Suppression of Enhancer Overactivation by a RACK7-Histone Demethylase Complex.

Regulation of enhancer activity is important for controlling gene expression programs. Here, we report that a biochemical complex containing a potential chromatin reader, RACK7, and the histone lysine 4 tri-methyl (H3K4me3)-specific demethylase KDM5C occupies many active enhancers, including almost all super-enhancers. Loss of RACK7 or KDM5C results in overactivation of enhancers, characterized by the deposition of H3K4me3 and H3K27Ac, together with increased transcription of eRNAs and nearby genes. Furthermore, loss of RACK7 or KDM5C leads to de-repression of S100A oncogenes and various cancer-related phenotypes. Our findings reveal a RACK7/KDM5C-regulated, dynamic interchange between histone H3K4me1 and H3K4me3 at active enhancers, representing an additional layer of regulation of enhancer activity. We propose that RACK7/KDM5C functions as an enhancer "brake" to ensure appropriate enhancer activity, which, when compromised, could contribute to tumorigenesis.

Dynamic control of chromatin-associated m6A methylation regulates nascent RNA synthesis.

N6-methyladenosine (m6A) methylation is co-transcriptionally deposited on mRNA, but a possible role of m6A on transcription remains poorly understood. Here, we demonstrate that the METTL3/METTL14/WTAP m6A methyltransferase complex (MTC) is localized to many promoters and enhancers and deposits the m6A modification on nascent transcripts, including pre-mRNAs, promoter upstream transcripts (PROMPTs), and enhancer RNAs. PRO-seq analyses demonstrate that nascent RNAs originating from both promoters and enhancers are significantly decreased in the METTL3-depleted cells. Furthermore, genes targeted by the Integrator complex for premature termination are depleted of METTL3, suggesting a potential antagonistic relationship between METTL3 and Integrator. Consistently, we found the Integrator complex component INTS11 elevated at promoters and enhancers upon loss of MTC or nuclear m6A binders. Taken together, our findings suggest that MTC-mediated m6A modification protects nascent RNAs from Integrator-mediated termination and promotes productive transcription, thus unraveling an unexpected layer of gene regulation imposed by RNA m6A modification.

Loss of 5-hydroxymethylcytosine is an epigenetic hallmark of melanoma.

DNA methylation at the 5 position of cytosine (5-mC) is a key epigenetic mark that is critical for various biological and pathological processes. 5-mC can be converted to 5-hydroxymethylcytosine (5-hmC) by the ten-eleven translocation (TET) family of DNA hydroxylases. Here, we report that "loss of 5-hmC" is an epigenetic hallmark of melanoma, with diagnostic and prognostic implications. Genome-wide mapping of 5-hmC reveals loss of the 5-hmC landscape in the melanoma epigenome. We show that downregulation of isocitrate dehydrogenase 2 (IDH2) and TET family enzymes is likely one of the mechanisms underlying 5-hmC loss in melanoma. Rebuilding the 5-hmC landscape in melanoma cells by reintroducing active TET2 or IDH2 suppresses melanoma growth and increases tumor-free survival in animal models. Thus, our study reveals a critical function of 5-hmC in melanoma development and directly links the IDH and TET activity-dependent epigenetic pathway to 5-hmC-mediated suppression of melanoma progression, suggesting a new strategy for epigenetic cancer therapy.

METTL3 regulates heterochromatin in mouse embryonic stem cells.

