MFAP5 variant-induced multiple giant thoracic aortic aneurysm.

Heritable thoracic aortic aneurysms are complex conditions characterised by the dilation or rupture of the thoracic aorta, often occurring as an autosomal-dominant disorder associated with life-threatening complications. In this case report, we present a de novo variant, MFAP5 c.236_237insA (p.N79Kfs9), which is implicated in the development of inherited thoracic aortic aneurysm. The proband, a 15-year-old male, presented with recurrent cough, dull chest pain, chest distress, vomiting, and reduced activity tolerance, leading to the diagnosis of heritable thoracic aortic aneurysms. Whole-exome sequencing identified a novel heterozygous variant in MFAP5 (NM_003480, c.236_237insA, and p.N79Kfs9). MutationTester and PolyPhen-s predicted this variant to be damaging and disease-causing (probability = 1), while the SFIT score indicated protein damage (0.001). Structural analysis using the AlphaFold Protein structure database revealed that this mutation disrupted the N-linked glycosylation site, resulting in a frameshift, amino acid sequence alteration, and truncation of an essential protein site. To our knowledge, this is the first case report describing a young patient with heritable thoracic aortic aneurysm carrying the novel MFAP5 c.236_237insA (p.N79Kfs*9) variant. This variant represents the third identified mutation site associated with heritable thoracic aortic aneurysm. Given the high mortality and morbidity rates associated with thoracic aortic aneurysms, the prevention of severe and fatal complications is crucial in the clinical management of this condition. Our case highlights the importance of whole-exome sequencing and genetic screening in identifying potential pathogenic or likely pathogenic variants, particularly in early-onset patients with aortic dilation, to inform appropriate management strategies.

Comparison of efficacy between laparoscopic pectopexy and laparoscopic high uterosacral ligament suspension in the treatment of apical prolapse-short term results.

To compare the clinical efficacy of laparoscopic pectopexy and laparoscopic high uterosacral ligament suspension in women suffering from apical prolapse. The clinical data of 170 patients with apical prolapse (POP-Q score ≥ II) treated in the Third Affiliated Hospital of Zhengzhou University from January 2018 to July 2020 were retrospectively analyzed to assess the clinical efficacy of three surgical methods [laparoscopic pectopexy with uterine preservation, laparoscopic pectopexy with hysterectomy, laparoscopic high uterosacral ligament suspension (LHUSLS) with hysterectomy]. Patients were divided into three groups depending on Surgical methods: laparoscopic uterine pectopexy group (n = 23), laparoscopic pectopexy with hysterectomy group (n = 78) and LHUSLS with hysterectomy group (n = 69). The POP-Q points before and after operation were analyzed. The operation-related indices, perioperative periods and post-operative complications were compared. 1. The operation time of laparoscopic uterine pectopexy group was the shortest (p < 0.05). There was no significant difference in the incidence of apical prolapse and new stress urinary incontinence among the three groups during the follow-up period (p > 0.05). 2. The POP-Q points (Aa, Ba, C) in the three groups were better than those before operation (p < 0.05). Laparoscopic pectopexy with hysterectomy group had better Ap, Bp and C points and a longer TVL than LHUSLS with hysterectomy group (p < 0.05). 3. The postoperative PFDI-20, PFIQ-7 and PISQ-12 scores of the three groups were significantly improved than those before operation (p < 0.05). The PISQ-12 scores in laparoscopic uterine pectopexy group were significantly higher than that in the other two groups one year after operation (p < 0.05). The study concludes that laparoscopic pectopexy and LHUSLS can significantly improve the quality of life and sexual function for patients with apical prolapse. One year after operation, laparoscopic pectopexy has a more satisfactory anatomical reduction than LHUSLS with hysterectomy. The laparoscopic uterine pectopexy group had lower postoperative complications and better sexual function than that with hysterectomy group. Laparoscopic pectopexy should be used for the treatment of apical prolapse (POP-Q score ≥ II) patients who aim to better clinical efficacy and sexual function improvement.

MLNAN: Multi-level noise-aware network for low-dose CT imaging implemented with constrained cycle Wasserstein generative adversarial networks.

