A nomogram for predicting cerebral white matter lesions in elderly men.

Objective: This study aimed to develop a nomogram tool to predict cerebral white matter lesions (WMLs) in elderly men. Methods: Based on a retrospective cohort from January 2017 to December 2019, a multivariate logistic analysis was performed to construct a nomogram for predicting WMLs. The nomogram was further validated using a follow-up cohort between January 2020 and December 2022. The calibration curve, receiver operating characteristics (ROC) curves, and the decision curves analysis (DCA) were used to evaluate discrimination and calibration of this nomogram. Result: A total of 436 male patients were enrolled in this study, and all 436 patients were used as the training cohort and 163 follow-up patients as the validation cohort. A multivariate logistic analysis showed that age, cystatin C, uric acid, total cholesterol, platelet, and the use of antiplatelet drugs were independently associated with WMLs. Based on these variables, a nomogram was developed. The nomogram displayed excellent predictive power with the area under the ROC curve of 0.951 [95% confidence interval (CI), 0.929-0.972] in the training cohort and 0.915 (95% CI, 0.864-0.966) in the validation cohort. The calibration of the nomogram was also good, as indicated by the Hosmer-Lemeshow test with p-value of 0.594 in the training cohort and 0.178 in the validation cohort. The DCA showed that the nomogram holds good clinical application value. Conclusion: We have developed and validated a novel nomogram tool for identifying elderly men at high risk of WMLs, which exhibits excellent predictive power, discrimination, and calibration.

A novel "signal on-off-super on" sandwich-type aptamer sensor of CRISPR-Cas12a coupled voltage enrichment assay for VEGF detection.

Vascular endothelial growth factor (VEGF) plays an important role in atherosclerosis, and the detection of VEGF is critical for the prevention, monitoring, and diagnosis of cardiovascular diseases. Here, a novel "signal on-off-super on" sandwich-type aptamer sensor with a triple signal amplification strategy was developed for the first time. Based on the capture aptamer was labeled with methylene blue (MB) on the internal bases, clustered regularly interspaced short palindromic repeats (CRISPR)-Cas12a-coupled voltage enrichment was used to amplify the electrochemical signal. To improve the analytical performance of the aptamer sensor, gold nanoparticles@Ti3C2Tx-Mxene (AuNPs@Ti3C2Tx-Mxene) were synthesized through the electrodeposition of AuNPs on the Ti3C2Tx-Mxene surface, providing active sites for the immobilization of the aptamer and amplifying the electrochemical signals. The excellent trans-cleavage activity of the CRISPR-Cas12a system was harnessed to cleave signal probes. The cleaved signal probes were enriched using an electrochemical signal instead of complicated target amplification steps before detection. Hence, we report a simplified detection process for amplifying electrochemical signals. Under optimal conditions, the aptamer sensor exhibited high sensitivity, acceptable stability, and reproducibility with a wide linear range from 1 pM to 10 µM (R2 = 0.9917) and an ultralow detection limit of 0.33 pM (S/N = 3). Therefore, we propose a novel strategy of CRISPR-Cas12a-based protein detection that opens a new window for the diagnostic applications of various biomarkers.

Estrogen Mediates an Atherosclerotic-Protective Action via Estrogen Receptor Alpha/SREBP-1 Signaling.

