Hypoxia-induced pulmonary hypertension (PH), which is characterized by vascular remodeling of blood vessels, is a significant complication of chronic obstructive pulmonary disease (COPD). In this study, we screened 13 candidate miRNAs in pulmonary artery smooth muscle cells (PASMCs) harvested from COPD patients with PH (n = 18) and normal controls (n = 15) and found that the expression of miR-214 was differentially expressed between these two groups. Additionally, cyclin L2 (CCNL2) was validated as a target of miR-214 in PASMCs using a luciferase assay. Based on real-time PCR, immunohistochemistry and western blot, the expression of CCNL2 was substantially downregulated in PASMCs from COPD patients with PH compared with those from normal controls. Moreover, the relationship between miRNA and mRNA expression was confirmed using real-time PCR and western blot in PASMCs transfected with miR-214 mimics. Furthermore, the introduction of miR-214 significantly promoted the proliferation of PASMCs by suppressing cell apoptosis, and this effect was mediated by the downregulation of CCNL2. Exposure of PASMCs to hypoxia significantly increased the expression of miR-214, decreased the expression of CCNL2, and promoted cell proliferation. However, these effects were significantly attenuated by the introduction of miR-214 inhibitors, which significantly downregulated miR-214 expression and upregulated CCNL2 expression.

Hydrogen sulfide (H2S) is a gasotransmitter with a variety of cardiovascular protective effects. Sirtuin 3 (SIRT3) is closely related to mitochondrial function and oxidative stress. We found that NaHS increased SIRT3 expression in the preventive effect on isoproterenol- (ISO-) induced myocardial hypertrophy. We further investigated whether exogenous H2S supplement improved ISO-induced myocardial hypertrophy in a SIRT3-dependent manner. 10-week-old male 129S1/SvImJ (WT) mice and SIRT3 knockout (KO) mice were intraperitoneally injected with NaHS (50 μmol/kg/d) for two weeks and then intraperitoneally injected with ISO (60 mg/kg/d) for another two weeks. In WT mice, NaHS significantly reduced the cardiac index of ISO-induced mice, decreased the cross-sectional area of cardiomyocytes, and inhibited the expressions of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) mRNA. The activity of total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) in the myocardium was increased, but the level of malondialdehyde (MDA) was decreased. The fluorescence intensity of dihydroethidium staining for superoxide anion was attenuated. Optic atrophy 1 (OPA1) expression was upregulated, while dynamin-related protein 1 (DRP1) expression was downregulated. ERK, but not P38 and JNK, phosphorylation was downregulated. However, all above protective effects were unavailable in ISO-induced SIRT3 KO mice. Our present study suggested that exogenous H2S supplement inhibited ISO-induced cardiac hypertrophy depending on SIRT3, which might be associated with antioxidant stress.

Ghrelin, a peptide derived from stomach, is an endogenous ligand for growth hormone secretagogue receptor (GHSR). So far, the exact role of ghrelin in depression and anxiety is still being debated. The p38 mitogen-activated protein kinase (p38-MAPK) is known to be activated in response to various stress stimuli. Thus, we hypothesize that ghrelin has an antidepressant effect, to which the p38-MAPK signaling pathway significantly contributes. To test this hypothesis, chronic social defeat stress (CSDS) was used as a model of depression. We employed the adeno-associated virus-mediated siRNA approach to down-regulate GHSR expression in the hippocampus of mice in vivo. Both ghrelin and the p38 inhibitor, SB203580, were administered to identify the effect of ghrelin on depressive-like behavior of stressed mice and to better assess the role of the p38-MAPK signaling pathway in this process. We found that CSDS activated the endogenous ghrelin-GHSR in hippocampal neurons, which possibly resulted in opposing the formation of depression- and anxiety-like behaviors in mice. Furthermore, the p38-MAPK signaling pathway had an important role in the antidepressant effect of ghrelin. Therefore, we conclude that ghrelin may reduce CSDS-induced depression- and anxiety-like behaviors via inhibiting the p38-MAPK signaling pathway in hippocampal neurons of mice.

