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Myocardial ischemia/reperfusion (I/R) injury is associated with the poor outcome and higher mortality after myocardial infarction. Recent studies have revealed that miR-199a-5p participates in the process of myocardial I/R injury, but the precise roles and molecular mechanisms of miR-199a-5p in myocardial I/R injury remain not well-studied. Ferroptosis has been proposed to promote cardiomyocyte death, closely associated with myocardial I/R injury. Herein, the present study aimed to explore the function and mechanisms by which miR-199a-5p regulates whether miR-199a-5p contributes to ferroptosis-induced cardiomyocyte death responding to oxygen-glucose deprivation/reoxygenation (OGD/R) injury, an in vitro model of myocardial I/R injury focusing on Akt/eNOS signaling pathway. The results found that ferroptosis-induced cardiomyocyte death occurs and is accompanied by an increase in miR-199a-5p level in OGD/R-treated H9c2 cells. MiR-199a-5p inhibitor ameliorated ferroptosis-induced cardiomyocyte death as evidenced by the increased cell viability, the reduced reactive oxygen species (ROS) generation, lactate dehydrogenase (LDH) activity, malondialdehyde (MDA) and Fe

Maternal-to-zygotic transition (MZT) occurs when maternal transcripts decay and zygotic genome is activated gradually at the early stage of embryo development. Previously, single-cell RNA-seq (scRNA-seq) has helped us to uncover the MZT-associated mRNA dynamics of in vitro-produced pig early embryos. Here, to further investigate functional modules and hub genes associated with MZT process, the weighted gene co-expression network analysis (WGCNA) was performed on our previously generated 45 scRNA-seq datasets. For the in vitro fertilized embryo (IVF) group, 5 significant modules were identified (midnight blue/black/red and blue/brown modules, positively correlated with 1-cell (IVF1) and 8-cell (IVF8), respectively), containing genes mainly enriched in signalling pathways such as Wnt, regulation of RNA transcription, fatty acid metabolic process, poly(A) RNA binding and lysosome. For the parthenogenetically activated embryo (PA) group, 9 significant modules were identified (black/purple/red, brown/turquoise/yellow, and magenta/blue/green modules, positively correlated with MII oocytes, 1-cell (PA1) and 8-cell (PA8), respectively), mainly enriched in extracellular exosome, poly(A) RNA binding, mitochondrion and transcription factor activity. Moreover, some of identified hub genes within 3 IVF and 9 PA significant modules, including ADCY2, DHX34, KDM4A, GDF10, ABCC10, PAFAH2, HEXIM2, COQ9, DCAF11, SGK1 and ESRRB, have been reported to play vital roles in different biological processes. Our findings provide information and resources for subsequent in-depth study on the regulation and function of MZT in pig embryos.

Cardiac troponins are highly sensitive and specific biomarkers for cardiac injury. Previous studies evaluating the effect of positive airway pressure (PAP) on cardiac troponins in patients with sleep-disordered breathing (SDB) have yielded conflicting results. The meta-analysis was performed to examine the effect of PAP on cardiac troponins in SDB patients.PubMed, Web of Science, and EMBASE before September 2021 on original English language studies were searched. The data on cardiac troponins in both baseline and post-PAP treatment were extracted from all studies. The data on the change of cardiac troponins in both PAP and control group were extracted from randomized controlled trials. Standardized mean difference (SMD) was used to synthesize quantitative results.A total of 11 studies were included. PAP treatment was not associated with a significant change in cardiac troponin T between the baseline and post-PAP treatment (SMD = -0.163, 95% confidence interval [CI] = -0.652 to 0.326, z = 0.65, p = .514). The pooled estimate of SMD of cardiac troponin I between the pre- and post-PAP treatment was 0.287, and the 95% CI was -0.586 to 1.160 (z = 0.64, p = .519). The pooled SMD of change of cardiac troponin T between the PAP group and control group was -0.473 (95% CI = -1.198 to 0.252, z = 1.28, p = .201).This meta-analysis revealed that PAP treatment was not associated with any change of cardiac troponin in SDB patients.

Bisphenol F (BPF), a substitute for bisphenol A (BPA), is progressively used to manufacture various consumer products. Despite the established reproductive toxicity of BPF, the underlying mechanisms remain to elucidate. This in-vitro study deep in sighted the BPF toxicity on mouse oocyte meiotic maturation and quality. After treating oocytes with BPF (300 μM), the oocyte meiotic progression was blocked, accentuated by a reduced rate in the first polar body extrusion (PBE). Next, we illustrated that BPF induced α-tubulin hyper-acetylation disrupted the spindle assembly and chromosome alignment. Concurrently, BPF resulted in severe oxidative stress and DNA damage, which triggered the early apoptosis in mouse oocytes. Further, altered epigenetic modifications following BPF exposure were proved by increased H3K27me3 levels. Concerning the toxic effects on spindle structure, oxidative stress, and DNA damage in mouse oocytes, BPF toxicity was less severe to oocyte maturation and spindle structure than BPA and induced low oxidative stress. However, compared with BPA, oocytes treated with BPF were more prone to DNA damage, indicating not less intense or even more severe toxic effects of BPF than BPA on some aspects of oocytes maturation. In brief, the present study established that like wise to BPA, BPF could inhibit meiotic maturation and reduce oocyte quality, suggesting it is not a safe substitute for BPA.