METTL3 (methyltransferase-like 3) mediates the N6-methyladenosine (m6A) methylation of mRNA, which affects the stability of mRNA and its translation into protein1. METTL3 also binds chromatin2-4, but the role of METTL3 and m6A methylation in chromatin is not fully understood. Here we show that METTL3 regulates mouse embryonic stem-cell heterochromatin, the integrity of which is critical for silencing retroviral elements and for mammalian development5. METTL3 predominantly localizes to the intracisternal A particle (IAP)-type family of endogenous retroviruses. Knockout of Mettl3 impairs the deposition of multiple heterochromatin marks onto METTL3-targeted IAPs, and upregulates IAP transcription, suggesting that METTL3 is important for the integrity of IAP heterochromatin. We provide further evidence that RNA transcripts derived from METTL3-bound IAPs are associated with chromatin and are m6A-methylated. These m6A-marked transcripts are bound by the m6A reader YTHDC1, which interacts with METTL3 and in turn promotes the association of METTL3 with chromatin. METTL3 also interacts physically with the histone 3 lysine 9 (H3K9) tri-methyltransferase SETDB1 and its cofactor TRIM28, and is important for their localization to IAPs. Our findings demonstrate that METTL3-catalysed m6A modification of RNA is important for the integrity of IAP heterochromatin in mouse embryonic stem cells, revealing a mechanism of heterochromatin regulation in mammals.

RuPHOX-Ru Catalyzed Asymmetric Cascade Hydrogenation of 3-Substituted Chromones for the Synthesis of Corresponding Chiral Chromanols.

An efficient RuPHOX-Ru catalyzed asymmetric cascade hydrogenation of 3-substituted chromones has been achieved under mild reaction conditions, affording the corresponding chiral 3-substituted chromanols in high yields with excellent enantio- and diastereoselectivities (up to 99 % yield, >99 % ee and >20 : 1 dr). Control reactions and deuterium labelling experiments revealed that a dynamic kinetic resolution process occurs during the subsequent hydrogenation of the C=O double bond, which is responsible for the high performance of the asymmetric cascade hydrogenation. The resulting products allow for several transformations and it was shown that the protocol provides a practical and alternative strategy for the synthesis of chiral 3-substituted chromanols and their derivatives.

Association of air pollution and risk of chronic kidney disease: A systematic review and meta-analysis.

Although epidemiological studies have evaluated the association between ambient air pollution and chronic kidney disease (CKD), the results remain mixed. To clarify the nature of the association, we conducted a comprehensive systematic review and meta-analysis to assess the global relationship between air pollution and CKD. The Web of Science, PubMed, Embase and Cochrane Library databases systematically were searched for studies published up to July 2023 and included 32 studies that met specific criteria. The random effects model was used to derive overall risk estimates for each pollutant. The meta-analysis estimated odds ratio (ORs) of risk for CKD were 1.42 (95% confidence interval [CI]: 1.31-1.54) for each 10 µg/m3 increase in PM2.5 ; 1.20 (95% CI: 1.14-1.26) for each 10 µg/m3 increase in PM10 ; 1.07 (95% CI: 1.05-1.09) for each 10 µg/m3 increase in NO2 ; 1.03 (95% CI: 1.02-1.03) for each 10 µg/m3 increase in NOX ; 1.07 (95% CI: 1.01-1.12) for each 1 ppb increase in SO2 ; 1.03 (95% CI: 1.00-1.05) for each 0.1 ppm increase in CO. Subgroup analysis showed that this effect varied by gender ratio, age, study design, exposure assessment method, and income level. Furthermore, PM2.5 , PM10 , and NO2 had negative effects on CKD even within the World Health Organization-recommended acceptable concentrations. Our results further confirmed the adverse effect of air pollution on the risk of CKD. These findings can contribute to enhance the awareness of the importance of reducing air pollution among public health officials and policymakers.

Changes in Life's Essential 8 and risk of cardiovascular disease in Chinese people.