The purpose of this study was to use magnetic resonance imaging (MRI) to compare the volumes and three-dimensional configurations of the soft palate and nasopharynx in non-brachycephalic and brachycephalic dogs with different body weights, and infer which factors influence nasopharyngeal volume. This was a retrospective observational study. The brain MRI medical records of all dogs referred to the Veterinary Medical Center, Chungbuk National University, between 2013 and 2016, for evaluation of intracranial disease were reviewed. There was a significant difference in the two-dimensional parameters including soft palate length/skull length ratio (P<0.01) and maximum soft palate thickness (P<0.01), and three-dimensional parameters which included soft palate volume (P<0.01), nasopharyngeal volume (P<0.01), soft palate/total upper airway volume ratio (P<0.01), and nasopharyngeal volume/total upper airway volume ratio (P<0.01), between brachycephalic and non-brachycephalic dog breeds. Nasopharyngeal volume correlated positively with the maximum soft palate thickness and body weight in all breeds. The three-dimensional morphologic grades of soft palate were significantly different between the two groups. In brachycephalic breeds, Grade 3 was observed in 33% of cases but was absent in non-brachycephalic breeds, where Grade 1 was present in 85% of the cases. We can conclude that three-dimensional morphology and upper airway volume are significantly different between brachycephalic and non-brachycephalic breeds, and body weight and maximum soft palate thickness are the key factors associated with a decreased nasopharyngeal volume.

The aim of the study was to compare transesophageal echocardiography (TEE) and fluoroscopy for percutaneous atrial septal defect (ASD) closure.This was a retrospective analysis of children who underwent percutaneous ASD closure. The procedure was guided by TEE without fluoroscopy in 130 patients (TEE group) and by fluoroscopy in 163 patients (fluoroscopy group). Baseline demographic/clinical characteristics were recorded. Patients were followed until hospital discharge. Outcomes were procedure duration, peri/postoperative complications, hospital stay, and costs.The TEE and fluoroscopy groups showed no significant differences in age (71.7 ± 40.7 vs 62.5 ± 38.8 months), male/female ratio (54/76 vs 66/97), weight (22.0 ± 12.0 vs 20.1 ± 9.0 kg), ASD diameter (9.9 ± 4.2 vs 9.3 ± 3.9 cm), distances to the superior vena cava (13.4 ± 4.6 vs 13.3 ± 4.2 cm), inferior vena cava (13.4 ± 4.3 vs 13.9 ± 4.1 cm) and atrial septal roof (12.1 ± 4.0 vs 12.3 ± 3.2 cm), or atrial septal size (38.2 ± 6.2 vs 39.4 ± 26.6 cm); distance to the mitral valve was greater in the TEE group (13.2 ± 4.4 vs 11.3 ± 3.9 cm; P < .001). The TEE and fluoroscopy groups showed no significant differences in occlusion device size (14.3 ± 4.6 vs 13.8 ± 4.0 cm) or sheath size (8.7 ± 1.8 vs 8.7 ± 0.9 cm), but procedure duration was shorter in the TEE group (21.5 ± 14.6 vs 28.6 ± 10.9 minutes; P < .001). Postoperative fever (>38°C) occurred less frequently in the TEE group than in the fluoroscopy group (0.8% vs 9.2%; P < .001); there were no significant differences for the other complications. No patient had postoperative residual shunt, occlusion device shedding/displacement, or pericardial effusion. The TEE group had longer hospital stay (3.2 ± 0.6 vs 2.9 ± 0.6 days; P < .001) and higher procedure cost (29,687 ± 4218 vs 28,530 ± 1668 CNY (China Yuan); P = .002) than the fluoroscopy group.TEE-guided percutaneous ASD closure can be used as an alternative to fluoroscopy-guided procedures and avoids the use of radiation or contrast agents.

In this study, we investigate the proliferation of adult neural stem cells (NSCs) in a chronic unpredictable stress (CUS) rat model of depression, the effects of electroacupunture (EA) on depressive-like symptoms and the corresponding signaling pathways.

