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Biomedical subjects

Ke Zhang

Publications and source records attributed to Ke Zhang.

7 recordsLinked to original sources

Fetal hypoxia causes oocyte oxidative stress damage via the Sirt3/Sod2 pathway and can be alleviated by nicotinamide mononucleotide.

Environmental hypoxia exerts detrimental effects on the reproductive capabilities of both humans and animals. A fetal hypoxia model was established in which fetal mice were kept in a high-plateau hypoxic setting from embryonic day (E) 0 to 16.5. In our previous research, we found that fetal hypoxia exposure perturbs the methylation of imprinted genes in adult sperm and causes intergenerational placental impairments in male offspring. However, the specific impacts of fetal hypoxia on the female reproductive system, particularly regarding oocyte maturation, remain poorly understood. First, we found that fetal hypoxia mice exhibited a significant reduction in the average number of pups per litter. We conducted a comprehensive analysis of the transcriptome in oocytes from the hypoxic group and investigated the metabolic alterations within the follicular microenvironment. Fetal hypoxic stress contributed to cleavage and blastocyst rate reduction and induced early apoptosis and DNA damage triggered by mitochondrial dysfunction, oxidative stress aggravation and Sirt3/Sod2 downregulation. Additionally, administration of nicotinamide mononucleotide (NMN) has been shown to prevent oocytes from mitochondrial dysfunction and developmental impairment by increasing the expression of Sirt3/Sod2 and autophagy. The number of pups per litter in fetal hypoxia mice was reduced by 57.7% compared to the control group, while NMN intervention could restore it to 73.1% of the control group. These results indicate that fetal hypoxia exposure exerts multiple potential damages to adult female reproduction, while highlighting the clinical potential of NMN supplementation as a targeted intervention to alleviate such hypoxia-associated female reproductive impairment.

Animals

Causal relationship between asthma and hernia risk: A Mendelian randomization study.

Epidemiological associations between asthma and various hernia subtypes have been reported, but the causality and direction remain unclear. This study employs a two&#x2011;sample Mendelian randomization (MR) approach to systematically assess the causal associations between asthma and 6 hernia subtypes. Using publicly available summary data of genome-wide association studies, asthma was selected as the exposure, and diaphragmatic hernia, umbilical hernia, femoral hernia, hiatus hernia, inguinal hernia, and ventral hernia were selected as outcomes. Instrumental variables were strictly screened (F-statistic&#x2005;>&#x2005;10). The inverse&#x2011;variance weighted method was used as the primary analytical approach, supplemented with MR Egger and weighted median methods. Sensitivity analyses included heterogeneity tests, horizontal pleiotropy tests, Steiger directionality tests, leave&#x2011;one&#x2011;out analyses, and Radial MR. Reverse MR was performed for validation. Forward MR analyses revealed a significant positive causal effect of asthma on diaphragmatic hernia (odds ratio [OR]&#x2005;=&#x2005;1.19, 95% confidence interval [CI]: 1.08-1.31, P&#x2005;<&#x2005;.001) and a suggestive association with umbilical hernia (OR&#x2005;=&#x2005;1.19, 95% CI: 1.05-1.34, P&#x2005;=&#x2005;.007). The umbilical hernia association was significant only by the inverse&#x2011;variance weighted method; weighted median (P&#x2005;=&#x2005;.102) and MR-Egger (P&#x2005;=&#x2005;.210) estimates were not statistically significant, and the estimate attenuated after outlier removal (confirmatory OR&#x2005;=&#x2005;1.13, 95% CI: 1.01-1.26, P&#x2005;=&#x2005;.028). Sensitivity analyses showed no significant heterogeneity or pleiotropy. Reverse MR did not identify significant causal effects of hernias on asthma, although power limitations for certain hernia subtypes should be considered. No significant associations were observed between asthma and the other hernia subtypes, although the null findings for femoral and ventral hernias should be interpreted with caution due to limited statistical power. This study provides genetic evidence supporting asthma as a causal risk factor for diaphragmatic hernia, with a suggestive association for umbilical hernia. The diaphragmatic hernia finding was robust across multiple sensitivity analyses, whereas the umbilical hernia association was less consistent and requires further confirmation. These findings contribute to a deeper understanding of the mechanistic links between asthma and specific hernia subtypes.

Mendelian Randomization Analysis

Phenacetin inhibited but acetaminophen stabilized partial nitrification/anammox system: Studies on microbial metabolism and resistance genes in biofilm and plastisphere.

