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Oligoasthenospermia is the primary cause of infertility. However, there are still enormous challenges in the screening of critical candidates and targets of oligoasthenospermia owing to its complex mechanism. In this study, stem cell factor (SCF), c-kit, and transient receptor potential vanilloid 1 (TRPV1) biosensors were successfully established and applied to studying apoptosis and autophagy mechanisms. Interestingly, the detection limit reached 2.787 × 10−15 g/L, and the quantitative limit reached 1.0 × 10−13 g/L. Furthermore, biosensors were used to investigate the interplay between autophagy and apoptosis. Schisandrin A is an excellent candidate to form a system with c-kit similar to SCF/c-kit with a detection constant (KD) of 5.701 × 10−11 mol/L, whereas it had no affinity for SCF. In addition, it also inhibited autophagy in oligoasthenospermia through antagonizing TRPV1 with a KD of up to 4.181 × 10−10 mol/L. In addition, in vivo and in vitro experiments were highly consistent with the biosensor. In summary, high-potency schisandrin A and two potential targets were identified, through which schisandrin A could reverse the apoptosis caused by excessive autophagy during oligoasthenospermia. Our study provides promising insights into the discovery of effective compounds and potential targets via a well-established in vitro-in vivo strategy.

Biological control agents (BCAs) are considered as one of the most important strategies for controlling Fusarium wilt, and bioorganic fertilizer, in particular, has been extensively investigated. However, little is known regarding how a biocontrol microorganism affects the suppression mechanisms when combined with different amendments. In this study, a pot experiment was performed using banana plants to investigate the different mechanisms by which the biocontrol bacterium Bacillus velezensis HN03 (isolated from our laboratory) and amendments suppress Fusarium wilt. The incidence of banana wilt was decreased under HN03 and was reduced further when HN03 was combined with compost, particularly wormcast. In the suppression of Fusarium wilt, HN03 was found to influence the soil environment in various ways. HN03 increased the peroxidase level, which improves plant defense, and was highest when combined with wormcast, being 69 times higher than when combined with cow dung compost. The high accumulation of Mg and P in the “HN03 + wormcast” and Zn and Mn in the “HN03 + cow dung” treatments was negatively correlated with disease incidence. Furthermore, HN03 re-established the microbial community destroyed by the pathogen and further increased the level of suppression in the wormcast. HN03 also enhanced the functional traits of the soil, including defensive mechanism-related traits, and these traits were further enhanced by the combination of HN03 + wormcast.

Due to toxicity and persistence of paraquat (a widely used herbicide), eco-friendly remediation approaches to its contamination and effective antidotes to its poisoning have been highly desired and raised increasing concerns. Paraquat degradation was lesser in aerobic soil in comparison with anaerobic soil, and humic-reducing microorganisms (HRMs) play a key role in paraquat anaerobic transformation process. However, the degradation pathways and related mechanisms remain poorly understood. In this study, we investigated the specific interaction mechanisms of the paraquat transformation processes mediated by a humic-reducing strain under anaerobic conditions. A strain of pure culture, designated as PQ01, was successfully isolated from paddy soil using anaerobic enrichment procedure, and identified as Pseudomonas geniculata using phenotypic and phylogenetic analysis. Sucrose, glucose, pyruvate, formic acid, and acetic acid were shown to be favorable electron donors for the reduction of anthrahydroquinone-2,6-disulfonate (AQDS) reduction by PQ01. The strain also had the ability of reducing Fe(III) (hydr)oxides in the presence of sucrose with efficiencies in the order of ferrihydrite > α-FeOOH/γ-FeOOH > γ-Fe2O3 > α-Fe2O3. In the “PQ01 + paraquat + AQDS + sucrose” system, AQDS reduction and paraquat biotransformation by strain PQ01 occurred simultaneously, and the presence of sucrose significantly enhanced the biotransformation. Specific mechanisms of the electron transfer processes are promoted by both PQ01 and AQDS, and proceed in two aspects: (1) paraquat served as electron donor in the anaerobic reduction of AQDS by strain PQ01; (2) AQDS was reduced by PQ01 anaerobic metabolism to produce AH2QDS, which can directly react with paraquat under anaerobic conditions to generate a single crystal compound (molecular formula of the unit structure is C26H20N2O8S2), causing the paraquat to decline dramatically. In conclusion, this main mechanism included the microbial reduction of AQDS to AH2QDS, followed by the abiotic reaction between AH2QDS and paraquat. This study reported the new characteristics of P. geniculata capable of reducing humics analogs, Fe(III) (hydr)oxides, and paraquat, and proposed a novel electron transformation mechanism of the HRMs’ mediated degradation of organic contaminants.

