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Abstract Treatment of advanced triple-negative breast cancer (TNBC) is a great challenge in clinical practice. The immune checkpoints are a category of immunosuppressive molecules that cancer could hijack and impede anti-tumor immunity. Targeting immune checkpoints, such as anti-programmed cell death 1 (PD-1) therapy, is a promising therapeutic strategy in TNBC. The efficacy and safety of PD-1 monoclonal antibody (mAb) with chemotherapy have been validated in TNBC patients. However, the precise mechanisms underlying the synergistic effect of chemotherapy and anti-PD-1 therapy have not been elucidated, causing the TNBC patients that might benefit from this combination regimen not to be well selected. In the present work, we found that IL-23, an immunological cytokine, is significantly upregulated after chemotherapy in TNBC cells and plays a vital role in enhancing the anti-tumor immune response of cytotoxic T cells (CTLs), especially in combination with PD-1 mAb. In addition, the combination of IL-23 and PD-1 mAb could synergistically inhibit the expression of Phosphoinositide-3-Kinase Regulatory Subunit 1 (PIK3R1), which is a regulatory subunit of PI3K and inhibit p110 activity, and promote phosphorylation of AKT in TNBC-specific CTLs. Our findings might provide a molecular marker that could be used to predict the effects of combination chemotherapy therapy and PD-1 mAb in TNBC.

Abstract Cuproptosis is a new mechanism of cell death that differs from previously identified regulatory cell death mechanisms. Cuproptosis induction holds promise as a new tumour treatment. Therefore, we investigated the value of cuproptosis-related genes in the management of hepatocellular carcinoma (HCC). The cuproptosis-related gene Dihydrolipoamide S-Acetyltransferase (DLAT) were significantly upregulated in liver cancer tissues. High levels of DLAT were an independent prognostic factor for shorter overallsurvival (OS) time. DLAT and its related genes were mainly involved in cell metabolism, tumor progression and immune regulation. DLAT was significantly associated with the level of immune cell infiltration and immune checkpoints in HCC. HCC with high DLAT expression was predicted to be more sensitive to sorafenib treatment. The risk prognostic signature established based on DLAT and its related genes had a good prognostic value. The cuproptosis-related gene DLAT is a promising independent prognostic marker and therapeutic target in HCC. The new prognostic signature can effectively predict the prognosis of HCC patients.

Abstract Considering the high fatality of hepatocellular carcinoma (HCC), current prognostic systems are insufficient to accurately forecast HCC patients' outcomes. In our study, nine anoikis‑related genes (PTRH2, ITGAV, ANXA5, BIRC5, BDNF, BSG, DAP3, SKP2, and EGF) were determined to establish a risk scoring model using LASSO regression, which could be validated in ICGC dataset. Kaplan–Meier curves and time-dependent receiver operating characteristic (ROC) curve analysis confirmed the risk score possessed an accurate predictive value for the prognosis of HCC patients. The high-risk group showed a higher infiltration of aDCs, macrophages, T-follicular helper cells, and Th2 cells. Besides, PD-L1 was significantly higher in the high-risk group compared to the low-risk group. Several anoikis‑related genes, such as ANX5, ITGAV, BDNF and SKP2, were associated with drug sensitivity in HCC. Finally, we identified BIRC5 and SKP2 as hub genes among the nine model genes using WGCNA analysis. BIRC5 and SKP2 were over-expressed in HCC tissues, and their over-expression was associated with poor prognosis, no matter in our cohort by immunohistochemical staining or in the TCGA cohort by mRNA-Seq. In our cohort, BIRC5 expression was highly associated with the T stage, pathologic stage, histologic grade and AFP of HCC patients. In general, our anoikis-related risk model can enhance the ability to predict the survival outcomes of HCC patients and provide a feasible therapeutic strategy for immunotherapy and drug resistance in HCC. BIRC5 and SKP2 are hub genes of anoikis‑related genes in HCC.

BackgroundThe increasing prevalence of nonalcoholic fatty liver disease (NAFLD) in China presents a significant public health concern. Traditional ultrasound, commonly used for fatty liver screening, often lacks the ability to accurately quantify steatosis, leading to insufficient follow-up for patients with moderate-to-severe steatosis. Transient elastography (TE) provides a more quantitative diagnosis of steatosis and fibrosis, closely aligning with biopsy results. Moreover, machine learning (ML) technology holds promise for developing more precise diagnostic models for NAFLD using a variety of laboratory indicators. ObjectiveThis study aims to develop a novel ML-based diagnostic model leveraging TE results for staging hepatic steatosis. The objective was to streamline the model’s input features, creating a cost-effective and user-friendly tool to distinguish patients with NAFLD requiring follow-up. This innovative approach merges TE and ML to enhance diagnostic accuracy and efficiency in NAFLD assessment. MethodsThe study involved a comprehensive analysis of health examination records from Suzhou Municipal Hospital, spanning from March to May 2023. Patient data and questionnaire responses were meticulously inputted into Microsoft Excel 2019, followed by thorough data cleaning and model development using Python 3.7, with libraries scikit-learn and numpy to ensure data accuracy. A cohort comprising 978 residents with complete medical records and TE results was included for analysis. Various classification models, including logistic regression (LR), k-nearest neighbor (KNN), support vector machine (SVM), random forest (RF), light gradient boosting machine (LightGBM), and extreme gradient boosting (XGBoost), were constructed and evaluated based on the area under the receiver operating characteristic curve (AUROC). ResultsAmong the 916 patients included in the study, 273 were diagnosed with moderate-to-severe NAFLD. The concordance rate between traditional ultrasound and TE for detecting moderate-to-severe NAFLD was 84.6% (231/273). The AUROC values for the RF, LightGBM, XGBoost, SVM, KNN, and LR models were 0.91, 0.86, 0.83, 0.88, 0.77, and 0.81, respectively. These models achieved accuracy rates of 84%, 81%, 78%, 81%, 76%, and 77%, respectively. Notably, the RF model exhibited the best performance. A simplified RF model was developed with an AUROC of 0.88, featuring 62% sensitivity and 90% specificity. This simplified model used 6 key features: waist circumference, BMI, fasting plasma glucose, uric acid, total bilirubin, and high-sensitivity C-reactive protein. This approach offers a cost-effective and user-friendly tool while streamlining feature acquisition for training purposes. ConclusionsThe study introduces a groundbreaking, cost-effective ML algorithm that leverages health examination data for identifying moderate-to-severe NAFLD. This model has the potential to significantly impact public health by enabling targeted investigations and interventions for NAFLD. By integrating TE and ML technologies, the study showcases innovative approaches to advancing NAFLD diagnostics.

