Transformation of Natural Resin Resina Draconis to 3D Functionalized Fibrous Scaffolds for Efficient Chronic Wound Healing.

Chronic wound healing is a major challenge in clinical practice. Secondary dressing damage and antibiotic resistance are the main obstacles for traditional wound dressings. Resina draconis (RD), a natural resin traditionally used in powder form for wound care, is now considered unsuitable due to the lack of gas permeability and moist environment required for wound healing. Here, RD is incorporated in situ by constructing a 3D coiled fibrous scaffold with polycaprolactone/polyethylene oxide. Due to the high porosity of 3D scaffold, the RD-3D dressings have a favorable swelling capacity, providing permeability and moisture for wound repair. Meanwhile, the transformation of RD powder into 3D dressings fully demonstrates capabilities of RD in rapid hemostasis, bactericidal, and inflammation-regulating activities. In vivo evaluations using pressure ulcer and infected wound models confirm the high efficacy of RD-3D dressing in early wound healing, particularly beneficial in the infected wound model compared to recombinant bovine FGF-basic. Further biological analysis shows that resveratrol, loureirin A, and loureirin B, as potentially bioactive components of RD, individually contribute to different aspects of wound healing. Collectively, RD-3D integrated dressings represent a simple, cost-effective, and safe approach to wound healing, providing an alternative therapy for translating medical dressings from bench to bedside.

Causal Relationships between Homocysteine and the Polycystic Ovary Syndrome: A Mendelian Randomization Analysis.

Background: Polycystic ovary syndrome (PCOS) is an endocrine disease attributed to multiple genetic variants and environmental factors. We aimed to find the causal association of homocysteine (Hcy) with PCOS. Methods: A two-sample Mendelian randomization (MR) analysis was performed. We selected 14 single-nucleotide polymorphisms (SNPs) as instrumental variables to predict the risk of PCOS from genome-wide association studies (GWAS). The summary statistics of PCOS were obtained from 3 large genome-wide association studies in the European population, involving 4,138 cases and 20,129 controls, 3,609 cases and 229,788 controls, 994 cases and 165,817 controls, separately. Results: The IVM analyses revealed that plasma Hcy levels were not causally associated with the risk of PCOS in the meta-analysis (combined effect = 1.032, 95% confidence interval (CI): 0.885-1.203, p=0.688). Conclusions: There was no sufficient evidence to support the causal association of the Hcy with the risk of PCOS.

Identification and validation of IRF6 related to ovarian cancer and biological function and prognostic value.

BACKGROUND: Ovarian cancer (OC) is a severe gynecological malignancy with significant diagnostic and therapeutic challenges. The discovery of reliable cancer biomarkers can be used to adjust diagnosis and improve patient care. However, serous OC lacks effective biomarkers. We aimed to identify novel biomarkers for OC and their pathogenic causes. METHODS: The present study used the differentially expressed genes (DEGs) obtained from the "Limma" package and WGCNA modules for intersection analysis to obtain DEGs in OC. Three hub genes were identified-claudin 3 (CLDN3), interferon regulatory factor 6 (IRF6), and prostasin (PRSS8)-by searching for hub genes through the PPI network and verifying them in GSE14407, GSE18520, GSE66957, and TCGA + GTEx databases. The correlation between IRF6 and the prognosis of OC patients was further confirmed in Kaplan-Miller Plotter. RT-qPCR and IHC confirmed the RNA and protein levels of IRF6 in the OC samples. The effect of IRF6 on OC was explored using transwell invasion and scratch wound assays. Finally, we constructed a ceRNA network of hub genes and used bioinformatics tools to predict drug sensitivity. RESULTS: The joint analysis results of TCGA, GTEx, and GEO databases indicated that IRF6 RNA and protein levels were significantly upregulated in serous OC and were associated with OS and PFS. Cell function experiments revealed that IRF6 knockdown inhibited SKOV3 cell proliferation, migration and invasion. CONCLUSION: IRF6 is closely correlated with OC development and progression and could be considered a novel biomarker and therapeutic target for OC patients.

