Function via Suppressing RIPK1-Driven Neuronal Apoptosis and Necroptosis in Rats with Chronic Hypertension.

Chronic hypertension is a major risk factor for cognitive impairment, which can promote neuroinflammation and neuronal loss in the central nervous system. Transforming growth factor ß-activated kinase 1 (TAK1) is a key molecular component in determining cell fate and can be activated by inflammatory cytokines. This study aimed to investigate the role of TAK1 in mediating neuronal survival in the cerebral cortex and hippocampus under chronic hypertensive conditions. To that end, we used stroke-prone renovascular hypertension rats (RHRSP) as chronic hypertension models. Adeno-associated virus (AAV) designed to overexpress or knock down TAK1 expression were injected into the lateral ventricles of rats and the subsequent effects on cognitive function and neuronal survival under chronic hypertensive conditions were assessed. We found that, TAK1 knockdown in RHRSP markedly increased neuronal apoptosis and necroptosis and induced cognitive impairment, which could be reversed by Nec-1s, an inhibitor of receptor interacting protein kinase 1 (RIPK1). In contrast, overexpression of TAK1 in RHRSP significantly suppressed neuronal apoptosis and necroptosis and improved cognitive function. Further knockdown of TAK1 in sham-operated rats received similar phenotype with RHRSP. The results have been verified in vitro. In this study, we provide in vivo and in vitro evidence that TAK1 improves cognitive function by suppressing RIPK1-driven neuronal apoptosis and necroptosis in rats with chronic hypertension.

Lower urinary tract symptoms as an independent predictor of aortic regurgitation in women with cardiac symptoms.

BACKGROUND: Very few studies have focused on the correlation between structural heart disease and lower urinary tract symptoms. In this study, we applied echocardiography to explore the correlation between lower urinary tract symptoms and structural heart disease. METHODS: In this single-center, prospective, cross-sectional study, we enrolled adult women undergoing echocardiography for suspected cardiac abnormalities causing cardiac symptoms between February 1, 2021, and March 31, 2021. All participants completed a questionnaire regarding demographic information and lower urinary tract symptoms, which were assessed according to the International Prostate Symptom Score. RESULTS: A total of 165 women aged 69.96 ± 10.20 years were enrolled. The prevalence of moderate-to-severe aortic regurgitation in patients with moderate-to-severe lower urinary tract symptoms was significantly higher than that in patients with mild lower urinary tract symptoms (33.3% vs 13.6%, p = 0.008). The prevalence of other echocardiographic abnormalities was not associated with severity of lower urinary tract symptoms. Multivariable logistic regression analyses revealed that moderate-to-severe lower urinary tract symptoms predicted moderate-to-severe aortic regurgitation ( p = 0.007; odds ratio: 3.560; 95% confidence interval: 1.409-8.993). Furthermore, the International Prostate Symptom Score storage subscore ( p = 0.001; odds ratio: 1.285; 95% confidence interval: 1.111-1.486), except the voiding subscore, was an independent predictor of moderate-to-severe aortic regurgitation. CONCLUSION: Moderate-to-severe lower urinary tract symptoms, especially storage symptoms, are an independent predictor of the co-existence of moderate-to-severe aortic regurgitation in women with cardiac symptoms. Early cardiological referral of patients with moderate-to-severe lower urinary tract symptoms and cardiac symptoms may improve their general health.