Background. Allicin, the major component of freshly crushed garlic, is one of the most biologically active compounds of garlic; it has been reported to induce apoptosis in cancer cells; however, the mechanism by which allicin exerts its apoptotic effects is not fully understood. The aim of the present study was to further elucidate the apoptotic pathways induced by allicin in the human ovarian cancer cell line SKOV3. Methods. Cell proliferation and apoptosis were measured by cell-counting assay and flow cytometry analysis. Activation of the signaling pathway was screened by human phospho-kinase array analysis, and the activated pathway and its related proteins were further confirmed by western blot analysis. Results. Allicin induced SKOV3 cell apoptosis and JNK phosphorylation in a time- and dose-dependent manner, but these were significantly blocked by SP600125 (an inhibitor of JNK). The findings suggest that JNK phosphorylation is related to the action of allicin on SKOV3 cells. Furthermore, JNK activation induced Bcl-2 family activation, triggered mitochondria-mediated signaling pathways, and led to the translocation of a considerable amount of Bax and cytochrome c release. Conclusions. JNK activation and mitochondrial Bax translocation are involved in allicin-induced apoptosis in SKOV3 cells. Our data input new insights to the literature of allicin-induced apoptosis.

Decline in the ovarian hormones with menopause may influence somatosensory, cognitive, and affective processing. The present study investigated whether hormonal depletion alters the nociceptive, depressive-like and learning behaviors in experimental rats after ovariectomy (OVX), a common method to deplete animals of their gonadal hormones. OVX rats developed thermal hyperalgesia in proximal and distal tail that was established 2 weeks after OVX and lasted the 7 weeks of the experiment. A robust mechanical allodynia was also occurred at 5 weeks after OVX. In the 5th week after OVX, dilute formalin (5%)-induced nociceptive responses (such as elevating and licking or biting) during the second phase were significantly increased as compared to intact and sham-OVX females. However, chronic constriction injury (CCI) of the sciatic nerve-induced mechanical allodynia did not differ as hormonal status (e.g. OVX and ovarian intact). Using formalin-induced conditioned place avoidance (F-CPA), which is believed to reflect the pain-related negative emotion, we further found that OVX significantly attenuated F-CPA scores but did not alter electric foot-shock-induced CPA (S-CPA). In the open field and forced swimming test, there was an increase in depressive-like behaviors in OVX rats. There was no detectable impairment of spatial performance by Morris water maze task in OVX rats up to 5 weeks after surgery. Estrogen replacement retrieved OVX-induced nociceptive hypersensitivity and depressive-like behaviors. This is the first study to investigate the impacts of ovarian removal on nociceptive perception, negative emotion, depressive-like behaviors and spatial learning in adult female rats in a uniform and standard way.

The present study was designed to investigate the effects of electroacupuncture (EA) on depressive-like and anxiety-like behaviours and neural progenitors in the hippocampal dentate gyrus (DG) in a chronic unpredictable stress (CUS) rat model of depression. After being exposed to a CUS procedure for 2 weeks, rats were subjected to EA treatment, which was performed on acupoints Du-20 (Bai-Hui) and GB-34 (Yang-Ling-Quan), once every other day for 15 consecutive days (including 8 treatments), with each treatment lasting for 30 min. The behavioural tests (i.e., forced swimming test, elevated plus-maze test, and open-field entries test) revealed that EA alleviated the depressive-like and anxiety-like behaviours of the stressed rats. Immunohistochemical results showed that proliferative cells (BrdU-positive) in the EA group were significantly larger in number compared with the Model group. Further, the results showed that EA significantly promoted the proliferation of amplifying neural progenitors (ANPs) and simultaneously inhibited the apoptosis of quiescent neural progenitors (QNPs). In a word, the mechanism underlying the antidepressant-like effects of EA is associated with enhancement of ANPs proliferation and preserving QNPs from apoptosis.

Here, we studied the complete process of a viral T7 RNA polymerase (RNAP) translocation on DNA during transcription elongation by implementing extensive all-atom molecular dynamics (MD) simulations to construct a Markov state model (MSM). Our studies show that translocation proceeds in a Brownian motion, and the RNAP thermally transits among multiple metastable states. We observed non-synchronized backbone movements of the nucleic acid (NA) chains with the RNA translocation accomplished first, while the template DNA lagged. Notably, both the O-helix and Y-helix on the fingers domain play key roles in facilitating NA translocation through the helix opening. The helix opening allows a key residue Tyr639 to become inserted into the active site, which pushes the RNA-DNA hybrid forward. Another key residue, Phe644, coordinates the downstream template DNA motions by stacking and un-stacking with a transition nucleotide (TN) and its adjacent nucleotide. Moreover, the O-helix opening at pre-translocation (pre-trans) likely resists backtracking. To test this hypothesis, we computationally designed mutants of T7 RNAP by replacing the amino acids on the O-helix with counterpart residues from a mitochondrial RNAP that is capable of backtracking. The current experimental results support the hypothesis.