Objective To evaluate clinical significance and application outcomes of using the neutrophil-to-lymphocyte count ratio (NLR) and C-reactive protein to albumin ratio (CRP/ALB) in the aged patients hospitalized with acute exacerbation of chronic obstructive pulmonary disease(AECOPD). Methods 172 aged patients with AECOPD who were hospitalized in the Department of Geriatrics and Department of Respiratory Medicine of the Second People's Hospital of Hefei from January 2016 to January 2020 were recruited. According to clinical outcomes, they were divided into survival group (n=155) and death group (n=17). Survival group was divided into groups according to hospitalization days of more or less than ten days. Parameters were got through contrast of clinical and laboratory test indexes of patients in each group. Logistic regression and receiver operating characteristic curve (ROC) were used to analyze the risk factors and their correlation with in-hospital mortality. Results Among 172 aged AECOPD in-patients, 17 patients died during hospitalization with mortality as 9.88%. There were differences between the death group and the survival group in NLR, CRP, CRP/ALB, red blood cell distribution width (RDW), cigarette consumption, community acquired pneumonia (CAP) and various comorbidities. Parameters above mentioned in the death group was higher than the survival group(P＜0.01). At the same time, 155 aged patients with AECOPD who survived and discharged were divided into two subgroups according to the hospitalization ≥10 days and ＜10 days. It was found that NLR, CRP, CRP/ALB, RDW, smoking and CAP in group with hospitalization longer than ten days were significantly more common than those in group of less than ten days hospitalization(P＜0.01). The Logistic regression analysis of NLR, CRP, CRP/ALB and RDW showed that NLR and CRP/ALB might be independent risk factors for in-hospital death. From the analysis of the ROC, the cut-off value of NLR was 11.04, the area under the curve was 77%, and the cut-off value of CRP/ALB was 1.12, and the area under the curve was 65%. Conclusions NLR and CRP/ALB may be the risk factors for in-hospital death of aged patients with AECOPD, which are associated with poor prognosis.

Abstract Living in a disadvantaged neighborhood is associated with adverse clinical outcomes among breast cancer patients, but the underlying pathway is still unclear. Limited evidence has suggested that accelerated biological aging may play an important role. In this study, using a sub-sample of 906 women with newly diagnosed breast cancer at M.D. Anderson, we examined whether levels of selected markers of biological aging (e.g., allostatic load, telomere length, and global DNA methylation) were affected by neighborhood disadvantage. The Area Deprivation Index was used to determine the neighborhood disadvantage. Based on the median ADI at the national level, the study population was divided into low and high ADI groups. Overall, breast cancer patients from the high ADI group were more likely to be younger and non-Hispanic Black than those from the low ADI group (P

Chitinase is a kind of glycoside hydrolase which is widely distributed in nature and encoded by multiple genes to catalyze the decomposition of chitin, which plays an important role in the molting and pathogen defense of crustaceans. However, the research on chitinase in crustaceans is mainly focused on a few species with economic value. In this study, full-length cDNA sequences of the HtCHT1, HtCHT3 and HtCHT4 genes were cloned from the mudflat crab Helice tientsinensis by RACE, and the sequences were analyzed. The results showed that the full-length 2,229 bp of HtCHT1 gene encoded 627 amino acids, while the full-length 2,191 bp of HtCHT3 gene produced 489 amino acids, and the full-length 3,312 bp of HtCHT4 gene encoded 664 amino acids. Bioinformatics analysis showed that all the obtained chitinase proteins had the glycosyl hydrolase family 18 (GH18) catalytic domain and chitin-binding domain (ChtBD2), furthermore, HtCHT1 and HtCHT4 proteins had signal peptide domains at N-terminal. Phylogenetic analysis showed that different types of chitinase were clustered, and HtCHTs were closely related to chitinases in the Eriocheir sinensis. Expression profile analysis showed that the HtCHT1, HtCHT3 and HtCHT4 were significantly expressed in hepatopancreas. Furthermore, the expression of three genes was significantly up-regulated in hepatopancreas after the Vibrio parahaemolyticus challenge. These results suggested that HtCHT1, HtCHT3 and HtCHT4 were belonged to the CHITINASE gene family in H. tientsinensis and were potentially involved in the antibacterial immune response. This study provides essential information for further research of chitinase in H. tientsinensis and even crustaceans.

Objective To investigate the effects of eukaryotic elongation factor-2 kinase (eEF2K) gene transfection and sodium tanshinone Ⅱ A sulfonate (STS) on proliferation, invasion and migration of lung adenocarcinoma cell line A549 and its mechanism. Methods The optimal concentration of STS was screened out by preliminary experiment. A549 cells were divided into siRNA-NC group (transfected with siRNA-NC), siRNA-eEF2K group (transfected with siRNA-eEF2K), siRNA-NC+STS group (treated with 10 μg/mL STS after siRNA-NC) and siRNA-eEF2K+STS group (treated with 10 μg/mL STS after siRNA-eEF2K).The survival rate, clone formation, cell counting of transmembrane cells, migration and apoptosis of A549 cells were detected by CCK-8 method, clone formation test, Transwell chamber test, scratch test and flow cytometry. The protein expression levels of protein kinase B (AKT), phosphorylation (p)-AKT, Ki67, matrix metalloproteinase-2 (MMP-2) and B-cell lymphoma-2 genes (Bcl-2) were detected by Western blot. Results Compared with those in siRNA-NC group, the cell survival rate, clone formation rate, number of transmembrane cells, migration rate and p-AKT, Ki67, MMP-2 and Bcl-2 in proteins siRNA-eEF2K+STS group were significantly lower, while the apoptosis rate was significantly higher (P＜0.05). The siRNA-eEF2K+STS group had the largest range of changes in the above indexes. Conclusions Silencing eEF2K combined with STS can synergistically inhibit the proliferation, invasion and migration of A549 cells and promote cell apoptosis. The mechanism is potentially related to the inhibition of protein expression of p-AKT, Ki67, MMP-2 and Bcl-2.

Though numerous empirical and theoretical studies have been conducted on the determinants and effects of executive compensation, empirical evidence regarding the bargaining effect on the monetary compensation decisions of executives, especially in a large emerging economy such as China, remains scarce. In this study, a two-tier stochastic frontier and endogenous correction model was developed to quantitatively estimate the bargaining effect on the monetary compensation decisions of investment bank executives. Our study is the first to provide comprehensive empirical evidence that bargaining between investment banks and executives in China significantly affects the compensation decisions of executives. In the bargaining process, investment banks are more proficient than executives, and the comprehensive bargaining effect tends to lower the negotiated compensation of executives. The bargaining effect exhibited obvious heterogeneity in the characteristics of executives and investment banks. When these characteristics tend to augment the bargaining power of executives, the negotiated compensation exhibits a limited decrease; when these characteristics augment the bargaining power of investment banks, the negotiated compensation decreases substantially. Our results provide deep insight into factors that determine executive compensation and help compensation designers of investment banks better understand and design executive pay packages.

