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991.
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Xinxin Wang Xin Ma Gaobo Wei Weirui Ma Zhen Zhang Xuepeng Chen Lei Gao Zhenbo Liu Yue Yuan Lizhi Yi Jun Wang Toshinobu Tokumoto Junjiu Huang Dahua Chen Jian Zhang Jiang Liu 《基因组蛋白质组与生物信息学报(英文版)》2021,19(1):48-63
DNA methylation is a prevalent epigenetic modification in vertebrates, and it has been shown to be involved the regulation of gene expression and embryo development. However, it remains unclear how DNA methylation regulates sexual development, especially in species without sex chromosomes. To determine this, we utilized zebrafish to investigate DNA methylation reprogramming during juvenile germ cell development and adult female-to-male sex transition.We reveal that primordial germ cells(PGCs) undergo significant DNA methylation reprogramming during germ cell development, and the methylome of PGCs is reset to an oocyte/ovary-like pattern at 9 days post fertilization(9 dpf). When DNA methyltransferase(DNMT) activity in juveniles was blocked after 9 dpf, the zebrafish developed into females. We also show that Tet3 is involved in PGC development. Notably, we find that DNA methylome reprogramming during adult zebrafish sex transition is similar to the reprogramming during the sex differentiation from 9 dpf PGCs to sperm. Furthermore, inhibiting DNMT activity can prevent the female-to-male sex transition, suggesting that methylation reprogramming is required for zebrafish sex transition. In summary, DNA methylation plays important roles in zebrafish germ cell development and sexual plasticity. 相似文献
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Jingwen Ai Haocheng Zhang Qiran Zhang Yi Zhang Ke Lin Zhangfan Fu Jieyu Song Yuanhan Zhao Mingxiang Fan Hongyu Wang Chao Qiu Yang Zhou Wenhong Zhang 《Cell research》2022,32(1):103-106
Dear Editor,
As of October,2021,SARS-CoV-2 has infected more than 230 million people;promoting roll-out vaccinations could help build herd immunity for the pand... 相似文献
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Michael S. Dahabieh Fan Huang Christophe Goncalves Raúl Ernesto Flores Gonzlez Sathyen Prabhu Alicia Bolt Erminia Di Pietro Elie Khoury John Heath Zi Yi Xu Joelle Rmy-Sarrazin Koren K. Mann Alexandre Orthwein Franois-Michel Boisvert Nancy Braverman Wilson H. Miller Sonia V. del Rincn 《Autophagy》2022,18(3):540
997.
Cailian Fan Sui Liang Mengnan Ye Wanjun Cai Miao Chen Yunlong Hou Jun Guo Yi Dai 《Journal of cellular and molecular medicine》2022,26(9):2607
Pathological cardiac hypertrophy is the most important risk factor for developing chronic heart failure. Therefore, the discovery of novel agents for treating pathological cardiac hypertrophy remains urgent. In the present study, we examined the therapeutic effect and mechanism of periplocymarin (PM)‐mediated protection against pathological cardiac hypertrophy using angiotensinII (AngII)‐stimulated cardiac hypertrophy in H9c2 cells and transverse aortic constriction (TAC)‐induced cardiac hypertrophy in mice. In vitro, PM treatment significantly reduced the surface area of H9c2 cells and expressions of hypertrophy‐related proteins. Meanwhile, PM markedly down‐regulated AngII‐induced translocation of p‐STAT3 into the nuclei and enhanced the phosphorylation levels of JAK2 and STAT3 proteins. The STAT3 specific inhibitor S3I‐201 or siRNA‐mediated depleted expression could alleviate AngII‐induced cardiac hypertrophy in H9c2 cells following PM treatment; however, PM failed to reduce the expressions of hypertrophy‐related proteins and phosphorylated STAT3 in STAT3‐overexpressing cells, indicating that PM protected against AngII‐induced cardiac hypertrophy by modulating STAT3 signalling. In vivo, PM reversed TAC‐induced cardiac hypertrophy, as determined by down‐regulating ratios of heart weight to body weight (HW/BW), heart weight to tibial length (HW/TL) and expressions of hypertrophy‐related proteins accompanied by the inhibition of the JAK2/STAT3 pathway. These results revealed that PM could effectively protect the cardiac structure and function in experimental models of pathological cardiac hypertrophy by inhibiting the JAK2/STAT3 signalling pathway. PM is expected to be a potential lead compound of the novel agents for treating pathological cardiac hypertrophy. 相似文献
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Delwyn Catley Thandi Puoane Lungiswa Tsolekile Ken Resnicow Kandace K. Fleming Emily A. Hurley Joshua M. Smyth Frank T. Materia Estelle V. Lambert Mara Z. Vitolins Naomi S. Levitt Kathy Goggin 《PLoS medicine》2022,19(4)
BackgroundLow- and middle-income countries (LMICs) are experiencing major increases in diabetes and cardiovascular conditions linked to overweight and obesity. Lifestyle interventions such as the United States National Diabetes Prevention Program (DPP) developed in high-income countries require adaptation and cultural tailoring for LMICs. The objective of this study was to evaluate the efficacy of “Lifestyle Africa,” an adapted version of the DPP tailored for an underresourced community in South Africa compared to usual care.Methods and findingsParticipants were residents of a predominantly Xhosa-speaking urban township of Cape Town, South Africa characterized by high rates of poverty. Participants with body mass index (BMI) ≥ 25 kg/m2 who were members of existing social support groups or “clubs” receiving health services from local nongovernmental organizations (NGOs) were enrolled in a cluster randomized controlled trial that compared Lifestyle Africa (the intervention condition) to usual care (the control condition). The Lifestyle Africa intervention consisted of 17 video-based group sessions delivered by trained community health workers (CHWs). Clusters were randomized using a numbered list of the CHWs and their assigned clubs based on a computer-based random allocation scheme. CHWs, participants, and research team members could not be blinded to condition. Percentage weight loss (primary outcome), hemoglobin A1c (HbA1c), blood pressure, triglycerides, and low-density lipoprotein (LDL) cholesterol were assessed 7 to 9 months after enrollment. An individual-level intention-to-treat analysis was conducted adjusting for clustering within clubs and baseline values. Trial registration is at ClinicalTrials.gov (). Between February 2018 and May 2019, 782 individuals were screened, and 494 were enrolled. Participants were predominantly retired (57% were receiving a pension) and female (89%) with a mean age of 68 years. Participants from 28 clusters were allocated to Lifestyle Africa (15, n = 240) or usual care (13, n = 254). Fidelity assessments indicated that the intervention was generally delivered as intended. The modal number of sessions held across all clubs was 17, and the mean attendance of participants across all sessions was 61%. Outcome assessment was completed by 215 (90%) intervention and 223 (88%) control participants. Intent-to-treat analyses utilizing multilevel modeling included all randomized participants. Mean weight change (primary outcome) was −0.61% (95% confidence interval (CI) = −1.22, −0.01) in Lifestyle Africa and −0.44% (95% CI = −1.06, 0.18) in control with no significant difference (group difference = −0.17%; 95% CI = −1.04, 0.71; p = 0.71). However, HbA1c was significantly lower at follow-up in Lifestyle Africa compared to the usual care group (mean difference = −0.24, 95% CI = −0.39, −0.09, p = 0.001). None of the other secondary outcomes differed at follow-up: systolic blood pressure (group difference = −1.36; 95% CI = −6.92, 4.21; p = 0.63), diastolic blood pressure (group difference = −0.39; 95% CI = −3.25, 2.30; p = 0.78), LDL (group difference = −0.07; 95% CI = −0.19, 0.05; p = 0.26), triglycerides (group difference = −0.02; 95% CI = −0.20, 0.16; p = 0.80). There were no unanticipated problems and serious adverse events were rare, unrelated to the intervention, and similar across groups (11 in Lifestyle Africa versus 13 in usual care). Limitations of the study include the lack of a rigorous dietary intake measure and the high representation of older women.ConclusionsIn this study, we found that Lifestyle Africa was feasible for CHWs to deliver and, although it had no effect on the primary outcome of weight loss or secondary outcomes of blood pressure or triglycerides, it had an apparent small significant effect on HbA1c. The study demonstrates the potential feasibility of CHWs to deliver a program without expert involvement by utilizing video-based sessions. The intervention may hold promise for addressing cardiovascular disease (CVD) and diabetes at scale in LMICs.Trial registrationClinicalTrials.gov NCT03342274.In a cluster randomized trial, Delwyn Catley and colleagues evaluate an adapted version of the Diabetes Prevention Program in South Africa. NCT03342274相似文献
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Bryan T. Mayer Allan C. deCamp Yunda Huang Joshua T. Schiffer Raphael Gottardo Peter B. Gilbert Daniel B. Reeves 《PLoS computational biology》2022,18(4)
Broadly neutralizing antibodies (bNAbs) are promising agents to prevent HIV infection and achieve HIV remission without antiretroviral therapy (ART). As with ART, bNAb combinations are likely needed to cover HIV’s extensive diversity. Not all bNAbs are identical in terms of their breadth, potency, and in vivo longevity (half-life). Given these differences, it is important to optimally select the composition, or dose ratio, of combination bNAb therapies for future clinical studies. We developed a model that synthesizes 1) pharmacokinetics, 2) potency against a wide HIV diversity, 3) interaction models for how drugs work together, and 4) correlates that translate in vitro potency to clinical protection. We found optimization requires drug-specific balances between potency, longevity, and interaction type. As an example, tradeoffs between longevity and potency are shown by comparing a combination therapy to a bi-specific antibody (a single protein merging both bNAbs) that takes the better potency but the worse longevity of the two components. Then, we illustrate a realistic dose ratio optimization of a triple combination of VRC07, 3BNC117, and 10–1074 bNAbs. We apply protection estimates derived from both a non-human primate (NHP) challenge study meta-analysis and the human antibody mediated prevention (AMP) trials. In both cases, we find a 2:1:1 dose emphasizing VRC07 is nearly optimal. Our approach can be immediately applied to optimize the next generation of combination antibody prevention and cure studies. 相似文献
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精准输血对疾病治疗、急诊抢救意义重大。开展输血前多项标志物检测是保障精准治疗的关键,是降低输血风险的前提。输血前检测主要是指为保证输血安全、预防交叉感染,从而对血型、凝血、感染等进行检测。其常规检测指标包括血型、交叉配血、纤维蛋白原、病毒性肝炎、人类免疫缺陷病毒和梅毒等。传统的临床输血前检测技术以免疫分析为主。随着临床救治需求由院内向现场救治拓展,电化学传感技术、微流控技术、光谱技术等新技术也逐步发展用于输血前快速检测。基于此,本文综述了不同输血前检测技术的应用场景和优缺点,分析了系列新技术在输血前检测中的应用及未来发展趋势,为推动输血前检测乃至疾病标志物快速检测技术的发展提供参考。 相似文献