Abstract Statins have been shown to induce a phosphoprotein signature that modifies MYC (myelocytomatosis viral oncogene) activation and to have anti‐inflammatory activity that may impact the risk of Non‐Hodgkin's lymphoma (NHL). We analyzed the relationship between statins and risk of NHL using data from the Women's Health Initiative (WHI). The study population included 161,563 postmenopausal women ages 50–79 years from which 712 cases of NHL were diagnosed after 10.8 years of follow‐up. Information on statin use and other risk factors was collected by self‐ and interviewer‐administered questionnaires. Multivariable‐adjusted HR and 95% CI evaluating the relationship between statin use at baseline, as well as in a time‐dependent manner and risk of NHL, were computed from Cox proportional hazards analyses. A separate analysis was performed for individual NHL subtypes: diffuse large B‐Cell lymphoma (DLBCL) (n = 228), follicular lymphoma (n = 169), and small lymphocytic lymphoma (n = 74). All statistical tests were two‐sided. There was no significant association between use of statins at baseline and risk of NHL (HR 0.85, 95% C.I. 0.67–1.08). However, in the multivariable‐adjusted time‐dependent models, statin use was associated with a borderline lower risk of NHL (HR 0.81, 95% C.I. 0.66–1.00). Considering subtypes of NHL, statin use was associated with a lower risk of DLBCL (HR 0.62, 95% C.I. 0.42–0.91). This effect was driven by lipophilic statins (HR 0.62, 95% C.I. 0.40–0.96). In the WHI, statins were associated with a lower overall risk of DLBCL, particularly attributable to lipophilic statins. These results may have impact on primary or secondary prevention of NHL, particularly DLBCL.

IntroductionTenofovir (TDF)-containing PrEP is effective for HIV prevention, but its effect on health-related quality of life (QOL) is unknown. Using data from HPTN 069/ACTG A5305, a randomized study of potential PrEP regimens comparing maraviroc alone, or together with TDF or emtricitabine (FTC), to TDF + FTC (control), we evaluated the impact of these regimens on QOL in at-risk HIV-uninfected U.S. women and men.MethodsQOL was measured at baseline (before starting medications) and every 8 weeks through week 48 using the EQ-5D-3L. Responses were converted to a scale from 0.0 (death) to 1.0 (perfect health), using published valuation weights. Mean scores were compared between groups at each time point using nonparametric testing. Multivariable linear regression was used to adjust for potential confounders.ResultsWe analyzed 186 women (median age 35 years, 65% black, 17% Hispanic) and 405 men (median age 30 years, 28% black, 22% Hispanic), including 9 transgender participants analyzed based on sex-at-birth. Mean baseline QOL was 0.91 for women and 0.95 for men. There were minimal changes in mean QOL over time for any regimen (women: p = 0.29; men: p = 0.14). There were no significant differences between participants who continued the regimen compared to participants who discontinued early (women: p = 0.61; men: p = 0.1). Mean QOL did not differ significantly by regimen at any time point, both unadjusted and after adjustment for age, race/ethnicity, adherence, and use of alcohol, marijuana, opiates, and other substances.ConclusionsQOL in at-risk individuals starting candidate PrEP regimens in a clinical trial is similar to the general population and maintained over time. This finding did not vary among regimens or when adjusted for demographics, adherence, and substance use. Our findings are the first to show that starting a candidate PrEP regimen in at-risk HIV-uninfected U.S. women and men was not associated with significant changes in QOL.Trial registrationClinicaltrials.gov NCT01505114.