BACKGROUND: The American Heart Association recently released an updated algorithm for evaluating cardiovascular health-Life's Essential 8 (LE8). However, the associations between changes in LE8 score over time and risk of cardiovascular disease (CVD) remain unclear. METHODS: We investigated associations between 6-year changes (2006-12) in LE8 score and risk of subsequent CVD events (2012-20) among 53 363 Chinese men and women from the Kailuan Study, who were free from CVD in 2012. The LE8 score was calculated based on eight components: diet quality, physical activity, smoking status, sleep health, body mass index, blood lipids, blood glucose and blood pressure. Multivariable-adjusted Cox proportional-hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: We documented 4281 incident CVD cases during a median of 7.7 years of follow-up. Compared with participants whose LE8 scores remained stable in a 6-year period, those with the large increases of LE8 score over the 6-year period had a lower risk of CVD, heart disease and stroke in the subsequent 8 years [HRs and 95% CIs: 0.67 (0.64, 0.70) for CVD, 0.65 (0.61, 0.69) for heart disease, 0.71 (0.67, 0.76) for stroke, all Ptrend < 0.001]. Conversely, those with the large decreases of LE8 score had 47%, 51% and 41% higher risk for CVD, heart disease and stroke, respectively. These associations were consistent across the subgroups stratified by risk factors. CONCLUSIONS: Improving LE8 score in a short- and moderate-term was associated with a lower CVD risk, whereas decreased LE8 score over time was associated with a higher risk.

3,5,6-Trichloro-2-pyridinol confirms ototoxicity in mouse cochlear organotypic cultures and induces cytotoxicity in HEI-OC1 cells.

The metabolite of organophosphate pesticide chlorpyrifos (CPF), 3,5,6-Trichloro-2-pyridinol (TCP), is persistent and mobile toxic substance in soil and water environments, exhibiting cytotoxic, genotoxic, and neurotoxic properties. However, little is known about its effects on the peripheral auditory system. Herein, we investigated the effects of TCP exposure on mouse postnatal day 3 (P3) cochlear culture and an auditory cell line HEI-OC1 to elucidate the underlying molecular mechanisms of ototoxicity. The damage of TCP to outer hair cells (OHC) and support cells (SC) was observed in a dose and time-dependent manner. OHC and SC were a significant loss from basal to apical turn of the cochlea under exposure over 800 µM TCP for 96 h. As TCP concentrations increased, cell viability was reduced whereas reactive oxygen species (ROS) generation, apoptotic cells, and the extent of DNA damage were increased, accordingly. TCP-induced phosphorylation of the p38 and JNK MAPK are the downstream effectors of ROS. The antioxidant agent, N-acetylcysteine (NAC), could reverse TCP-mediated intracellular ROS generation, inhibit the expressive level of cleaved-caspase 3 and block phosphorylation of p38/JNK. Overall, this is the first demonstration of TCP damaging to peripheral sensory HCs and SC in organotypic cultures from the postnatal cochlea. Data also showed that TCP exposure induced oxidase stress, cell apoptosis and DNA damage in the HEI-OC1 cells. These findings serve as an important reference for assessing the risk of TCP exposure.

A Nationwide Survey on Detection of Chlamydia trachomatis in Health Facilities in China.

BACKGROUND: This study evaluated the clinical laboratory capacity for the diagnosis of Chlamydia trachomatis (CT) in China to provide recommendations to improve the diagnostic capacity and quality of this clinically important sexually transmitted disease. METHODS: An electronic questionnaire-based cross-sectional, survey study was conducted by the National Center for STD Control among different types of healthcare facilities in China from July to December 2021. RESULTS: The surveyed laboratory facilities were located in 332 cities in 31 provinces in China. A total of 4640 records from clinical laboratories were included in the data set for the final analysis. Less than half of the laboratories (41.6% [1931 of 4640]) performed the CT diagnostic test; of these, 721 laboratories (15.5% [721 of 4640]) carried out nucleic acid amplification test (NAAT) methods, and 1318 laboratories (28.4% [1318 of 4640]) performed antigen-based immunochromatographic assays. Most laboratories were equipped with biological safety cabinets (93.7% [4348 of 4640]), 49.2% (2283 of 4640) were equipped with fully automated nucleic acid extractors, and 55.2% (2560 of 4640) were equipped with polymerase chain reaction amplification instruments. The laboratories from Southern China or third-class hospitals (i.e., the highest rated hospitals) had the highest proportion using NAATs to diagnose CT among the surveyed health facilities. CONCLUSIONS: Advancing laboratories to use NAAT to detect CT should be phased step-by-step by different areas and levels of hospitals according to the current situation.