Low-dose CT techniques attempt to minimize the radiation exposure of patients by estimating the high-resolution normal-dose CT images to reduce the risk of radiation-induced cancer. In recent years, many deep learning methods have been proposed to solve this problem by building a mapping function between low-dose CT images and their high-dose counterparts. However, most of these methods ignore the effect of different radiation doses on the final CT images, which results in large differences in the intensity of the noise observable in CT images. What'more, the noise intensity of low-dose CT images exists significantly differences under different medical devices manufacturers. In this paper, we propose a multi-level noise-aware network (MLNAN) implemented with constrained cycle Wasserstein generative adversarial networks to recovery the low-dose CT images under uncertain noise levels. Particularly, the noise-level classification is predicted and reused as a prior pattern in generator networks. Moreover, the discriminator network introduces noise-level determination. Under two dose-reduction strategies, experiments to evaluate the performance of proposed method are conducted on two datasets, including the simulated clinical AAPM challenge datasets and commercial CT datasets from United Imaging Healthcare (UIH). The experimental results illustrate the effectiveness of our proposed method in terms of noise suppression and structural detail preservation compared with several other deep-learning based methods. Ablation studies validate the effectiveness of the individual components regarding the afforded performance improvement. Further research for practical clinical applications and other medical modalities is required in future works.

A novel compound heterozygous variant in ALPK3 induced hypertrophic cardiomyopathy: a case report.

Background: Malignant hypertrophic cardiomyopathy (HCM) phenotypes have potential risks of severe heart failure, fatal arrhythmia, and sudden cardiac death. Therefore, it is critical to predict the clinical outcomes of these patients. It was reported recently that the alpha kinase 3 (ALPK3) gene was involved in the occurrence of HCM. Herein we reported a girl with HCM, while whole-exome sequencing found novel compound heterozygous variants in ALPK3 gene, which identified a potential association. Case presentation: We reported a 14-year-girl who suffered from clinical manifestations of cardiac failure, with sudden cardiac arrest before admission. The heartbeat recovered after cardiopulmonary resuscitation, though she remained unconscious without spontaneous breath. The patient stayed comatose when she was admitted. Physical examination indicated enlargement of the heart boundary. Laboratory results revealed a significant increment of myocardial markers, while imaging demonstrated hypertrophy of the left heart and interventricular septum. Whole-exome sequencing (WES) identified a compound heterozygous variant in ALPK3 gene consisting of c.3907_3922del and c.2200A>T, which was inherited from her parents. Both variants (p.G1303Lfs*28 and p.R734*) were disease-causing evaluated by MutationTaster (probability 1.000). The crystal structure of the complete amino acid sequence is predicted and evaluated by AlphaFold and SWISS-MODEL software (July, 2022), which revealed three domains. Moreover, both variants resulted in a wide protein-truncating variant and damaged protein function. Thus, a novel compound heterozygous variant in ALPK3 associated with HCM was diagnosed. Conclusion: We described a young patient with ALPK3-associated HCM who experienced sudden cardiac arrest. Through WES, we identified a compound heterozygous variant in the ALPK3 gene, c.3907_3922del and c.2200A>T, which were inherited from the patient's parents and resulted in a truncated protein, indirectly causing the symptoms of HCM. In addition, WES provided clues in evaluating potential risks of gene variants on fatal clinical outcomes, and the nonsense and frameshift variants of ALPK3 were related to adverse clinical outcomes in HCM patients, which required implantable cardioverter defibrillator (ICD) timely.

hMOF induces cisplatin resistance of ovarian cancer by regulating the stability and expression of MDM2.

