COVID-19 and retinal layer thickness: A bidirectional Mendelian randomization study.

BACKGROUND: Observational studies have reported that COVID-19 is associated with alterations in retinal layer thickness, including changes in the ganglion cell inner plexiform layer (GCIPL) and retinal nerve fiber layer (RNFL). However, the causal relationships remain unknown. Therefore, we assessed the direction and strength of the causal relationship between COVID-19 and GCIPL and RNFL thicknesses using a bidirectional two-sample Mendelian randomization (MR) design. METHODS: Data were obtained from a large-scale COVID-19 Host Genetics Initiative (Nsample = 6,512,887), GCIPL dataset (Ncase = 31,434), and RNFL dataset (Ncase = 31,434). The inverse-variance weighted (IVW) method is the primary approach used to estimate causal effects. MR Egger, weighted median, weighted mode, MR Egger (bootstrap), and penalized weighted median methods were applied. Sensitivity analyses were implemented with RadialMR, MRPRESSO, MR-Egger regression, Cochran's Q statistic, leave-one-out analysis, and the funnel plot. RESULTS: Forward MR analysis revealed that genetically identified COVID-19 susceptibility significantly increased the risk of GCIPL thickness (OR = 2.428, 95 % confidence interval [CI]:1.493-3.947, PIVW = 3.579 × 10-4) and RNFL thickness (OR = 1.735, 95 % CI:1.198-2.513, PIVW = 3.580 × 10-3) after Bonferroni correction. Reverse MR analysis did not indicate a significant causal association between GCIPL and RNFL thicknesses and COVID-19 phenotypes. No significant horizontal pleiotropy was found in the sensitivity analysis. CONCLUSIONS: The host genetic liability to COVID-19 susceptibility was causally associated with increased GCIPL and RNFL thicknesses. Documenting this association increases our understanding of the pathophysiological mechanisms underlying COVID -19 susceptibility in retinopathy.

Global, regional, and national trends in metabolic risk factor-associated mortality among the working-age population from 1990-2019: An age-period-cohort analysis of the Global Burden of Disease 2019 study.

BACKGROUND: Metabolic diseases contribute significantly to premature mortality worldwide, with increasing burdens observed among the working-age population (WAP). This study assessed global, regional, and national trends in metabolic disorders and associated mortality over three decades in WAP. METHODS: Data from the Global Burden of Disease 2019 study were leveraged to assess global metabolism-associated mortality and six key metabolic risk factors in WAP from 1990-2019. An age-period-cohort model was employed to determine the overall percentage change in mortality. RESULTS: The 2019 global metabolic risk-related mortality rate in WAP rose significantly by 50.73%, while the age-standardized mortality rate declined by 21.5%. India, China, Indonesia, the USA, and the Russian Federation were the top contributing countries to mortality in WAP, accounting for 51.01% of the total. High systolic blood pressure (HSBP), high body mass index (HBMI), and high fasting plasma glucose (HFPG) were the top metabolic risk factors for the highest mortality rates. Adverse trends in HBMI-associated mortality were observed, particularly in lower sociodemographic index (SDI) regions. HFPG-related mortality declined globally but increased in older age groups in lower SDI countries. CONCLUSIONS: Despite a general decline in metabolic risk-related deaths in WAP, increasing HBMI- and HFPG-related mortality in lower SDI areas poses ongoing public health challenges. Developing nations should prioritize interventions addressing HBMI and HFPG to mitigate mortality risks in WAP.

Distinct time trends in colorectal cancer incidence in countries with SDI levels from 1990 to 2019: an age-period-cohort analysis for the Global Burden of Disease 2019 study.