Menopause is associated with dyslipidemia and an increased risk of cardiovascular disease, the underlying mechanism of dyslipidemia is attributed to an insufficiency of estrogen. In this study, we find that estrogen mediates an atherosclerotic-protective action via estrogen receptor alpha/SREBP-1 signaling. Increased lipid accumulation and low-density lipoprotein (LDL)-uptake in HepG2 cells and THP-1 macrophages were induced by treatment of mixed hyperlipidemic serum from postmenopausal women; 17ß-estradiol [estrogen (E2)] (10 nM) administration significantly improved hyperlipidemic profiles, relieved fatty-liver damage and attenuated the plaque area in the heart chamber of high-fat diet (HFD)-fed ovariectomized (OVX) ApoE -/ - mice. Expression of sterol regulatory element-binding protein (SREBP)-1 mRNA of circulating leukocytes in postmenopausal women was strongly correlated to the serum E2 level. Exploration of data from the Gene Expression Profiling Interactive Analysis (GEPIA) database revealed that expression of SREBP-1 protein correlated to expression of estrogen receptor (ESR)α protein in the liver, blood and in normal tissue. Genetic overexpression/inhibition of ESRα resulted in increased/decreased SREBP-1 expression as well as attenuated/deteriorated lipid deposition in vitro. An inhibitor of the protein kinase B/mammalian target of rapamycin (AKT/mTOR) pathway, AZD8055, abolished ESRα-induced SREBP-1 expression in HepG2 cells. Moreover, E2 and statin co-treatment significantly reduced lipid accumulation in vitro and hindered the progression of atherosclerosis and fatty-liver damage in OVX ApoE -/ - mice. Collectively, our results suggest that estrogen could exerted its atherosclerotic-protective action via ESRα/SREBP-1 signaling. E2 might enhance the cellular sensitivity of statins and could be used as a novel therapeutic strategy against atherosclerotic disorders in postmenopausal women.

Human Plasma Transcriptome Implicates Dysregulated S100A12 Expression: A Strong, Early-Stage Prognostic Factor in ST-Segment Elevated Myocardial Infarction: Bioinformatics Analysis and Experimental Verification.

The ability of blood transcriptome analysis to identify dysregulated pathways and outcome-related genes following myocardial infarction remains unknown. Two gene expression datasets (GSE60993 and GSE61144) were downloaded from Gene Expression Omnibus (GEO) Datasets to identify altered plasma transcriptomes in patients with ST-segment elevated myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention. GEO2R, Gene Ontology/Kyoto Encyclopedia of Genes and Genomes annotations, protein-protein interaction analysis, etc., were adopted to determine functional roles and regulatory networks of differentially expressed genes (DEGs). Dysregulated expressomes were verified at transcriptional and translational levels by analyzing the GSE49925 dataset and our own samples, respectively. A total of 91 DEGs were identified in the discovery phase, consisting of 15 downregulated genes and 76 upregulated genes. Two hub modules consisting of 12 hub genes were identified. In the verification phase, six of the 12 hub genes exhibited the same variation patterns at the transcriptional level in the GSE49925 dataset. Among them, S100A12 was shown to have the best discriminative performance for predicting in-hospital mortality and to be the only independent predictor of death during follow-up. Validation of 223 samples from our center showed that S100A12 protein level in plasma was significantly lower among patients who survived to discharge, but it was not an independent predictor of survival to discharge or recurrent major adverse cardiovascular events after discharge. In conclusion, the dysregulated expression of plasma S100A12 at the transcriptional level is a robust early prognostic factor in patients with STEMI, while the discrimination power of the protein level in plasma needs to be further verified by large-scale, prospective, international, multicenter studies.

Non-targeted metabonomic analysis of plasma in patients with atherosclerosis by liquid chromatography-mass spectrometry.

Background: This study sought to analyze non-targeted plasma metabolites in patients with atherosclerosis (AS). Methods: The plasma of patients with AS (the patient group) and the plasma of age-matched and gender-matched healthy individuals (the control group) at the Taihe Hospital was collected. One hundred patients were included in the study (60 in the patient group and 40 in the control group). Fasting venous plasma was collected in the morning. The metabolites in the plasma were examined by liquid chromatography-mass spectrometry (LC-MS). An unsupervised principal component analysis (PCA) was conducted to observe the overall distribution of each sample and the stability of the analysis process. Next, a supervised partial least squares-discriminant analysis (PLS-DA) and an orthogonal partial least squares-discriminant analysis (OPLS-DA) were conducted to examine the overall differences among the metabolic profiles of the groups and identify different metabolites in the groups. Pathway enrichment was analyzed using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Results: In total, 1,126 different metabolites were detected in the patient and control groups. Compared to the control group, 411 species decreased, and 715 species increased in the patient group. There were 61 different metabolites with a variable weight in the projection (VIP) >1 and a P<0.05. There were 34 types of lipid metabolites, 10 types of carbon and oxygen compounds, 8 types of organic acids and derivatives, 4 types of organoheterocyclic compounds, 3 types of nitrogen-containing organic compounds, and 2 types of nucleotides and analogs. Compared to the control group, 47 species decreased, and 14 species increased in the patient group. The following 9 metabolites had the most significant differences (|log2fold change| >1; P<0.05): 2-tetradecanone, pantothenol, all-trans-13,14-dihydroretinol, linoleoyl ethanolamide, N-oleoylethanolamine, 4-methyl-2-pentenal, Cer (d18:1/14:0), chenodeoxycholic acid glycine conjugate, and 5-acetamidovalerate. The enrichment analysis results of the 61 different metabolite pathways identified 17 metabolic pathways with significant differences (P<0.05), including the choline metabolism, lipid metabolism, autophagy, amino acid metabolism, vitamin digestion, and absorption pathways. Conclusions: There are significant differences in non-targeted plasma metabolites between patients with AS and healthy individuals. The above-mentioned 9 most significantly different metabolites may be potential markers of AS.