Abstract. Background:. Nitinol-containing devices are widely used in clinical practice. However, there are concerns about nickel release after nitinol-containing device implantation. This study aimed to compare the efficacy and safety of a parylene-coated occluder vs. a traditional nitinol-containing device for atrial septal defect (ASD). Methods:. One-hundred-and-eight patients with ASD were prospectively enrolled and randomly assigned to either the trial group to receive a parylene-coated occluder (n = 54) or the control group to receive a traditional occluder (n = 54). The plugging success rate at 6 months after device implantation and the pre- and post-implantation serum nickel levels were compared between the two groups. A non-inferiority design was used to prove that the therapeutic effect of the parylene-coated device was non-inferior to that of the traditional device. The Cochran–Mantel–Haenszel chi-squared test with adjustment for central effects was used for the comparison between groups. Results:. At 6 months after implantation, successful ASD closure was achieved in 52 of 53 patients (98.11%) in both the trial and control groups (95% confidence interval (CI): [−4.90, 5.16]) based on per-protocol set analysis. The absolute value of the lower limit of the 95% CI was 4.90%, which was less than the specified non-inferiority margin of 8%. No deaths or severe complications occurred during 6 months of follow-up. The serum nickel levels were significantly increased at 2 weeks and reached the maximum value at 1 month after implantation in the control group (P 0.05). Conclusions:. The efficacy of a parylene-coated ASD occluder is non-inferior to that of a traditional uncoated ASD occluder. The parylene-coated occluder prevents nickel release after device implantation and may be an alternative for ASD, especially in patients with a nickel allergy.

Abstract Remarkable spots and lines were clearly observed at the two interfaces of indium-tin-oxide coated Z-cut Fe-doped lithium noibate plates under illumination by milliwatt continuous-wave laser light; this occurred because of the visible surface plasmons (SPs) supported by the promising non-metal plasmonic system. The intriguing observations are here explained via the SP-strengthened nonlinear effect, through consideration of the electrostatic field (which is comparable to the atomic field) and its large gradient; this hints at a promising, highly sensitive plasmonic system. The gigantic nonlinear effect discussed in this paper should be ubiquitously existed in many oxide ferroelectric/semiconductor combinations and is promising for visible plasmonic applications.

Abstract It has been well-known that built environment features influence the risk of chronic diseases. However, the existing data of its relationship with telomere length, a biomarker of biological aging, is still limited, with no study available for Mexican Americans. This study investigates the relationship between several factors of the built environment with leukocyte telomere length among 5508 Mexican American adults enrolled in Mano-A-Mano, the Mexican American Cohort Study (MACS). Based on the quartile levels of telomere length, the study population was categorized into four groups, from the lowest (1st quartile) to the highest telomere length group (4th quartile). For individual built environment factors, their levels did not differ significantly across four groups. However, in the multinominal logistic regression analysis, increased Rundle’s land use mixture (LUM) and Frank’s LUM were found statistically significantly associated with increased odds of having high levels of telomere length (Rundle’s LUM: 2nd quartile: Odds ratio (OR) 1.26, 95% Confidence interval (CI) 1.07, 1.48; 3rd quartile: OR 1.25, 95% CI 1.06, 1.46; 4th quartile: OR 1.19, 95% CI 1.01, 1.41; Frank’s LUM: 2nd quartile: OR 1.34, 95% CI 1.02, 2.63; 3rd quartile: OR 1.55, 95% CI 1.04, 2.91; 4th quartile: OR 1.36, 95% CI 1.05, 2.72, respectively). The associations for Rundle’s LUM remained significant after further adjusting other non-redundant built environment factors. Finally, in stratified analysis, we found the association between Rundle’s LUM and telomere length was more evident among younger individuals (

Acral melanoma (AM) exhibits a high incidence in Asian patients with melanoma, and it is not well treated with immunotherapy. However, little attention has been paid to the characteristics of the immune microenvironment in AM. Therefore, in this study, we collected clinical samples from Chinese patients with AM and conducted single-cell RNA sequencing to analyze the heterogeneity of its tumor microenvironments (TMEs) and the molecular regulatory network. Our analysis revealed that genes, such as TWIST1, EREG, TNFRSF9, and CTGF could drive the deregulation of various TME components. The molecular interaction relationships between TME cells, such as MIF-CD44 and TNFSF9-TNFRSF9, might be an attractive target for developing novel immunotherapeutic agents.

Introduction Given the evidence that the matrix metalloproteinases (MMPs) play an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD), a number of case-control studies have attempted to assess the relationship between genetic polymorphisms in MMP genes and COPD risk. However, reliable measures of these results are lacking. Material and methods We assessed the published evidence for association of the MMP-3, MMP-9 and MMP-12 polymorphisms with COPD risk using meta-analytic techniques. The odds ratio (OR) and 95% confidence interval (CI) were calculated for each study using fixed or random effect models. Results A total of 23 case-control studies were included in the meta-analysis. No significant association was observed between the MMP-9 rs3918242 polymorphism and COPD risk in the overall populations under the dominant (T/T + C/T vs. C/C: OR = 1.30, 95% CI: 1.00–1.69, p = 0.054) and allele contrast (T allele vs. C allele: OR = 1.22, 95% CI: 0.97–1.53, p = 0.088) models. However, in sub-group analysis the polymorphism rs3918242 was significant in Asians under the dominant model (T/T + C/T vs. C/C: OR = 1.66, 95% CI: 1.02–2.72, p = 0.043). The results for MMP-12 rs2276109 showed an association with COPD only in mixed populations (G/G + A/G vs. A/A: OR = 1.57, 95% CI: 1.10–2.24, p = 0.013; G allele vs. A allele: OR = 1.52, 95% CI: 1.09–2.14, p = 0.015). We did not find any significant association of the MMP-12 rs652438 and MMP-3 rs35068180 polymorphisms with COPD. Conclusions The findings of this meta-analysis suggest that there is a risk of COPD associated with the MMP-9 rs3918242 and MMP-12 rs2276109 polymorphisms in certain ethnic groups.

Tomato zonate spot virus (TZSV), a member of the genus orthotospovirus, causes severe damage to vegetables and ornamental crops in southwest China. The NSs protein is an RNA silencing suppressor in various orthotospovirus like TZSV, but its mechanism and role in virus infection are poorly understood. Here, we observed that an NSs-GFP fusion protein was transiently expressed on the plasma membrane and Golgi bodies in Nicotiana benthamiana plants. The TZSV NSs gene was silenced and infiltrated into N. benthamiana and N. tabacum cv. K326. RT-qPCR and Indirect enzyme-linked immunosorbent assay (ID-ELISA) showed that the transcription and the protein expression of the NSs gene were inhibited by more than 90.00%, and the symptoms on silenced plants were alleviated. We also found that the expression of the Zingipain-2-like gene significantly decreased when the NSs gene was silenced, resulting in co-localization of the NSs-GFP and the Zingipain-2-like-mCherry fusion protein. The findings of this study provide new insights into the mechanism of silencing suppression by NSs, as well as its effect on systemic virus infection, and also support the theory of disease resistance breeding and control and prevention of TZSV in the field.