CNKSR2 expression is correlated with immune infiltrates in Cervical Cancer as a favorable prognostic factor.

Connector enhancer of kinase suppressor of Ras 2 (CNKSR2) is a scaffold protein that mediates mitogen-activated protein kinase pathways. However, the molecular function of CNKSR2 in cervical squamous cell carcinoma (CESC) remains unknown. This study aimed to characterize the role of CNKSR2 in patients with CESC. Immunohistochemistry revealed that the expression of CNKSR2 in CESCs is relatively low compared with that in normal cells. We also explored the gene expression profile of high- and low-CNKSR2 expression in patients with cervical cancer. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the expression of CNKSR2 was upregulated in synapse assembly, which was coordinately regulated using the cAMP signaling pathway and calcium signaling pathway. The correlation between CNKSR2 and cancer immune cell infiltration was investigated via single-sample gene set enrichment analysis (ssGSEA). High CNKSR2 expression was associated with better overall survival (OS) and disease-free survival (DFS). Interestingly, high CNKSR2 expression was a good predictor of the survival outcome in cervical cancer patients. Additionally, CNKSR2 expression was strongly correlated with diverse immune cells in CESCs, including NK cells and T cells. These findings suggest that CNKSR2 is correlated with prognosis and immune infiltration, laying the foundation for future studies on the functional role of CNKSR2 in CESC.

Bacteria-Targeting Nanosilver-Based Antibacterial Drugs for Efficient Treatment of Drug-Resistant Bacterial-Infected Keratitis.

Keratitis caused by drug-resistant bacteria is a severe condition that can lead to corneal perforation and even blindness, making effective treatment a top priority amid growing antibiotic resistance. Eye drops for anti-inflammatory treatment necessitate frequent administration of high doses throughout every day due to bacterial resistance resulting from antibiotic overuse and the low bioavailability of drugs. To overcome these issues, an antibacterial nanocomposite is prepared via conjugating random copolymers of galactose and 3-(acrylamide)phenylboronic acid to the surface of silver nanoparticles. The customized nanocomposites trigger specific binding to bacteria, resulting in excellent retention of the drug on the ocular surface, resulting in rapid and powerful killing of bacteria and inhibition of bacterial proliferation. Due to its superior drug delivery capabilities to the ocular surface, the functionalized nanocomplex markedly amplifies the anti-inflammatory efficacy, even at low doses. This effect is achieved by impeding immune cell infiltration and diminishing the synthesis of inflammatory mediators and cytokines, thereby suggesting enhanced healing properties for corneal inflammation. This study demonstrates a promising nanocomposite which is an effective and safe antibacterial strategy for bacterial keratitis with favorable prognostic and clinical conversion potential.

A spiropyran-decorated nanocoating for dynamically regulating bacteria/cell adhesion and detachment.

Microorganism adhesion and the resulting contamination of the biomaterial is one of the major causes of biomedical device failure. Stimuli-responsive materials based on dynamically regulating interactions with reversible characteristics of on-off states have attracted increasing attention. Here, a facile self-assembled biomaterial nanocoating constructed using acidity- and photoregulated spiropyran-modified nanoparticles was developed for reversibly regulating bacteria or mammalian cell adhesion-and-detachment. The coating was formed by coating a solution of spiropyran-conjugated nanoparticles around the surface of a silica gel followed by curing and drying at 60 °C for 30 min. Importantly, efficient adhesion-and-detachment of bacteria or cells could be controlled even after 8 cycles owing to the excellent acidity- and light-switched ability. Collectively, this well-defined self-assembled nanocoating as a dynamical and reversible agent provides promising insight for the development of biomedical devices, especially for biomaterial medical coatings.

Benefits of topical indigo naturalis nanofibrous patch on psoriatic skin: A transdermal strategy for botanicals.