Which glucose parameter best predicts poor outcome after mechanical thrombectomy for acute large vessel occlusion stroke?

BACKGROUND: Hyperglycaemia is related to adverse outcomes in patients with acute ischaemic stroke (AIS) treated with mechanical thrombectomy (MT). AIMS: To compare the predictive ability of admission blood glucose (ABG), fasting blood glucose (FBG) and glycated haemoglobin (HbA1c) in patients with acute large vessel occlusion (ALVO) stroke undergoing MT. METHODS: The study retrospectively analysed the data of 329 consecutive acute stroke patients treated with MT. Multivariate logistic regression analysis was performed to investigate the predictors of poor functional outcome. Receiver operating characteristic (ROC) analysis was performed to identify the predictive ability of ABG, FBG and HbA1c for poor functional independence in patients with ALVO stroke undergoing MT. In addition, subgroup analyses were performed for both diabetic and non-diabetic patients. RESULTS: Multiple logistic regression analysis demonstrated that ABG and FBG were independent predictors of 3-month poor functional outcome; however, HbA1c could not predict poor functional outcome. ROC analysis showed that FBG has a higher predictive ability than ABG (areas under the ROC curve (AUC): 0.689 vs 0.624; P = 0.037) and HbA1c (AUC: 0.689 vs 0.541; P < 0.001) for poor function outcome. CONCLUSIONS: ABG and FBG are independent predictors of poor functional outcome in patients with AIS undergoing MT, and FBG has a higher predictive ability than ABG and HbA1c.

Analysis of residents' food safety satisfaction from the perspective of income heterogeneity.

Food is the paramount necessity of the people, while food safety is the priority. Facing the increasingly serious food safety problems in China, how to improve food safety has become the responsibility of the whole society, and also the obligation of social development. Based on the 8000 residents' survey data, the ordinal logistic model was used to analyze the residents' satisfaction with food safety. The results show that residents are generally worried about food safety, and there is a strong demand for safe food. Gender, age, educational background, supervision, publicity, and complaint handling significantly affect residents' food safety satisfaction. In terms of income heterogeneity, low-income residents have the highest degree of satisfaction with food safety. With the improvement of income level, their degree of satisfaction is decreasing. The high-income class residents have a strong consciousness of rights safeguarding after purchasing unsafe food. For low-income residents, their awareness of rights protection is declining due to insufficient income. In the way of rights protection, most respondents choose to return or refund money after negotiation with the seller. The lack of punishment for unscrupulous sellers is one of the main reasons for the frequent occurrence of food safety problems in China.

Impact of leukoaraiosis severity on the association of outcomes of mechanical thrombectomy for acute ischemic stroke: a systematic review and a meta-analysis.