Experimental results from studies with inbred mice and their syngeneic tumors indicated that the inoculation of semi-allogeneic cell hybrids (derived from the fusion between syngeneic tumor cells and an allogeneic cell line) protects the animal host from a subsequent lethal challenge with unmodified syngeneic tumor cells.

Yield improvement is an ever-important objective of wheat breeding. Studying and understanding the phenotypes and genotypes of yield-related traits has potential for genetic improvement of crops.

Variations in PRKN or HTRA2 are associated with Parkinson's disease. We generated a human induced pluripotent stem cell (iPSC) line CIBi007-A from a patient with young-onset Parkinson's disease (YOPD) who carried variants in PRKN and HTRA2. The generated iPSCs resembled human embryonic stem cells, expressed pluripotency markers, exhibited a normal karyotype, and could be differentiated into three germ layers in vitro. This line will be valuable for investigating disease mechanisms of YOPD and screening candidate drugs.

Objective: This study aimed to explore the relationship between the fecal metabolites and gut microbiota in obese patients with PCOS and provide a new strategy to elucidate the pathological mechanism of obesity and PCOS. Methods: The fecal samples of obese patients with PCOS (n = 18) and obese women without PCOS (n = 15) were analyzed by 16S rRNA gene sequencing and untargeted metabolomics. The peripheral venous blood of all subjects was collected to detect serum sex hormones. The association among fecal metabolites, gut microbiota, and serum sex hormones was analyzed with the R language. Results: A total of 122 named differential fecal metabolites and 18 enrichment KEGG pathways were obtained between the groups. Seven fecal metabolites can be used as characteristic metabolites, including DHEA sulfate. The richness and diversity of gut microbiota in the obese PCOS group were lower than those in the control group. Lachnoclostridium, Fusobacterium, Coprococcus_2, and Tyzzerela 4 were the characteristic genera of the obese patients with PCOS. Serum T level significantly and positively correlated with the abundance of fecal DHEA sulfate (p < 0.05), and serum DHEAS level significantly and negatively correlated with the abundance of fecal teasterone (p < 0.05). Conclusion: Specific fecal metabolites may be used as characteristic metabolites for obese patients with PCOS. The closely relationship among gut microbiota, fecal metabolites, and serum sex hormones may play a role in the related changes caused by hyperandrogenemia.

Polycystic ovary syndrome (PCOS) is a chronic endocrine and metabolic disease. Gut microbiota is closely related to many chronic diseases. In this study, we conducted a cross-sectional study and recruited 30 obese (OG) and 30 non-obese (NG) women with PCOS, 30 healthy women (NC) and 11 healthy but obese women (OC) as controls to investigate the characteristic gut microbiota and its metabolic functions in obese and non-obese patients with PCOS. The blood and non-menstrual faecal samples of all the participants were collected and analysed. As a result, the Hirsutism score, LH/FSH and serum T level in NG and OG both increased significantly compared with their controls (P < 0.05). High-throughput 16S rRNA gene sequencing revealed that the abundance and diversity of the gut microbiota changed in patients with PCOS. The linear discriminant analysis (LDA) indicated that Lactococcus was the characteristic gut microbiota in NG, while Coprococcus_2 in OG. Correlation heatmap analysis revealed that the sex hormones and insulin levels in human serum were closely related to the changes in the gut microbiota of NG and OG. Functional prediction analysis demonstrated that the citrate cycle pathway enriched both in NG and OG, and other 12 gut bacterial metabolic pathways enriched in NG. This study highlighted significant differences in the gut microbiota and predictive functions of obese and non-obese women with PCOS, thereby providing insights into the role and function of the gut microbiota that may contribute to the occurrence and development of PCOS in obese and non-obese women.