Indigo naturalis (IN) has been extensively used as a topical treatment for psoriasis. However, clinical applications of IN in ointment were hampered by its limited transdermal efficiency and dark stains. To address the aforementioned issues, nanopatches carrying IN were fabricated using poly(ε-caprolactone, PCL)/poly(ethylene oxide, PEO) and topically applied to psoriasiform skin. The ideal ratio of 5% PCL/PEO was established to be 80:20 (w/w), and 15% IN as payload was confirmed. Investigations on the three principal active components of IN release indicated that indirubin and tryptanthrin were released in bursts, while indigo was released in a limited and controlled manner. Further biological analyses confirmed a favorable biocompatibility of amphiphilic IN-PCL/PEO, which coincided with the intended therapeutic outcomes as measured by severity index scoring and pathological evaluations in vivo. The advantages of IN as nanopatches over ointment could be due to improved transdermal distribution of indirubin and tryptanthrin, resulting in effective management of epidermal hyperplasia and blood vessel remodeling. Meanwhile, due to the lower preservation of epidermal indigo, IN-PCL/PEO nanopatches caused no skin coloration. Similarly, during a 4-week topical treatment of IN-PCL/PEO nanopatches, the safety and anti-psoriatic benefits were obtained in an initial human test. The conversion of IN from topical cream to electrospun nanofibers opens up new avenues for bench-to-bedside translation of this herbal therapy and provides mechanistic insight into IN's roles in the management of psoriasis.

Kaempferol inhibits SARS-CoV-2 invasion by impairing heptad repeats-mediated viral fusion.

BACKGROUND: The continuous evolution of SARS-CoV-2 has underscored the development of broad-spectrum prophylaxis. Antivirals targeting the membrane fusion process represent promising paradigms. Kaempferol (Kae), an ubiquitous plant flavonol, has been shown efficacy against various enveloped viruses. However, its potential in anti-SARS-CoV-2 invasion remains obscure. PURPOSE: To evaluate capabilities and mechanisms of Kae in preventing SARS-CoV-2 invasion. METHODS: To avoid interference of viral replication, virus-like particles (VLPs) constructed with luciferase reporter were applied. To investigate the antiviral potency of Kae, human induced pluripotent stem cells (hiPSC)-derived alveolar epithelial cells type II (AECII) and human ACE2 (hACE2) transgenic mice were utilized as in vitro and in vivo models, respectively. Using dual split protein (DSP) assays, inhibitory activities of Kae in viral fusion were determined in Alpha, Delta and Omicron variants of SARS-CoV-2, as well as in SARS-CoV and MERS-CoV. To further reveal molecular determinants of Kae in restricting viral fusion, synthetic peptides corresponding to the conserved heptad repeat (HR) 1 and 2, involved in viral fusion, and the mutant form of HR2 were explored by circular dichroism and native polyacrylamide gel electrophoresis. RESULTS: Kae inhibited SARS-CoV-2 invasion both in vitro and in vivo, which was mainly attributed to its suppressive effects on viral fusion, but not endocytosis, two pathways that mediate viral invasion. In accordance with the proposed model of anti-fusion prophylaxis, Kae functioned as a pan-inhibitor of viral fusion, including three emerged highly pathogenic coronaviruses, and the currently circulating Omicron BQ.1.1 and XBB.1 variants of SARS-CoV-2. Consistent with the typical target of viral fusion inhibitors, Kae interacted with HR regions of SARS-CoV-2 S2 subunits. Distinct from previous inhibitory fusion peptides which prevent the formation of six-helix bundle (6-HB) by competitively interacting with HRs, Kae deformed HR1 and directly reacted with lysine residues within HR2 region, the latter of which was considered critical for the preservation of stabilized S2 during SARS-CoV-2 invasion. CONCLUSIONS: Kae prevents SARS-CoV-2 infection by blocking membrane fusion and possesses a broad-spectrum anti-fusion ability. These findings provide valuable insights into potential benefits of Kae-containing botanical products as a complementary prophylaxis, especially during the waves of breakthrough infections and re-infections.

Comparative analysis between high-grade serous ovarian cancer and healthy ovarian tissues using single-cell RNA sequencing.

