Genome-wide profiling of gene expression in the epididymis of alpha-chlorohydrin-induced infertile rats using an oligonucleotide microarray

<p>Abstract</p> <p>Background</p> <p>As one of the chlorinated antifertility compounds, alpha-chlorohydrin (ACH) can inhibit glyceraldehyde-3-phosphate dehydrogenase (G3PDH) activity in epididymal sperm and affect sperm energy metabolism, maturation and fertilization, eventually leading to male infertility. Further studies demonstrated that the inhibitory effect of ACH on G3PDH is not only confined to epididymal sperm but also to the epididymis. Moreover, little investigation on gene expression changes in the epididymis after ACH treatment has been conducted. Therefore, gene expression studies may indicate new epididymal targets related to sperm maturation and fertility through the analysis of ACH-treated infertile animals.</p> <p>Methods</p> <p>Rats were treated with ACH for ten consecutive days, and then each male rat copulated with two female rats in proestrus. Then sperm maturation and other fertility parameters were analyzed. Furthermore, we identified epididymal-specific genes that are associated with fertility between control and ACH groups using an Affymetrix Rat 230 2.0 oligo-microarray. Finally, we performed RT-PCR analysis for several differentially expressed genes to validate the alteration in gene expression observed by oligonucleotide microarray.</p> <p>Results</p> <p>Among all the differentially expressed genes, we analyzed and screened the down-regulated genes associated with metabolism processes, which are considered the major targets of ACH action. Simultaneously, the genes that were up-regulated by chlorohydrin were detected. The genes that negatively regulate sperm maturation and fertility include apoptosis and immune-related genes and have not been reported previously. The overall results of PCR analysis for selected genes were consistent with the array data.</p> <p>Conclusions</p> <p>In this study, we have described the genome-wide profiles of gene expression in the epididymides of infertile rats induced by ACH, which could become potential epididymal specific targets for male contraception and infertility treatment.</p

Genetic variants in the PIWI-piRNA pathway gene DCP1A predict melanoma disease-specific survival

The Piwi-piRNA pathway is important for germ cell maintenance, genome integrity, DNA methylation and retrotransposon control and thus may be involved in cancer development. In this study, we comprehensively analyzed prognostic roles of 3,116 common SNPs in PIWI-piRNA pathway genes in melanoma disease-specific survival. A published genome-wide association study (GWAS) by The University of Texas M.D. Anderson Cancer Center was used to identify associated SNPs, which were later validated by another GWAS from the Harvard Nurses' Health Study and Health Professionals Follow-up Study. After multiple testing correction, we found that there were 27 common SNPs in two genes (PIWIL4 and DCP1A) with false discovery rate < 0.2 in the discovery dataset. Three tagSNPs (i.e., rs7933369 and rs508485 in PIWIL4; rs11551405 in DCP1A) were replicated. The rs11551405 A allele, located at the 3' UTR microRNA binding site of DCP1A, was associated with an increased risk of melanoma disease-specific death in both discovery dataset [adjusted Hazards ratio (HR) = 1.66, 95% confidence interval (CI) = 1.21-2.27, p =1.50 × 10-3 ] and validation dataset (HR = 1.55, 95% CI = 1.03-2.34, p = 0.038), compared with the C allele, and their meta-analysis showed an HR of 1.62 (95% CI, 1.26-2.08, p =1.55 × 10-4 ). Using RNA-seq data from the 1000 Genomes Project, we found that DCP1A mRNA expression levels increased significantly with the A allele number of rs11551405. Additional large, prospective studies are needed to validate these findings

Understanding PITX2-Dependent Atrial Fibrillation Mechanisms through Computational Models

