Reproductive capacity in women starts to decline beyond their mid-30s and pregnancies in older women result in higher rates of miscarriage with aneuploidy. Age-related decline in fertility is strongly attributed to ovarian aging, diminished ovarian reserves, and decreased developmental competence of oocytes. In this review, we discuss the underlying mechanisms of age-related decline in oocyte quality, focusing on oxidative stress (OS) in oocytes. The primary cause is the accumulation of spontaneous damage to the mitochondria arising from increased reactive oxygen species (ROS) in oocytes, generated by the mitochondria themselves during daily biological metabolism. Mitochondrial dysfunction reduces ATP synthesis and influences the meiotic spindle assembly responsible for chromosomal segregation. Moreover, reproductively aged oocytes produce a decline in the fidelity of the protective mechanisms against ROS, namely the ROS-scavenging metabolism, repair of ROS-damaged DNA, and the proteasome and autophagy system for ROS-damaged proteins. Accordingly, increased ROS and increased vulnerability of oocytes to ROS lead to spindle instability, chromosomal abnormalities, telomere shortening, and reduced developmental competence of aged oocytes.
[structure: see text] The enantioselective synthesis of the enantiomer of the haterumalide NA methyl ester, a cytotoxic macrolide from an Okinawan sponge, was achieved from the threitol derivative in 26 steps. The key steps are the stereoselective construction of a chloroolefin unit and the intramolecular Reformatsky-type reaction. This synthesis revised the absolute stereochemistry of haterumalide NA.
This paper reports a fast and highly sensitive all-graphene humidity sensor working in a novel alternating current (ac) detection mode for the first time, which is capable of sensing humidity on a smartphone for portable electronics. The humidity sensor is based on an interdigitated reduced graphene oxide/graphene oxide/rGO (rGO/GO/rGO) structure patterned by a facile laser direct writing method. It works in an ac sensing mode with a rectangular input voltage wave and measures the output voltage wave instead of conventional resistance, impedance, or capacitance, exhibiting a dramatically enhanced sensitivity by about 45 times compared to the low and unstable response in dc mode. The humidity sensor shows an obvious response to the relative humidity (RH) ranging from RH 6.3% to RH 100%. The response and recovery toward humidity change are almost instantaneous, and the corresponding costed times including humidity rise and decay times are less than 1.9 and 3.9 s, respectively, which are among the best results in the literature. The sensor also exhibits outstanding cycling stability, flexibility, and long-term stability (>1 year), as well as good reproducibility of device preparation. Besides, it can be easily connected to an iPhone and the humidity sensing can be conducted with an oscilloscope application on iOS. What's more, an electronic circuit simulation method was employed to fit the output waves, which can not only explain the sensing mechanism, but also determine the resistance and capacitance of the rGO/GO/rGO structure, agreeing well with the results obtained from the electrochemical measurements. It can be reasonably expected that the approach combining humidity sensing and electronic circuit simulation can be applied in real-time monitoring on a smartphone based on the Internet of things and big data technologies.
As the interface between the gut microbiota and the mucosal immune system, there has been great interest in the maintenance of colonic epithelial integrity through mitochondrial oxidation of butyrate, a short-chain fatty acid produced by the gut microbiota. Herein, we showed that the intestinal epithelium can also oxidize long-chain fatty acids, and that luminally-delivered acylcarnitines in bile can be consumed via apical absorption by the intestinal epithelium resulting in mitochondrial oxidation. Finally, intestinal inflammation led to mitochondrial dysfunction in the apical domain of the surface epithelium that may reduce the consumption of fatty acids, contributing to higher concentrations of fecal acylcarnitines in murine Citrobacter rodentiuminduced colitis and human inflammatory bowel disease. These results emphasized the importance of both the gut microbiota and the liver in the delivery of energy substrates for mitochondrial metabolism by the intestinal epithelium.
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