Histone acetyltransferase human males absent on the first (hMOF) is a member of MYST family which participates in posttranslational chromatin modification by controlling the acetylation level of histone H4K16. Abnormal activity of hMOF occurs in multiple cancers and biological alteration of hMOF expression can affect diverse cellular functions including cell proliferation, cell cycle progression and embryonic stem cells (ESCs) self-renewal. The relationship between hMOF and cisplatin resistance was investigated in The Cancer Genome Atlas (TCGA) and Genomics of Drug Sensitivity in Cancer (GDSC) database. Lentiviral-mediated hMOF-overexpressed cells or hMOF-knockdown cells were established to investigate its role on cisplatin-based chemotherapy resistance in vitro ovarian cancer cells and animal models. Furthermore, a whole transcriptome analysis with RNA sequencing was used to explore the underlying molecular mechanism of hMOF affecting cisplatin-resistance in ovarian cancer. The data from TCGA analysis and IHC identification demonstrated that hMOF expression was closely associated with cisplatin-resistance in ovarian cancer. The expression of hMOF and cell stemness characteristics increased significantly in cisplatin-resistant OVCAR3/DDP cells. In the low hMOF expressing ovarian cancer OVCAR3 cells, overexpression of hMOF improved the stemness characteristics, inhibited cisplatin-induced apoptosis and mitochondrial membrane potential impairment, as well as reduced the sensitivity of OVCAR3 cells to cisplatin treatment. Moreover, overexpression of hMOF diminished tumor sensitivity to cisplatin in a mouse xenograft tumor model, accompanied by decrease in the proportion of cisplatin-induced apoptosis and alteration of mitochondrial apoptosis proteins. In addition, opposite phenotype and protein alterations were observed when knockdown of hMOF in the high hMOF expressing ovarian cancer A2780 cells. Transcriptomic profiling analysis and biological experimental verification orientated that MDM2-p53 apoptosis pathway was related to hMOF-modulated cisplatin resistance of OVCAR3 cells. Furthermore, hMOF reduced cisplatin-induced p53 accumulation by stabilizing MDM2 expression. Mechanistically, the increased stability of MDM2 was due to the inhibition of ubiquitinated degradation, which resulted by increased of MDM2 acetylation levels by its direct interaction with hMOF. Finally, genetic inhibition MDM2 could reverse hMOF-mediated cisplatin resistance in OVCAR3 cells with up-regulated hMOF expression. Meanwhile, treatment with adenovirus expressing shRNA of hMOF improved OVCAR3/DDP cell xenograft sensitivity to cisplatin in mouse. Collectively, the results of the study confirm that MDM2 as a novel non-histone substrate of hMOF, participates in promoting hMOF-modulated cisplatin chemoresistance in ovarian cancer cells. hMOF/MDM2 axis might be a potential target for the treatment of chemotherapy-resistant ovarian cancer.

Role of non­coding RNA intertwined with the Wnt/ß­catenin signaling pathway in endometrial cancer (Review).

Endometrial cancer (EC) ranks as the sixth most common malignancy in women around the world. Although low­grade and early­stage EC commonly have an excellent prognosis, ~20% of EC patients experience an unfavorable prognosis. Identifying the pathogenesis and novel therapeutic targets may help address this group of patients. Non­coding (nc)RNAs, such as long non­coding RNAs (lncRNAs), microRNAs and circular RNAs (circRNAs), have been associated with EC occurrence and development. In addition, the aberrant activation of the Wnt/ß­catenin signaling pathway can promote the proliferation, invasion, migration and epithelial­to­mesenchymal transition (EMT) of EC cells. The network of ncRNAs has also been demonstrated to inhibit or activate the Wnt/ß­catenin signaling pathway. In the present review, ncRNAs, the Wnt/ß­catenin signaling pathway, and their crosstalk in EC were summarized and highlighted. This information is expected to provide novel insights into improving the management of EC using RNA as therapeutics.

Water causes divergent responses of specific carbon sink to long-term grazing in a desert grassland.

Heavy grazing generally reduces grassland biomass, further decreasing its carbon sink. Grassland carbon sink is determined by both plant biomass and carbon sink per unit biomass (specific carbon sink). This specific carbon sink could reflect grassland adaptative response, because plants generally tend to adaptively enhance the functioning of their remaining biomass after grazing (i.e. higher leaf nitrogen content). Though we know well about the regulation of grassland biomass on carbon sink, little attention is paid to the role of specific carbon sink. Thus, we conducted a 14-year grazing experiment in a desert grassland. Ecosystem carbon fluxes, including net ecosystem CO2 exchange (NEE), gross ecosystem productivity (GEP) and ecosystem respiration (ER), were measured frequently during five consecutive growing seasons with contrasting precipitation events. We found that heavy grazing reduced NEE more in drier (-94.0 %) than wetter (-33.9 %) years. However, grazing did not reduce community biomass much more in drier (-70.4 %) than wetter years (-66.0 %). These meant a positive response of specific NEE (NEE per unit biomass) to grazing in wetter years. This positive response of specific NEE was mainly caused by a higher biomass ratio of other species versus perennial grasses with greater leaf nitrogen content and specific leaf area in wetter years. In addition, we also detected a shift of grazing effects on specific NEE from positive in wetter years to negative in drier years. Overall, this study is among the first to reveal the adaptive response of grassland specific carbon sink to experimental grazing in plant trait view. The stimulation response of specific carbon sink can partially compensate for the loss of grassland carbon storage under grazing. These new findings highlight the role of grassland adaptive response in decelerating climate warming.

