No abstract

NCT03169517.

Previously, we have demonstrated that human tissue kallikrein 1 (hKLK1) improves age-related erectile dysfunction (ED). Autophagy has been implicated in age-related diseases, including ED. However, the molecular mechanisms underlying hKLK1-mediated amelioration of age-related ED via regulation of autophagy remains unknown. To explore the potential mechanism, male wild-type Sprague-Dawley rats (WTR) and transgenic rats harboring human KLK1 (TGR) were bred till 4 or 18 months of age and divided into three groups: young WTR (yWTR) as the control group, aged WTR (aWTR) group, and aged TGR (aTGR) group. The erectile function of each rat was evaluated using cavernous nerve electrostimulation. The ratio of intracavernous pressure/mean arterial pressure (ICP/MAP) and total ICP were also measured. Western blotting, immunohistochemistry, and transmission electron microscopy were performed to detect the levels of autophagy. The expression levels of related signaling pathways were determined by western blotting and immunohistochemistry. We found that hKLK1 improved the impaired erectile function of aged rats. Compared to the yWTR and aTGR groups, the aWTR group showed reduced smooth muscle/collagen ratio, fewer autophagosomes, and lower expression of Beclin 1 and LC3-II, which indicate impaired smooth muscle function and low level of autophagy in the smooth muscle cells. Moreover, the PI3K/Akt/mTOR signaling pathway, which is considered to be a negative regulator of autophagy, was upregulated in the aWTR group. hKLK1 may partially restore erectile function in aged transgenic rats by upregulating protective autophagy via the PI3K/Akt/mTOR pathway. These observations indicate that hKLK1 is a potential gene therapy candidate for age-related ED.

No abstract

Proposed and demonstrated is a novel scheme of a dual-channeloutput all-optical logic AND gate. Using cascaded sum-and difference-frequency generation in a periodically poled lithium niobate (PPLN) waveguide, 20 Gbit=s logic AND operation with dual-channel outputs is successfully observed in the experiment.

The current study provides evidence that iNOS is strongly associated with hypertension.

Kallmann syndrome (KS) is a clinically and genetically heterogeneous condition characterised by hypogonadotropic hypogonadism with anosmia or hyposmia. More than nineteen genes causing KS have been reported to date. KAL1, first identified to causing the X-linked form of KS, accounts for 10%-20% of KS patients. In this study, we designed a panel including 17 known genes causing KS for genetic diagnosis and research and report a typical and rare family of which three generations had been affected by KS. A novel CNV in Xp22.3 was identified through targeted next-sequencing technology and high-resolution microarray. The breakpoint (chrX:8536480 and chrX:8730416) was defined, and the size of deletion is about 0.24 Mb. The CNV including KAL1 and FAM9A had a negative effect on the expression of KAL1, resulting in decreased level of KAL1 mRNA in whole blood. In addition, the proband had significant improvement in testicular volumes and secondary sex characters except spermatogenesis after regular treatment, which indicates the CNV may have a negative effect on spermatogenesis. Our study expands the genotypic spectrum of KAL1 mutations associated with KS and provides a practical pipeline for genetic diagnosis or research.

No abstract