Sef1, rapid-cycling Brassica napus for large-scale functional genome research in a controlled environment.

KEY MESSAGE: We demonstrated a short-cycle B. napus line, Sef1, with a highly efficient and fast transformation system, which has great potential in large-scale functional gene analysis in a controlled environment. Rapeseed (Brassica napus L.) is an essential oil crop that accounts for a considerable share of global vegetable oil production. Nonetheless, studies on functional genes of B. napus are lagging behind due to the complicated genome and long growth cycle, this is largely due to the limited availability of gene analysis and modern genome editing-based molecular breeding. In this study, we demonstrated a short-cycle semi-winter-type Brassica napus 'Sef1' with very early-flowering and dwarf phenotype, which has great potential in large-scale indoor planting. Through the construction of an F2 population of Sef1 and Zhongshuang11, bulked segregant analysis (BSA) combined with the rape Bnapus50K SNP chip assay method was used to identify the early-flowering genes in Sef1, and a mutation in BnaFT.A02 was identified as a major locus significantly affecting the flowering time in Sef1. To further investigate the mechanism of early flowering in Sef1 and discover its potential in gene function analysis, an efficient Agrobacterium-mediated transformation system was established. The average transformation efficiency with explants of hypocotyls and cotyledons was 20.37% and 12.8%, respectively, and the entire transformation process took approximately 3 months from explant preparation to seed harvest of transformed plants. This study demonstrates the great potential of Sef1 for large-scale functional gene analysis.

Comparative genomics predict specific genes in potential mucorales identification.

Mucoralean fungi could cause mucormycosis in humans, particularly in immunodeficient individuals and those with diabetes mellitus or trauma. With plenty of species and genera, their molecular identification and pathogenicity have a large deviation. Reported cases of mucormycosis showed frequent occurrence in Rhizopus species, Mucor species, and Lichtheimia species. We analyzed the whole genome sequences of 25 species of the top 10 Mucorales genera, along with another 22 important pathogenic non-Mucorales species, to dig the target genes for monitoring Mucorales species and identify potential genomic imprints of virulence in them. Mucorales-specific genes have been found in various orthogroups extracted by Python script, while genus-specific genes were annotated covering cellular structure, biochemistry metabolism, molecular processing, and signal transduction. Proteins related to the virulence of Mucorales species varied with distinct significance in copy numbers, in which Orthofinder was conducted. Based on our fresh retrospective analysis of mucormycosis, a comparative genomic analysis of pathogenic Mucorales was conducted in more frequent pathogens. Specific orthologs between Mucorales and non-Mucoralean pathogenic fungi were discussed in detail. Referring to the previously reported virulence proteins, we included more frequent pathogenic Mucorales and compared them in Mucorales species and non-Mucorales species. Besides, more samples are needed to further verify the potential target genes.

Association of the time course of Chinese visceral adiposity index accumulation with cardiovascular events in patients with hypertension.