Introduction: High-grade serous ovarian cancer (HGSOC) is the most common histological subtype of ovarian cancer, and is associated with high mortality rates. Methods: In this study, we analyzed specific cell subpopulations and compared different gene functions between healthy ovarian and ovarian cancer cells using single-cell RNA sequencing (ScRNA-seq). We delved deeper into the differences between healthy ovarian and ovarian cancer cells at different levels, and performed specific analysis on endothelial cells. Results: We obtained scRNA-seq data of 6867 and 17056 cells from healthy ovarian samples and ovarian cancer samples, respectively. The transcriptional profiles of the groups differed at various stages of ovarian cell development. A detailed comparison of the cell cycle, and cell communication of different groups, revealed significant differences between healthy ovarian and ovarian cancer cells. We also found that apoptosis-related genes, URI1, PAK2, PARP1, CLU and TIMP3, were highly expressed, while immune-related genes, UBB, RPL11, CAV1, NUPR1 and Hsp90ab1, were lowly expressed in ovarian cancer cells. The results of the ScRNA-seq were verified using qPCR. Discussion: Our findings revealed differences in function, gene expression and cell interaction patterns between ovarian cancer and healthy ovarian cell populations. These findings provide key insights on further research into the treatment of ovarian cancer.

Application and discoveries of metabolomics and proteomics in the study of female infertility.

Introduction: Female infertility is defined as the absence of clinical pregnancy after 12 months of regular unprotected sexual intercourse. Methods: This study employed metabolomics and proteomics approaches to investigate the relationship between metabolites and proteins and female infertility. The study used metabolomics and proteomics data from the UK Biobank to identify metabolites and proteins linked to infertility. Results: The results showed that GRAM domain-containing protein 1C and metabolites fibrinogen cleavage peptides ADpSGEGDFXAEGGGVR and 3-Hydroxybutyrate had a positive correlation with infertility, whereas proteins such as Interleukin-3 receptor subunit alpha, Thrombospondin type-1 domain-containing protein 1, Intestinal-type alkaline phosphatase, and platelet and endothelial cell adhesion molecule 1 exhibited a negative correlation. These findings provide new clues and targets for infertility diagnosis and treatment. However, further research is required to validate these results and gain a deeper understanding of the specific roles of these metabolites and proteins in infertility pathogenesis. Discussion: In conclusion, metabolomics and proteomics techniques have significant application value in the study of infertility, allowing for a better understanding of the biological mechanisms underlying infertility and providing new insights and strategies for its diagnosis and treatment. These research findings provide a crucial biological mechanistic basis for early infertility screening, prevention, and treatment.

Corrigendum: Comprehensive analysis of the transcriptome-wide m6A methylation in mouse pachytene spermatocytes and round spermatids.

[This corrects the article DOI: 10.3389/fgene.2022.832677.].

Comparative analysis of the testes from wild-type and Alkbh5-knockout mice using single-cell RNA sequencing.

The RNA demethylase ALKBH5 is regarded as the "eraser" in N6-methyladenosine modification. ALKBH5 deficiency causes male infertility in mice; however, the mechanisms that confer disruption of spermatogenesis are not completely clear. In this study, we profiled testis samples from wild-type and Alkbh5-knockout mice using single-cell RNA sequencing. We obtained single-cell RNA sequencing data of 5,596 and 6,816 testis cells from a wild-type and a knockout mouse, respectively. There were differences detected between the transcriptional profiles of the groups at various germ cell developmental stages. This ranged from the development of spermatogonia to sperm cells, in macrophages, Sertoli cells, and Leydig cells. We identified the differentially expressed genes related to spermatogenesis in germ cells and somatic cells (Sertoli cells and Leydig cells) and evaluated their functions and associated pathways, such as chromatin-related functional pathways, through gene ontology enrichment analysis. This study provides the first single-cell RNA sequencing profile of the testes of ALKBH5-deficient mice. This highlights that ALKBH5 is an important gene for germ cell development and spermatogenesis and offers new molecular mechanistic insights. These findings could provide the basis for further research into the causes and treatment of male infertility.

Comprehensive Analysis of the Transcriptome-Wide m6A Methylation in Mouse Pachytene Spermatocytes and Round Spermatids.