Long non-coding RNAs (lncRNAs) function through multiple tiers of molecular circuits, and are vital to gamete maturation and early embryo development. However, in pig early embryos, identification and expression dynamics of lncRNAs remain less studied. Here, we systematically analyzed the expression dynamics of lncRNAs based on our previously published single cell RNA-seq data from pig mature oocytes (GSE160334), and single blastomeres biopsied from pig in vitro fertilized (IVF) and early parthenogenetically activated (PA) embryos (1- to 8-cell stages; GSE164812). With the progression of embryo development, the total number of expressed lncRNAs gradually decreased, and showed great variation at each developmental stage for both IVF and PA groups. Consecutive stage pairwise comparison of MII oocytes, 1-cell zygotes, 2-cell, 4-cell and 8-cell IVF embryos identified 151, 245, 1119 and 188 differentially expressed (DE) lncRNAs, including 119, 80, 867, 77 up-regulated and 32, 165, 252, 111 down-regulated, while 289, 437, 895 and 495 DE lncRNAs (141, 89, 768, 97 up-regulated and 148, 348, 127, 398 down-regulated) were identified in PA embryos at the same stages. The DE lncRNAs identified within IVF embryos were much different from that identified within PA embryos, showing embryo type specific manner. Further cross comparison between PA and IVF embryos identified 184, 656, 2502 and 266 DE lncRNAs for the 1- to 8-cell embryo stages, respectively. Further GO and KEGG enrichment analysis of DE mRNAs targeted by DELs indicated that different signaling pathways were involved in maternal-only and bi-parental embryo development. Collectively, comparative profiling of lncRNA expression dynamics between pig IVF and PA embryos provides a valuable resource, to investigate further regulatory mechanisms of lncRNAs associated with ZGA and maternal RNA decay during early embryo development.

Benzophenone-3 (BP-3), one of the most commonly utilized ultraviolet filters in personal care products, has aroused public concern in recent years for its high chances of human exposure. Previous studies have found that BP-3 can impair testes development and spermatogenesis, but the targets of BP-3 are still unknown. In this study, primary Sertoli cells from 20-day-old mice were treated in vitro with 0-100 μM BP-3 for 24 h to identify its toxicity on Sertoli cells and Sertoli cell barrier. Results demonstrated that BP-3 could induce a notable change in cell morphology and impair Sertoli cell viability. The analysis of transepithelial electrical resistance showed that the integrity of the Sertoli cell barrier was destroyed by BP-3 (100 μM). Some structural proteins of the barrier including ZO-1, Occludin, and Connexin43 were lower expressed and the localization of basal ectoplasmic specializations protein β-catenin was altered because of BP-3 treatment. Further exploration suggested that BP-3 led to Sertoli cell F-actin disorganization by affecting the expression of Rictor, a key component of the mTORC2 complex. Moreover, although increased DNA damage marker γH2A.X was observed in the treatment group, the cell apoptosis rate was changeless which was further confirmed by increased BAX and stable Bcl-2 (two primary apoptosis regulating proteins). In conclusion, this study revealed that BP-3 had the potential to perturb the Sertoli cell barrier through altered junction proteins and disorganized F-actin, but it could hardly evoke Sertoli cell apoptosis.