From MDPI via Jisc Publications RouterHistory: accepted 2021-07-16, pub-electronic 2021-07-19Publication status: PublishedFunder: National Key Research and Development Program of China; Grant(s): 2019YFC0120100, 2019YFC0121907Funder: National Natural Science Foundation of China; Grant(s): 61901192Atrial fibrillation (AF) is a common arrhythmia. Better prevention and treatment of AF are needed to reduce AF-associated morbidity and mortality. Several major mechanisms cause AF in patients, including genetic predispositions to AF development. Genome-wide association studies have identified a number of genetic variants in association with AF populations, with the strongest hits clustering on chromosome 4q25, close to the gene for the homeobox transcription PITX2. Because of the inherent complexity of the human heart, experimental and basic research is insufficient for understanding the functional impacts of PITX2 variants on AF. Linking PITX2 properties to ion channels, cells, tissues, atriums and the whole heart, computational models provide a supplementary tool for achieving a quantitative understanding of the functional role of PITX2 in remodelling atrial structure and function to predispose to AF. It is hoped that computational approaches incorporating all we know about PITX2-related structural and electrical remodelling would provide better understanding into its proarrhythmic effects leading to development of improved anti-AF therapies. In the present review, we discuss advances in atrial modelling and focus on the mechanistic links between PITX2 and AF. Challenges in applying models for improving patient health are described, as well as a summary of future perspectives

Case Report: Mycobacterium kansasii causing infective endocarditis explored by metagenomic next-generation sequencing

In this report, we describe the first case of infective endocarditis caused by Mycobacterium kansasii in a 45-year-old male patient who presented with a 10-day fever and decompensated cirrhosis. Despite negative results in blood culture and pathology, we employed metagenomic next-generation sequencing (mNGS) to analyze the genome sequences of both the host and microbe. The copy number variation (CNV) indicated a high risk of liver disease in the patient, which correlated with biochemical examination findings. Notably, M. kansasii sequences were detected in peripheral blood samples and confirmed through Sanger sequencing. Unfortunately, the patient’s condition deteriorated, leading to his demise prior to heart surgery. Nevertheless, we propose that mNGS could be a novel approach for diagnosing M. kansasii infection, particularly in cases where blood culture and pathology results are unavailable. It is important to consider M. kansasii infection as a potential cause of endocarditis and initiate appropriate anti-infection treatment

Podophyllotoxin Extracted from Juniperus sabina

This study aimed to investigate the antifertility effect of Juniperus sabina fruit on male rats and its possible mechanism, and hence it might be developed as a potential nonhormonal male contraceptive. Male rats were intragastrically fed for consecutive 8-week and 4-week recovery with the fruit of J. Sabina, and sperm maturation, serum testosterone level, and histopathology were analyzed. Epididymal epithelial cell culture was prepared for detection of podophyllotoxin activities. Furthermore, cell proliferation, transmission electron microscopy, Annexin V/Propidium iodide, TUNEL, RT-PCR, ELISA, and western blotting were examined. The results showed that rat sperm motility and fertility were remarkably declined after feeding the fruit. Moreover, the fruit targeted the epididymis rather than the testis. After 4-week recovery, more than half of the male rats resumed normal fertility. It was found that podophyllotoxin significantly inhibited epididymal epithelial cell proliferation, promoted cell apoptosis, and increased the mRNA and protein levels of TNF-α and the expression levels of cytochrome c, caspase-8, caspase-9, and caspase-3. Our findings suggest that the fruit of J. sabina could inhibit male rat sperm maturation and fertility. The potential mechanism might be related to podophyllotoxin, inducing epididymal epithelial cell apoptosis through TNF-α and caspase signaling pathway

The potential impacts of climate change factors on freshwater eutrophication: Implications for research and countermeasures of water management in China

Water eutrophication has become one of the most serious aquatic environmental problems around the world. More and more research has indicated climate change as a major natural factor that will lead to the acceleration of eutrophication in rivers and lakes. However, understanding the mechanism of climate change's effect on water eutrophication is difficult due to the uncertainties caused by its complex, non-linear process. There is considerable uncertainty about the magnitude of future temperature changes, and how these will drive eutrophication in water bodies at regional scales under the effect of human activities. This review collects the existing international and domestic literature from the last 10 years, discussing the most sensitive factors of climate change (i.e., temperature, precipitation, wind, and solar radiation) and analyzing their interaction with water eutrophication. Case studies of serious eutrophication and algal bloom problems in China are discussed to further demonstrate the conclusion. Finally, adaptation countermeasures and related implications are proposed in order to foster the development of sustainability strategies for water management in China

Simultaneous Removal of Nitrate and Phosphate in a Pyrrhotite and Sulfur-Circulating Packed Bed Reactor