Partial nitrification (PN) inhibitors, such as phenacetin (PNCT) and acetaminophen (APAP), ensure a stable nitrite supply for anaerobic ammonium oxidation (anammox). But the unknown impact of inhibitors on anammox limit the application of inhibitors. In addition to the biofilm carriers used in biological nitrogen removal systems, microplastics (MPs) (a type of emerging contaminants) are the common substrate for microbial colonization, even enriched resistance genes (RGs). This research compared the effects of 0.5, 1 and 5&#xa0;mg/L PNCT or APAP on partial nitrification-anammox (PN/A) biofilm and plastisphere. 1&#xa0;mg/L PNCT inhibited the nitrogen removal functional bacteria (Nitrosomonas, Candidatus Kuenenia, Candidatus Brocadia and Nitrospira), resulting in the sharp deteriorated performance of PN/A system. 5&#xa0;mg/L PNCT inhibited multiple metabolism pathways, resulting in the absence of electrons and energy supply of microorganisms. 0.5-1&#xa0;mg/L APAP maintained the stable operation of PN/A system. Nitrospira abundances declined from 2.8% to 1.1% after 0.5&#xa0;mg/L APAP exposure. But 5&#xa0;mg/L APAP inhibited the abundance of amoA and the production of extracellular polymeric substances, which caused the slight fluctuation of PN/A performance. PN inhibitors did not cause the sharp increase of most RGs in biofilm and water. However, MPs exhibited the huge capacity of enriching RGs, which should be removed. This study proposed that 0.5&#xa0;mg/L of APAP was suitable for the PN/A system to control dosage for practical application.

Biofilms

Comparative transcriptome analysis of Qinchuan and Wagyu cattle reveals lnc11599 as a negative regulator of intramuscular fat deposition.

BACKGROUND: Intramuscular fat (IMF) content is a critical factor determining beef quality, influenced by various factors including breed and age. However, the regulatory role of long non-coding RNAs (lncRNAs) in IMF deposition remains unclear. METHODS: This study investigated IMF deposition in the longissimus dorsi muscle of one- and two-year-old Qinchuan and Wagyu cattle through histological examination and fat content measurement. Based on transcriptome sequencing data of intramuscular fat tissue, differential expression analysis and weighted gene co-expression network analysis (WGCNA) were performed to identify lncRNAs associated with IMF deposition. The effects of a key candidate lncRNA on the adipogenic differentiation of cattle intramuscular preadipocytes were further examined. RESULTS: Results showed that Wagyu cattle exhibited stronger IMF deposition capacity than Qinchuan cattle across all age groups, with IMF content increasing with age in both breeds. We identified 7,910 lncRNAs from intramuscular fat tissue transcriptome data, including 6,455 novel lncRNAs. Through integrated differential expression analysis and WGCNA, 88 lncRNAs closely associated with IMF deposition were screened from two-year-old Qinchuan and Wagyu cattle. Notably, lnc11599 was significantly upregulated in Qinchuan cattle intramuscular fat tissue, but its expression decreased during intramuscular preadipocyte differentiation. Functional experiments demonstrated that lnc11599 knockdown enhanced adipogenic differentiation capacity, manifested as a highly significant increase in lipid accumulation, upregulation of key adipogenic genes at the mRNA level, together with increases in total fatty acid content and unsaturated fatty acid proportion. CONCLUSIONS: This study established the lncRNA expression profiles in intramuscular fat tissue of Qinchuan and Wagyu cattle across different developmental stages, and demonstrated that lnc11599 acts as a negative regulator of intramuscular fat deposition. These findings provide new directions for elucidating the mechanisms of cattle IMF deposition and offer potential targets for genetic improvement of beef quality.

Animals

Evolutionary conservation of heat shock proteins in Blattodea and their roles in wing morphogenesis and ovarian development of Blattella germanica.