BACKGROUND: Leukoaraiosis (LA) severity is associated with poor outcome after mechanical thrombectomy (MT) for acute ischemic stroke (AIS) caused by large vessel occlusion. This meta-analysis aimed to assess the association of LA severity with AIS-related risk factors and outcomes of MT. METHODS: PubMed, Web of Science, EMBASE, and Cochrane Collaboration Database was searched for studies on MT for AIS with LA. We conducted a random-effects meta-analysis for the prevalence of stroke risk factors and the MT outcome in the absent to moderate LA and severe LA groups. RESULTS: We included seven cohort studies involving 1294 participants (1019 with absent to moderate LA and 275 with severe LA). The absent to moderate LA group had a significantly lower prevalence of coronary artery disease (odds ratio [OR] 0.43; 95% CI 0.29-0.66), atrial fibrillation (OR, 0.26; 95% CI 0.17-0.38), hypertension (OR, 0.39; 95% CI 0.24-0.61), and ischemic stroke (OR, 0.27; 95% CI 0.15-0.50) than the severe LA group. There were no significant between-group differences in symptom onset to recanalization time (364.4 versus 356.2 min, mean difference 19.4; 95% CI - 28.3 to 67.2), final recanalization rate (modified thrombolysis in cerebral infarction score of 2b/3; OR, 0.87; 95% CI 0.55-1.38), and symptomatic intracranial hemorrhage (OR, 0.62; 95% CI 0.34-1.11). The absent to moderate LA group had a higher good functional outcome (modified Rankin Scale score of 0-2 at 90 days; OR, 4.55; 95% CI 3.20-6.47) and a lower mortality rate (179/1019 vs 108/275; OR, 0.28; 95% CI 0.20-0.39). CONCLUSION: There are unique differences in the characteristics of risk factors and clinical outcomes of ischemic stroke across patients with LA of different severity. Patients with severe LA are more likely to be associated with risk factors for cerebrovascular disease and have a poor post-MT outcome.

Tellurene Nanoflake-Based NO2 Sensors with Superior Sensitivity and a Sub-Parts-per-Billion Detection Limit.

Industrial production, environmental monitoring, and clinical medicine put forward urgent demands for high-performance gas sensors. Two-dimensional (2D) materials are regarded as promising gas-sensing materials owing to their large surface-to-volume ratio, high surface activity, and abundant surface-active sites. However, it is still challenging to achieve facilely prepared materials with high sensitivity, fast response, full recovery, and robustness in harsh environments for gas sensing. Here, a combination of experiments and density functional theory (DFT) calculations is performed to explore the application of tellurene in gas sensors. The prepared tellurene nanoflakes via facile liquid-phase exfoliation show an excellent response to NO2 (25 ppb, 201.8% and 150 ppb, 264.3%) and an ultralow theory detection limit (DL) of 0.214 ppb at room temperature, which is excellent compared to that of most reported 2D materials. Furthermore, tellurene sensors present a fast response (25 ppb, 83 s and 100 ppb, 26 s) and recovery (25 ppb, 458 s and 100 ppb, 290 s). The DFT calculations further clarify the reasons for enhanced electrical conductivity after NO2 adsorption because of the interfacial electron transfer from tellurene to NO2, revealing an underlying explanation for tellurene-based gas sensors. These results indicate that tellurene is eminently promising for detecting NO2 with superior sensitivity, favorable selectivity, an ultralow DL, fast response-recovery, and high stability.

Dysregulated circulating SOCS3 and haptoglobin expression associated with stable coronary artery disease and acute coronary syndrome: An integrated study based on bioinformatics analysis and case-control validation.