Airway epithelial cells, the first barrier of the respiratory tract, play an indispensable role in innate immunity. Integrin β4 (ITGB4) is a structural adhesion molecule that is involved in the pathological progression of acute inflammatory diseases and is downregulated in asthmatic patients. Research has shown that endothelial ITGB4 has proinflammatory properties in acute lung injury (ALI). However, the role of epithelial ITGB4 in a murine ALI model is still unknown. This study investigated the role of ITGB4 in lipopolysaccharide (LPS)-induced ALI. We found that ITGB4 in the airway epithelium had remarkably increased after the introduction of LPS in vivo and in vitro. Then, we constructed airway epithelial cell-specific ITGB4 knockout (ITGB4-/- ) mice to study its role in ALI. At a time point of 12 h after the tracheal injection of LPS, ITGB4-/- mice showed increased macrophages (mainly M1-type macrophages) and neutrophil infiltration into the lungs; inflammation-related proteins including interleukin (IL)-6, tumor necrosis factor, and IL-17A were significantly elevated compared to their levels in ITGB4+/+ mice. Furthermore, we investigated the role of ITGB4 in the anti-inflammatory response. Intriguingly, in the ITGB4-/- + LPS group, we found significantly reduced expression of anti-inflammatory factors, including IL-10 messenger RNA (mRNA) and ARG-1 mRNA. We also observed that monocyte chemotactic protein (MCP-1) increased significantly both in vivo and in vitro. Airway epithelium activates macrophages, most likely driven by MCP-1, which we confirmed in the coculture of epithelia and macrophages. These phenomena indicate that ITGB4 in airway epithelial cells plays an important role in the process of inflammation and activation of macrophages in ALI. Overall, these data demonstrated a novel link between airway epithelial ITGB4 and the inflammatory response in LPS-induced ALI.

This study used astragalus membranaceus (AM) to treat systemic lupus erythematosus (SLE) model mice during pregnancy, aiming to explore the role of AM in Helper T cell 17 (Th17) differentiation and SLE during pregnancy.We used lipopolysaccharide to constructed the SLE mouse model. AM decoction given by intragastric administration lasted from the eighth week of the mouse age until the mouse was killed. We estimated the messenger RNA levels of IL-17a and Rorc, counted the Th17 cell number and examined the levels of cytokines including interleukin (IL)-12, tumor necrosis factor α, interferon gamma, IL-17A in mouse serum. Periodic acid-Schiff staining and renal glomerular/tubulointerstitial (TI) score were used to evaluate the progression of lupus nephritis (LN).AM treatment improved the conception rate and increased the number and average weight of fetuses in SLE mice. It significantly decreased the urinary albumin/creatinine ratios and reduced the glomerular scores and TI scores in the pregnant SLE mice. AM gavage significantly decreased the weight of spleen, mesenteric lymph node, total splenocytes and T cells, and the expression of proinflammatory factors. Furthermore, AM treatment reduced the ratio of Th17 cells and the expression levels of RORγt and IL-17A.AM significantly improved pregnancy outcomes and inhibited lupus nephritis during pregnancy in SLE mice.

The faithful execution of molecular programme underlying oocyte maturation and meiosis is vital to generate competent haploid gametes for efficient mammalian reproduction. However, the organization and principle of molecular circuits and modules for oocyte meiosis remain obscure. Here, we employed the recently developed single-cell RNA-seq technique to profile the transcriptomes of germinal vesicle (GV) and metaphase II (MII) oocytes, aiming to discover the dynamic changes of mRNAs and long non-coding RNAs (lncRNAs) during oocyte in vitro meiotic maturation. During the transition from GV to MII, total number of detected RNAs (mRNAs and lncRNAs) in oocytes decreased. Moreover, 1,807 (602 up- and 1,205 down-regulated) mRNAs and 313 (177 up- and 136 down-regulated) lncRNAs were significantly differentially expressed (DE), i.e., more mRNAs down-regulated, but more lncRNAs up-regulated. During maturation of pig oocytes, mitochondrial mRNAs were actively transcribed, eight of which (ND6, ND5, CYTB, ND1, ND2, COX1, COX2 and COX3) were significantly up-regulated. Both DE mRNAs and targets of DE lncRNAs were enriched in multiple biological and signal pathways potentially associated with oocyte meiosis. Highly abundantly expressed mRNAs (including DNMT1, UHRF2, PCNA, ARMC1, BTG4, ASNS and SEP11) and lncRNAs were also discovered. Weighted gene co-expression network analysis (WGCNA) revealed 20 hub mRNAs in three modules to be important for oocyte meiosis and maturation. Taken together, our findings provide insights and resources for further functional investigation of mRNAs/lncRNAs in in vitro meiotic maturation of pig oocytes.