Early growth response 2 in the mPFC regulates mouse social and cooperative behaviors.

Adolescent social neglect impairs social performance, but the underlying molecular mechanisms remain unclear. Here we report that isolation rearing of juvenile mice caused cooperation defects that were rescued by immediate social reintroduction. We also identified the transcription factor early growth response 2 (Egr2) in the medial prefrontal cortex (mPFC) as a major target of social isolation and resocialization. Isolation rearing increased corticosteroid production, which reduced the expression of Egr2 in the mPFC, including in oligodendrocytes. Overexpressing Egr2 ubiquitously in the mPFC, but not specifically in neurons nor in oligodendroglia, protected mice from the isolation rearing-induced cooperation defect. In addition to synapse integrity, Egr2 also regulated the development of oligodendroglia, specifically the transition from undifferentiated oligodendrocyte precursor cells to premyelinating oligodendrocytes. In conclusion, this study reveals the importance of mPFC Egr2 in the cooperative behavior that is modulated by social experience, and its unexpected role in oligodendrocyte development.

Mycoplasma infection aggravates cardiac involvements in Kawasaki diseases: a retrospective study.

Background: Mycoplasma pneumoniae (MP) infection serves as a substantial cofactor in Kawasaki disease (KD) among patients. Although the dominant issue triggering KD has recently focused on MP infection, the complete demonstration of the relationship between MP infection and KD remains elusive. This study endeavors to scrutinize and compare the clinical manifestations and cardiac involvement between MP-triggered KD and non-infection-associated KD. Method: This retrospective study (2023-039, approved by the Institutional Review Board of West China Second University Hospital of Sichuan University) encompassed 247 consecutive patients diagnosed with KD between June 2017 and December 2022. Patients were categorized into two groups: the MP group (n = 38) and the non-MP group (n = 209). Univariable analysis was utilized to discern differences in clinical features, severity of inflammation, and initial or persistent cardiac complications between the two groups. Results: The MP group exhibited a more intricate clinical profile compared with the non-MP group, characterized by prolonged hospital stays, a higher incidence of incomplete KD, and elevated comorbidities. In addition, MP infection correlated with severe hematological disorders, coagulation dysfunction, and myocardial injuries. Our findings revealed that MP infection led to prolonged inflammation after initial treatment with intravenous immunoglobulin. Although initial cardiac assessments failed to discern disparities between the two groups, MP infection notably exacerbated coronary artery aneurysms (CAAs), resulting in sustained dilation. Conclusions: Recognizing MP infection as a significant infectious factor associated with KD is imperative. In patients with KD, MP infection significantly prolongs inflammation and causes hematological disturbances during the initial treatment phase. Moreover, the presence of MP infection exacerbates the progression of CAAs and myocardial injuries during the subacute phase of KD, consequently contributing to the persistence of CAAs.

Identification of a novel pyridine derivative with inhibitory activity against ovarian cancer progression in vivo and in vitro.

Ovarian cancer is the second leading cause of death of female gynecological malignant tumor patients worldwide. Although surgery and chemotherapy have achieved dramatic achievement, the mortality remains high, resulting in the demand for new specific drug discovery. Disrupting ovarian cancer growth via histone deacetylase (HDAC) inhibition is a strategy for cancer therapy or prevention. In this work, we synthesized a novel pyridine derivative named compound H42 and investigated its anti-cancer activity in vivo and in vitro. We found that compound H42 inhibited ovarian cancer cell proliferation with IC50 values of 0.87 µM (SKOV3) and 5.4 µM (A2780). Further studies confirmed that compound H42 induced apoptosis, intracellular ROS production, and DNA damage. Moreover, compound H42 downregulated the expression of histone deacetylase 6 (HDAC6) with a distinct increase in the acetylation of α-tubulin and heat shock protein 90 (HSP90), followed by the degradation of cyclin D1, resulting in cell cycle arrest at the G0/G1 phase. Importantly, ectopic expression of HDAC6 induced deacetylation of HSP90 and α-tubulin, while HDAC6 knockdown upregulated the acetylation of HSP90 and α-tubulin. However, in the nude xenograft mouse study, compound H42 treatment can inhibit ovarian cancer growth without obvious toxicity. These findings indicated that compound H42 inhibited ovarian cancer cell proliferation through inducing cell cycle arrest at the G0/G1 phase via regulating HDAC6-mediated acetylation, suggesting compound H42 could serve as a lead compound for further development of ovarian cancer therapeutic agents.

miR-124 regulates early isolation-induced social abnormalities via inhibiting myelinogenesis in the medial prefrontal cortex.