Spermatogenesis, an efficient and complex system in male germline development, requires a series of elaborately regulated genetic events in which diploid spermatogonia differentiate into haploid spermatozoa. N6-methyladenosine (m6A) is an important epigenetic RNA modification that occurs during spermatogenesis. ALKBH5 is an m6A eraser and knocking out Alkbh5 increases the level of total m6A methylation and causes male infertility. In this study, comprehensive analyses of MeRIP-seq and RNA-seq data revealed differences between wild-type (WT) and Alkbh5 knockout (KO) mice. In pachytene spermatocytes (PA), 8,151 m6A peaks associated with 9,959 genes were tested from WT and 10,856 m6A peaks associated with 10,016 genes were tested from KO mice. In the round spermatids (RO), 10,271 m6A peaks associated with 10,109 genes were tested from WT mice and 9,559 m6A peaks associated with 10,138 genes were tested from KO mice. The peaks were mainly concentrated in the coding region and the stop codon of the GGAC motif. In addition, enrichment analysis showed significant m6A methylation genes in related pathways in spermatogenesis. Furthermore, we conducted joint analyses of the m6A methylome and RNA transcription, suggesting an m6A regulatory mechanism of gene expression. Finally, seven differentially expressed mRNAs from RNA-seq data in both PA and RO were verified using qPCR. Overall, our study provides new information on m6A modification changes between WT and KO in PA and RO, and may provide new insights into the molecular mechanisms of m6A modification in germ cell development and spermatogenesis.

Approaches to text mining for analyzing treatment plan of quit smoking with free-text medical records: A PRISMA-compliant meta-analysis.

BACKGROUND: Smoking is a complex behavior associated with multiple factors such as personality, environment, genetics, and emotions. Text data are a rich source of information. However, pure text data requires substantial human resources and time to extract and apply the knowledge, resulting in many details not being discovered and used. This study proposes a novel approach that explores a text mining flow to capture the behavior of smokers quitting tobacco from their free-text medical records. More importantly, the paper examines the impact of these changes on smokers. The goal is to help smokers quit smoking. The study population included adult patients that were >20 years old of age who consulted the medical center's smoking cessation outpatient clinic from January to December 2016. A total of 246 patients visited the clinic in the study period. After excluding incomplete medical records or lost follow up, there were 141 patients included in the final analysis. There are 141 valid data points for patients who only treated once and patients with empty medical records. Two independent review authors will make the study selection based on the study eligibility criteria. Our participants are from all the patients that were involved in this study and the staff of Division of Family Medicine, National Taiwan University Hospital. Interventions and study appraisal are not required. METHODS: The paper develops an algorithm for analyzing smoking cessation treatment plans documented in free-text medical records. The approach involves the development of an information extraction flow that uses a combination of data mining techniques, including text mining. It can use not only to help others quit smoking but also for other medical records with similar data elements. The Apriori associations of our algorithm from the text mining revealed several important clinical implications for physicians during smoking cessation. For example, an apparent association between nicotine replacement therapy (NRT) and other medications such as Inderal, Rivotril, Dogmatyl, and Solaxin. Inderal and Rivotril use in patients with anxiety disorders as anxiolytics frequently. RESULTS: Finally, we find that the rules associating with NRT combination with blood tests may imply that the use of NRT combination therapy in smokers with chronic illness may result in lower abstinence. Further large-scale surveys comparing varenicline or bupropion with NRT combination in smokers with a chronic disease are warranted. The Apriori algorithm suffers from some weaknesses despite being transparent and straightforward. The main limitation is the costly wasting of time to hold a vast number of candidates sets with frequent itemsets, low minimum support, or large itemsets. CONCLUSION: In the paper, the most visible areas for the therapeutic application of text mining are the integration and transfer of advances made in basic sciences, as well as a better understanding of the processes involved in smoking cessation. Text mining may also be useful for supporting decision-making processes associated with smoking cessation. Systematic review registration number is not registered.

Race- and sex-specific association between alcohol consumption and hypertension in 22 cohort studies: A systematic review and meta-analysis.