Introduction: The burden of colorectal cancer (CRC) plays a pivotal role in the global cancer epidemic. Our study reported the incidence trends in CRC and the associated effects of age, period, and birth cohort in 204 countries and territories over the past 30 years. Methods: The incidence data of CRC were extracted from the Global Burden of Disease Study (GBD) 2019. We performed the age-period-cohort (APC) model to estimate the overall annual percentage change (net drift) in the incidence rate, the annual percentage change by age group (local drift), and the relative risk (period and cohort effects) of the period and cohort in CRC during 1990-2019. This approach allows examining and distinguishing age, period, and cohort effects in incidence and potentially distinguishing colorectal cancer gaps in prevention and screening. Results: In 2019, the incidence of CRC was 2.17 (95% UI 2.00-2.34) million, of which China, the United States of America, and Japan had the highest incidence population, accounting for 45.9% of the global population. The age-standardized incidence rate (ASIR) was 26.7 (95% UI 28.9-24.6) per 100,000 people, of which 30 countries had an incidence rate greater than 40.0 per 100,000 people. From 1990 to 2019, the middle SDI region had the largest increase in incidence rate, with a net drift of 2.33% (95% CI 2.2-2.46%, p < 0.001). Globally, the incidence population was concentrated in the age group of 50-69 years, and the age group of 30-34 years had the largest increase in incidence rate (local drift 1.19% (95% CI 1.01-1.37%)). At the same time, the sex and age distributions of CRC incidence had significant heterogeneity across regions and countries. In the past 30 years, the incidence rate in 31 countries has been well controlled (net drift <0), and most of them were concentrated in high-and high-middle-SDI regions, such as Australia, Czechia, and Belgium, and the relative risk of incidence generally improved over time and consecutive young birth cohorts. CRC incidence showed an unfavorable trend (net drift ≥1%) in 89 countries, of which 27 countries were more significant (net drift >2%), mostly concentrated in the middle SDI region, such as China, Mexico, and Brazil, and the risk of period and birth cohort was unfavorable. Conclusion: Globally, the incidence of CRC has shown an overall upward trend over the past 30 years, with the exception of some countries with higher SDI values. Significant age-period-cohort differences were observed in the risk of incidence in CRC worldwide. Effective prevention and control policies need to take into account the age-period-cohort effect characteristics of different regions.

The factors of job crafting in emergency nurses: regression models versus qualitative comparative analysis.

BACKGROUND: Job crafting is defined as a series of proactive behaviors exhibited by employees in order to balance work resources and needs, which has a significant positive impact on the nurses. It is necessary to find the core factors that influence the job crafting, as emergency nurses deal with the most complex tasks, so as to improve their job satisfaction. OBJECTIVES: To investigate the core factors of job crafting among emergency nurses. METHODS: A cross-sectional design was used in the study. A total of 255 nurses were recruited from two hospitals in Zhengzhou and Shenzhen, China in December 2021. 255 nurses completed an online questionnaire. Hierarchical regression models and fsQCA models were used to explore the factors influencing job crafting among emergency nurses and helped us to identify core factors. RESULTS: The hierarchical regression model and the fsQCA model found that the occupational benefit, psychological empowerment, and research experience were the core factors affecting their job crafting. Job involvement was not significant in the regression model, but the QCA model indicated that it needs to be combined with other factors to impact on job crafting. The QCA model uncovered seven key conditional configurations that led to high and low job crafting among emergency nurses, explaining 80.0% of the results for high job crafting and 82.6% of the results for the low job crafting, respectively. CONCLUSIONS: The results of this study provide valuable insights into the job crafting experienced by emergency nurses. Junior emergency nurses should be granted a high level of psychological empowerment without assigning them overly complex tasks, such as research tasks, as these challenges can stop their job crafting. Intermediate and senior emergency nurses, on the other hand, can be assigned research tasks coupled with high psychological empowerment to enhance their job crafting.

Design, synthesis and neuroprotective biological evaluation of novel HDAC6 inhibitors incorporating benzothiadiazinyl systems as cap groups.