BACKGROUND: The Chinese visceral adiposity index (CVAI), a simple surrogate measure of visceral fat, is significantly associated with cardiovascular disease (CVD) risk in the general population. This study aimed to evaluate the association of cumulative CVAI (cumCVAI) exposure and its accumulation time course with CVD risk among patients with hypertension. METHODS: This prospective study involved 15,350 patients with hypertension from the Kailuan Study who were evaluated at least three times in the observation period of 2006 to 2014 (2006-2007, 2010-2011, and 2014-2015) and who were free of myocardial infarction and stroke before 2014. The cumCVAI was calculated as the weighted sum of the mean CVAI for each time interval (value × time). The time course of CVAI accumulation was categorized by splitting the overall accumulation into early (cumCVAI06 - 10) and late (cumCVAI10 - 14) accumulation, or the slope of CVAI versus time from 2006 to 2014 into positive and negative. RESULTS: During the 6.59-year follow-up period, 1,184 new-onset CVD events were recorded. After adjusting for confounding variables, the hazard ratios (HRs) and 95% confidence intervals (CIs) for CVD were 1.35 (1.13-1.61) in the highest quartile of cumCVAI, 1.35 (1.14-1.61) in the highest quartile of the time-weighted average CVAI, 1.26 (1.12-1.43) in those with a cumulative burden > 0, and 1.43 (1.14-1.78) for the group with a 10-year exposure duration. When considering the time course of CVAI accumulation, the HR (95% CI) for CVD was 1.33 (1.11-1.59) for early cumCVAI. When considering the combined effect of cumCVAI accumulation and its time course, the HR (95% CI) for CVD was 1.22 (1.03-1.46) for cumCVAI ≥ median with a positive slope. CONCLUSIONS: In this study, incident CVD risk depended on both long-term high cumCVAI exposure and the duration of high CVAI exposure among patients with hypertension. Early CVAI accumulation resulted in a greater risk increase than later CVAI accumulation, emphasizing the importance of optimal CVAI control in early life.

Relationship between early-onset stroke and triglyceride-glucose index among young Chinese adults.

BACKGROUND: The triglyceride-glucose index (TyG index), an alternative indicator of peripheral insulin resistance (IR), is associated with cardiovascular disease (CVD) in the general population. The aim of this research was to determine the correlation between early-onset stroke and the TyG index among young Chinese adults. METHODS: Participants (age ≤ 40 years) who attended their first physical examination in Kailuan General Hospital or its 11 subsidiary hospitals between 2006 and 2012 were enrolled. The subjects were divided into four equal points according to the quartile of the TyG index, with the lowest quartile (Q1) as the reference group. A Cox proportional hazard model was employed to assess the correlation between early-onset stroke incidence and the TyG index. Restricted cubic spline analysis was further conducted to examine nonlinear associations. The TyG index was calculated as Ln [Triglyceride (TG, mg/dL) × Fasting Blood Glucose (FBG, mg/dL)/2]. RESULTS: Overall, 35,999 subjects met the inclusion criteria. Their mean age was 30.8 ±  5.7 years, and 77.1% of subjects were males. During a median observation period of 11 years, 281 stroke events occurred (62 hemorrhagic strokes and 219 ischemic strokes). Compared to the Q1 group (as the lowest group), subjects in groups Q2-Q4 had significantly higher risks of early-onset stroke (P < 0.05) after adjustment for relevant confounders in the Cox proportional hazards model. Similar results were consistent with ischemic stroke. However, no significant associations were observed between the risk of hemorrhage and the baseline TyG index. The restricted cubic splines revealed that the risk of stroke progressively increased with a high TyG index ≥ 8.41. CONCLUSIONS: The TyG index may be a major risk factor for early-onset stroke among young Chinese adults. A TyG index ≥ 8.41 can be used as an indicator for screening high-risk stroke groups.

U-shaped association between sleep duration and subjective cognitive complaints in Chinese elderly: a cross-sectional study.