Diabetic hearts are vulnerable to myocardial ischemia/reperfusion injury (IRI), but are insensitive to sevoflurane postconditioning (SPC), activating peroxiredoxins that confer cardioprotection. Previous studies have demonstrated that hydrogen sulfide (H2 S) can suppress oxidative stress of diabetic rats through increasing the expression of silent information regulator factor 2-related enzyme 1 (SIRT1), but whether cardioprotection by SPC can be restored afterward remains unclear. Diabetic rat was subjected to IRI (30 min of ischemia followed by 120 min reperfusion). Postconditioning treatment with sevoflurane was administered for 15 min upon the onset of reperfusion. The diabetic rats were treated with GYY4137 (H2 S donor) 5 days before the experiment. Myocardial infarct size, mitochondrial structure and function, ATP content, activities of complex I-IV, marker of oxidative stress, SIRT1, nuclear factor E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NADPH Oxidase-2 (Nox-2) protein expression were detected after reperfusion, and cardiac function was evaluated by echocardiography at 24 h after reperfusion. After H2 S activated SIRT1 in the impaired myocardium of diabetic rats, SPC significantly upregulated the expression of Nrf2 and its downstream mediator HO-1, thus reduced the expression of Nox-2. In addition, H2 S remarkably increased cytoplasmic and nuclear SIRT1 which was further enhanced by SPC. Furthermore, H2 S combined with SPC reduced the production of reactive oxygen species, increased the content of ATP, and maintained mitochondrial enzyme activity. Finally, myocardial infarct size and myocardium damage were decreased, and cardiac function was improved. Taken together, our study proved that H2 S could restore SPC-induced cardioprotection in diabetic rats by enhancing and promoting SIRT1/Nrf2 signaling pathway mediated mitochondrial dysfunction and oxidative stress.

Cadmium selenide (CdSe) quantum dots (QDs) were biosynthesized rapidly in 18 h in Bacillus licheniformis ATCC 11946 (B. licheniformis); this process benefited from the cellular machinery of bacteria metal metabolism, in which inorganic Na2 SeO3 and CdCl2 were chosen as raw materials to produce high quality CdSe QDs by a designed two-step protocol. Research outcomes demonstrated that the purified CdSe QDs possessed maximum fluorescence intensities at weak alkalinity solutions and had good fluorescence stabilities at 4°C as well as at room temperature after standing for 1 week. Glutathione (GSH) concentration and superoxide dismutase (SOD) content, both of which were reported to be greatly related to biosynthetic activities in some bacterial matrices, were monitored during the biosynthetic process in B. licheniformis. Bacterial resistance research further showed that the change in rates in bacterial inhibition zone diameter to seven different antibiotics was less than 9% after B. licheniformis was used to manufacture CdSe QDs, showing a relative lower environmental risk in short-term heavy metal exposure.

The objective of this study was to investigate the characteristics of ruminal microbial communities of alpacas (Lama pacos) and sheep (Ovis aries) fed three diets with varying ratios of roughage (corn stalk) to concentrate, 3:7 (LS), 5:5 (MS) and 7:3 (HS). Six alpacas (one-year-old and weighing 29.5 ± 7.1 kg) and six sheep (one-year-old and weighing 27.9 ± 2.7 kg) were used in this study, in a replicated 3 × 3 Latin square experiment. Total protozoa concentration was determined under the microscope; total fungi and methanogens were assessed using quantitative polymerase chain reaction and expressed as a percentage of total bacterial 16S rRNA gene copies; bacterial communities were investigated by targeted 16S rRNA gene (V3-V4 region) sequencing. The percentage of fungi was significantly higher in alpacas than in sheep under the LS diet, while the concentration of protozoa was significantly lower in alpacas under HS, MS and LS diets. The alpha diversity including Shannon, Chao l and ACE indices of bacterial communities was higher in alpacas than in sheep, under the LS diet. A total of 299 genera belonging to 22 phyla were observed in the forestomach of alpaca and sheep, with Bacteroidetes and Firmicutes dominating both animal species. Phyla Armatimonadetes and Fusobacteria, as well as 64 genera, were detected only in alpacas, whereas phyla Acidobacteria and Nitrospira, as well as 44 genera, were found only in sheep. The abundance of cellulolytic bacteria, including Butyrivibrio and Pseudobutyrivibrio, was higher in alpacas than in sheep under all three diets. These differences in the forestomach microbial communities partly explained why alpacas displayed a higher poor-quality roughage digestibility, and a lower methane production. Results also revealed that the adverse effects of high-concentrate diets (70%) were lesser in alpacas than in sheep.

A novel series of Aloe-emodin derivatives containing N-heterocyclic moieties was designed and synthesized. The structure-activity relationship studies (SARs) indicated that the replacement of hydroxyethyl and benzhydryl piperazine groups could improve efficacy. Compounds 12r and 14a-14c exhibited a higher inhibitory effect on LPS-induced nitric oxide (NO) production in RAW264.7 macrophages than Aloe-emodin did. Among them, 12r showed the most potent inhibition with an IC50 value of 5.66 ± 0.47 μM. Further toxicity and pharmacokinetic studies were carried out and 12r was found to be the most active structure with low toxicity risk and good metabolic properties. It could also decrease the levels of IL-1β, TNF-α, PGE2 and inhibit the activation of nuclear factor-κB signalling pathway. Importantly, 12r showed oral bioavailability of up to 55.16% and attenuated the inflammatory symptoms in an ulcerative colitis mouse model in vivo. These results indicate that 12r is suitable for development as an anti-inflammatory agent.