Patients with autism spectrum disorder (ASD) typically experience substantial social isolation, which may cause secondary adverse effects on their brain development. miR-124 is the most abundant miRNA in the human brain, acting as a pivotal molecule regulating neuronal fate determination. Alterations of miR-124 maturation or expression are observed in various neurodevelopmental, neuropsychiatric, and neurodegenerative disorders. In the present study, we analyzed a panel of brain-enriched microRNAs in serums from 2 to 6 year old boys diagnosed with ASD. The hsa-miR-124 level was found significantly elevated in ASD boys than in age and sex-matched healthy controls. In an isolation-reared weanling mouse model, we evidenced elevated mmu-miR-124 level in the serum and the medial prefrontal cortex (mPFC). These mice displayed significant sociability deficits, as well as myelin abnormality in the mPFC, which was partially rescued by expressing the miR-124 sponge in the bilateral mPFC, ubiquitously or specifically in oligodendroglia. In cultured mouse oligodendrocyte precursor cells, introducing a synthetic mmu-miR-124 inhibited the differentiation process through suppressing expression of nuclear receptor subfamily 4 group A member 1 (Nr4a1). Overexpressing Nr4a1 in the bilateral mPFC also corrected the social behavioral deficits and myelin impairments in the isolation-reared mice. This study revealed an unanticipated role of the miR-124/Nr4a1 signaling in regulating early social experience-dependent mPFC myelination, which may serve as a potential therapy target for social neglect or social isolation-related neuropsychiatric disorders.

Fatty acid metabolism-related genes are associated with flavor-presenting aldehydes in Chinese local chicken.

Aldehydes are primary volatile organic compounds (VOCs) in local Chinese chicken meat and contribute green grass, fatty, citrus, and bitter almond aromas to chicken meat. To understand the genetic basis of these aldehyde VOC aromas, we used approximately 500 Chinese Jingxing Yellow (JXY) chickens to conduct genome-wide association studies (GWAS) on the flavor traits with the data of single nucleotide polymorphisms (SNPs) and insertions and deletions (INDELs). In total, 501 association variants (253 SNPs and 248 INDELs) were found to be suggestively (SNPs: p-value < 2.77e-06 and INDELs: p-value < 3.78e-05) associated with total aldehydes (the sum of nine aldehydes), hexanal, heptanal, benzaldehyde, (E,E)-2,4-nonadienal, octanal, (E)-2-decenal, nonanal, decanal, and octadecanal. Of them, six SNPs and 23 INDELs reached a genome-wide significance level (SNPs: p-value < 1.38e-07 and INDELs: p-value < 1.89e-06). Potential candidate aldehyde genes were functionally annotated for lipid metabolism, especially fatty acid-related pathways and phospholipid-related gene ontology (GO) terms. Moreover, the GWAS analysis of total aldehydes, hexanal, and nonanal generated the most significant signals, and phenotypic content differed between different genotypes at candidate gene-related loci. For total aldehydes and hexanal traits, candidate genes were annotated based on the significant and suggestive variants on chromosomes 3 and 8 with highly polymorphic linkage blocks. The following candidate genes were also identified: GALM, MAP4K3, GPCPD1, RPS6KA2, CRLS1, ASAP1, TRMT6, SDC1, PUM2, ALDH9A1, MGST3, GMEB1, MECR, LDLRAP1, GPAM and ACSL5. We also found that polyunsaturated fatty acids (PUFAs) (C18:2n6c linoleic acid and C18:3n3 linolenic acid) were significantly correlated with total aldehydes and hexanal contents. PUFAs are important aldehyde precursors, and consistently, our results suggested that candidate genes involved in fatty acid pathways and phospholipid GO terms were identified in association loci. This work provides an understanding of the genetic basis of aldehyde formation, which is a key flavor-forming compound.

A Comparison of Different Tissues Identifies the Main Precursors of Volatile Substances in Chicken Meat.