BACKGROUND: Subjective cognitive decline (SCD) may be the early screening signal to distinguish susceptible population with Alzheimer's disease (AD) and mild cognitive impairment (MCI). Subjective cognitive complaints (SCCs) have been proved strongly associated with SCD. This study aimed to explore the association between sleep duration and SCCs in the Chinese elderly. METHODS: We conducted a cross-sectional study involving 688 participants aged 60 years and older in Guangdong Province, China. SCCs were assessed by the Subjective Cognitive Decline questionnaire 9 (SCD-Q9), which contained 9 items with two dimensions, including the overall memory function and time comparison (OMTC) and daily activity ability (DAA). Restricted cubic splines and generalized additive model (GAM) were used to fit the association between sleep duration and SCD-Q9 score. RESULTS: There were significant U-shaped associations between sleep duration and overall score of SCD-Q9 (EDF = 3.842, P < 0.001), as well as the OMTC dimension (EDF = 4.471, P < 0.001) in the age- and gender-adjusted GAM. The lowest points on the overall score of SCD-Q9 and OMTC score were observed in those sleeping 8 h per night. After further adjusting for other demographic characteristics, lifestyle behaviors, hypertension and diabetes, the U-shaped associations between sleep duration and the overall score of SCD-Q9 (EDF = 3.575, P = 0.004), sleep duration and the OMTC score (EDF = 4.478, P = 0.010) were still found. The daily activity ability (DAA) score was also non-linear associated with sleep duration both in the age- and gender-adjusted GAM (EDF = 2.314, P < 0.001) and further adjusted GAM (EDF = 2.080, P = 0.010). CONCLUSIONS: Both longer sleep duration (> 8 h) and shorter duration (< 8 h) were linked to worse SCCs. Future studies should explore the protective effect of managing sleep duration on SCD and its progression to dementia.

BS69/ZMYND11 reads and connects histone H3.3 lysine 36 trimethylation-decorated chromatin to regulated pre-mRNA processing.

BS69 (also called ZMYND11) contains tandemly arranged PHD, BROMO, and PWWP domains, which are chromatin recognition modalities. Here, we show that BS69 selectively recognizes histone variant H3.3 lysine 36 trimethylation (H3.3K36me3) via its chromatin-binding domains. We further identify BS69 association with RNA splicing regulators, including the U5 snRNP components of the spliceosome, such as EFTUD2. Remarkably, RNA sequencing shows that BS69 mainly regulates intron retention (IR), which is the least understood RNA alternative splicing event in mammalian cells. Biochemical and genetic experiments demonstrate that BS69 promotes IR by antagonizing EFTUD2 through physical interactions. We further show that regulation of IR by BS69 also depends on its binding to H3K36me3-decorated chromatin. Taken together, our study identifies an H3.3K36me3-specific reader and a regulator of IR and reveals that BS69 connects histone H3.3K36me3 to regulated RNA splicing, providing significant, important insights into chromatin regulation of pre-mRNA processing.

Characterization of mitogenomes from four Mucorales species and insights into pathogenicity.

BACKGROUND: Mucorales, as one major order of Zygomycetes fungi, can infect human beings and cause serious consequence. We have noticed the pathogenicity of Mucorales is closely related to energy metabolism, while mitochondria play the role of energy factories in almost all biological activities. METHODS: Virulence of M irregularis, M hiemalis, L corymbifera and R arrhizus were verified in Galleria mellonella larvae, as well as mitochondrial gene copies analysed with RT-qPCR. Mitogenomes of the four Mucorales species were sequenced based on illumina NovaSeq technology to study their characteristic features and functional regions. RESULTS: Variant virulence of M irregularis, M hiemalis, L corymbifera and R arrhizu were verified by clinical retrospective data and our G mellonella infection models, also copies of mitochondrial genes indicated the significant associations with pathogenicity. A total of 274.18 clean reads were generated to be assembled; the complete mitogenomes of the four Mucorales species were obtained with totally different length. After the genomes annotated and compared, M irregularis was found more similar with M hiemalis than those of L corymbifera and R arrhizus, especially the small (rrns) and large (rrnl) subunits of mitochondrial ribosomal RNA (rRNA) genes. The GC content, ncRNAs and the distribution of the SNPs and InDels were also compared, and the GC content rate of fungi seems to be related to the fungal thermal adaptability. In addition, linear mitogenomes of these four Mucorales showed diverse arrangements of orf genes and directionality of some conserved gene elements. CONCLUSION: This study uncovered the pathogenicity variances among the four Mucorales species and the relationship between their mitogenomic features and clinical pathogenicity. Further studies like spatial structure of mitochondrial genomes and the comprehensive analysis of transcription regulation are needed.