Risk of non-Hodgkin lymphoma (NHL) is higher among individuals with a family history or a prior diagnosis of other cancers. Genome-wide association studies (GWAS) have suggested that some genetic susceptibility variants are associated with multiple complex traits (pleiotropy).We investigated whether common risk variants identified in cancer GWAS may also increase the risk of developing NHL as the first primary cancer.As part of the Population Architecture using Genomics and Epidemiology (PAGE) consortium, 113 cancer risk variants were analyzed in 1,441 NHL cases and 24,183 controls from three studies (BioVU, Multiethnic Cohort Study, Women's Health Initiative) for their association with the risk of overall NHL and common subtypes [diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL)] using an additive genetic model adjusted for age, sex and ethnicity. Study-specific results for each variant were meta-analyzed across studies.The analysis of NHL subtype-specific GWAS SNPs and overall NHL suggested a shared genetic susceptibility between FL and DLBCL, particularly involving variants in the major histocompatibility complex region (rs6457327 in 6p21.33: FL OR=1.29, p=0.013; DLBCL OR=1.23, p=0.013; NHL OR=1.22, p=5.9 × E-05). In the pleiotropy analysis, six risk variants for other cancers were associated with NHL risk, including variants for lung (rs401681 in TERT: OR per C allele=0.89, p=3.7 × E-03; rs4975616 in TERT: OR per A allele=0.90, p=0.01; rs3131379 in MSH5: OR per T allele=1.16, p=0.03), prostate (rs7679673 in TET2: OR per C allele=0.89, p=5.7 × E-03; rs10993994 in MSMB: OR per T allele=1.09, p=0.04), and breast (rs3817198 in LSP1: OR per C allele=1.12, p=0.01) cancers, but none of these associations remained significant after multiple test correction.This study does not support strong pleiotropic effects of non-NHL cancer risk variants in NHL etiology; however, larger studies are warranted.

African Americans have the highest rate of mortality due to coronary heart disease (CHD). Although multiple loci have been identified influencing CHD risk in European-Americans using a genome-wide association (GWAS) approach, no GWAS of incident CHD has been reported for African Americans. We performed a GWAS for incident CHD events collected during 19 years of follow-up in 2,905 African Americans from the Atherosclerosis Risk in Communities (ARIC) study. We identified a genome-wide significant SNP (rs1859023, MAF = 31%) located at 7q21 near the PFTK1 gene (HR = 0.57, 95% CI 0.46 to 0.69, p = 1.86×10(-08)), which replicated in an independent sample of over 8,000 African American women from the Women's Health Initiative (WHI) (HR = 0.81, 95% CI 0.70 to 0.93, p = 0.005). PFTK1 encodes a serine/threonine-protein kinase, PFTAIRE-1, that acts as a cyclin-dependent kinase regulating cell cycle progression and cell proliferation. This is the first finding of incident CHD locus identified by GWAS in African Americans.

BACKGROUND To investigate the relationships of hypertension, antihypertensive treatment, and sodium intake on cognitive decline in older women. METHODS Prospective follow-up of 6,426 cognitively intact women aged 65.79 years enrolled in the Women's Health Initiative Memory Study (WHIMS) with a median follow-up of 9.1 years. Dietary sodium intake was determined by food frequency questionnaires. Hypertension was defined as self-report of current drug therapy for hypertension. Blood pressure (BP) control was assessed by treatment for hypertension and clinic measurement of systolic BP . 140 mm Hg or diastolic BP . 90 mm Hg at baseline. Cognitive functioning was assessed annually by global cognitive screening, neurocognitive, and neuropsychiatric evaluations. Cognitive decline was identified by the incidence of mild cognitive impairment (MCI) or probable dementia (PD). Cox proportional hazards analyses were used to calculate hazard ratios (HRs). RESULTS Hypertension was associated with an increased risk for cognitive decline (HR 1.20; 95% confidence interval (CI) 1.04, 1.39; P = 0.02). Among women with antihypertensive medication, those with BP .140/90 mm Hg (uncontrolled BP) were at highest risk for developing cognitive decline (HR 1.30; 95% CI 1.05, 1.60) compared to women without treatment and BP <140/90 mm Hg (controlled BP). Sodium intake >1,500 mg/day did not alter the risk for cognitive decline in hypertensive women or women with antihypertensive treatment (Pfor interaction = 0.96 or 0.97). CONCLUSIONS Women with antihypertensive treatment and uncontrolled BP showed highest risk estimates for developing cognitive decline compared to non-hypertensive women. Sodium intake did not modify the risk for cognitive decline in women with hypertension or receiving antihypertensive medication. clinical trial registration http://www.clinicaltrials.gov. Unique identifier: NCT00685009 and NCT00745056 [ABSTRACT FROM AUTHOR]

The article discusses the research that investigates the shared molecular pathways and gene networks for cardiovascular disease (CVD) and type 2 diabetes mellitus (T2D) in women across different ethnicities including African Americans, Hispanic Americans, and Caucasian American women. It states the identification of ethnicity-specific pathways such as cell cycle and tight junction. It mentions that ethnicity-specific susceptibility genes and process are involved in CVD and T2D.

