Association Between Remnant Cholesterol and Nonalcoholic Fatty Liver Disease: A Systemic Review and Meta-Analysis.

Lipid disorders are related to the risk of nonalcoholic fatty liver disease (NAFLD). Remnant cholesterol (RC), a nonclassical and once-neglected risk factor for NAFLD, has recently received new attention. In this study, we assessed the relationship between the RC levels and NAFLD risk. We searched across PubMed, Web of Science, Embase, Cochrane Library, and China National Knowledge Infrastructure, with no restrictions on publication languages. Retrospective cohort studies and cross-sectional studies were enrolled from the inception of the databases until August 6, 2023. A random-effect model was applied to construct the mean difference, and a 95% confidence interval was applied to assess the relationship between the RC levels and NAFLD risk. We used two methods to estimate RC levels: Calculated-1 subtracts low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol from total cholesterol; Calculated-2 uses the Friedewald formula for LDL-C when triglycerides are <4.0 mmol/L, otherwise directly measured. A total of 265 published studies were selected through preliminary retrieval. Of these, six studies met the inclusion requirements and were enrolled in the meta-analysis. The RC level in the NAFLD group was significantly higher than that in the non-NAFLD group (mean difference: 0.18, 95% confidence interval: 0.10-0.26, P < 0.00001). We conducted subgroup analyses of computational methods and geographic regions. Notably, in the subgroup analysis of Calculation Method 2, the NAFLD group had significantly higher RC levels than the non-NAFLD group. On the other hand, in Calculation Method 1, the difference between the two groups was insignificant. In both the Asian and non-Asian populations, the RC levels were significantly higher in the NAFLD group than in the non-NAFLD group. The association of RC with an increased NAFLD risk was not dependent on the triglyceride. This meta-analysis suggests that elevated RC levels are associated with an increased risk of NAFLD. In addition to the conventional risk factors for fatty liver, clinicians should be concerned about the RC levels in the clinic.

GWAS combined with QTL mapping reveals the genetic loci of leaf morphological characters in Nicotiana tabacum.

BACKGROUND: Leaf morphology plays a crucial role in photosynthetic efficiency and yield potential in crops. Cigar tobacco plants, which are derived from common tobacco (Nicotiana tabacum L.), possess special leaf characteristics including thin and delicate leaves with few visible veins, making it a good system for studying the genetic basis of leaf morphological characters. RESULTS: In this study, GWAS and QTL mapping were simultaneously performed using a natural population containing 185 accessions collected worldwide and an F2 population consisting of 240 individuals, respectively. A total of 26 QTLs related to leaf morphological traits were mapped in the F2 population at three different developmental stages, and some QTL intervals were repeatedly detected for different traits and at different developmental stages. Among the 206 significant SNPs identified in the natural population using GWAS, several associated with the leaf thickness phenotype were co-mapped via QTL mapping. By analyzing linkage disequilibrium and transcriptome data from different tissues combined with gene functional annotations, 7 candidate genes from the co-mapped region were identified as the potential causative genes associated with leaf thickness. CONCLUSIONS: These results presented a valuable cigar tobacco resource showing the genetic diversity regarding its leaf morphological traits at different developmental stages. It also provides valuable information for novel genes and molecular markers that will be useful for further functional verification and for molecular breeding of leaf morphological traits in crops in the future.

Associations between metabolic dysfunction-associated fatty liver disease and atherosclerotic cardiovascular disease.