OBJECTIVE: To extensively use blood transcriptome analysis to identify potential diagnostic and therapeutic targets for cardiovascular diseases. METHODS: Two gene expression datasets (GSE59867 and GSE62646) were downloaded from GEO DataSets to identify altered blood transcriptomes in patients with ST-segment elevation myocardial infarction (STEMI) compared to stable coronary artery disease (CAD). Thereafter, several computational approaches were taken to determine functional roles and regulatory networks of differentially expressed genes (DEGs). Finally, the expression of dysregulated two hub genes-suppressor of cytokine signaling 3 (SOCS3) and haptoglobin (HP)-were validated in a case-control study. RESULTS: A total of 119 DEGs were identified in the discovery phase, consisting of 71 downregulated genes and 48 upregulated genes; two hub modules consisting of two hub genes-SOCS3 and HP-were identified. In the validation phase, both SOCS3 and HP were significantly downregulated in the stable CAD and acute coronary syndrome (ACS) patients when compared with healthy controls. Meanwhile, HP was significantly upregulated in STEMI patients when compared with stable CAD patients (p=0.041). Logistic regression analysis indicated that: downregulated expression of HP correlated with increased risk of CAD [odds ratio (OR)=0.52, 95% confidence interval (CI)=0.31~0.87, p=0.013]; and downregulated expression of SOCS3 correlated with increased risk of ACS (OR=0.66, 95% CI=0.46~0.94, p=0.023) when age, gender, history of hyperlipidemia, diabetes and hypertension were included as covariates. CONCLUSION: Future clarification of how SOCS3 and HP influence the pathogenesis of disease may pave the way for the development of novel diagnostic and therapeutic methods.

Development, application, and evaluation of a problem-based learning method in clinical laboratory education.

BACKGROUND: There is a big gap between theory and real clinical practice with respect to the structure of clinical laboratory medicine (CLM) education in China. An integrated teaching method is urgently required, to improve student competency and prepare students to deal with complex challenges in the working environment. METHODS: A total of 122 fourth-year CLM students studying at Hubei University between 2018 and 2019 were randomly assigned to a traditional teaching methods group or a problem-based learning (PBL) group. In the PBL group students were instructed to exchange their thoughts, identify information gaps, rehearse and perform simulated clinical scenarios, and incorporate the new information into cases in small groups. Theory tests, questionnaires, and clinical performance assessments were used to evaluate the effectiveness of PBL and compare it with that of traditional teaching methods. RESULTS: PBL resulted in significantly better theory test scores, better student feedback scores, and clinical performance assessments, and a higher rate of satisfaction among students and teachers. CONCLUSION: PBL is an effective way to help CLM students develop comprehensive abilities to deal with real clinical laboratory work. It is a promising education method and should be generalized to all subtypes of clinical laboratory curriculums in the future.

Identification of risks of herdsmen's grassland transfer behavior in Xinjiang and Inner Mongolia and a possible risk prevention mechanism.

Effective identification of the risks of grassland circulation is an important prerequisite for improving the management of the grassland rental market. In this study, the potential risks in the game among the subjects of grassland transfer are analyzed through the lens of repeated game theory. With the help of interpretive structural modeling, we analyze the relationships and hierarchy among the risk factors in grassland circulation. We find that social, economic, and ecological risks are the main potential risks of grassland circulation, and there are strong correlations among risk factors. A risk hierarchy analysis shows that social risk is at the upper level, economic risk is at the middle level, ecological risk is at the bottom level, and there are cross-layer effects among the various risk levels. Contract risk, social security risk, and wealth gap risk are the core risk factors that trigger the risks associated with grassland transfer. Therefore, the first priority of the pasture manager (i.e., the government) should be to regulate the grassland circulation market and strengthen supervision and punishment of defaulting subjects. Second, a social security system in which the herdsmen and the government are both invested should be established. Third, the government should strengthen the construction of a "rule of law" system instead of "rule of man," to avoid the loss of government credibility caused by rent-seeking.

Down-regulated of SREBP-1 in circulating leukocyte is a risk factor for atherosclerosis: a case control study.