Histone deacetylase 6 (HDAC6), as the key regulatory enzyme, plays an important role in the development of the nervous system. More and more studies indicate that HDAC6 has become a promising therapeutic target for CNS diseases. Herein we designed and synthesized a series of novel HDAC6 inhibitors with benzothiadiazinyl systems as cap groups and evaluated their activity in vitro and in vivo. Among them, compound 3 exhibited superior selective inhibitory activity against HDAC6 (IC50 = 5.1 nM, about 30-fold selectivity over HDAC1). The results of docking showed that compound 3 can interact well with the key amino acid residues of HDAC6. Compound 3 showed lower cytotoxicity (20 µM to SH-SY5Y cells, inhibition rate = 25.75%) and better neuroprotective activity against L-glutamate-induced SH-SY5Y cell injury model in vitro. Meanwhile, compound 3 exhibited weak cardiotoxicity (10 µM hERG inhibition rate = 17.35%) and possess good druggability properties. Especially, compound 3 could significantly reduce cerebral infarction from 49.87% to 32.18%, and similar with butylphthalide in MCAO model, indicating potential clinical application prospects for alleviating ischemic stroke-induced brain infarction.

The loss of dissolved organic matter from biological soil crust at various successional stages under rainfall of different intensities: Insights into the changes of molecular components at different rainfall stages.

Biological soil crusts (BSCs) are typical covers in arid and semiarid regions. The dissolved organic matter (DOM) of BSCs can be transported to various aquatic ecosystems by rainfall-runoff processes. However, the spatiotemporal variation in quality and quantity of DOM in runoff remains unclear. Herein, four kinds of runoff plots covered by four successional stages of BSCs were set up on slopes, including bare runoff plot (BR), cyanobacteria crust covered runoff plot (CR), mixed crust covered runoff plot (MIR), and moss crust covered runoff plot (MOR). The quantity and quality of DOM in runoff during rainfall was investigated based on the stimulated rainfall experiments combined with optical spectroscopy and ultra-high resolution mass spectrometry analyses. The results showed that the DOM concentrations (i.e., 0.30 to 45.25 mg L-1) in runoff followed the pattern of MOR>MIR>CR>BR, and they were exponentially decreased with rainfall duration. The DOM loss rate of BR (8.26 to 11.64 %) was significantly greater than those of CR, MIR, and MOR (0.84 to 3.22 %). Highly unsaturated compounds (HUCs), unsaturated aliphatic compounds (UACs), saturated compounds (SCs), and peptide-like compounds (PLCs) were the dominated compounds of the water extractable DOM from the original soils. Thereinto, PLCs and UACs were more easily leached into runoff during rainfall. The relatively intensity of HUCs in runoff generally decreased with rainfall duration, while the relatively intensities of UACs, PLCs, and SCs slightly increased with rainfall duration. These findings suggested that the DOM loss rate was effectively decreased with the successional of BSCs during rainfall; meanwhile, some labile compounds (e.g., PLCs and UACs) were transported into various aquatic ecosystems by rainfall-runoff processes.

The white matter characteristic of the genu of corpus callosum coupled with pain intensity and negative emotion scores in patients with trigeminal neuralgia: a multivariate analysis.

Background: Trigeminal neuralgia (TN) is a chronic neuropathic pain disorder that not only causes intense pain but also affects the psychological health of patients. Since TN pain intensity and negative emotion may be grounded in our own pain experiences, they exhibit huge inter-individual differences. This study investigates the effect of inter-individual differences in pain intensity and negative emotion on brain structure in patients with TN and the possible pathophysiology mechanism underlying this disease. Methods: T1 weighted magnetic resonance imaging and diffusion tensor imaging scans were obtained in 46 patients with TN and 35 healthy controls. All patients with TN underwent pain-related and emotion-related questionnaires. Voxel-based morphometry and regional white matter diffusion property analysis were used to investigate whole brain grey and white matter quantitatively. Innovatively employing partial least squares correlation analysis to explore the relationship among pain intensity, negative emotion and brain microstructure in patients with TN. Results: Significant difference in white matter integrity were identified in patients with TN compared to the healthy controls group; The most correlation brain region in the partial least squares correlation analysis was the genus of the corpus callosum, which was negatively associated with both pain intensity and negative emotion. Conclusion: The genu of corpus callosum plays an important role in the cognition of pain perception, the generation and conduction of negative emotions in patients with TN. These findings may deepen our understanding of the pathophysiology of TN.