Malignant melanoma (MM) is a malignant tumor originating from melanocytes, with high aggressiveness, high metastasis and extremely poor prognosis. MM accounts for 4% of skin cancers and 80% of mortality, and the median survival of patients with metastatic melanoma is only about 6 months, with a five-year survival rate of less than 10%. In recent years, the incidence of melanoma has gradually increased and has become one of the serious diseases that endanger human health. Competitive endogenous RNA (ceRNA) is the main model of the mechanism by which long chain non-coding RNAs (lncRNAs) play a regulatory role in the disease. LncRNAs can act as a “sponge”, competitively attracting small RNAs (micoRNAs; miRNAs), thus interfering with miRNA function, and affect the expression of target gene messenger RNAs (mRNAs), ultimately promoting tumorigenesis and progression. Bioinformatics analysis can identify potentially prognostic and therapeutically relevant differentially expressed genes in MM, finding lncRNAs, miRNAs and mRNAs that are interconnected through the ceRNA network, providing further insight into gene regulation and prognosis of metastatic melanoma. Weighted co-expression networks were used to identify lncRNA and mRNA modules associated with the metastatic phenotype, as well as the co-expression genes contained in the modules. A total of 17 lncRNAs, six miRNAs, and 11 mRNAs were used to construct a ceRNA interaction network that plays a regulatory role in metastatic melanoma patients. The prognostic risk model was used as a sorter to classify the survival prognosis of melanoma patients. Four groups of ceRNA interaction triplets were finally obtained, which miR-3662 might has potential implication for the treatment of metaststic melanoma patients, and futher experiments confirmed the regulating relationship and phenotype of this assumption. This study provides new targets to regulate metastatic process, predict metastatic potential and indicates that the miR-3662 can be used in the treatment of melanoma.

There have been no studies as to whether parthanatos, a poly (adenosine diphosphate-ribose) polymerase-1 (PARP-1)-dependent and apoptosis-inducing factor (AIF)-mediated caspase-independent programmed cell death, is present in pulmonary hypertension (PH). Basic studies have, however, been conducted on several of the key molecules in parthanatos, such as PARP-1, AIF, and macrophage migration inhibitory factor (MIF). For this study, we collected blood samples from 88 incident male patients with PH and 50 healthy controls at the Shanghai Pulmonary Hospital. We measured the key factors of parthanatos (PARP-1, PAR, AIF, and MIF) by enzyme-linked immunosorbent assay and performed a logistic regression, Cox proportional hazards analysis, and Kaplan–Meier test to assess the prognostic value of the key molecules in diagnosing and predicting survival. The patients who ultimately died had a significantly poorer clinical status during the study than those who survived. The PARP-1, PAR, AIF, and MIF levels were significantly higher in the patients than in the controls (all p < .0001), and the PARP-1, PAR, and AIF levels were higher in the nonsurvivors than in the survivors (all p < .0001). PARP-1 and AIF levels served as independent predictors of disease onset and mortality in these patients (all p < .005). Patients with PARP-1 levels

Fatty liver disease: Bacterial metabolite protects liver by maintaining gut integrity A molecule made by beneficial microbes in the gut helps protect against a severe form of fatty liver disease by preventing bacterial toxins from leaking out of the intestines into the bloodstream. A research team in China led by Yu Li from the Shanghai Institute of Nutrition and Health (CAS) and Jian-Gao Fan from Xinhua Hospital (SJTU) showed in a rat model of non-alcoholic steatohepatitis that indole-3-propionic acid (IPA), a metabolite produced by gut bacteria, helps maintain the integrity of the intestinal inner lining. The more robust intestinal barrier ensures that bacterial toxins do not enter the bloodstream and eventually reach the liver, where they can trigger injury-inducing inflammation. The findings reveal an interaction between the gut microbiome and the liver, and suggest a role for IPA in the treatment of fatty liver disease.

Abstract. Background. Imbalance of intestinal microbiota was closely related to colitis. Under these circumstances, regulation of enteric flora may be beneficial to the repair of inflammation. We aimed to investigate the effects of probiotics (Bifidobacterium and Lactobacillus), prebiotics and their combination on inflammation, and microflora in mice of acute colitis. Methods. C57BL/6J mice were divided into six groups randomly (blank control group, model control group, probiotics group, synbiotics group, lactitol group and probiotics + lactitol group). Each group was given 2.5% dextran sulfate sodium drinking water for 5 days other than the blank control group. Except for the model control group, the other four groups were intervened with probiotics, synbiotics (probiotics and inulin), lactitol, and probiotics + lactitol. Mice were sacrificed after 1 week of gavage, and pathologic scores were calculated. The feces of different periods and intestinal mucosa samples were collected to analyze the differences of intestinal microbiota by 16S rRNA sequencing. Differences of two groups or multiple groups were statistically examined through unpaired Student t test and analysis of variance (ANOVA), respectively. ANOVA, Tukey, Anosim, and metastats analysis were used to compare differences of microbiota among different groups. Results. After gavage for 1 week, the pathologic scores of groups with the intervention were significantly lower than those in the model control group, and the difference was statistically significant (P

Background: MicroRNAs (miRNAs) are involved in oncogenesis of esophageal squamous cell carcinoma (ESCC). miR-134 is reported to have a tumour-suppressive role but its role in ESCC is not known. The present study was designed to examine whether miR-134 inhibits ESCC development and further explored relevant underlying mechanisms. Methods: Differentially expressed genes related to ESCC were identified from microarray gene expression profiles. Immunohistochemical staining and RT-qRCR assays identified elevated PLXNA1 expression levels and low miR-134. The relationship between miR-134 and PLXNA1 was predicted and further verified by a dual-luciferase reporter assay. The expression levels of miR-134 and PLXNA1 in ESCC cells were modified by miR-134 mimic/inhibitor and siRNA against PLXNA1, respectively. Thereafter, the expression of MAPK signalling pathway-related proteins, as well as the viability, migration, invasion, cell cycle and cell apoptosis of ESCC cells was investigated. Findings: The results showed that miR-134 could block the MAPK signalling pathway by downregulating PLXNA1. When miR-134 was overexpressed or PLXNA1 was silenced, cell apoptosis was enhanced, the cell cycle was retarded, and the cell proliferation, migration and invasion were suppressed. In vivo experiments confirmed that miR-134 overexpression or PLXNA1 silencing restrained tumour growth and lymph node metastasis. Interpretation: These findings demonstrate that cancer cell proliferation, migration, invasion, and tumour metastasis of ESCC can be suppressed by overexpression of miR-134 through downregulating PLXNA1, which subsequently blocks the MAPK signalling pathway. These results provide new potential targets and strategies for the treatment of ESCC. Keywords: microRNA-134, PLXNA1, MAPK signalling pathway, Esophageal squamous cell carcinoma, Proliferation, Apoptosis, Lymph node metastasis