BACKGROUND: Sterol regulatory-element binding proteins (SREBPs) and mir-33 (miR-33a, miR-33b), which are encoded by the introns of SREBPs, are key factors in the lipid metabolism pathway. SREBPs mRNA in circulating leucocyte and carotid plaques, along with various risk factors that associated with Coronary Atherosclerotic Disease (CAD) were investigated in a central Chinese cohort. METHODS: A total of 218 coronary atherosclerotic disease (CAD) patients, and 178 non-CAD controls, were recruited to collect leukocytes. Carotid plaques and peripheral blood were obtained from CAD patients undergoing carotid endarterectomy (CEA) (n = 12) while THP-1 and peripheral blood mononuclear cells (PBMCs) were stimulated with Oxidized low-density lipoprotein (ox-LDL) to establish an in vitro foam cell formation model. SREBPs and miR-33 levels were quantified by qPCR. Routine biochemical markers were measured using standard procedures. RESULTS: SREBP-1 mRNA level of circulating leucocytes in CAD patients were significantly lower than in non-CAD controls (p = 0.005). After stratification coronary artery atherosclerotic complexity, we detected a significant reduction of SREBP-1 in high-risk complexity CAD patients (SYNTAX score > 23) (p = 0.001). Logistic regression analysis indicated that decreased expression of SREBP-1 was a risk factor of CAD (odds ratio (OR) =0.48, 95% confidence interval (CI) = 0.30~0.76, p = 0.002) after adjusting clinical confounders; the mRNA levels of SREBPs in carotid plaques correlated with the corresponding value in circulating leukocytes (SREBP-1 r = 0.717, p = 0.010; SREBP-2 r = 0.612, p = 0.034). Finally, there was no significant difference in serum miR-33 levels between CAD patients and controls. CONCLUSIONS: Our finding suggesting a potential role in the adjustment of established CAD risk. The future clarification of how SREBP-1 influence the pathogenesis of CAD might pave the way for the development of novel therapeutic methods.

Molecular Epidemiology and Risk Factors of Ventilator-Associated Pneumonia Infection Caused by Carbapenem-Resistant Enterobacteriaceae.

Ventilator-associated pneumonia (VAP) infection caused by carbapenem-resistant Enterobacteriaceae (CRE) is becoming more prevalent, thus seriously affecting patient outcomes. In this paper, we studied the drug resistance mechanism and epidemiological characteristics of CRE, and analyzed the infection and prognosis factors of VAP caused by CRE, to provide evidence for effective control of nosocomial infection in patients with VAP. A total of 58 non-repetitive CRE strains of VAP were collected from January 2016 to June 2018. To explore the risk factors of CRE infection, 1:2 group case control method was used to select non CRE infection patients at the same period as the control group. Among the 58 CRE strains, the most common isolates included Klebsiella pneumoniae and Escherichia coli. All strains were sensitive to polymyxin B, which features better sensitivity to other antibiotics such as minocycline, trimethoprim/sulfamethoxazole, and amikacin. Multiple drug resistance genes were detected at the same time in most strains. KPC-2 was the most common carbapenemase-resistant gene in Klebsiella pneumoniae, whereas NDM-1 was more common in Escherichia coli. The risk factors correlated with CRE infection included intensive care unit (ICU) occupancy time >7 days (OR = 2.793; 95% CI 1.439~5.421), antibiotic exposure during hospital stay including those to enzyme inhibitors (OR = 1.977; 95% CI 1.025~3.812), carbapenems (OR = 3.268; 95% CI 1.671~6.392), antibiotic combination therapy(OR = 1.951; 95% CI 1.020~3.732), and nerve damage (OR = 3.013; 95% CI 1.278~7.101). Multivariable analysis showed that ICU stay >7 days (OR = 1.867; 95% CI 1.609~20.026), beta-lactamase inhibitor antibiotics (OR = 7.750; 95% CI 2.219~27.071), and carbapenem (OR = 9.143; 95% CI 2.259~37.01) are independent risk factors for VAP carbapenem caused by Carbapenem-resistant Enterobacteriaceae. A high resistance rate of CRE isolated from VAP indicated that the infected patients featured higher mortality and longer hospital stay time than the control group. Multiple risk factors for CRE infection and their control can effectively prevent the spread of VAP.

Fourier transform infrared and Raman-based biochemical profiling of different grades of pure foetal-type hepatoblastoma.