A pyrrhotite and sulfur-circulating packed bed reactor (PS-CPBR) was constructed to study the removal process and mechanism of NO3−-N and PO43−-P with different electron donors. The results showed that the NO3−-N and PO43−-P removal performance of mixed electron donors (pyrrhotite and sulfur) was superior to the single electron donor (pyrrhotite). The optimum conditions of NO3−-N and PO43−-P removal in the PS-CPBR were a hydraulic retention time (HRT) of 12 h and a C/N of 0, and the average removal efficiency was 100% and 86.39%. The sulfur in mixed electron donors was able to promote the dissolution of pyrrhotite and the formation of polysulfide to increase the effectiveness of electron donors, promoting the removal of NO3−-N, while the PO43−-P was removed in the form of FePO4 precipitation. Microbial and functional gene analyses demonstrated that different electron donors were able to influence the abundance of microbial communities and denitrification functional genes. Meanwhile, mixed electron donors were able to increase the protein content of biofilms and reduce the resistance of electron transfer between microorganisms and electrons

Detection of QTL for High-Temperature Tolerance in Rice Using a High-Density Bin Map

Rice is sensitive to high-temperature stress during almost all stages of growth and development. High-temperature stress has become one of the main factors restricting high yield and superior quality of rice. In this study, recombinant inbred lines (RILs) derived from an indica rice cross between two restorer lines were planted in two years. One sowing date was applied in 2019, and four sowing dates were set in 2020 according to the period of local high temperatures in recent years. Two traits closely related to high-temperature tolerance, heading date (HD), and spikelet fertility (SF) were measured. In each trial, the HD showed a bimodal distribution, whereas SF had a continuous and left-skewed distribution. QTL analysis was performed using a high-density bin map. For HD, a total of six QTL were detected. All of them correspond in position to the cloned genes, among which qHD8 in the DTH8/Ghd8 region showed the largest genetic effect. For SF, a total of eight QTL were detected. Five of them, qSF1, qSF2, qSF3.1, qSF3.2, and qSF8, showed high-temperature tolerance and had an important potential in rice breeding

Identification and Validation of Quantitative Trait Loci for Grain Number in Rice (Oryza sativa L.)

Grains number is one of the most important agronomic traits in the determination of rice productivity. To explore the underlying genetic basis of grain number in rice, quantitative trait locus (QTL) analysis was performed using three recombinant inbred line populations derived from indica rice crosses of Teqing/IRBB lines, Zhenshan 97/Milyang 46, and Xieqingzao/Milyang 46, respectively. A total of 58 QTLs distributed on all 12 rice chromosomes were identified, including 22 for number of grains per panicle (NGP), 17 for number of spikelets per panicle, and 19 for spikelet fertility. The individual QTL counted for 1.5 to 22.1% of phenotypic variation. Among them, 15 QTLs shared by two or three populations and eight QTLs showed large effects with R2 larger than 10%. Furthermore, three QTLs with minor effects for NGP, qNGP5.5, qNGP9.1, and qNGP12.1, were detected and validated by eliminating the segregation of major-effect QTL using four residual heterozygote-derived populations. These results not only enrich our understanding of the mechanism of grain number, but also provide a foundation for cloning and selecting candidate for marker-assisted selection breeding in rice

Efficacy and safety of modified Valsalva maneuver for treatment of paroxysmal supraventricular tachycardia: a meta-analysis

Objective To compare the efficacy and safety of the modified versus standard Valsalva maneuver in the treatment of paroxysmal supraventricular tachycardia (PSVT). Methods The PubMed, Embase, Web of Science, CNKI, WanFang Data, and VIP electronic databases were searched to identify studies comparing the modified and standard Valsalva maneuvers in the treatment of PSVT from database inception to 1 May 2023. Two reviewers independently screened the literature, extracted the data, and assessed the risk of bias of all included studies. Results Nineteen randomized controlled trials involving 2527 patients with PSVT were included. The overall rate of cardioversion was higher in the modified than standard Valsalva group (risk ratio [RR] = 1.80, 95% confidence interval [CI] = 1.61–2.01), as was the success rate of cardioversion after a single Valsalva maneuver (RR = 2.05, 95% CI = 1.74–2.41). There was no statistically significant difference in adverse reactions between the two groups (RR = 1.07, 95% CI = 0.82–1.38). Conclusion Current evidence suggests that the modified Valsalva maneuver can significantly improve the success rate of cardioversion in patients with PSVT without increasing adverse reactions. The modified Valsalva maneuver is therefore worth promoting and should be considered as a routine first treatment. INPLASY registration number: 202310009