MicroRNA expression profiles reveal wool development and fineness regulation in Gansu alpine fine-wool sheep.

The development of wool has a complex regulatory mechanism both influenced by genetic and environmental factors. MicroRNAs (miRNA) were involved in various biological processes of animals, and may play an important role in the regulation of wool development. In this study, we comprehensively analyzed and identified the histological parameters of hair follicles, as well as the miRNAs, target genes, pathways, and Gene Ontology terms related to wool fineness regulation and wool growth and development using HE staining and RNA-Seqs methods. Both coarse (group C, mean fiber diameter (MFD) = 22.26 ± 0.69 µm, n = 6) and fine (group F, MFD = 16.91 ± 0.29 µm, n = 6) of Gansu alpine fine-wool sheep with different wool fineness were used in this study. The results showed that the primary follicle diameter and secondary wool fiber diameter in group C were significantly higher than those in group F (P < 0.05). And the number of primary and secondary hair follicles in group C was significantly lower than that in group F (P < 0.05). Furthermore, a total of 67 DE miRNAs and 290 potential DE miRNAs target genes were screened in the skin tissues of sheep from groups F and C, and some potential target genes related to wool fineness regulation were screened, such as CDH2, KRT82, FOXN1, LOC101106296, KRT20, MCOLN3, KRT71, and TERT. These genes were closely related to Glutathione metabolism, epidermal cell differentiation, keratinization, and regulation of hair cycle. Moreover, the regulatory network of miRNAs-mRNAs suggested that miRNAs (miR-129-x, novel m0079-3p, miR-2484-z, novel m0025-5P, etc.) may play a key role in the wool development and wool fineness regulation of Gansu alpine fine-wool sheep. In summary, this study expands the existing miRNAs database and provides new information for studying the regulation of wool development in Gansu alpine fine wool sheep.

Observation of Near-Field Thermal Radiation between Coplanar Nanodevices with Subwavelength Dimensions.

With the continuous advancement of nanotechnology, nanodevices have become crucial components in computing, sensing, and energy conversion applications. The structures of nanodevices typically possess subwavelength dimensions and separations, which pose significant challenges for understanding energy transport phenomena in nanodevices. Here, on the basis of a judiciously designed thermal photonic nanodevice, we report the first measurement of near-field energy transport between two coplanar subwavelength structures over temperature bias up to ∼190 K. Our experimental results demonstrate a 20-fold enhancement in energy transfer beyond blackbody radiation. In contrast with the well-established near-field interactions between two semi-infinite bodies, the subwavelength confinements in nanodevices lead to increased polariton scattering and reduction of supporting photonic modes and, therefore, a lower energy flow at a given separation. Our work unveils exciting opportunities for the rational design of nanodevices, particularly for coplanar near-field energy transport, with important implications for the development of efficient nanodevices for energy harvesting and thermal management.

Macrophage KLF15 prevents foam cell formation and atherosclerosis via transcriptional suppression of OLR-1.

BACKGROUND: Macrophage-derived foam cells are a hallmark of atherosclerosis. Scavenger receptors, including lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (OLR-1), are the principal receptors responsible for the uptake and modification of LDL, facilitating macrophage lipid load and the uptake of oxidized LDL by arterial wall cells. Krüppel-like factor 15 (KLF15) is a transcription factor that regulates the expression of genes by binding to the promoter during transcription. Therefore, this study aimed to investigate the precise role of macrophage KLF15 in atherogenesis. METHODS: We used two murine models of atherosclerosis: mice injected with an adeno-associated virus (AAV) encoding the Asp374-to-Tyr mutant version of human PCSK9, followed by 12 weeks on a high-fat diet (HFD), and ApoE-/-- mice on a HFD. We subsequently injected mice with AAV-KLF15 and AAV-LacZ to assess the role of KLF15 in the development of atherosclerosis in vivo. Oil Red O, H&E, and Masson's trichome staining were used to evaluate atherosclerotic lesions. Western blots and RT-qPCR were used to assess protein and mRNA levels, respectively. RESULTS: We determined that KLF15 expression was downregulated during atherosclerosis formation, and KLF15 overexpression prevented atherosclerosis progression. KLF15 expression levels did not affect body weight or serum lipid levels in mice. However, KLF15 overexpression in macrophages prevented foam cell formation by reducing OLR-1-meditated lipid uptake. KLF15 directly targeted and transcriptionally downregulated OLR-1 levels. Restoration of OLR-1 reversed the beneficial effects of KLF15 in atherosclerosis. CONCLUSION: Macrophage KLF15 transcriptionally downregulated OLR-1 expression to reduce lipid uptake, thereby preventing foam cell formation and atherosclerosis. Thus, our results suggest that KLF15 is a potential therapeutic target for atherosclerosis.