The biomolecular events resulting from the progression of hepatoblastoma remain to be elucidated. Fourier-transform infrared (FTIR) and Raman spectroscopies are capable of noninvasively and accurately capturing the biochemical properties of biological tissue from its pathological status. Our aim was to probe critial biomolecular changes of liver accompanying the progression of pure foetal hepatoblastoma (PFH) by FTIR and Raman spectroscopies. Herein, biochemical alterations were both evident in the FTIR spectra (regions of 3100-2800 cm-1 and 1800-900 cm-1 ) and the Raman spectra (region of 1800-400 cm-1 ) among normal, borderline and malignant liver tissues. Compared with normal tissues, the ratios of protein-to-lipid, α-helix-to-ß-sheet, RNA-to-DNA, CH3 methyl-to-CH2 methylene, glucose-to-phospholipids, and unsaturated-to-saturated lipids intensities were significantly higher in malignant tissues, while the ratios of RNA-to-Amide II, DNA-to-Amide II, glycogen-to-cholesterol and Amide I-to-Amide II intensities were remarkably lower. These biochemical alterations in the transition from normal to malignant have profound implications not only for cyto-pathological classification but also for molecular understanding of PFH progression. The successive changes of the spectral characteristics have been shown to be consistent with the development of PFH, indicating that FTIR and Raman spectroscopies are excellent tools to interrogate the biochemical features of different grades of PFH.

4-Nonylphenol effects on rat testis and sertoli cells determined by spectrochemical techniques coupled with chemometric analysis.

Herein, vibrational spectroscopy has been applied for qualitative identification of biomolecular alterations that occur in cells and tissues following chemical treatment. Towards this end, we combined attenuated total reflection Fourier-transform infrared (ATR-FTIR) and Raman spectroscopy to assess testicular toxicology after 4-nonylphenol (NP) exposure, an estrogenic endocrine disruptor affecting testicular function in rats and other species. Rats aged 21, 35 or 50 days received NP at intra-peritoneal doses of 0, 25, 50 or 100 mg/kg for 20 consecutive days. Primary Sertoli cells (SCs) were treated with NP at various concentrations (0, 2.5, 5, 10 or 20 µM) for 12 h. Post-exposure, testicular cells, interstitial tissue and SCs were interrogated respectively using spectrochemical techniques coupled with multivariate analysis. Distinct biomolecular segregation between the NP-exposed samples vs. control were observed based on infrared (IR) spectral regions of 3200-2800 cm-1 and 1800-900 cm-1, and the Raman spectral region of 1800-900 cm-1. For in vivo experiments, the main wavenumbers responsible for segregation varied significantly among the three age classes. The main IR and Raman band differences between NP-exposed and control groups were observed for Amide (proteins), lipids and DNA/RNA. An interesting finding was that the peptide aggregation level, Amide Ӏ-to-Amide II ratio, and phosphate-to-carbohydrate ratio were considerably reduced in ex vivo NP-exposed testicular cells or SCs in vitro. This study demonstrates that ATR-FTIR and Raman spectroscopy techniques can be applied towards analysing NP-induced testicular biomolecular alterations.

Mutual promotion of apoptosis and autophagy in prepubertal rat testes induced by joint exposure of bisphenol A and nonylphenol.

BPA and NP are both typical endocrine disruptors, the exposed populations are widespread, and the health risks mustn't be ignored. However, the interactions between them on spermatogenesis are rarely mentioned. And the underlying mechanism is unclear yet. In the present study, prepubertal SD rats were exposed to different low doses of BPA and NP separately or jointly for 4 weeks. The results indicate that the joint exposure induced excessive apoptosis and autophagy in the testes, as proved by a series of characteristics such as chromatin condensation and autophagosomes formation. Besides, endocrine disorders and oxidative stress were also caused by the exposure. Apoptosis was mediated by the mitochondrial apoptosis pathway, since the Bax and Caspase-3 gene expressions significantly increased with a prominent decrease of Bcl-2. While autophagy was caused by the inhibition of the Akt/mTOR pathway, as the expressions of the downstream genes Beclin-1, Atg5, Atg12 and the split of LC3 protein increased altogether. Worse yet, autophagy and apoptosis might reinforce each other and make the situation more severe in the joint group. What's more, remarkable histopathological changes such as spermatogenic epithelium atrophy, germ cell loss, and various ultrastructural modifications were strongly related to the apoptosis and autophagy. In aggregate, this study shows the enormous risk on male reproductive system brought by the interactions between BPA and NP. The findings provide a broader vision to understand the roles of apoptosis and autophagy induced by the joint exposure in the aggravation of spermatogenesis impairment, which could be a reference for the situation of complex EDCs exposure-induced male reproductive toxicity, and possibly inspire us to find new ideas for preventive and therapeutic treatments.