Abstract. Background:. Extranodal natural killer/T-cell lymphoma (ENKTL), nasal type, is an aggressive entity within the World Health Organization classification of lymphoid tumors. The International Prognostic Index is reported to be prognostically meaningful for ENKTL, but lacks discriminatory power for stage I/II ENKTL with extensive local invasion. This study aimed to evaluate the prognostic effects of local invasion by site and tissue type in patients with ENKTL. Methods:. We retrospectively analyzed data of 86 patients who were diagnosed with ENKTL by the Department of Pathology of Beijing Tongren Hospital from June 2002 to April 2016, and ascertained tumor infiltration of adjacent structures (AS), bone, and soft tissue for each patient, using physical findings and imaging scans. We used univariate and multivariate analysis to assess the association of each involved tissue or site with patients’ overall survival (OS). Results:. Of the 86 patients, 71 (82.6%) experienced invasion of AS, 22 (25.6%) of soft tissue, and 26 (30.2%) had bone involvement. Overall, patients with AS involvement did not show significantly shorter survival than those without AS involvement (Log rank χ2 = 1.177, P = 0.278); however, patients who had involved eyeballs or brains showed significantly lower 2-year OS rates than those without eyeball involvement (Log rank χ2 = 4.105, P = 0.043) or brain involvement (Log rank χ2 = 7.126, P = 0.008). Patients with involved local soft tissue or bones, respectively, showed lower 2-year OS rates than those without involved local soft tissue (Log rank χ2 = 10.390, P = 0.001) or bones (Log rank χ2 = 8.993, P = 0.003). Multivariate analysis showed that involvement of the cheek or facial muscles (hazard ratio, HR = 5.471, 95% confidence interval [CI]: 1.466–20.416, P = 0.011) and the maxilla bone (HR = 6.120, 95% CI: 1.517–24.694, P = 0.011) were significantly independent predictors of lower 2-year OS rates. Conclusions:. Imaging can accurately detect ENKTL invasion of AS, soft tissue, and bone. Involvement of local soft tissue or bone was significantly associated with lower 2-year OS rates. Involvements of the cheek or facial muscle, as well as maxilla bone, are independent predictors of lower 2-year OS rates in ENKTL patients.

Abstract. Background:. The zone of calcified cartilage (ZCC) plays an important role in the pathogenesis of osteoarthritis (OA) but has never been imaged in vivo with magnetic resonance (MR) imaging techniques. We investigated the feasibility of direct imaging of the ZCC in both cadaveric whole knee specimens and in vivo healthy knees using a 3-dimensional ultrashort echo time cones (3D UTE-Cones) sequence on a clinical 3T scanner. Methods:. In all, 12 cadaveric knee joints and 10 in vivo healthy were collected. At a 3T MR scanner with an 8-channel knee coil, a fat-saturated 3D dual-echo UTE-Cones sequence was used to image the ZCC, following with a short rectangular pulse excitation and 3D spiral sampling with conical view ordering. The regions of interests (ROIs) were delineated by a blinded observer. Single-component T2∗ and T2 values were calculated from fat-saturated 3D dual-echo UTE-Cones and a Carr-Purcell-Meiboom-Gill (T2 CPMG) data using a semi-automated MATLAB code. Results:. The single-exponential fitting curve of ZCC was accurately obtained with R2 of 0.989. For keen joint samples, the ZCC has a short T2∗ ranging from 0.62 to 2.55 ms, with the mean ± standard deviation (SD) of 1.49 ± 0.66 ms, and with 95% confidence intervals (CI) of 1.20–1.78 ms. For volunteers, the short T2∗ ranges from 0.93 to 3.52 ms, with the mean ± SD of 2.09 ± 0.56 ms, and the 95% CI is 1.43 to 2.74 ms in ZCC. Conclusions:. The high-resolution 3D UTE-Cones sequence might be used to directly image ZCC in the human knee joint on a clinical 3T scanner with a scan time of more than 10 min. Using this non-invasive technique, the T2∗ relaxation time of the ZCC can be further detected.

Abstract. Background:. Studies on the relationship between antiepileptic drug (AED) administration and clinical outcomes in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) remain scarce. Levetiracetam (LEV) is an AED that is neuroprotective in various neurologic disorders. This study aimed to determine the impact of LEV on the outcome of MELAS. Methods:. A retrospective, single-center study was performed based on a large cohort of patients with MELAS with a history of seizures (n = 102). Decisions on antiepileptic therapies were made empirically. Patients were followed up for 1 to 8 years (median, 4 years) and divided into 2 groups based on whether LEV was administered (LEV or non-LEV). The modified Rankin scale (mRS) scores and mortality risks were analyzed in all patients. Results:. LEV, carbamazepine, benzodiazepines, topiramate, oxcarbazepine, valproate, and lamotrigine were administered in 48, 37, 18, 13, 11, 9, and 9 patients, singly or in combination, respectively. The mean mRS score of the LEV group (n = 48) was lower than that of the non-LEV group (n = 54; mean ± standard deviation, 2.79 ± 1.47 vs. 3.83 ± 1.93, P = 0.006) up to the end of the study. Nevertheless, there was no difference in the proportion of subjects without disability (mRS ranging 0–1) between the groups (P = 0.37). The multivariate regressions revealed that LEV treatment was associated with lower mRS scores (odds ratio 0.32, 95% confidence interval [CI] 0.15–0.68, P = 0.003) and mortality rates (hazard ratio 0.24, 95% CI 0.08–0.74, P = 0.013). There was a significant difference in the Kaplan-Meier survival curves between the groups (χ2 = 4.29, P = 0.04). Conclusions:. The LEV administration is associated with lower mortality in patients with MELAS in this retrospective study. Further laboratory research and prospective cohort studies are needed to confirm whether LEV has neuroprotective effects on patients with mitochondrial diseases.

Fatty liver disease: A gutsy way to prevent disease progression A treatment for non-alcoholic fatty liver disease that incorporates a metabolite found in the gut could prevent progression to a more serious liver condition. Drugs that enhance the activity of glucagon-like peptide-1 (GLP-1), a protein involved in regulating metabolic processes, have shown promise in targeting non-alcoholic fatty liver disease and the more serious condition, steatohepatitis. However, some patients appear resistant to treatment. Jian-Gao Fan at Shanghai Jiao Tong University in China, Huiping Zhou at McGuire VA Medical Center in Richmond, USA, and co-workers demonstrated that a gut metabolite called sodium butyrate may help encourage responsiveness to GLP-1 treatment. The team found that liver GLP-1R expression was considerably reduced in patients with liver disease compared with healthy controls. Experiments on mouse models showed that treatment incorporating sodium butyrate improved GLP-1R levels and reduced fatty liver deposits.