Impact of immune checkpoint inhibitors (ICIs) therapy on interferon-γ release assay (IGRA) and diagnostic value in non-small cell lung cancer (NSCLC) patients.

BACKGROUND: Tuberculosis (TB), a highly contagious respiratory disease, presents a significant global health threat, with a notable increase in incidence reported by the WHO in 2022. Particularly, the interplay between TB and non-small cell lung cancer (NSCLC) gains attention, especially considering the rising use of immune checkpoint inhibitors (ICIs) in cancer treatment. This interplay may influence TB diagnostics and reactivation, warranting a closer examination. METHODS: A retrospective analysis was conducted on clinical data of NSCLC patients with positive T-SPOT results before undergoing anti-tumor treatment at Zhongshan Hospital (Xiamen), Fudan University, from January 1, 2021 to December 31, 2022. We assessed the incidence of tuberculosis reactivation and treatment outcomes among these patients. Moreover, we compared the differences in tuberculosis activity between the ICIs and non-ICIs treatment groups. Additionally, we observed the changes in T-SPOT spot count before and after immunotherapy, analyzing their association with tuberculosis activity and prognosis. RESULTS: A total of 40 NSCLC patients with positive T-SPOT results before treatment were included in the study, with 26 patients in the ICIs treatment group and 14 patients in the non-ICIs treatment group. The study found no significant differences between the two groups in terms of gender, age, stage, histological type, performance status, driver gene expression, and distant metastasis. With a median follow-up time of 10.0 (6.0-14.5) months, three cases (11.5%) in the ICIs treatment group developed tuberculosis activity, diagnosed at 2, 3, and 12 months after ICIs treatment initiation. Conversely, no tuberculosis activity was observed in the non-ICIs treatment group, and the difference between the two groups was not significant (P = 0.186). Among the 32 patients who received ICIs treatment, spot count dynamics were diverse: four cases (12.5%) showed an increase, 12 cases (37.5%) had no change, and 16 cases (50.0%) had a decrease. During the follow-up, the progression rate (PD) was 50.0%, 75.0%, and 62.5% in the three groups, respectively (P = 0.527). Similarly, the mortality rate was 0%, 25.0%, and 25.0%, respectively (P = 0.106). Interestingly, among the patients with decreased spot counts, three cases (18.75%) were diagnosed with active pulmonary tuberculosis. CONCLUSIONS: For NSCLC patients with a positive T-SPOT response undergoing ICIs treatment, our study observed indications of active tuberculosis. The varied T-SPOT spot count changes post-ICIs treatment suggest a complex interaction, potentially linking T-SPOT spot count reduction to tuberculosis reactivation risk. These preliminary findings underscore the importance of further research to more accurately assess T-SPOT's diagnostic utility in this context.

Hypoxia and low-glucose environments co-induced HGDILnc1 promote glycolysis and angiogenesis.