Subjective cognitive decline symptoms and its association with socio-demographic characteristics and common chronic diseases in the southern Chinese older adults.

BACKGROUND: Subjective cognitive decline (SCD) may be the first symptomatic manifestation of Alzheimer's disease, but information on its health correlates is still sparse in Chinese older adults. This study aimed to estimate SCD symptoms and its association with socio-demographic characteristics, common chronic diseases among southern Chinese older adults. METHODS: Participants aged 60 years and older from 7 communities and 2 nursing homes in Guangzhou were recruited and interviewed with standardized assessment tools. Pittsburgh Sleep Quality Index (PSQI), Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) were used to measure poor sleep quality, depression symptoms and anxiety symptoms. The SCD symptoms were measured by SCD questionnaire 9 (SCD-Q9) which ranged from 0 to 9 points, with a higher score indicating increased severity of the SCD. Participants were divided into low score group (SCD-Q9 score ≤ 3) and higher score group (SCD-Q9 score > 3). Chi-square tests and multivariate logistic regression analysis were used for exploring the influences of different characteristics of socio-demographic and lifestyle factors on SCD symptoms. Univariate and multivariate logistic regression analysis were applied to explore the association between SCD symptoms with common chronic diseases. RESULTS: A total of 688 participants were included in our analysis with a mean age of 73.79 (SD = 8.28, range: 60-101), while 62.4% of the participants were females. The mean score of the SCD-Q9 was 3.81 ± 2.42 in the whole sample. A total of 286 participants (41.6%) were defined as the low score group (≤3 points), while 402 participants (58.4%) were the high score group (> 3 points). Multivariate logistic regression analysis revealed that female (OR = 1.99, 95%CI: 1.35-2.93), primary or lower education level (OR = 2.58, 95%CI: 1.38-4.83), nursing home (OR = 1.90, 95%CI: 1.18-3.05), napping habits (OR = 1.59, 95%CI: 1.06-2.40), urolithiasis (OR = 2.72, 95%CI: 1.15-6.40), gout (OR = 2.12, 95%CI: 1.14-3.93), poor sleep quality (OR = 1.93, 95%CI: 1.38-2.71), depression symptoms (OR = 3.01, 95%CI: 1.70-5.34) and anxiety symptoms (OR = 3.11, 95%CI: 1.29-7.46) were independent positive related to high SCD-Q9 score. On the other hand, tea-drinking habits (OR = 0.64, 95%CI: 0.45-0.92), current smoking (OR = 0.46, 95%CI: 0.24-0.90) were independent negative related to high SCD-Q9 score. CONCLUSIONS: Worse SCD symptoms were closely related to common chronic diseases and socio-demographic characteristics. Disease managers should pay more attention to those factors to early intervention and management for SCD symptoms among southern Chinese older adults.

Diagnosis of Neisseria Gonorrhoeae by Loop-Mediated Isothermal Amplification: Systematic Review and Meta-Analysis.

Neisseria gonorrhoeae (gonococci) is the pathogen of gonorrhea. At present, there is no robust statistical analysis targeting the detection accuracy for N.gonorrhoeae of loop-mediated isothermal amplification (LAMP). We performed a full search of five databases for studies using the LAMP method to detect N.gonorrhoeae in this study. Nine datasets derived from eight studies satisfying the inclusion requirement were collected for this study. The pooled sensitivity rate and specificity were calculated as 98.53 and 99.49%. The pooled positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratio (DOR) were 66.0, 0.04 and 1863.8. After plotting the summary receiver operating characteristic (sROC), the area under the curve (AUC) and Q* index was calculated as 0.99 and 0.9774. Subgroup analyses based on the type of samples, location, and gold standard did not find sources of significant heterogeneity. In conclusion, the LAMP method could be an effective and convenient method with high accuracy for the clinical detection of N.gonorrhoeae. Moreover, the confirmation of this finding needs more high-quality studies with regional data and large samples.