Amino acids and fatty acids are the main precursors of volatile organic compounds (VOCs) in meat. The purpose of this study was to determine the main VOC components in chicken breast muscle (BM) and abdominal fat (AF) tissue, as well as the source of VOCs, to provide a basis for quality improvement of broilers. BM and AF served as experimental and control groups, and gas chromatography-mass spectrometry (GC-MS) and untargeted metabolomics were employed to identify the source of VOCs. The results revealed nine VOCs in BM and AF tissues, including hexanal, octanal, and nonanal. VOCs including 1-octen-3-ol, (E,E)-2, 4-nonadienal, and benzaldehyde were significantly elevated in BM compared with AF (p < 0.05), while heptane and diethyl disulphide showed the opposite trend (p < 0.05). Levels of hexanal, heptanal, and octanal were similar in the two tissues. Metabolites of VOCs in chicken BM were investigated by weighted co-expression network analysis. However, only blue module in BM tissue was positively correlated with hexanal (r = 0.66, p = 0.01), heptanal (r = 0.67, p = 0.008), and (E,E)-2,4-nonadienal (r = 0.88, p = 3E-05). L-tyrosine, L-asparagine, adenosine, and valine were the main precursors of (E,E)-2,4-nonadienal and heptanal in BM tissue. Amino acids are the main precursors of 1-octen-3-ol, (E,E)-2, 4-nonadienal, and heptanal in chicken meat, while fatty acids are the main precursors of diethyl disulfide. However, hexanal can be synthesized from amino acids and small amounts of fatty acids as precursors. These findings expand our understanding of VOCs in chicken.

Inhibition of cholesterol biosynthesis promotes the production of 1-octen-3-ol through mevalonic acid.

1-Octen-3-ol makes an important contribution to meat flavor. The goal of this study was to identify the metabolic pathways of 1-octen-3-ol formation in meat. We found 218 metabolites associated with 1-octen-3-ol content in 20 samples of chicken meat, including mevalonic acid (positive correlation), corticosterone (negative correlation), and other lipids and lipid-like molecules. Among these 218 metabolites, 17 metabolites were differentially expressed in different 1-octen-3-ol content groups. Similarly, 37 genes were not only differentially expressed, but were significantly correlated with 1-octen-3-ol. The regulation of HSP90AA1, PTPN9, and other genes converted more mevalonic acid to 1-octen-3-ol. Meanwhile, mevalonic acid, a key material in the synthesis of cholesterol, caused a decrease in corticosterone content, affecting ZNF414 and KLF15 gene expression. These findings reveal the effect of cholesterol on 1-octen-3-ol content, as well as a positive regulation of mevalonic acid on the production of 1-octen-3-ol in chicken meat.

Effect of Nrf2 on Phenotype Changes of Macrophages in the Anterior Vaginal Wall of Women With Pelvic Organ Prolapse.

OBJECTIVE: The aim of this study was to observe the effect of nuclear factor-erythroid 2-related factor 2 (Nrf2) on the phenotype changes of macrophages in the anterior vaginal wall of patients with pelvic organ prolapse (POP). METHODS: The tissues of the anterior vaginal wall of the control group (n = 30) and POP groups (n = 60) were collected during operation. The expressions of Nrf2, iNOS (representative factor of M1 macrophages), and CD206 (representative factor of M2 macrophages) were determined by immunohistochemical staining and Western blot. Morphological changes and collagen distribution of the anterior vaginal wall were observed by hematoxylin-eosin staining and Masson trichrome staining. RESULTS: Compared with the control group, the expression levels of Nrf2 and CD206 protein in the anterior vaginal wall tissues of the POP groups were significantly decreased ( P < 0.05), and were negatively proportional to the degree of prolapse ( P < 0.05). The expression of iNOS was significantly increased and was directly proportional to the degree of prolapse ( P < 0.05). Hematoxylin-eosin staining and Masson trichrome staining showed that the collagen fibers are more sparsely arranged and disordered in the POP group than the control. CONCLUSIONS: In patients with POP, the expression of antioxidant factor Nrf2 is reduced in the vaginal anterior wall tissues and the antioxidant capacity is weakened, leading to the blocked polarization of macrophages and the accumulation of a large number of M1 macrophages in the tissue, affecting the occurrence and development of POP.

Serum Cortisol, 25 (OH)D, and Cardiovascular Risk Factors in Patients with Type 2 Diabetes Mellitus.