Small bowel vascular malformation disease (SBVM) commonly causes obscure gastrointestinal bleeding (OGIB). However, the pathogenetic mechanism and the role of lncRNAs in SBVM remain largely unknown. Here, we found that hypoxia and low-glucose environments co-augment angiogenesis and existed in SBVM. Mechanistically, hypoxia and low-glucose environments supported angiogenesis via activation of hypoxia and glucose deprivation-induced lncRNA (HGDILnc1) transcription by increasing binding of the NeuroD1 transcription factor to the HGDILnc1 promoter. Raised HGDILnc1 acted as a suppressor of α-Enolase 1 (ENO1) small ubiquitin-like modifier modification (SUMOylation)-triggered ubiquitination, and an activator of transcription of Aldolase C (ALDOC) via upregulation of Histone H2B lysine 16 acetylation (H2BK16ac) level in the promoter of ALDOC, and consequently promoting glycolysis and angiogenesis. Moreover, HGDILnc1 was clinically positively correlated with Neurogenic differentiation 1 (NeuroD1), ENO1, and ALDOC in SBVM tissues, and could function as a biomarker for SBVM diagnosis and therapy. These findings suggest that hypoxia and low-glucose environments were present in SBVM tissues, and co-augmented angiogenesis. Hypoxia and low-glucose environments co-induced HGDILnc1, which is higher expressed in SBVM tissue compared with normal tissue, could promoted glycolysis and angiogenesis.

Design, synthesis, and biological evaluation of aralkyl piperazine and piperidine derivatives targeting SSRI/5-HT1A/5-HT7.

Serotonin reuptake inhibition combined with the action targeting 5-hydroxytryptamine receptor subtypes can serve as a potential target for the development of antidepressant drugs. Herein a series of new aralkyl piperazines and piperidines were designed and synthesized by the structural modifications of the previously discovered aralkyl piperidine compound 1, targeting SSRI/5-HT1A/5-HT7. The results exhibited that compound 5a showed strong binding to 5-HT1A and 5-HT7 (Ki of 0.46 nM, 2.7 nM, respectively) and a high level of serotonin reuptake inhibition (IC50 of 1.9 nM), all of which were significantly elevated compared to 1. In particular, compound 5a showed weaker inhibitory activity against hERG than 1, and demonstrated good stability in liver microsomes in vitro. The preliminary screening using FST indicated that orally administered 5a, at a high dose, could reduce immobility time in mice markedly, indicating potential antidepressant activity.

Work Function Prediction by Graph Neural Networks for Configurationally Hybridized Boron-Doped Graphene.

Graphene, serving as electrodes, is widely applied in electronic and optoelectronic devices. Work function as one of the fundamental intrinsic characteristics of graphene directly affects the interfacial properties of the electrodes, thereby affecting the performance of the devices. Much work has been done to regulate the work function of graphene to expand its application fields, and doping has been demonstrated as an effective method. However, the numerous types of doped graphene make the investigation of its work function time-consuming and labor-intensive. In order to quickly obtain the relationship between the structure and property, a deep learning method is employed to predict the work function in this study. Specifically, a data set of over 30,000 compositions with the work function on boron-doped graphene at different concentrations and doping positions via density functional theory simulations was established through ab initio calculations. Then, a novel fusion model (GT-Net) combining transformers and graph neural networks (GNNs) was proposed. After that, improved effective GNN-based descriptors were developed. Finally, three different GNN methods were compared, and the results show that the proposed method could accurately predicate the work function with the R2 = 0.975 and RMSE = 0.027. This study not only provides the possibility of designing materials with specific properties at the atomic level but also demonstrates the performance of GNNs on graph-level tasks with the same graph structure and atomic number.

Multi-step validation of a deep learning-based system with visual explanations for optical diagnosis of polyps with advanced features.

Artificial intelligence (AI) has been found to assist in optical differentiation of hyperplastic and adenomatous colorectal polyps. We investigated whether AI can improve the accuracy of endoscopists' optical diagnosis of polyps with advanced features. We introduced our AI system distinguishing polyps with advanced features with more than 0.870 of accuracy in the internal and external validation datasets. All 19 endoscopists with different levels showed significantly lower diagnostic accuracy (0.410-0.580) than the AI. Prospective randomized controlled study involving 120 endoscopists into optical diagnosis of polyps with advanced features with or without AI demonstration identified that AI improved endoscopists' proportion of polyps with advanced features correctly sent for histological examination (0.960 versus 0.840, p < 0.001), and the proportion of polyps without advanced features resected and discarded (0.490 versus 0.380, p = 0.007). We thus developed an AI technique that significantly increases the accuracy of colorectal polyps with advanced features.