Circular RNA_015343 sponges microRNA-25 to regulate viability, proliferation, and milk fat synthesis of ovine mammary epithelial cells via INSIG1.

In our previous study, circ_015343 was found to inhibit the viability and proliferation of ovine mammary epithelial cells (OMECs) and the expression levels of milk fat synthesis marker genes, but the regulatory mechanism underlying the processes is still unclear. Accordingly in this study, the target relationships between circ_015343 with miR-25 and between miR-25 with insulin induced gene 1 (INSIG1) were verified, and the functions of miR-25 and INSIG1 were investigated in OMECs. The dual-luciferase reporter assay revealed that miR-25 mimic remarkably decreased the luciferase activity of circ_015343 in HEK293T cells cotransfected with a wild-type vector, while it did not change the activity of circ_015343 in HEK293T cells cotransfected with a mutant vector. These suggest that cic_015343 can adsorb and bind miR-25. The miR-25 increased the viability and proliferation of OMECs, and the content of triglycerides in OMECs. In addition, INSIG1 was found to be a target gene of miR-25 using a dual-luciferase reporter assay. Overexpression of INSIG1 decreased the viability, proliferation, and level of triglycerides of OMECs. In contrast, the inhibition of INSIG1 in expression had the opposite effect on activities and triglycerides of OMECs with overexpressed INSIG1. A rescue experiment revealed that circ_015343 alleviated the inhibitory effect of miR-25 on the mRNA and protein abundance of INSIG1. These results indicate that circ_015343 sponges miR-25 to inhibit the activities and content of triglycerides of OMECs by upregulating the expression of INSIG1 in OMECs. This study provided new insights for understanding the genetic molecular mechanism of lactation traits in sheep.

Expression Localization of the KRT32 Gene and Its Association of Genetic Variation with Wool Traits.

Changes in keratin gene expression and spatiotemporal regulation determine the compositional content and cellular localization of wool keratin, thereby affecting wool traits. Therefore, keratin gene family member 32 (KRT32) was selected for a study using RT-qPCR, immunofluorescence, and penta-primer amplification refractory mutation system (PARMS) techniques. The results showed that KRT32 mRNA was highly expressed in the skin and localized to the inner root sheath (IRS), outer root sheath (ORS) and dermal papilla (DP). Sequencing results identified eight SNPs in KRT32, and association analyses revealed that the variations were significantly associated with multiple traits in wool (p < 0.05), including MFD, CF and MFC. The constructed haplotype combination H2H3 has higher CF and smaller MFD than other haplotype combination (p < 0.05). In conclusion, KRT32 can be used as a candidate gene for molecular genetic improvement of wool in Gansu Alpine Fine-wool sheep.

Nuclear miR-204-3p mitigates metabolic dysfunction-associated steatotic liver disease in mice.