Concentrations of vanadium in urine and seminal plasma in relation to semen quality parameters, spermatozoa DNA damage and serum hormone levels.

Widespread human exposure to vanadium has been well documented. Vanadium exposure was reported to induce male reproductive toxicity in toxicological studies, yet human epidemiologic studies are lacking. Here we determined the associations between environmental exposure to vanadium and semen quality, spermatozoa DNA damage and serum reproductive hormones. Concentrations of vanadium in seminal plasma and repeated urine samples were determined among 764 men recruited from a reproductive medicine centre. Associations of vanadium concentrations with semen quality parameters (n = 764), DNA integrity measures (n = 404) and serum reproductive hormones (n = 381) were assessed by logistic or linear regression models with adjustment for potential confounders. Significant positive dose-response relationships were observed between vanadium concentrations in seminal plasma and tail length and serum estradiol, as well as odds ratios for a below-reference-value sperm concentration; whereas inverse relationships between seminal plasma vanadium with total testosterone (T) and free T (all p values for trends <0.05) were observed. These relationships were maintained after adjusting for seminal plasma concentrations of other elements (i.e., arsenic, cadmium, copper, selenium, or tin). No significant associations was revealed between urinary vanadium concentrations and semen quality, spermatozoa DNA integrity and reproductive hormones. Our findings suggested that elevated vanadium exposure may be adversely associated with male reproductive health, and that seminal plasma vanadium may be a more direct exposure biomarker for the male reproductive system than urinary vanadium.

Up- regulation of miR-328-3p sensitizes non-small cell lung cancer to radiotherapy.

MicroRNAs (miRNAs) are believed to be resistant against radiotherapy in certain types of cancers. The aim of our study was to determine the clinical application of miRNAs in non-small cell lung cancer (NSCLC). Sixty NSCLC tissue samples and adjacent histologically normal tissues were obtained for miRNAs microarray analysis and validated by RT-qPCR. Correlation between miRNA expression level and clinicopathological features was evaluated. Our study examined the influence of changed miRNA expression on the damaged DNA and its associated radio sensitivity. Luciferase assay was performed to determine potential effects on the targeted gene. Our study identified fifteen altered miRNAs in which miR-328-3p was down regulated in NSCLC tumour tissue as compared to normal tissues. Down-expression of miR-328-3p was positively associated with an enhanced lymph node metastasis, advanced clinical stage and a shortened survival rate. miR-328-3p expression was decreased in A549 cells compared to other NSCLC cell lines. Up-regulation of miR-328-3p demonstrated a survival inhibition effect in A549 and restored NSCLC cells' sensitivity to radio therapy. An increased miR-328-3p expression promoted irradiation-induced DNA damage in cells. γ-H2AX was identified as the direct target of miR-328-3p. Over-expressed miR-328-3p can improve the radiosensitvity of cells by altering the DNA damage/repair signalling pathways in NSCLC.

StIL-17 gene polymorphisms in the development of pulmonary tuberculosis.

UNLABELLED: We conduct a case-control study to explore the possible association between IL-17 gene polymorphisms and development of TB. METHODS: The study population comprised 428 TB subjects and 428 control subjects between January 2013 and June 2014. Genotyping analyses of IL-17A rs2275913 and rs3748067 and IL-17F rs763780 and rs9382084 were analyzed using polymerase chain reaction-restriction fragment length of polymorphism (PCR-RFLP). RESULTS: The TB cases were more likely to have a habit of smoking when comparing with controls. By conditional logistic regression analysis, individuals carrying CC genotype of rs763780 were more likely to have a significantly increased risk of TB when compared with TT genotype. The OR (95% CI) for CC genotype of rs763780 was 2.98 (1.58-5.92). CONCLUSION: In conclusion, we suggest that rs763780 play a critical role in the etiology of TB. These findings could be helpful in identifying individuals at increased risk for developing TB.