The article discusses a study which assessed the relationship between statins and breast cancer risk in postmenopausal women ages 50 to 79 years. Topics covered include how information on statins was collected, the measures used for association analyses and the rate of breast cancer among statin users and nonusers.

Fibroadenomas are the most common benign breast condition among women and account for up to 50% of all breast biopsies being performed. Although considered a benign condition, fibroadenomas utilize substantial resources for management and treatment to rule out potential malignancies. Dietary factors may influence benign fibrocystic breast conditions, but little is known of their association with fibroadenomas. We examined possible associations between a broad spectrum of circulating biomarkers of dietary intake and risk of fibroadenomas. Participants were women in a breast self-examination trial in Shanghai, China who were diagnosed with fibroadenomas (n = 258) and 1035 controls. Conditional logistic regression was used to estimate adjusted odds ratios (OR) and 95% CI. Isoflavone concentrations were inversely associated with risk of fibroadenomas. Adjusted OR (95% CI) for the highest versus the lowest quartile of plasma concentration were 0.36 (0.16-0.79; P-trend < 0.001) for daidzein and 0.39 (0.19-0.84; P-trend = 0.010) for genistein. We also observed inverse associations between higher percentages of the RBC (n-3) fatty acids, eicosapentaenoic acid (EPA) ([0.38 (0.19-0.77); P-trend = 0.007] and docosapentaenoic acid (DPA) [0.32 (0.15-0.70); P-trend = 0.024], and fibroadenoma risk. Circulating concentrations of carotenoids, vitamin C, retinol, and ferritin were not associated with fibroadenoma risk. The inverse associations between plasma isoflavone concentrations and RBC EPA and DPA and fibroadenoma risk suggest that higher intakes of soy foods and fatty fish may lower the risk of fibroadenomas. [ABSTRACT FROM AUTHOR]

Fibroadenomas are common benign breast conditions among women and account for approximately 50% of breast biopsies performed. Dietary factors are known to influence benign breast conditions in the aggregate, but little is known of their association specifically with fibroadenoma. Our objective in this study was to evaluate the association between dietary and other factors and fibroadenoma risk. A case-control study, nested in a randomized trial of breast self-examination (BSE) in Chinese textile workers in Shanghai, China, was conducted between 1989 and 2000. The study sample included 327 affected women and 1070 controls. Women were administered a FFQ and a questionnaire that elicited reproductive and gynecological history and other information. Odds ratios, as estimates of relative risks, were calculated using multivariate conditional logistic regression. Significant decreasing trends in risk of fibroadenoma were observed with intake of fruits and vegetables and with number of live births, and a reduced risk was also associated with natural menopause, oral contraceptive use, and moderate exercise (walking and gardening). Increased risk of fibroadenoma was associated with heavy physical activity in one's 20s, breast cancer in a first-degree relative, and a history of prior benign breast lumps; and significant increasing trends in risk were observed with numbers of BSE per year and years of education. In conclusion, a diet rich in fruits and vegetables and the use of oral contraceptives may reduce risk of fibroadenoma. [ABSTRACT FROM AUTHOR]