Co3O4 nanoparticle modified N, P co-doped carbon paper as sodium carrier to construct stable anodes for Na-metal batteries.

Sodium (Na) metal batteries such as Na-ion batteries and Na-CO2 batteries are considered to be excellent alternatives to lithium batteries in terms of their potential applications because of their high specific capacity and low cost. However, the sodium anode showed low efficiency and poor cycling in Na-metal battery performance due to the formation of sodium dendrites and serious corrosion. In this work, nitrogen (N), phosphorus (P) co-doped carbon paper (NP-CP) modified with cobalt tetroxide (Co3O4) nanoparticles was prepared as the Na anode carrier (Co3O4@NP-CP), and a sodium-based composite anode (Na-Co@NP-CP) was further prepared by electrodepositing sodium. The experimental results indicate that the N, P and Co3O4 multi-doped carbon paper has good sodiophilicity, which can induce the uniform plating/stripping of Na+ ions and inhibit the growth of Na dendrites. The N, P doped carbon paper provides a high surface area and tremendous three-dimensional (3D) framework to effectively reduce the areal current density, facilitate the transfer of electrons, and enhance battery life. Therefore, Na-Co@NP-CP based symmetric cells exhibit stable cycling of over 1100 hours at current densities of 1 mA cm-2 and fixed capacity of 1 mA h cm-2. When the Na-Co@NP-CP anode couples with CO2, the assembled batteries can deliver a stable cycling of 165 cycles at current densities of 500 mA g-1 and limited capacity of 500 mA h g-1. When Na-Co@NP-CP anode couples with Na3V2(PO4)3 (NVP) cathode, the assembled cells exhibit lower hysteresis and batter cycling performance.

Global, regional, and national time trends in incidence for tuberculosis, 1990-2019: An age-period-cohort analysis for the Global Burden of Disease 2019 study.

BACKGROUND: Tuberculosis (TB) represents a significant global health concern, being the leading cause of mortality from a single infectious agent worldwide. The investigation of TB incidence and epidemiological trends is critical for evaluating the effectiveness of control strategies and identifying ongoing challenges. OBJECTIVES: This study presents the trend in TB incidence across 204 countries and regions over a 30-year period. METHODS: The study utilises data sourced from the Global Burden of Disease (GBD) database. The age cohort model and gender subgroup analysis were employed to estimate the net drift (overall annual percentage change), local drift (age annual percentage change), longitudinal age curve (expected age ratio), and cycle and cohort effect (relative risk of cycle and birth cohort) of TB incidence from 1990 to 2019. This approach facilitates the examination and differentiation of age, period, and cohort effects in TB incidence trends, potentially identifying disparities in TB prevention across different countries. RESULTS: Over the past three decades, a general downward trend in TB incidence has been observed in most countries. However, in 15 of the 204 countries, the overall incidence rate is still on the rise (net drift ≥0.0 %) or stagnant decline (≥-0.5 %). From 1990 to 2019, the net drift of tuberculosis mortality ranged from -2.2 % [95 % confidence interval (CI): -2.33, -2.05] in high Socio-demographic Index (SDI) countries to -1.7 % [95 % CI: -1.81, -1.62] in low SDI countries. In some below-average SDI countries,men in the birth cohort are at a disadvantage and at risk of deterioration, necessitating comprehensive TB prevention and treatment. CONCLUSIONS: While the global incidence of TB has declined, adverse period and cohort effects have been identified in numerous countries, raising questions about the adequacy of TB healthcare provision across all age groups. Furthermore, this study reveals gender disparities in TB incidence.

Analysis of the current state of cervical cancer prevention awareness and its influencing factors among rural women in Luohe City.