Background and Aims: The effects of cortisol on cardiovascular diseases (CVD) and CVD risk are unknown, especially in patients with type 2 diabetes mellitus (T2DM). Furthermore, it is unclear whether 25 (OH)D can alter the associations of cortisol with CVD and CVD risk factors. Thus, the present study was to investigate the associations of serum cortisol with CVD and CVD risk factors and whether 25 (OH)D altered these associations among patients with T2DM. Materials and methods. A total of 762 patients diagnosed with T2DM were recruited. The levels of serum cortisol and 25 (OH)D were measured with a liquid chromatography-tandem mass spectrometry. Logistic regression and linear regression were used to assess the association of cortisol with CVD and multiple cardiovascular risk factors. Modification analyses were performed to identify whether 25 (OH)D altered the above associations. Results: A 1 SD increase in cortisol was associated with a higher prevalence of stroke (odds ratio (OR): 1.25, 95% confidence interval (CI): 1.05, 1.50). Elevated cortisol was associated with related cardiovascular risk factors, including deceased ß cell function, high-density lipoprotein-cholesterol (HDL-C), and fasting insulin, as well as increased triglycerides (TG), low-density lipoprotein-cholesterol (LDL-C), fasting plasma glucose (FPG), and glycated hemoglobin (HbA1c). In addition, modification analyses suggested that the associations of cortisol with ß cell function, fasting insulin, FPG, and HbA1c were modified by 25 (OH)D. Conclusions: Serum cortisol was associated with the prevalence of stroke and cardiovascular risk factors, and the associations of cortisol with cardiovascular risk factors were moderated by 25 (OH)D, suggesting that T2DM patients with exposure to lower 25 (OH)D levels and higher cortisol levels were more susceptible to have higher cardiovascular risk factors.

Effects of miR-363 on the Biological Activities of Eutopic Endometrial Stromal Cells in Endometriosis.

EMs is a kind of benign disease with certain malignant behaviors. The adhesion, invasive growth, and angiogenesis of ectopic endometrial cells are the pathological basis of EMs occurrence, but its etiology and pathogenesis have not been completely illustrated yet. In our research, we aim to investigate the role of miR-363 in the pathogenesis of endometriosis. Real-time quantitative PCR was used to detect the expression of miR-363 before and after ESC/NSC transfection. CCK-8, flow cytometry, and transwell assay were used to detect the effect of the miR-363 expression on cell proliferation, apoptosis, and invasion. The effects of the miR-363 expression on the contents of Fas/APO-1 and ICAM-1 in cell culture supernatant were detected by ELISA. qRT-PCR and WB assay were used to detect the effects of the miR-363 expression on the mRNA and protein expression levels of ICAM-1, MMP-7, and VEGF in ESC. The increased expression of miR-363 could inhibit the proliferation and invasion of ESC, promote apoptosis, and inhibit the secretion of FAS/APO-1 and ICAM-1. The knockdown expression of miR-363 promoted proliferation and invasion of NSC, inhibited apoptosis, and promoted secretion of FAS/APO-1 and ICAM-1. VCAM-1, VEGF, and MMP-7 were detected in ESCs before transfection. The protein expression level was higher than that of NSCs. Compared with pretransfection, the protein levels of VCAM-1, VEGF, and MMP-7 in the M-363 group were significantly downregulated. The downregulated expression of miR-363 was associated with a stronger cell proliferation ability, a lower cell apoptosis rate, and a stronger ESC. Migration is associated with invasiveness, proliferation, angiogenesis, and immune escape. The low expression of miR-363 promotes endogenesis through posttranscriptional regulation of target genes VCAM-1, MMP-7, and VEGF. The differential expression of miR-363 between ESC and NSC may be an important factor in the many biological differences between ESC and NSC.

Differential regulation of intramuscular fat and abdominal fat deposition in chickens.

BACKGROUND: Chicken intramuscular fat (IMF) content is closely related to meat quality and performance, such as tenderness and flavor. Abdominal fat (AF) in chickens is one of the main waste products at slaughter. Excessive AF reduces feed efficiency and carcass quality. RESULTS: To analyze the differential deposition of IMF and AF in chickens, gene expression profiles in the breast muscle (BM) and AF tissues of 18 animals were analyzed by differential expression analysis and weighted co-expression network analysis. The results showed that IMF deposition in BM was associated with pyruvate and citric acid metabolism through GAPDH, LDHA, GPX1, GBE1, and other genes. In contrast, AF deposition was related to acetyl CoA and glycerol metabolism through FABP1, ELOVL6, SCD, ADIPOQ, and other genes. Carbohydrate metabolism plays an essential role in IMF deposition, and fatty acid and glycerol metabolism regulate AF deposition. CONCLUSION: This study elucidated the molecular mechanism governing IMF and AF deposition through crucial genes and signaling pathways and provided a theoretical basis for producing high-quality broilers.