Mosses compose one of the three lineages of bryophytes. Today, about 13,000 species of mosses are recognized from across the globe, and at least one-third of this diversity composes the Hypnales, a lineage characterized by an early rapid radiation. We sequenced and de novo assembled the genomes of two hypnalean mosses, namely Entodon seductrix and Hypnum curvifolium, based on the 10x genomics and Hi-C data. The genome assemblies of E. seductrix and H. curvifolium comprise 348.4 and 262.0 Mb, respectively, estimated by k-mer analyses to represent 93.3% and 97.2% of their total genome size. Both genomes were assembled at the chromosome level, with scaffold N50 of 30.0 and 20.7 Mb, respectively. The annotated genome of E. seductrix comprises 25,801 protein-coding genes and that of H. curvifolium 29,077, estimated to represent 96.8% and 97.2%, respectively, of the total gene spaces based on BUSCO (Benchmarking Universal Single-Copy Ortholog) assessment. For both genomes, most contigs were anchored to the largest 11 pseudomolecules, corresponding to the 11 chromosomes of the two species, and each with a putative sex-related chromosome characterized by low gene density. The chromosomes of E. seductrix and H. curvifolium are highly syntenic, suggests limited architectural shifts occurred following the rapid radiation of the Hypnales. We compared their genomic features to the model moss Physcomitrium patens. The hypnalean moss genomes lack signatures of recent whole-genome duplication. The presented high-quality moss genomes provide new resources for comparative genomics to potentially unveil the genomic evolution of derived moss lineages.

Intra-abdominal candidiasis (IAC) is the predominant type of invasive candidiasis with high mortality in critically ill patients. This study aimed to investigate whether the polymerase chain reaction (PCR) assay for detecting Candida DNA in peritoneal fluids (PF) is useful in diagnosing and management of IAC in high-risk patients in intensive care unit (ICU).

Ghrelin is an orexigenic hormone that also plays an important role in mood disorders. Our previous studies demonstrated that ghrelin administration could protect against depression-like behaviors of chronic unpredictable mild stress (CUMS) in rodents. However, the mechanism related to the effect of ghrelin on CUMS mice has yet to be revealed. This article shows that ghrelin (5 nmol/kg/day for 2 weeks, i.p.) decreased depression-like behaviors induced by CUMS and increased hippocampal integrity (neurogenesis and spine density) measured via Ki67, 5-bromo-2-deoxyuridine (BrdU), doublecortin (DCX) labeling and Golgi-cox staining, which were decreased under CUMS. The behavioral phenotypes of Growth hormone secretagogue receptor (Ghsr)-null and wild type (WT) mice were evaluated under no stress condition and after CUMS exposure to determine the effect of Ghsr knockout on the behavioral phenotypes and stress susceptibility of mice. Ghsr-null mice exhibited depression-like behaviors under no stress condition. CUMS induced similar depression- and anxiety-like behavioral manifestations in both Ghsr-null and WT mice. A similar pattern of behavioral changes was observed after hippocampal GHSR knockdown. Additionally, both Ghsr knockout as well as CUMS exhibited deleterious effects on neurogenesis and spine density in the dentate gyrus (DG). Besides, CCK8 assay and 5-Ethynyl-2'-deoxyuridine (EdU) incorporation assay showed that ghrelin has a proliferative effect on primary cultured hippocampal neural stem cells (NSCs) and this proliferation was blocked by D-Lys3-GHRP-6 (DLS, the antagonist of GHSR, 100 μM) pretreatment. Ghrelin-induced proliferation is associated with the inhibition of G1 arrest, and this inhibition was blocked by LY294002 (specific inhibitor of PI3K, 20 μM). Furthermore, the in vivo data displayed that LY294002 (50 nmol, i.c.v.) can significantly block the antidepressant-like action of exogenous ghrelin treatment. All these results suggest that ghrelin/GHSR signaling maintains the integrity of hippocampus and has an inherent neuroprotective effect whether facing stress or not.

To identify new biomarkers of prostate cancer (PCa) for the diagnosis and prediction of clinical outcomes.

Hepatocellular carcinoma (HCC) is a common disease with a significant mortality, and there is no effective treatment for advanced patients. Growing evidence indicates that circRNAs are closely related to HCC progression, may be used as biomarkers and targets for the diagnosis and treatment of HCC. Recent researches have shown that circPUM1 may play an oncogene role in a variety of human cancers, but its role in HCC development has not been reported. Our study found that circPUM1 could promote the proliferation, migration and invasion of HCC cells in vitro. In addition, in vivo studies showed that circPUM1 could increase the development of HCC tumours and regulate the expression of EMT-related proteins. Furthermore, we demonstrated that circPUM1 could promote the development of HCC by up-regulating the expression of MAP3K2 via sponging miR-1208. Our study suggested that circPUM1 may be a potential therapeutic target for HCC.