Non-alcoholic fatty liver disease (NAFLD) is closely related to metabolic syndrome and remains a major global health burden. The increased prevalence of obesity and type 2 diabetes mellitus (T2DM) worldwide has contributed to the rising incidence of NAFLD. It is widely believed that atherosclerotic cardiovascular disease (ASCVD) is associated with NAFLD. In the past decade, the clinical implications of NAFLD have gone beyond liver-related morbidity and mortality, with a majority of patient deaths attributed to malignancy, coronary heart disease (CHD), and other cardiovascular (CVD) complications. To better define fatty liver disease associated with metabolic disorders, experts proposed a new term in 2020 - metabolic dysfunction associated with fatty liver disease (MAFLD). Along with this new designation, updated diagnostic criteria were introduced, resulting in some differentiation between NAFLD and MAFLD patient populations, although there is overlap. The aim of this review is to explore the relationship between MAFLD and ASCVD based on the new definitions and diagnostic criteria, while briefly discussing potential mechanisms underlying cardiovascular disease in patients with MAFLD.

Impact of Social Capital on Health Behaviors of Middle-Aged and Older Adults in China-An Analysis Based on CHARLS2020 Data.

To actively respond to the challenges posed by population aging, people are paying more and more attention to healthy behavioral lifestyles, and the impact of social capital as an informal system on health behaviors cannot be ignored. This paper explores the impact of social capital on health behaviors of middle-aged and older adults based on 2020 CHARLS data. Using binary logistic regression models, we discussed the association between social capital and five health behaviors. The results suggest that structural social capital significantly increases physical activity and physical examination behaviors among middle-aged and older adults but also decreases the probability of abstinence behaviors. Cognitive social capital increases the probability that middle-aged and older adults will have a reasonable amount of sleep and physical activity. However, it also decreases the probability that smoking cessation behaviors will occur. Further attention needs to be paid to the role of social capital, the creation of a harmonious social environment and the enhancement of social trust, the strengthening of communities and grass-roots social organizations, and the provision of more platforms for the participation of middle-aged and older adults in social activities, to improve the quality of the healthy lives of middle-aged and older adults and, in turn, to promote the establishment of healthy behaviors.

LncRNA AFAP1-AS1 Promotes Oral Squamous Cell Carcinoma Development by Ubiquitin-Mediated Proteolysis.

BACKGROUND AND PURPOSE: Long noncoding RNA (lncRNA) dysregulation has been reported to play a pivotal role in the development of cancers. In this study, we aimed to screen the key lncRNA in oral squamous cell carcinoma (OSCC) via bioinformatics analysis and further validate the function of lncRNA in vitro and in vivo. METHODS: Bioinformatics analysis was conducted to identify differentially expressed lncRNAs between control and OSCC samples. Quantitative real-time-polymerase chain reaction was employed to detect the expression of differentially expressed lncRNAs in human tongue squamous cell carcinoma and human oral keratinocytes cell lines. The biological function of lncRNA and its mechanism were examined via the experimental assessment of the cell lines with the lncRNA overexpressed and silenced. Additionally, to further explore the function of lncRNA in the progression of OSCC, xenograft tumour mouse models were established using 25 mice (5 groups, each with 5 mice). Tumour formation was observed at 2 weeks after the cell injection, and the tumours were resected at 5 weeks post-implantation. RESULTS: Two lncRNAs, LINC00958 and AFAP1-AS1, were found to be correlated with the prognosis of OSCC. The results of the quantitative real-time-polymerase chain reaction indicated that the 2 lncRNAs were highly expressed in OSCC. In combination with the previous literature, we found AFAP1-AS1 to be a potentially important biomarker for OSCC. Thus, we further investigated its biological function and found that AFAP1-AS1 silencing inhibited cell proliferation, migration, and invasion whereas AFAP1-AS1 overexpression reversed the effect of AFAP1-AS1 silencing (P < .05). Mechanism analysis revealed that AFAP1-AS1 regulated the development of OSCC through the ubiquitin-mediated proteolysis pathway. CONCLUSIONS: AFAP1-AS1 is an oncogene that aggravates the development of OSCC via the ubiquitin-mediated proteolysis pathway. It also provides a novel potential therapy for OSCC.

A Radiological-Radiomics model for differentiation between minimally invasive adenocarcinoma and invasive adenocarcinoma less than or equal to 3 cm: A two-center retrospective study.