BACKGROUND AND AIMS: The alcohol-hypertension relation has been well documented, but whether women have protective effect or race and type of beverage consumed affect the association remain unclear. To quantify the relation between total or beverage-specific alcohol consumption and incident hypertension by considering the effect of sex and race. METHODS AND RESULTS: Articles were identified in PubMed and Embase databases with no restriction on publication date. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated by random effects models. Restricted cubic splines were used to model the dose-response association. This study involved 22 articles (31 studies) and included 414,477 participants. The hypertension risk was different among liquor, wine, and beer at 5.1-10 g/d of ethanol consumption (P-across subgroups = 0.002). The hypertension risk differed between men (RR: 1.14, 95% CI: 1.07, 1.20) and women (RR: 0.98, 95% CI: 0.89, 1.06) at 10 g/d (P-across subgroups = 0.005). We found a linear alcohol-hypertension association among white (P-linearity = 0.017), black people (P-linearity = 0.035), and Asians (P-linearity<0.001). With 10 g/d increment of consumption, the RRs for hypertension were 1.06 (95% CI: 1.04, 1.08), 1.14 (95% CI: 1.01, 1.28), and 1.06 (95% CI: 1.01, 1.10) for Asians, black, and white people, respectively. CONCLUSION: Sex modifies the alcohol-hypertension association at low level of alcohol consumption and we did not find evidence of a protective effect of alcohol consumption among women. Black people may have higher hypertension risk than Asians and white people at the same ethanol consumption.

The association between fasting plasma glucose and all-cause and cause-specific mortality by gender: The rural Chinese cohort study.

BACKGROUND: To evaluate the association between fasting plasma glucose (FPG) and mortality by gender. METHODS: A total of 17 248 eligible participants from a rural Chinese prospective cohort population were included. The same questionnaire interview and anthropometric and laboratory measurements were performed at both baseline (2007-2008) and follow-up (2013-2014). Participants were classified according to baseline FPG and diabetic status by sex. Restricted cubic splines and Cox proportional-hazards regression models, estimating hazard ratio (HR) and 95% confidence interval (CI), were used to assess the FPG-mortality relation. RESULTS: During the 6-year follow-up, 618 men and 489 women died. The FPG-mortality relation was J shaped for both sexes. For men, risk of all-cause and noncardiovascular disease (CVD)/noncancer mortality was greater with low fasting glucose (LFG) than with normal fasting glucose (adjusted HR [aHR] 1.60; 95% CI, 1.05-2.43; and aHR 2.16; 95% CI, 1.15-4.05). Men with diabetes mellitus (DM) showed increased risk of all-cause (aHR 2.04; 95% CI, 1.60-2.60), CVD (aHR 1.98; 95% CI, 1.36-2.89), and non-CVD/noncancer mortality (aHR 2.62; 95% CI, 1.76-3.91). Men with impaired fasting glucose (IFG) had borderline risk of CVD mortality (aHR 1.34; 95% CI, 1.00-1.79). Women with LFG had increased risk of non-CVD/noncancer mortality (aHR 2.27; 95% CI, 1.04-4.95), and women with DM had increased risk of all-cause (aHR 1.73; 95% CI, 1.35-2.23), CVD (aHR 1.76; 95% CI, 1.24-2.50), and non-CVD/noncancer mortality (aHR 1.97; 95% CI, 1.27-3.08). CONCLUSIONS: LFG is positively associated with all-cause mortality risk in rural Chinese men but not in women.

MFGE8 polymorphisms are significantly associated with metabolism-related indicators rather than metabolic syndrome in Chinese people: A nested case-control study.

