Consistent age-dependent declines in human semen quality: A systematic review and meta-analysis

Reduced fertility typically occurs among women in their late 30s, but increasing evidence indicates that advanced paternal age is associated with changes in reproduction as well. Numerous studies have investigated age-based declines in semen traits, but the impact of paternal age on semen parameter values remains inconclusive. Using data from 90 studies (93,839 subjects), we conducted a systematic review and meta-analysis to quantify the effect of male age on seven ejaculate traits (semen volume, sperm concentration, total sperm count, morphology, total motility, progressive motility and DNA fragmentation). Age-associated declines in semen volume, percentage motility, progressive motility, normal morphology and unfragmented cells were statistically significant and results generally seemed to be robust against confounding factors. Unexpectedly, sperm concentration did not decline with increasing male age, even though we found that sperm concentration declined over time. Our findings indicate that male age needs more recognition as a potential contributor to the negative pregnancy outcomes and reduced offspring health associated with delayed first reproduction. We suggest that greater focus on collection of DNA fragmentation and progressive motility in a clinical setting may lead to better patient outcomes during fertility treatments of aging couples.     

醋甘遂成分群B,C对正常大鼠粪便代谢组学的研究

基于代谢组学方法,对给予醋甘遂不同成分群(B,C)前后大鼠的粪便代谢物进行比较研究,探求与醋甘遂毒性相关的差异性代谢物和代谢通路,揭示醋甘遂的毒性作用机制。采用快速液相色谱串联四极杆飞行时间质谱(UFLC-Q-TOF-MS)技术,对大鼠粪便样本进行测定,结合主成分分析(PCA)和偏最小二乘-判别分析(OPLS-DA)等多种方法筛选并鉴定与醋甘遂毒性相关的生物标志物,并采用t检验进行单变量统计分析,考察给予醋甘遂成分群B,C后正常大鼠粪便这些生物标志物的含量变化,揭示醋甘遂成分群B,C对大鼠粪便代谢组的影响程度,并结合基于MetaboAnalyst数据库的代谢通路分析探求醋甘遂成分群B,C的毒性作用机制。结果显示,与空白组相比,醋甘遂成分群B和C组大鼠粪便样本代谢组发生了明显改变,且醋B组改变程度更大,发现并鉴定了16种醋甘遂毒性潜在生物标志物及5条相关代谢通路。醋甘遂的毒性作用可能与色氨酸代谢、初级胆汁酸生物合成、氨基糖和核苷酸糖代谢、嘌呤代谢和缬氨酸,亮氨酸和异亮氨酸降解等代谢通路的紊乱有关。该研究为醋甘遂的临床安全应用提供了科学依据。     

基于FPGA的神经突触的硬件实现及放电性能比较

目前专门对化学突触硬件实现的研究较少,采用FPGA芯片技术硬件实现化学突触,对神经元网络的硬件实现具有重要价值。运用DSP Builder软件,对以Hodgkin-Huxley神经元为突触前神经元和突触后神经元的化学突触数学模型进行建模。在DSP Builder模型的基础上,将化学突触的DSP Builder模型进行合理的拆分,然后分别将各个模块在FPGA所对应的软件环境下进行编译运行,最后下载到FPGA核心芯片中,硬件实现5种基于不同机理的化学突触模型。采用相关系数法,对仿真结果和硬件结果在同一个周期内的突触前神经元动作电位、突触后神经元动作电位以及突触电流的幅值进行对比,验证硬件实现的准确性。5种硬件实现的化学突触均可以较好地传递动作电位,但是各个模型消耗资源不同,模型3所消耗的内部乘法器资源(69%),约为模型5资源(31%)的2倍,表明突触模型数学复杂度越高,其消耗的乘法器资源越多。相关系数法的对比结果显示,模型3相关度最高,为0.791 3,模型4相关度最低,为0.693 5。虽然模型3数学复杂度高、硬件资源消耗多,但是其表现的生物性最好。硬件实现的5种突触模型均能较好地呈现化学突触的单向传递性,其中模型5硬件资源消耗少、相关度高,建议以其作为化学突触硬件实现的首选。     

Increasing mitochondrial ATP synthesis with butyrate normalizes ADP and contractile function in metabolic heart disease

Metabolic heart disease (MHD), which is strongly associated with heart failure with preserved ejection fraction, is characterized by reduced mitochondrial energy production and contractile performance. In this study, we tested the hypothesis that an acute increase in ATP synthesis, via short chain fatty acid (butyrate) perfusion, restores contractile function in MHD. Isolated hearts of mice with MHD due to consumption of a high fat high sucrose (HFHS) diet or on a control diet (CD) for 4 months were studied using ³¹P NMR spectroscopy to measure high energy phosphates and ATP synthesis rates during increased work demand. At baseline, HFHS hearts had increased ADP and decreased free energy of ATP hydrolysis (ΔG _{~ ATP}), although contractile function was similar between the two groups. At high work demand, the ATP synthesis rate in HFHS hearts was reduced by over 50%. Unlike CD hearts, HFHS hearts did not increase contractile function at high work demand, indicating a lack of contractile reserve. However, acutely supplementing HFHS hearts with 4mM butyrate normalized ATP synthesis, ADP, ΔG _{~ ATP} and contractile reserve. Thus, acute reversal of depressed mitochondrial ATP production improves contractile dysfunction in MHD. These findings suggest that energy starvation may be a reversible cause of myocardial dysfunction in MHD, and opens new therapeutic opportunities.     