Miscanthus is a close relative of Saccharum and a potentially valuable genetic resource for improving sugarcane. Differences in flowering time within and between Miscanthus and Saccharum hinders intra- and interspecific hybridizations. A series of greenhouse experiments were conducted over three years to determine how to synchronize flowering time of Saccharum and Miscanthus genotypes. We found that day length was an important factor influencing when Miscanthus and Saccharum flowered. Sugarcane could be induced to flower in a central Illinois greenhouse using supplemental lighting to reduce the rate at which days shortened during the autumn and winter to 1 min d-1, which allowed us to synchronize the flowering of some sugarcane genotypes with Miscanthus genotypes primarily from low latitudes. In a complementary growth chamber experiment, we evaluated 33 Miscanthus genotypes, including 28 M. sinensis, 2 M. floridulus, and 3 M. ×giganteus collected from 20.9° S to 44.9° N for response to three day lengths (10 h, 12.5 h, and 15 h). High latitude-adapted M. sinensis flowered mainly under 15 h days, but unexpectedly, short days resulted in short, stocky plants that did not flower; in some cases, flag leaves developed under short days but heading did not occur. In contrast, for M. sinensis and M. floridulus from low latitudes, shorter day lengths typically resulted in earlier flowering, and for some low latitude genotypes, 15 h days resulted in no flowering. However, the highest ratio of reproductive shoots to total number of culms was typically observed for 12.5 h or 15 h days. Latitude of origin was significantly associated with culm length, and the shorter the days, the stronger the relationship. Nearly all entries achieved maximal culm length under the 15 h treatment, but the nearer to the equator an accession originated, the less of a difference in culm length between the short-day treatments and the 15 h day treatment. Under short days, short culms for high-latitude accessions was achieved by different physiological mechanisms for M. sinensis genetic groups from the mainland in comparison to those from Japan; for mainland accessions, the mechanism was reduced internode length, whereas for Japanese accessions the phyllochron under short days was greater than under long days. Thus, for M. sinensis, short days typically hastened floral induction, consistent with the expectations for a facultative short-day plant. However, for high latitude accessions of M. sinensis, days less than 12.5 h also signaled that plants should prepare for winter by producing many short culms with limited elongation and development; moreover, this response was also epistatic to flowering. Thus, to flower M. sinensis that originates from high latitudes synchronously with sugarcane, the former needs day lengths >12.5 h (perhaps as high as 15 h), whereas that the latter needs day lengths

Objective To develop mathematical models for skeletal age determination with multiple statistic method based on the correlation between age and the growth of the epiphysis of extremitas sternalis of clavicle in Shanxi adolescents. Methods The 562 Shanxi sternoclavicular joint samples（454 cases of modelling, 108 cases of external verification） were scanned by the thin-section computed tomography. After volume rendering was obtained, indicators such as area of epiphysis, area of metaphysis, longest diameter of epiphysis and longest diameter of metaphysis of both extremitas sternalis of clavicle were collected. Indicators such as the ratio of area of epiphysis to area of metaphysis, and the ratio of longest diameter of epiphysis to longest diameter of metaphysis of both sides were calculated. Then multiple linear regression and random forest discriminant models were used to build mathematical models for age determination of adolescents. Results The obtained indicators exhibited a strong correlation with age （r>0.85）. The multiple linear regression model for males and females （all 4 indicators entering the model） based on the ratio of longest diameter of epiphysis to longest diameter of metaphysis and the ratio of area of epiphysis to area of metaphysis had an internal validation accuracy rate （±1.0 year） of over 92% and 108 cases had an external validation accuracy rate of over 70% （±1.0 year）. The out of bag error rates of random forest discriminant models were less than 2% for people over 18.0 years old （≥18.0 years old） and under 18.0 years old. The external validation accuracy rates of the 108 cases were over 80% . Conclusion The regression and discriminant models established in this study have certain reliability and accuracy and can be used in age determination of Shanxi adolescents.

In the North China Plain, coal mining subsided lakes are surface water bodies that form after the conclusion of coal mining. In China, mining subsided lakes are often transformed into artificial wetland parks for ecological restoration. While many studies have focused on evaluating coal mining subsidence lake ecosystem service value and water pollution, little attention has been paid to changes in ecological regimes and ecological spillover effects before and after the reclamation of mining areas. This paper examines the Pan'an Lake artificial wetland in Jiawang District, Xuzhou, as a case study. Changes in the ecological regime of the mining subsidence area before and after land reclamation and corresponding spatial spillover effect on land prices are assessed based on remote sensing, GIS raster calculations and geostatistical methods. The results show that the ecosystem service value and ecological storage capacity changed significantly after the mining subsided lake was transformed into an artificial wetland and the wetland ecosystem has been developing well with significantly positive spillover effects on surrounding land prices. From 2008 to 2017, service functions of the artificial wetland ecosystem of Pan'an Lake increased by 81.95%, and the system's ecological storage capacity increased from RMB 6,754 yuan/hm2 in 2008 to RMB 12,289 yuan/hm2 in 2017. The average impact of the Pan'an Lake artificial wetland on the spillover effects of surrounding residential land prices was measured at RMB 195.18 yuan/m2, and the total spillover value of planned residential land in the study area was measured at RMB 805,422,100 yuan. The present study can serve as a useful guide for evaluating the economic feasibility of land reclamation planning and ecological restoration in mining subsidence areas.

Abstract Lead (Pb) is known to impair children’s cognitive function. It has been previously shown that developmental Pb exposure alters dendritic spine formation in hippocampal pyramidal neurons. However, the underlying mechanism has not yet been defined. In this study, a low-level gestational Pb exposure (GLE) rat model was employed to investigate the impact of Pb on the spine density of the hippocampal pyramidal neurons and its regulatory mechanism. Pb exposure resulted in impaired performance of the rats in the Morris water maze tasks, and in decreased EPSC amplitudes in hippocampal CA3-CA1 regions. With a 3D reconstruction by the Imaris software, the results from Golgi staining showed that the spine density in the CA1 region was reduced in the Pb-exposed rats in a dose-dependent manner. Decreased spine density was also observed in cultured hippocampal neurons following the Pb treatment. Furthermore, the expression level of NLGN1, a postsynaptic protein that mediates synaptogenesis, was significantly decreased following the Pb exposure both in vivo and in vitro. Up-regulation of NLGN1 in cultured primary neurons partially attenuated the impact of Pb on the spine density. Taken together, our resultssuggest that Pb exposure alters spine plasticity in the developing hippocampus by down-regulating NLGN1 protein levels.