Heat shock proteins (Hsps) are essential molecular chaperones for protein homeostasis and stress responses. However, the Hsp repertoires and functions in Blattodea remain underexplored. Our genome-scale survey of nine Blattodea species revealed 37-46 conserved Hsp90, Hsp70, and DNAJ (Hsp40) genes, with DNAJ the most abundant and Hsp90 the least. Phylogenetic analysis confirmed the evolutionary conservation of three Hsp90, seven Hsp70, and 29 DNAJ subclades in Blattodea. Selection pressure analysis revealed predominant purifying selection (dN/dS&#xa0;&#x226a;&#xa0;1) across lineages, strongest in DNAJ and highest in Hsp90 conservation. In Blattella germanica, expression of six representative BgHsp genes progressively increased during development, peaking in fifth-instar nymphs. Tissue expression profiling revealed that BgHspA1-2/3/4 were predominantly expressed in legs, BgDNAJB5 and BgHsp90AB1-2 were enriched in the fat body, and BgHsp90AB1 was highly expressed in the head. dsRNA injection targeting conserved Hsp gene regions achieved 61.9-94.1% knockdown of all six target genes. RNAi knockdown of six BgHsp genes disrupted wing morphogenesis, causing distinct phenotypes: wing whitening (56.7%, dsBgHspA1-4), unequal length (66.7%, dsBgHspA1-3; 76.7%, dsBgDNAJB5), and wing wrinkling (70%, dsBgHspA1-2; 63.3%, dsBgHsp90AB1; 76.7%, dsBgHsp90AB1-2). During ovarian formation, the developmental delay was most severe in the dsBgHsp90AB1 group, moderate in the dsBgHsp90AB1-2 and dsBgHspA1-2/3/4 groups, and weakest in the dsBgDNAJB5 group. Besides, knockdown significantly downregulated key developmental genes (apterous-a, nubbin, scalloped, ultrabithorax, wingless, and vitellogenin). These findings provide a reference for understanding the evolutionary patterns of Hsps in Blattodea, and offer mechanistic insights into the developmental regulation mediated by Hsps in this important public-health pest.

Animals

CRISPR-mediated intronic knock-in of pre-amiRNA enables targeted gene silencing.

This study introduces an intronic artificial microRNA (IamiRNA) strategy that combines CRISPR-Cas9-mediated knock-in with endogenous miRNA processing for targeted gene silencing in plants. By inserting amiRNA precursors into introns of endogenous genes, this approach enables effective, tissue-specific gene silencing without persistent transgene expression, offering a promising tool for functional genomics and crop improvement.

Introns

A 7-mm Covered TIPS Reduces&#xa0;Hepatic Encephalopathy Without Increasing Rebleeding in Cirrhotic Patients With Small Liver: A Randomized Study.

BACKGROUND/AIMS: International guidelines recommend initiating transjugular intrahepatic portosystemic shunt (TIPS) placement with an 8-mm stent. However, there is an evident lack of randomized controlled trials evaluating TIPS diameters <&#x2009;8&#x2009;mm in cirrhotic patients with a relatively small liver. The aim of this study was to determine whether 7&#x2009;mm-covered TIPS, compared with 8-mm stents, could achieve comparable shunt function with a lower incidence of hepatic encephalopathy (HE). METHODS: In this multicenter randomized controlled trial, patients with cirrhosis and relatively small liver were randomized 1:1 to receive TIPS with a 7-mm (n&#x2009;=&#x2009;92) or 8-mm (n&#x2009;=&#x2009;92) covered stent to prevent variceal rebleeding. The primary endpoint was the incidence of overt HE after randomization. All-cause rebleeding, orthotopic liver transplantation (OLT)-free survival and a composite of these outcomes, were designated as secondary endpoints. RESULTS: Among the 184 enrolled patients, the predominant etiologies of liver cirrhosis were hepatitis B virus infection (56.0%) and alcohol-related liver disease (20.7%). Over a median follow-up of 26.5&#x2009;months, overt HE occurred in 19 patients (20.7%) in the 7-mm group and 33 patients (35.9%) in the 8-mm group. The 2-year cumulative incidence of overt HE was significantly lower in the 7-mm group than in the 8-mm group (21.4% vs. 37.2%, p&#x2009;=&#x2009;0.02). Stent diameter, post-TIPS portosystemic pressure gradient, pre-covert HE and MELD-Na score were identified as independent risk factors for overt HE. The rates of shunt dysfunction were statistically similar between groups (8.7% vs. 8.7%, p&#x2009;=&#x2009;1.0), as were 2-year rebleeding rates (10.9% vs. 9.8%, p&#x2009;=&#x2009;0.81) and OLT-free survival rates (91.3% vs. 88.0%, p&#x2009;=&#x2009;0.82). CONCLUSIONS: A 7-mm covered TIPS demonstrated comparable shunt function to an 8-mm covered stents, with a significantly lower risk of overt HE. These findings support consideration of 7-mm TIPS stents for preventing variceal rebleeding in cirrhotic patients with a small liver who are undergoing TIPS. TRAIL REGISTRATION: ClinicalTrials.gov, NCT02541825.

Humans