OBJECTIVE: To develop a Radiological-Radiomics (R-R) combined model for differentiation between minimal invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IA) of lung adenocarcinoma (LUAD) and evaluate its predictive performance. METHODS: The clinical, pathological, and imaging data of a total of 509 patients (522 lesions) with LUAD diagnosed by surgical pathology from 2 medical centres were retrospectively collected, with 392 patients (402 lesions) from center 1 trained and validated using a five-fold cross-validation method, and 117 patients (120 lesions) from center 2 serving as an independent external test set. The least absolute shrinkage and selection operator (LASSO) method was utilized to filter features. Logistic regression was used to construct three models for predicting IA, namely, Radiological model, Radiomics model, and R-R model. Also, receiver operating curve curves (ROCs) were plotted, generating corresponding area under the curve (AUC), sensitivity, specificity, and accuracy. RESULTS: The R-R model for IA prediction achieved an AUC of 0.918 (95 % CI: 0.889-0.947), a sensitivity of 80.3 %, a specificity of 88.2 %, and an accuracy of 82.1 % in the training set. In the validation set, this model exhibited an AUC of 0.906 (95 % CI: 0.842-0.970), a sensitivity of 79.9 %, a specificity of 88.1 %, and an accuracy of 81.8 %. In the external test set, the AUC was 0.894 (95 % CI: 0.824-0.964), a sensitivity of 84.8 %, a specificity of 78.6 %, and an accuracy of 83.3 %. CONCLUSION: The R-R model showed excellent diagnostic performance in differentiating MIA and IA, which can provide a certain reference for clinical diagnosis and surgical treatment plans.

Investigating the impact of empagliflozin on the retina of diabetic mice.

BACKGROUND: Diabetic retinopathy (DR) frequently results in compromised visual function, with hyperglycemia-induced disruption of the blood-retinal barrier (BRB) through various pathways as a critical mechanism. Existing DR treatments fail to address early and potentially reversible microvascular alterations. This study examined the effects of empagliflozin (EMPA), a selective Sodium-glucose transporter 2 (SGLT2) inhibitor, on the retina of db/db mice. The objective of this study is to investigate the potential role of EMPA in the prevention and delay of DR. METHODS: db/db mice were randomly assigned to either the EMPA treatment group (db/db + Emp) or the model group (db/db), while C57 mice served as the normal control group (C57). Mice in the db/db + Emp group received EMPA for eight weeks. Body weight, fasting blood glucose (FBG), and blood VEGF were subsequently measured in all mice, along with the detection of specific inflammatory factors and BRB proteins in the retina. Retinal SGLT2 protein expression was compared using immunohistochemical analysis, and BRB structural changes were observed via electron microscopy. RESULTS: EMPA reduced FBG, blood VEGF, and retinal inflammatory factors TNF-α, IL-6, and VEGF levels in the eye tissues of db/db mice. EMPA also increased Claudin-1, Occludin-1, and ZO-1 levels while decreasing ICAM-1 and Fibronectin, thereby preserving BRB function in db/db mice. Immunohistochemistry revealed that EMPA reduced SGLT2 expression in the retina of diabetic mice, and electron microscopy demonstrated that EMPA diminished tight junction damage between retinal vascular endothelial cells and prevented retinal vascular basement membrane thickening in diabetic mice. CONCLUSION: EMPA mitigates inflammation and preserves BRB structure and function, suggesting that it may prevent DR or serve as an effective early treatment for DR.

Chloroflexus aurantiacus acetyl-CoA carboxylase evolves fused biotin carboxylase and biotin carboxyl carrier protein to complete carboxylation activity.