Objective: Currently, magnetic resonance imaging (MRI) is the most commonly used imaging modality for observing the growth and development of mesenchymal stem cells (MSCs) after in vivo transplantation to treat osteoarthritis (OA). However, it is a challenge to accurately monitor the treatment effects of MSCs in the zone of calcified cartilage (ZCC) with OA. This is especially true in the physiological and biochemical views that are not accurately detected by MRI contrast agents. In contrast, ultrashort time echo (UTE) MRI has been shown to be sensitive to the presence of the ZCC, creating the potential for more effectively observing the repair of the ZCC in OA by MSCs. A special focus is given to the outlook of the use of UTE MRI to detect repair of the ZCC with OA through MSCs. The limitations of the current techniques for clinical applications and future directions are also discussed. Data Sources: Using the combined keywords: “osteoarthritis”, “mesenchymal stem cells”, “calcified cartilage”, and “magnetic resonance imaging”, the PubMed/MEDLINE literature search was conducted up to June 1, 2017. Study Selection: A total of 132 published articles were initially identified citations. Of the 132 articles, 48 articles were selected after further detailed review. This study referred to all the important English literature in full. Results: In contrast, UTE MRI has been shown to be sensitive to the presence of the ZCC, creating the potential for more effectively observing the repair of the ZCC in OA by MSCs. Conclusions: The current studies showed that the ZCC could be described in terms of its histomorphology and biochemistry by UTE MRI. We prospected that UTE MRI has been shown the potential for more effectively observing the repair of the ZCC in OA by MSCs in vivo.

Background: Arterial grafts had better mid-term and long-term patency than saphenous vein grafts in coronary artery bypass grafting (CABG). We summarized our experience with total arterial off-pump coronary artery bypass grafting (OPCAB) and assessed the early clinical results, surgical complications, and follow-up. Methods: From January 2007 to May 2017, 508 coronary artery disease patients undergoing total arterial OPCAB were enrolled. Clinical features, approaches, outcomes of surgical treatments, and follow-up data of these patients were studied retrospectively. A total of 122 patients underwent single left internal mammary artery (IMA)-left anterior descending artery grafts, whereas the other 386 patients underwent multiple vessel grafts. Results: The average distal anastomosis was 2.34 ± 0.97 (range: 1–4). All the patients were discharged from hospital except one died. A total of 457 (90.32%) patients were followed up. In the 4-, 7-, and 10-year follow-up groups, the rate of death from any cause was 1.19%, 6.47%, and 10.67%; rate of cardiac death was 0.60%, 2.88%, and 3.33%; rate of repeat revascularization was 0.00%, 3.60%, and 8.67%; rate of ischemic symptoms was 1.79%, 7.91%, and 11.33%; and incidence of stroke was 2.38%, 4.32%, and 6.67%, respectively. Poor medication adherence was observed in 9.38% of the follow-up population. Conclusions: Total arterial OPCAB with bilateral IMA, radial artery, and right gastroepiploic artery grafting yielded satisfactory early and midterm outcomes in this patient group, without a significant increase in early mortality or morbidity. Moreover, the long-term outcomes are also positive.

Abstract In this study, a structure to realize a switchover between two different responses of electromagnetically induced transparency (EIT) was designed and implemented by simulation. Taking advantage of the anisotropy in the structure and the coupling between the radiative and dark elements, a metasurface switch with modulation depth of over 85% between orthogonal polarization incident light illuminations was demonstrated. The key mode switchover between the “on” and “off” states was achieved by electrically changing the dressing light polarization with a liquid crystals layer pre-aligned with a mature technology, without changing the incident light and an expected and reversible transition from an EIT-like spectrum to a strong spectral dip was observed. The modulation in the EIT switch fabricated with the proposed straightforward approach is a promising tool to control the groping velocity delay.

Abstract Stored-product psocids (Psocoptera: Liposcelididae) are cosmopolitan storage pests that can damage stored products and cause serious economic loss. However, because of the body size (~1 mm) of eggs, nymphs, and adults, morphological identification of most stored-product psocids is difficult and hampers effective identification. In this study, 10 economically important stored-product Liposcelis spp. psocids (Liposcelis brunnea, L. entomophila, L. decolor, L. pearmani, L. rufa, L.mendax, L. bostrychophila, L. corrodens, L. paeta, and L. tricolor) were collected from 25 geographic locations in 3 countries (China, Czech Republic, and the United States). Ten species-specific probes for identifying these 10 psocid species were designed based on ITS2 sequences. The microarray method and reaction system were optimized. Specificity of each of the ten probes was tested, and all probes were found suitable for use in identification of the respective10 Liposcelis spp. psocids at 66 °C. This method was also used to identify an unknown psocid species collected in Taian, China. This work has contributed to the development of a molecular identification method for stored-product psocids, and can provide technical support not only to facilitate identification of intercepted samples in relation to plant quarantine, but also for use in insect pest monitoring.

Abstract In crop plants, a high-density genetic linkage map is essential for both genetic and genomic researches. The complexity and the large size of wheat genome have hampered the acquisition of a high-resolution genetic map. In this study, we report a high-density genetic map based on an individual mapping population using the Affymetrix Wheat660K single-nucleotide polymorphism (SNP) array as a probe in hexaploid wheat. The resultant genetic map consisted of 119 566 loci spanning 4424.4 cM, and 119 001 of those loci were SNP markers. This genetic map showed good collinearity with the 90 K and 820 K consensus genetic maps and was also in accordance with the recently released wheat whole genome assembly. The high-density wheat genetic map will provide a major resource for future genetic and genomic research in wheat. Moreover, a comparative genomics analysis among gramineous plant genomes was conducted based on the high-density wheat genetic map, providing an overview of the structural relationships among theses gramineous plant genomes. A major stable quantitative trait locus (QTL) for kernel number per spike was characterized, providing a solid foundation for the future high-resolution mapping and map-based cloning of the targeted QTL.

Abstract Selection breeding has played a key role in the improvement of seed yield and quality in oilseed rape (Brassica napus L.). We genotyped Tapidor (European), Ningyou7 (Chinese) and their progenitors with the Brassica 60 K Illumina Infinium SNP array and mapped a total of 29,347 SNP markers onto the reference genome of Darmor-bzh. Identity by descent (IBD) refers to a haplotype segment of a chromosome inherited from a shared common ancestor. IBDs identified on the C subgenome were larger than those on the A subgenome within both the Tapidor and Ningyou7 pedigrees. IBD number and length were greater in the Ningyou7 pedigree than in the Tapidor pedigree. Seventy nine QTLs for flowering time, seed quality and root morphology traits were identified in the IBDs of Tapidor and Ningyou7. Many more candidate genes had been selected within the Ningyou7 pedigree than within the Tapidor pedigree. These results highlight differences in the transfer of favorable gene clusters controlling key traits during selection breeding in Europe and China.