The purpose of this cross-sectional study was to identify the current awareness about cervical cancer prevention among rural women in Luohe City as well as its potential influencing factors. Meanwhile, these data were expected to provide a theoretical basis for Luohe future cervical cancer prevention and therapy. Based on geographical distribution, 40 villages in Luohe City were randomly selected, and questionnaires were given to women in each village. In this study, a total of 4665 questionnaires were distributed, and 4561 valid questionnaires were returned, with a recovery rate of 97.98%. The average score was 4.06 ±â€…2.46 out of 10. It was found that women had a high awareness rate of cervical cancer screening (55.25%) but a low awareness rate of human papillomavirus (HPV) and HPV vaccine (10.17%). Moreover, univariate and multivariable analyses showed that age > 45 years, low household income, low education level, being a farmer, spouse unemployment, no pregnancy or birth delivery history, no family or personal history of cervical disease, and no previous complimentary 2-cancer screening (i.e., breast cancer and cervical cancer) were all factors influencing the cognitive level of rural women in Luohe City (P < .05). However, ethnicity, marital status, and spouse education level were not correlated with cognitive level (P > .05). In conclusion, low awareness of cervical cancer prevention among rural women in Luohe was correlated with individual, family, and social factors. So it was recommended to cultivate the rural population knowledge, optimize screening strategies, and conduct targeted cervical cancer prevention and treatment in rural regions.

Thymoma with immunodeficiency, combined diffuse panbronchiolitis, and latent autoimmune diabetes in adults- case report and systematic review.

Thymoma with Immunodeficiency (Good's Syndrome, GS) is a rare association between thymoma and immunodeficiency, first described over 60 years ago. Patients with GS typically present with thymomas, reduced or absent B cells in the peripheral blood, hypogammaglobulinemia, and defects in cell-mediated immunity. We report the case of a 67-year-old woman diagnosed with GS following the development of a progressive, severe, refractory pulmonary infection and diffuse panbronchiolitis (DPB). She also had diabetes, characterized by anti-glutamic acid decarboxylase antibody positivity, leading to a diagnosis of latent autoimmune diabetes in adults (LADA). A thorough review of existing literature revealed that GS is often confirmed after multiple episodes of opportunistic infections or autoimmune diseases post-thymoma surgery. Due to their immunodeficiency, GS patients frequently suffer from recurrent infections over extended periods, and some succumb to severe infections. Regular immunoglobulin infusions may be effective in treating GS.

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.

Assessing Global, Regional, and National Time Trends and Associated Risk Factors of the Mortality in Ischemic Heart Disease Through Global Burden of Disease 2019 Study: Population-Based Study.