NMR-Based Metabolomic Analysis on the Protective Effects of Apolipoprotein A-I Mimetic Peptide against Contrast Media-Induced Endothelial Dysfunction.

Endothelial dysfunction plays key roles in the pathological process of contrast media (CM)-induced acute kidney injury (CI-AKI) in patients undergoing vascular angiography or intervention treatment. Previously, we have demonstrated that an apolipoprotein A-I (apoA-I) mimetic peptide, D-4F, inhibits oxidative stress and improves endothelial dysfunction caused by CM through the AMPK/PKC pathway. However, it is unclear whether CM induce metabolic impairments in endothelial cells and whether D-4F ameliorates these metabolic impairments. In this work, we evaluated vitalities of human umbilical vein endothelial cells (HUVECs) treated with iodixanol and D-4F and performed nuclear magnetic resonance (NMR)-based metabolomic analysis to assess iodixanol-induced metabolic impairments in HUVECs, and to address the metabolic mechanisms underlying the protective effects of D-4F for ameliorating these metabolic impairments. Our results showed that iodixanol treatment distinctly impaired the vitality of HUVECs, and greatly disordered the metabolic pathways related to energy production and oxidative stress. Iodixanol activated glucose metabolism and the TCA cycle but inhibited choline metabolism and glutathione metabolism. Significantly, D-4F pretreatment could improve the iodixanol-impaired vitality of HUVECs and ameliorate the iodixanol-induced impairments in several metabolic pathways including glycolysis, TCA cycle and choline metabolism in HUVECs. Moreover, D-4F upregulated the glutathione level and hence enhanced antioxidative capacity and increased the levels of tyrosine and nicotinamide adenine dinucleotide in HUVECs. These results provided the mechanistic understanding of CM-induced endothelial impairments and the protective effects of D-4F for improving endothelial cell dysfunction. This work is beneficial to further exploring D-4F as a potential pharmacological agent for preventing CM-induced endothelial impairment and acute kidney injury.

Modified apple polysaccharide regulates microbial dysbiosis to suppress high-fat diet-induced obesity in C57BL/6J mice.

PURPOSE: Obesity, substantially increasing the risk of diseases such as metabolic diseases, becomes a major health challenge. In this study, we, therefore, investigated the effect of modified apple polysaccharide (MAP) on obesity. METHODS: Twelve male C57BL/6J mice were given a 45% high-fat diet (HFD) for 12 weeks to replicate an obesity model and six mice were given normal diet as control. Then, 1 g/kg MAP was administrated to six mice by gavage for 15 days. Illumina Miseq PE300 sequencing platform was used to analyze the microbial diversity of fecal samples. Flow cytometry was employed to investigate the effects of MAP on immune cells in adipose tissue. Bacterial culture and qPCR were used to assess the effects of MAP on the growth of whole fecal bacteria and representative microbiota in vitro. RESULTS: MAP could alleviate HFD-induced obesity and decrease body weight of mice effectively. The results of α diversity showed that Shannon index in HFD group was significantly lower than that in control group; Shannon index in MAP group was higher than that in HFD group. The results of ß diversity showed that the microbiota of MAP group was more similar to that of control group. HFD increased the number of T cells and macrophages in adipocytes; while MAP decreased the number of T cells and macrophages. MAP could promote the growth of fecal bacteria, and demonstrated a facilitated effect on the proliferation of Bacteroidetes, Bacteroides, Lactobacillus, and an inhibitory effect on Fusobacterium. CONCLUSIONS: MAP could reduce HFD-induced obesity of mice effectively. The possible mechanisms are that MAP restored HFD-induced intestinal microbiota disorder, downregulated the number of T cells and macrophages in adipose tissue.