BACKGROUND: The correlation between single nucleotide polymorphisms (SNPs) of milk fat globule-epidermal growth factor 8 (MFGE8) and metabolic syndrome (MetS) and metabolism-related indicators are limited. The present study explored the relation in Chinese adults. METHODS: We conducted a nested case-control study based on the Rural Chinese Cohort Study including 408 people with MetS and 408 controls matched by baseline sex, age (±2 years), marital status, and residence village. Four polymorphisms were selected and genotyped by using the SNPscan Genotyping system. Conditional logistic regression was used to estimate the association of MFGE8 polymorphisms with MetS incidence, and linear regression was used to assess the association with metabolism-related indicators in controls. RESULTS: We found no significant association of MFGE8 SNPs with MetS incidence or systolic blood pressure, or triglycerides level, or fasting plasma glucose (P > 0.05). However, MFGE8 rs4932450 was negatively associated with high-density lipoprotein cholesterol (HDL-C) level under the dominant model (ß = -0.0218, P = 0.007) and the additive model (ß = -0.0175, P = 0.012) and positively associated with diastolic blood pressure (DBP) under the recessive model (ß = 4.8848, P = 0.011). The rs3784751 SNP was associated with increased waist circumference (WC) in controls (ß = 0.0307, P = 0.028). CONCLUSIONS: MFGE8 polymorphisms were not associated with MetS but were related to DBP, HDL-C level, and WC in Chinese adults.

Sleep Duration Interacts With Lifestyle Risk Factors and Health Status to Alter Risk of All-Cause Mortality: The Rural Chinese Cohort Study.

STUDY OBJECTIVES: Many studies suggest an association of both short and long sleep duration with all-cause mortality, but the effect of co-occurrence of sleep duration and other lifestyle risk factors or health status remains unclear. METHODS: A total of 17,184 participants aged 18 years or older from rural areas of China were examined at baseline from 2007 to 2008 and followed up from 2013 to 2014. Cox proportional hazard models were used to estimate the hazard ratio (HR) and 95% confidence interval (CI). RESULTS: During 6-year follow-up, we identified 1,101 deaths. The multivariable-adjusted mortality risk was significantly higher with short-duration sleepers (< 6.5 hours) (HR = 1.37, 95% CI 1.01-1.86) and long-duration sleepers (≥ 9.5 hours) (HR = 1.35, 95% CI 1.05-1.74) versus 6.5-7.5 hours. The multiplicative interaction of long sleep duration with some lifestyle risk factors and health statuses increased the mortality risk in men (low level of physical activity: HR = 1.03, 95% CI 1.02-1.04; hypertension: HR = 1.06, 95% CI 1.04-1.09; type 2 diabetes mellitus [T2DM]: HR = 1.07, 95% CI 1.04-1.11). Similar results were found in women (low level of physical activity: HR = 1.03, 95% CI 1.02-1.05; T2DM: HR = 1.07, 95% CI 1.05-1.10). CONCLUSIONS: Sleep duration could be a predictor of all-cause mortality and its interaction with physical activity, hypertension, and T2DM may increase the risk of mortality.

CD36 gene variants is associated with type 2 diabetes mellitus through the interaction of obesity in rural Chinese adults.

BACKGROUND: Evidences show that cluster determinant 36 (CD36) protein plays a role in lipid metabolism and insulin resistance, and the expression of CD36 is inducible in obesity. The present study evaluated the association of CD36 variants and the interaction with obesity on type 2 diabetes mellitus (T2DM) risk. METHODS: We performed a case-control study nested in the Rural Chinese Cohort Study. We included 546 incident T2DM cases matched with non-T2DM controls in a 1:1 ratio by sex, age (within 2 years), marital status, and residence village. Four loci in CD36 (rs1194197, rs2151916, rs3211956, and rs7755) were genotyped by SNPscanTM Genotyping system. RESULTS: After adjusting for potential confounding, we observed no statistically significant association between the CD36 polymorphisms and T2DM risk. Compared to wild-type homozygous carriers with normal weight, overweight/obesity participants carrying the mutational allele rs7755 showed increased risk of T2DM, by 114% (OR = 2.14, 95% CI: 1.33-3.46; Pinteraction = 0.007); abdominal obesity participants carrying the mutational allele rs7755 showed increased risk of T2DM, by 133% (OR = 2.33, 95% CI: 1.48-3.66; Pinteraction = 0.002). Furthermore, rs2151916 polymorphism was associated with triglycerides level (P = 0.019), and the rs1194197 variant was related to systolic blood pressure (P = 0.023) within the group of controls. CONCLUSIONS: CD36 genotypes were not associated with the progression to T2DM independently. However, our results suggested a positive interaction between the CD36 variants and obesity on T2DM susceptibility, which might be through a cardiometabolic disorder.