中国南海石珊瑚Stylophora pistilata化学成分研究

目的 研究中国南海石珊瑚Stylopgora Stylophora pistillata的化学成分。方法 运用硅胶、凝胶(Sephadex LH-20)等多种柱色谱手段对化合物进行分离纯化；利用核磁共振、质谱等波谱学手段并结合其理化性质及文献数据鉴定化合物的结构。结果 从石珊瑚Stylopgora Stylophora pistillata的乙醇提取物中共分离鉴定了8个单体化合物：1,3-十四烷酸甘油二酯（1），正二十五烷（2），正二十三烷（3），肉豆蔻酸（4），2, 2"-氧代双(1, 4-二叔丁苯)（5），(R)-2-乙基己醇（6），2, 2"-bis(4-hydroxyphenyl)propane bis(2,3-epoxypropyl)ether（7）和5-hydroxy-3,4-dimethy-5- pentyl-2(5H)-furanone（8）。结论 化合物1～8均为首次从该石珊瑚中分离得到。细胞毒活性测试结果表明，化合物7对人慢性髓原白血病细胞（K562）、人肝癌细胞（BEL-7402）、人胃癌细胞（SGC-7901）、人肺癌细胞（A549）和人宫颈癌细胞(Hela)的增殖显示出一定的生长抑制活性，其余化合物对上述肿瘤细胞均无生长抑制活性。     

Thiol‐water proton exchange of glutathione,cysteine, and N‐acetylcysteine: Implications for CEST MRI

Amide‐, amine‐, and hydroxyl‐water proton exchange can generate MRI contrast through chemical exchange saturation transfer (CEST). In this study, we show that thiol‐water proton exchange can also generate quantifiable CEST effects under near‐physiological conditions (pH = 7.2 and 37°C) through the characterization of the pH dependence of thiol proton exchange in phosphate‐buffered solutions of glutathione, cysteine, and N‐acetylcysteine. The spontaneous, base‐catalyzed, and buffer‐catalyzed exchange contributions to the thiol exchange were analyzed. The thiol‐water proton exchange of glutathione and cysteine was found to be too fast to generate a CEST effect around neutral pH due to significant base catalysis. The thiol‐water proton exchange of N‐acetylcysteine was found to be much slower, yet still in the fast‐exchange regime with significant base and buffer catalysis, resulting in a 9.5% attenuation of the water signal at pH 7.2 in a slice‐selective CEST NMR experiment. Furthermore, the N‐acetylcysteine thiol CEST was also detectable in human serum albumin and agarose phantoms.     

A stapled POL κ peptide targets REV1 to inhibit mutagenic translesion synthesis

Stapled α-helical RIR (Rev1-interacting region) peptides of DNA POL κ bind more effectively to the RIR-interface of the C-terminal recruitment domain of the translesion synthesis DNA polymerase Rev1 than unstapled peptide. The tightest-binding stapled peptide translocates into cells and enhances the cytotoxicity of DNA damaging agents while reducing mutagenesis. Drugs with these characteristics could potentially serve as adjuvants to improve chemotherapy and reduce acquired resistance by inhibiting Rev1-dependent mutagenic translesion synthesis.     

Does proteostasis get lost in translation? Implications for protein aggregation across the lifespan

Protein aggregation is a phenomenon of major relevance in neurodegenerative and neuromuscular disorders, cataracts, diabetes and many other diseases. Research has unveiled that proteins also aggregate in multiple tissues during healthy aging yet, the biological and biomedical relevance of this apparently asymptomatic phenomenon remains to be understood. It is known that proteome homeostasis (proteostasis) is maintained by a balanced protein synthesis rate, high protein synthesis accuracy, efficient protein folding and continual tagging of damaged proteins for degradation, suggesting that protein aggregation during healthy aging may be associated with alterations in both protein synthesis and the proteostasis network (PN) pathways. In particular, dysregulation of protein synthesis and alterations in translation fidelity are hypothesized to lead to the production of misfolded proteins which could explain the occurrence of age-related protein aggregation. Nevertheless, some data on this topic is controversial and the biological mechanisms that lead to widespread protein aggregation remain to be elucidated. We review the recent literature about the age-related decline of proteostasis, highlighting the need to build an integrated view of protein synthesis rate, fidelity and quality control pathways in order to better understand the proteome alterations that occur during aging and in age-related diseases.