Background: Previous studies showed that combining apparent diffusion coefficient (ADC) value with the Spondyloarthritis Research Consortium of Canada (SPARCC) index value might provide a reliable evaluation of the activity of ankylosing spondylitis (AS), and that contrast-enhanced (CE) magnetic resonance imaging (MRI) is unnecessary. However, the results were based on confirming only a small random sample. This study aimed to assess the role of CE-MRI in differentiating the disease activity of AS by comparing ADC value with a large sample. Methods: A total of 115 patients with AS were enrolled in accordance with Bath AS Disease Activity Index and laboratory indices, and 115 patients were divided into two groups, including active group (n = 69) and inactive group (n = 46). SPARCC, ΔSI, and ADC values were obtained from the short tau inversion recovery (STIR), diffusion-weighted imaging (DWI), and CE-MRI, respectively. One-way analysis of variance and receiver operating characteristic analysis were performed for all parameters. Results: The optimal cutoff values (with sensitivity, specificity, respective area under the curve, positive likelihood ratio, and negative likelihood ratio) for the differentiation between active and inactive groups are as follows: SPARCC = 6 (72.06%, 82.61%, 0.836, 4.14, 0.34); ΔSI (%) = 153 (80.6%, 84.78%, 0.819, 5.3, 0.23); ADC value = 1.15 × 10−3 mm2/s (72.73%, 81.82%, 0.786, 4, 0.33). No statistical differences were found among the predictive values of SPARCC, ΔSI, and ADC. Multivariate analysis showed no significant difference between the combination of SPARCC and ADC values with and without ΔSI. Conclusions: Using large sample, we concluded that the combination of STIR and DWI would play significant roles in assessing the disease activity, and CE-MRI sequence is not routinely used in imaging of AS to avoid renal fibrosis and aggravation of kidney disease.

Objectives Liver kinase B1 (LKB1) is considered a tumour suppressor that can control cell growth and metabolism. Whether LKB1 expression levels are related to clinicopathology and prognosis is controversial. This review aimed to quantitatively examine the latest evidence on this question.Design An updated systematic review and meta-analysis on the association between LKB1 expression and prognosis of patients with solid tumours were performed.Data sources Eligible studies were identified through literature searches from database establishment until 15 June 2018 in the following databases: Embase, PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure and Wan Fang databases.Eligibility criteria The association between LKB1 expression and clinicopathological characteristics, overall survival (OS), disease-free survival (DFS) and relapse-free survival (RFS) of patients with solid tumours were reported. Sufficient data were available to calculate the OR or HR and 95% CI.Data extraction and synthesis Relevant data were meta-analysed for OS, DFS, RFS and various clinical parameters.Results The systematic review included 25 studies containing 6012 patients with solid tumours. Compared with patients with high LKB1 expression, patients with low expression showed significantly shorter OS in univariate analysis (HR=1.63, 95% CI 1.35 to 1.97, p

Objective To investigate the genetic polymorphisms of 18 autosomal short tandem repeats （STR） loci in Changsha Han population, and explore the population genetic relationships and evaluate its application value in forensic medicine. Methods The DNA of 2 004 unrelated individuals in Changsha Han population were amplified using Goldeneye?誖DNA ID System BASIC, and the PCR products were analyzed by electrophoresis using 3130xl genetic analyzer. The fragment sizes of alleles were analyzed subsequently by GeneMapper?誖ID v3.2. The frequency data and forensic genetic parameters ［observed heterozygosity （Ho）, expected heterozygosity （He）, power of discrimination （DP） and polymorphic information content （PIC）］ of 18 STR loci were statistically analyzed. Total probability of discrimination （TDP）, probability of exclusion in trio cases （PEtrio） and probability of exclusion in duo cases （PEduo） were calculated by Cervus 3.0. Hardy-Weinberg equilibrium and linkage disequilibrium of the loci were detected by Arlequin v3.5. The results were compared with the available data of other populations from different races and regions. Results The power of discrimination （DP）, and the polymorphic information content （PIC） of each locus of Changsha Han population ranged from 0.783 6 to 0.987 9 and 0.549 4 to 0.914 5, respectively. The TDP, cumulative probability of exclusion in trio cases （CPEtrio） and cumulative probability of exclusion in duo cases （CPEduo） were 0.999 999 999 999 999 999 999 865 2, 0.999 999 979 and 0.999 988 325, respectively. According to the Nei’s DA genetic distance, the genetic distance between Changsha Han and Hunan Han populations was the smallest （0.014 1）, while it was the largest （0.041 8） between Changsha Han and Xinjiang Kazakh populations. Conclusion The 18 STR loci shows abundant genetic polymorphisms in Changsha Han population. The study of genetic diversity among different populations has an important meaning for the research of their origins, migrations and their relationships.

Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in ≈131K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P < 1.0 x 10-5). In Stage 2, these SNVs were tested for independent external replication in ≈440K individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10-8). For African ancestry samples, we detected 18 potentially novel BP loci (P < 5.0 x 10-8) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2) have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.

Medical carbon material has been extensively studied due to their excellent biological and mechanical properties. However, the dissociation of the surface carbon particles greatly limited the application of medical carbon material (MCM). To overcome this defect, we introduced the polydimethylsiloxane, a polymer-coating material (PCM) that possesses acceptable biocompatibility, into medical carbon material to prevent the shedding of carbon debris. Additionally, to reduce inflammatory reactions and increase surface hydrophilicity, ferulic acid, also called Chinese medicine coating material (CCM), was used to modify the surface of polymer-coating material. We investigated the proliferation and adhesion of NIH-3T3 cells onto MCM, PCM and CCM in vitro. We showed that CCM exhibited excellent biological activity to promote cell growth. Twelve weeks after CCM implantation, bone defects were repaired, and the material showed acceptable chemical stability. The results indicated that the CCM composite possesses excellent mechanical property and favorable biocompatibility, which can be used for clinical bone repair.

The oral microbiome has been linked to a number of chronic inflammatory conditions, including obesity, diabetes, periodontitis, and cancers of the stomach and liver. These conditions disproportionately affect Mexican American women, yet few studies have examined the oral microbiota in this at-risk group. We characterized the 16S rDNA oral microbiome in 369 non-smoking women enrolled in the MD Anderson Mano a Mano Mexican American Cohort Study. Lower bacterial diversity, a potential indicator of oral health, was associated with increased age and length of US residency among recent immigrants. Grouping women by overarching bacterial community type (e.g., "Streptococcus," "Fusobacterium," and "Prevotella" clusters), we observed differences across a number of acculturation-related variables, including nativity, age at immigration, time in the US, country of longest residence, and a multi-dimensional acculturation scale. Participants in the cluster typified by higher abundance of Streptococcus spp. exhibited the lowest bacterial diversity and appeared the most acculturated as compared to women in the "Prevotella" group. Computationally-predicted functional analysis suggested the Streptococcus-dominated bacterial community had greater potential for carbohydrate metabolism while biosynthesis of essential amino acids and nitrogen metabolism prevailed among the Prevotella-high group. Findings suggest immigration and adaption to life in the US, a well-established mediator of disease risk, is associated with differences in oral microbial profiles in Mexican American women. These results warrant further investigation into the joint and modifying effects of acculturation and oral bacteria on the health of Mexican American women and other immigrant populations. The oral microbiome presents an easily accessible biomarker of disease risk, spanning biological, behavioral, and environmental factors.