BACKGROUND: Ischemic heart disease (IHD) is the leading cause of death among noncommunicable diseases worldwide, but data on current epidemiological patterns and associated risk factors are lacking. OBJECTIVE: This study assessed the global, regional, and national trends in IHD mortality and attributable risks since 1990. METHODS: Mortality data were obtained from the Global Burden of Disease 2019 Study. We used an age-period-cohort model to calculate longitudinal age curves (expected longitudinal age-specific rate), net drift (overall annual percentage change), and local drift (annual percentage change in each age group) from 15 to >95 years of age and estimate cohort and period effects between 1990 and 2019. Deaths from IHD attributable to each risk factor were estimated on the basis of risk exposure, relative risks, and theoretical minimum risk exposure level. RESULTS: IHD is the leading cause of death in noncommunicable disease-related mortality (118.1/598.8, 19.7%). However, the age-standardized mortality rate for IHD decreased by 30.8% (95% CI -34.83% to -27.17%) over the past 30 years, and its net drift ranged from -2.89% (95% CI -3.07% to -2.71%) in high sociodemographic index (SDI) region to -0.24% (95% CI -0.32% to -0.16%) in low-middle-SDI region. The greatest decrease in IHD mortality occurred in the Republic of Korea (high SDI) with net drift -6.06% (95% CI -6.23% to -5.88%), followed by 5 high-SDI nations (Denmark, Norway, Estonia, the Netherlands, and Ireland) and 2 high-middle-SDI nations (Israel and Bahrain) with net drift less than -5.00%. Globally, age groups of >60 years continued to have the largest proportion of IHD-related mortality, with slightly higher mortality in male than female group. For period and birth cohort effects, the trend of rate ratios for IHD mortality declined across successive period groups from 2000 to 2004 and birth cohort groups from 1985 to 2000, with noticeable improvements in high-SDI regions. In low-SDI regions, IHD mortality significantly declined in female group but fluctuated in male group across successive periods; sex differences were greater in those born after 1945 in middle- and low-middle-SDI regions and after 1970 in low-SDI regions. Metabolic risks were the leading cause of mortality from IHD worldwide in 2019. Moreover, smoking, particulate matter pollution, and dietary risks were also important risk factors, increasingly occurring at a younger age. Diets low in whole grains and legumes were prominent dietary risks in both male and female groups, and smoking and high-sodium diet mainly affect male group. CONCLUSIONS: IHD, a major concern, needs focused health care attention, especially for older male individuals and those in low-SDI regions. Metabolic risks should be prioritized for prevention, and behavioral and environmental risks should attract more attention to decrease IHD mortality.

Burden of cardiovascular disease among elderly: based on the Global Burden of Disease Study 2019.

BACKGROUND: The burden of elderly cardiovascular disease (CVD) has received increasing attention with population ageing worldwide. AIMS: We reported on the global CVD burden in elderly individuals over 70, 1990-2019. METHODS AND RESULTS: Based on the Global Burden of Disease Study 2019, elderly CVD burden data were analysed. Temporal burden trends were analysed with the joinpoint model. The slope index and concentration index were used to evaluate health inequality. From 1990 to 2019, the global elderly CVD incidence, prevalence, death, and disability-adjusted life year rates generally decreased. However, the current burden remains high. The rapid growth in burden in parts of sub-Saharan Africa and Asia is a cause for concern. Countries with a higher socio-demographic index (SDI) have generally seen a greater decrease in burden, while countries with a lower SDI have generally experienced increases or smaller declines in burden. Health inequality analysis confirmed that the burden was gradually concentrating towards countries with a low SDI. Among the different CVDs, ischaemic heart disease causes the greatest burden in elderly individuals. Most CVD burdens increase with age, but stroke and peripheral vascular disease show markedly different distributional characteristics. In addition, the burden of hypertensive heart disease shows an unusual shift towards high-SDI countries. High systolic blood pressure was consistently the leading risk factor for CVD among elderly individuals. CONCLUSION: The burden of CVD in older people remains severe and generally tends to shift to lower-SDI countries. Policymakers need to take targeted measures to reduce its harm.

Nickel-Catalyzed Enantioselective Synthesis of Dienyl Sulfoxide.

Sulfoxides are widely used in the pharmaceutical industry and as ligands in asymmetric catalysis. However, the efficient asymmetric synthesis of this structural motif remains limited. In this study, we disclosed a Ni-catalyzed enantioconvergent reaction that utilizes both racemic allenyl carbonates and ß-sulfinyl esters. Our method employs cheap and more sustainable Ni(II) as a precatalyst and successfully overcomes the challenging poisoning effect and instability of sulfenate generated in situ. This enables the synthesis of a series of dienyl sulfoxides with enantioselectivity of up to 98 % ee. The product exhibits tremendous potential in various applications, including diastereoselective Diels-Alder reactions, coordination with transition metals, and incorporation into medicinal compounds, among others. Using a combination of experimental and computational methods, we have uncovered an interesting associated outersphere mechanism that contrasts with conventional mechanisms commonly observed in asymmetric transition metal catalysis.