Acetyl-CoA carboxylases (ACCs) convert acetyl-CoA to malonyl-CoA, a key step in fatty acid biosynthesis and autotrophic carbon fixation pathways. Three functionally distinct components, biotin carboxylase (BC), biotin carboxyl carrier protein (BCCP), and carboxyltransferase (CT), are either separated or partially fused in different combinations, forming heteromeric ACCs. However, an ACC with fused BC-BCCP and separate CT has not been identified, leaving its catalytic mechanism unclear. Here, we identify two BC isoforms (BC1 and BC2) from Chloroflexus aurantiacus, a filamentous anoxygenic phototroph that employs 3-hydroxypropionate (3-HP) bi-cycle rather than Calvin cycle for autotrophic carbon fixation. We reveal that BC1 possesses fused BC and BCCP domains, where BCCP could be biotinylated by E. coli or C. aurantiacus BirA on Lys553 residue. Crystal structures of BC1 and BC2 at 3.2 Å and 3.0 Å resolutions, respectively, further reveal a tetramer of two BC1-BC homodimers, and a BC2 homodimer, all exhibiting similar BC architectures. The two BC1-BC homodimers are connected by an eight-stranded ß-barrel of the partially resolved BCCP domain. Disruption of ß-barrel results in dissociation of the tetramer into dimers in solution and decreased biotin carboxylase activity. Biotinylation of the BCCP domain further promotes BC1 and CTß-CTα interactions to form an enzymatically active ACC, which converts acetyl-CoA to malonyl-CoA in vitro and produces 3-HP via co-expression with a recombinant malonyl-CoA reductase in E. coli cells. This study revealed a heteromeric ACC that evolves fused BC-BCCP but separate CTα and CTß to complete ACC activity.IMPORTANCEAcetyl-CoA carboxylase (ACC) catalyzes the rate-limiting step in fatty acid biosynthesis and autotrophic carbon fixation pathways across a wide range of organisms, making them attractive targets for drug discovery against various infections and diseases. Although structural studies on homomeric ACCs, which consist of a single protein with three subunits, have revealed the "swing domain model" where the biotin carboxyl carrier protein (BCCP) domain translocates between biotin carboxylase (BC) and carboxyltransferase (CT) active sites to facilitate the reaction, our understanding of the subunit composition and catalytic mechanism in heteromeric ACCs remains limited. Here, we identify a novel ACC from an ancient anoxygenic photosynthetic bacterium Chloroflexus aurantiacus, it evolves fused BC and BCCP domain, but separate CT components to form an enzymatically active ACC, which converts acetyl-CoA to malonyl-CoA in vitro and produces 3-hydroxypropionate (3-HP) via co-expression with recombinant malonyl-CoA reductase in E. coli cells. These findings expand the diversity and molecular evolution of heteromeric ACCs and provide a structural basis for potential applications in 3-HP biosynthesis.

Association of LDL-C/HDL-C ratio with coronary heart disease: A meta-analysis.

BACKGROUND: Coronary heart disease (CHD) is a common heart disease and a leading cause of death in developed countries and some developing countries such as China. It is recognized as a multifactorial disease, with dyslipidemia being closely associated with the progression of coronary atherosclerosis. Numerous studies have confirmed the relationship between a single indicator of low-density lipoprotein cholesterol (LDL-C) or high-density lipoprotein cholesterol (HDL-C) and CHD. However, the association between LDL-C to HDL-C ratio (LHR) and CHD remains unclear. This study aimed to comprehensively explore the association between LHR and CHD. METHODS: This meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses. PubMed, Embase, Web of Science, and China National Knowledge Infrastructure databases were comprehensively searched up to June 15, 2023, to find the studies that indicated the connection between LHR and CHD. A total of 12 published studies were selected. The random-effects model was used to pool the data and mean difference (MD), and the 95% confidence intervals (CI) were taken as the overall outcome. No language restrictions existed in the study selection. The Review Manager 5.4 and Stata 12 were used to analyze the data. RESULTS: Twelve high-quality clinical studies involving 5544 participants, including 3009 patients with CHD, were enrolled in the meta-analysis. The findings revealed that the LHR was higher by 0.65 in patients with CHD than in those without CHD (MD, 0.65; 95% CI, 0.50-0.80). CONCLUSION: The LHR was found to be positively correlated with CHD, suggesting that it may serve as a potential indicator of CHD.