Background: The relationship between serum 25-hydroxyvitamin D [25(OH) vitamin D] concentration and hip fractures is unclear. Objective: To see whether low serum 25(OH) vitamin D concentrations are associated with hip fractures in community-dwelling women. Design: Nested case-control study. Setting: 40 clinical centers in the United States. Participants: 400 case-patients with incident hip fracture and 400 control participants matched on the basis of age, race or ethnicity, and date of blood draw. Both groups were selected from 39 795 postmenopausal women who were not using estrogens or other bone-active therapies and who had not had a previous hip fracture. Measurements: Serum 25(OH) vitamin D was measured and patients were followed for a median of 7.1 years (range, 0.7 to 9.3 years) to assess fractures. Results: Mean serum 25(OH) vitamin D concentrations were lower in case-patients than in control participants (55.95 nmol/L [SD, 20.28] vs. 59.60 nmol/L [SD, 18.05]; P = 0.007), and lower serum 25(OH) vitamin D concentrations increased hip fracture risk (adjusted odds ratio for each 25-nmol/L decrease, 1.33 [95% CI, 1.06 to 1.68]). Women with the lowest 25(OH) vitamin D concentrations (≤47.5 nmol/L) had a higher fracture risk than did those with the highest concentrations (≥70.7 nmol/L) (adjusted odds ratio, 1.71 [CI, 1.05 to 2.79]), and the risk increased statistically significantly across quartiles of serum 25(OH) vitamin D concentration (P for trend = 0.016). This association was independent of number of falls, physical function, frailty, renal function, and sex-steroid hormone levels and seemed to be partially mediated by bone resorption. Limitations: Few case-patients were nonwhite women. Bone mineral density and parathyroid hormone levels were not accounted for in the analysis. Conclusion: Low serum 25(OH) vitamin D concentrations are associated with a higher risk for hip fracture. [ABSTRACT FROM AUTHOR]

Consider a placebo-controlled preventive HIV vaccine efficacy trial. An HIV amino acid sequence is measured from each volunteer who acquires HIV, and these sequences are aligned together with the reference HIV sequence represented in the vaccine. We develop genome scanning methods to identify positions at which the amino acids in infected vaccine recipient sequences either (A) are more divergent from the reference amino acid than the amino acids in infected placebo recipient sequences or (B) have a different frequency distribution than the placebo sequences, irrespective of a reference amino acid. We consider t-test-type statistics for problem A and Euclidean, Mahalanobis, and Kullback–Leibler-type statistics for problem B. The test statistics incorporate weights to reflect biological information contained in different amino acid positions and mismatches. Position-specific p-values are obtained by approximating the null distribution of the statistics either by a permutation procedure or by a nonparametric estimation. A permutation method is used to estimate a cut-off p-value to control the per comparison error rate at a prespecified level. The methods are examined in simulations and are applied to two HIV examples. The methods for problem B address the general problem of comparing discrete frequency distributions between groups in a high-dimensional data setting. [ABSTRACT FROM AUTHOR]

The article focuses on a study which investigated the association of plasma isoflavones and fibrocystic breast conditions and breast cancer among women in Shanghai, China. A breast self-examination trial was conducted among women diagnosed with breast cancer or a benign breast condition and 1,003 aged-matched controls with no known breast disease. The study found that isoflavone concentrations were inversely associated with risk of nonproliferative and proliferative benign fibrocystic conditions, as well as with breast cancer.

This study was conducted to identify reproductive and dietary factors associated with benign proliferative mammary epithelial cell changes. Subjects were women enrolled in a randomized trial of breast self-examination in Shanghai, China. Women who developed fibrocystic breast conditions classified as nonproliferative (175 women), proliferative (181 women), or proliferative with atypia (33 women) between 1995 and 2000 and 1,070 unaffected trial participants were administered general risk factor and food frequency questionnaires. Conditional logistic regression was used to estimate adjusted odds ratios and 95% confidence intervals. High parity and consumption of fresh fruits and vegetables were more strongly associated with a reduced risk of proliferative and atypical lesions than with nonproliferative conditions. For the fourth quartile of consumption versus the first, odds ratios for lesions diagnosed as nonproliferative, proliferative, and proliferative with atypia were 0.4 (95% confidence interval (CI): 0.2, 0.7), 0.2 (95% CI: 0.1, 0.4), and 0.1 (95% CI: 0.03, 0.5), respectively, for fruit intake and 0.6 (95% CI: 0.3, 1.1), 0.4 (95% CI: 0.2, 0.7), and 0.1 (95% CI: 0.1, 0.9), respectively, for vegetable intake. Reduced but nonsignificant risks in relation to soy products were observed for proliferative and atypical lesions. No single nutrient or botanical family was appreciably more strongly associated with proliferative conditions than with nonproliferative conditions, after results were controlled for total fruit and vegetable consumption. A diet rich in fruits and vegetables may reduce cellular proliferation in the mammary epithelium; this is one mechanism by which such a diet could reduce risk of breast cancer. [ABSTRACT FROM AUTHOR]

Analyzes the randomized trial of breast self-examination in Shanghai, China. Estimated effect of breast self-examination on breast-cancer mortality; Impact of breast self-examination on a population-based registry; Role of breast self-examination in early detection of cancer.