The SLC27A1 Gene and Its Enriched PPAR Pathway Are Involved in the Regulation of Flavor Compound Hexanal Content in Chinese Native Chickens.

The role of hexanal in flavor as an indicator of the degree of oxidation of meat products is undeniable. However, the genes and pathways of hexanal formation have not been characterized in detail. In this study, we performed differential gene expression analysis and weighted gene co-expression network analysis (WGCNA) on groups of Tiannong partridge chickens with different relative hexanal content in order to find the genes involved in the formation of hexanal and the specific pathways of hexanal formation. Then we confirmed the relationship of these candidate genes with hexanal using Jingxing Yellow chicken and Wenchang chicken. In this study, WGCNA revealed a module of co-expressed genes that were highly associated with the volatile organic compound hexanal. We also compared transcriptome gene expression data of samples from chicken groups with high and low relative contents of hexanal and identified a total of 651 differentially expressed genes (DEGs). Among them, 356 genes were up regulated, and 295 genes were downregulated. The different biological functions associated with the DEGs, hub genes and hexanal were identified by functional analysis using the Kyoto Encyclopedia of Genes and Genomes (KEGG) annotations. Among all the hub genes in the significant module identified by WGCNA, more were enriched in the PPAR signaling pathway, the proteasome pathway, etc. Additionally, we found that DEGs and hub genes, including SLC27A1, ACOX3, NR4A1, VEGFA, JUN, EGR1, CACNB1, GADD45A and DUSP1, were co-enriched in the peroxisome proliferator-activated receptor (PPAR) signaling pathway, p53 signaling pathway and mitogen-activated protein kinases (MAPK) signaling pathway, etc. Transcriptome results of the Jingxing Yellow chicken population showed that the SLC27A1 gene was significantly associated with hexanal and enriched in the PPAR pathway. Our study provides a comprehensive insight into the key genes related to hexanal content, and can be further explored by functional and molecular studies.

Development and Validation of a Predictive Model for Spontaneous Hemorrhagic Transformation After Ischemic Stroke.

Background: Hemorrhagic transformation (HT) after reperfusion therapy for acute ischemic stroke (AIS) has been well studied; however, there is scarce research focusing on spontaneous HT (sHT). Spontaneous HT is no less important with a relatively high incidence and could be associated with neurological worsening. We aimed to develop and validate a simple and practical model to predict sHT after AIS (SHAIS) and compared the predictive value of the SHAIS score against the models of post-Reperfusion HT for sHT. Methods: Patients with AIS admitted within 24 h of onset were prospectively screened to develop and validate the SHAIS score. The primary outcome was sHT during hospitalization (within 30 days after onset), and the secondary outcomes were symptomatic sHT and parenchymal hematoma (PH). Clinical information, laboratory, and neuroimaging data were screened to construct the SHAIS score. We selected six commonly used scales for predicting HT after reperfusion therapy and compared their predictive ability for sHT with the SHAIS score using Delong's test. Results: The derivation cohort included 539 patients (mean age, 68.1 years; men, 61.4%), of whom 91 (16.9%) patients developed sHT with 25.3% (23/91) being symptomatic sHT and 62.6% (57/91) being PH. Five variables (atrial fibrillation, NIHSS score ≥ 10, hypodensity > 1/3 of middle cerebral artery territory, hyperdense artery sign, and anterior circulation infarction) composed the SHAIS score, which ranged from 0 to 11 points. The area under the receiver-operating characteristic curve (AUC) was 0.86 (95% CI 0.82-0.91, p < 0.001) for the overall sHT, 0.85 (95% CI 0.76-0.92, p < 0.001) for symptomatic sHT, and 0.89 (95% CI 0.85-0.94, p < 0.001) for PH. No evidence of miscalibration of the SHAIS score was found to predict the overall sHT (p = 0.19), symptomatic sHT (p = 0.44), and PH (p = 0.22). The internal (n = 245) and external validation cohorts (n = 200) depicted similar predictive performance compared to the derivation cohort. The SHAIS score had a higher AUC to predict sHT than any of the six pre-Existing models (p < 0.05). Conclusions: The SHAIS score provides an easy-to-use model to predict sHT, which could help providers with decision-making about treatments with high bleeding risk, and to counsel patients and families on the baseline risk of HT, aligning expectations with probable outcomes.