Progress in the treatment of diabetic cardiomyopathy, a systematic review.

Diabetic cardiomyopathy (DCM) is a condition characterized by myocardial dysfunction that occurs in individuals with diabetes, in the absence of coronary artery disease, valve disease, and other conventional cardiovascular risk factors such as hypertension and dyslipidemia. It is considered a significant and consequential complication of diabetes in the field of cardiovascular medicine. The primary pathological manifestations include myocardial hypertrophy, myocardial fibrosis, and impaired ventricular function, which can lead to widespread myocardial necrosis. Ultimately, this can progress to the development of heart failure, arrhythmias, and cardiogenic shock, with severe cases even resulting in sudden cardiac death. Despite several decades of both fundamental and clinical research conducted globally, there are currently no specific targeted therapies available for DCM in clinical practice, and the incidence and mortality rates of heart failure remain persistently high. Thus, this article provides an overview of the current treatment modalities and novel techniques pertaining to DCM, aiming to offer valuable insights and support to researchers dedicated to investigating this complex condition.

Efficacy and safety of outpatient parenteral antibiotic therapy in patients with infective endocarditis: a meta-analysis / Eficacia y seguridad del tratamiento antibiótico domiciliario endovenoso en pacientes con endocarditis infecciosa: un metaanálisis

Background. To investigate the clinical outcome of patients with infective endocarditis (IE) during and after outpatient parenteral antimicrobial treatment (OPAT), and to furtherclarify the safety and efficacy of OPAT for IE patients.Methods. Through December 20, 2021, a total of 331 articles were preliminarily searched in Pubmed, Web of Science,Cochrane Library and Embase, and 9 articles were eventuallyincluded in this study.Results. A total of 9 articles comprising 1,116 patientswere included in this study. The overall mortality rate of patients treated with OPAT was 0.04 (95% CI, 0.02-0.07), thatmeans 4 deaths per 100 patients treated with OPAT. Separately, mortality was low during the follow-up period after OPATtreatment, with an effect size (ES) of 0.03 (95%CI, 0.02-0.07)and the mortality of patients during OPAT treatment was 0.04(95% CI, 0.01-0.12). In addition, the readmission rate wasfound to be 0.14 (95% CI, 0.09-0.22) during the follow-upand 0.18 (95% CI, 0.08-0.39) during treatment, and 0.16 (95%CI, 0.10-0.24) for patients treated with OPAT in general. Regarding the relapse of IE in patients, our results showed a lowoverall relapse rate, with an ES of 0.03 (95% CI, 0.01-0.05). Inaddition, we found that the incidence of adverse events waslow, with an ES of 0.26 (95% CI, 0.19-0.33). (AU)

Introducción. Investigar el resultado clínico de los pacientes con endocarditis infecciosa (EI) durante y después deltratamiento antibiótico domiciliario endovenoso (TADE), y determinar la seguridad y eficacia del TADE para los pacientescon EI.Métodos. Hasta el 20 de diciembre de 2021, se realizaronbúsquedas preliminares en un total de 331 artículos en Pubmed, Web of Science, Cochrane Library y Embase, y finalmente se incluyeron 9 artículos en este estudio.Resultados. Se incluyeron un total de 9 artículos con1.116 pacientes. La tasa de mortalidad global de los pacientestratados con TADE fue de 0,04 (IC95%: 0,02-0,07), lo que significa 4 muertes por cada 100 pacientes tratados con TADE.Por separado, la mortalidad fue baja durante el período deseguimiento después del tratamiento con TADE, con un tamaño del efecto (TE) de 0,03 (IC95%: 0,02-0,07) y la mortalidadde los pacientes durante el tratamiento con TADE fue de 0,04(IC95%: 0,01-0,12). Además, se encontró que la tasa de readmisión fue de 0,14 (IC95%: 0,09-0,22) durante el seguimiento y de 0,18 (IC95%: 0,08-0,39) durante el tratamiento, y de 0,16 (IC95%: 0,10-0,24) para los pacientes tratados con TADEde forma global. En cuanto a la recaída de la EI en pacientes,nuestros resultados mostraron una baja tasa global de recaída, con un TE de 0,03 (IC95%: 0,01-0,05). Además, se encontróque la incidencia de eventos adversos fue baja, con una TE de0,26 (IC95%: 0,19-0,33). (AU)

Effect of probiotics on lipid profiles in hypercholesterolaemic adults: A meta-analysis of randomized controlled trials / Efecto de los probióticos en los perfiles lipídicos en adultos con hipercolesterolemia: metaanálisis de ensayos clinicos aleatorizados

Background: Recent clinical studies have yielded controversial results regarding the effect of probiotics on lipid profiles. To assess the efficacy of probiotics in lowering serum lipid concentrations, we conducted a meta-analysis of randomized controlled trials (RCTs). Methods: Literature from the PubMed, Embase and Cochrane databases were searched and screened. The effects of probiotics on lipid profiles were assessed by mean difference (MD) and 95% confidence interval (CI). All included studies were analyzed using Review Manager 5.3 (Cochrane Collaboration, 2014). Results: A total of 19 RCTs, including 967 participants, met the inclusion criteria. Probiotic interventions reduced total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) compared to controls (placebo or no treatment) by −0.25mmol/L (95% CI: −0.39, −0.12) and −0.17mmol/L (95% CI: −0.25, −0.09), respectively. No significant effects of probiotics on triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) levels were found. The effects of probiotics on decreasing TC and LDL-C levels were greater for longer intervention times, certain probiotic strains, and in younger mildly hypercholesterolaemic subjects. Conclusion: This meta-analysis revealed that the use of probiotics can significantly lower TC and LDL-C levels in hypercholesterolaemic adults, which brings hope for reducing the risk factors for developing cardiovascular disease

Antecedentes: Los resultados obtenidos por estudios clínicos recientes sobre el efecto de los probióticos en los perfiles lipídicos han generado cierta controversia. Para evaluar la eficacia de los probióticos en la reducción de las concentraciones séricas de lípidos, se realizó un metaanálisis de estudios comparativos aleatorizados (ECA). Métodos: Se realizó una búsqueda y posterior cribado bibliográfico en las bases de datos PubMed, Embase y Cochrane. Se evaluaron los efectos de los probióticos en los perfiles de lípidos mediante la diferencia de medias (DM) y el intervalo de confianza (IC) del 95%. Todos los estudios incluidos se analizaron con Review Manager 5.3 (Cochrane Collaboration, 2014). Resultados: Cumplieron con los criterios de inclusión un total de 19 ECA, que incluyeron 967 participantes. Las intervenciones probióticas redujeron el colesterol total (CT) y el colesterol de lipoproteínas de baja densidad (c-LDL) en −0,25mmol/l (IC 95%: −0,39, −0,12) y −0,17mmol/l (IC 95%: −0,25, −0,09), respectivamente, en comparación con los controles (placebo o ningún tratamiento). No se observaron efectos significativos de los probióticos en los niveles de triglicéridos (TG) y en el colesterol de lipoproteínas de alta densidad (c-HDL). Los efectos de los probióticos en la disminución de los niveles de CT y c-LDL fueron mayores en los casos donde la intervención duró más tiempo, en ciertas cepas probióticas y en sujetos más jóvenes con hipercolesterolemia leve. Conclusión: Este metaanálisis reveló que el uso de probióticos puede reducir significativamente los niveles de CT y c-LDL en adultos hipercolesterolémicos, lo que brinda la esperanza de reducir los factores de riesgo relativos al desarrollo de enfermedad cardiovascular