BACKGROUND & AIMS: Accumulating evidence has indicated the presence of mature microRNAs (miR) in the nucleus, but their effects on steatohepatitis remain elusive. We have previously demonstrated that the intranuclear miR-204-3p in macrophages protects against atherosclerosis, which shares multiple risk factors with metabolic dysfunction-associated steatotic liver disease (MASLD). Herein, we aimed to explore the functional significance of miR-204-3p in steatohepatitis. METHODS: miR-204-3p levels and subcellular localization were assessed in the livers and peripheral blood mononuclear cells of patients with MASLD. Wild-type mice fed high-fat or methionine- and choline-deficient diets were injected with an adeno-associated virus system containing miR-204-3p to determine the effect of miR-204-3p on steatohepatitis. Co-culture systems were applied to investigate the crosstalk between macrophages and hepatocytes or hepatic stellate cells (HSCs). Multiple high-throughput epigenomic sequencings were performed to explore miR-204-3p targets. RESULTS: miR-204-3p expression decreased in livers and macrophages in mice and patients with fatty liver. In patients with MASLD, miR-204-3p levels in peripheral blood mononuclear cells were inversely related to the severity of hepatic inflammation and damage. Macrophage-specific miR-204-3p overexpression reduced steatohepatitis in high-fat or methionine- and choline-deficient diet-fed mice. miR-204-3p-overexpressing macrophages inhibited TLR4/JNK signaling and pro-inflammatory cytokine release, thereby limiting fat deposition and inflammation in hepatocytes and fibrogenic activation in HSCs. Epigenomic profiling identified miR-204-3p as a specific regulator of ULK1 expression. ULK1 transcription and VPS34 complex activation by intranuclear miR-204-3p improved autophagic flux, promoting the anti-inflammatory effects of miR-204-3p in macrophages. CONCLUSIONS: miR-204-3p inhibits macrophage inflammation, coordinating macrophage actions on hepatocytes and HSCs to ameliorate steatohepatitis. Macrophage miR-204-3p may be a therapeutic target for MASLD. IMPACT AND IMPLICATIONS: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a chronic inflammatory disease ranging from simple steatosis to steatohepatitis. However, the molecular mechanisms underlying the progression of MASLD remain incompletely understood. Here, we demonstrate that miR-204-3p levels in circulating peripheral blood mononuclear cells are negatively correlated with disease severity in patients with MASLD. Nuclear miR-204-3p activates ULK1 transcription and improves autophagic flux, limiting macrophage activation and hepatic steatosis. Our study provides a novel understanding of the mechanism of macrophage autophagy and inflammation in steatohepatitis and suggests that miR-204-3p may act as a potential therapeutic target for MASLD.

Radiogenomic analysis of ultrasound phenotypic features coupled to proteomes predicts metastatic risk in primary prostate cancer.

BACKGROUND: Primary prostate cancer with metastasis has a poor prognosis, so assessing its risk of metastasis is essential. METHODS: This study combined comprehensive ultrasound features with tissue proteomic analysis to obtain biomarkers and practical diagnostic image features that signify prostate cancer metastasis. RESULTS: In this study, 17 ultrasound image features of benign prostatic hyperplasia (BPH), primary prostate cancer without metastasis (PPCWOM), and primary prostate cancer with metastasis (PPCWM) were comprehensively analyzed and combined with the corresponding tissue proteome data to perform weighted gene co-expression network analysis (WGCNA), which resulted in two modules highly correlated with the ultrasound phenotype. We screened proteins with temporal expression trends based on the progression of the disease from BPH to PPCWOM and ultimately to PPCWM from two modules and obtained a protein that can promote prostate cancer metastasis. Subsequently, four ultrasound image features significantly associated with the metastatic biomarker HNRNPC (Heterogeneous nuclear ribonucleoprotein C) were identified by analyzing the correlation between the protein and ultrasound image features. The biomarker HNRNPC showed a significant difference in the five-year survival rate of prostate cancer patients (p < 0.0053). On the other hand, we validated the diagnostic efficiency of the four ultrasound image features in clinical data from 112 patients with PPCWOM and 150 patients with PPCWM, obtaining a combined diagnostic AUC of 0.904. In summary, using ultrasound imaging features for predicting whether prostate cancer is metastatic has many applications. CONCLUSION: The above study reveals noninvasive ultrasound image biomarkers and their underlying biological significance, which provide a basis for early diagnosis, treatment, and prognosis of primary prostate cancer with metastasis.

Divergent projections of the prelimbic cortex mediate autism- and anxiety-like behaviors.

The comorbidity of autism spectrum disorder and anxiety is common, but the underlying circuitry is poorly understood. Here, Tmem74-/- mice showed autism- and anxiety-like behaviors along with increased excitability of pyramidal neurons (PNs) in the prelimbic cortex (PL), which were reversed by Tmem74 re-expression and chemogenetic inhibition in PNs of the PL. To determine the underlying circuitry, we performed conditional deletion of Tmem74 in the PNs of PL of mice, and we found that alterations in the PL projections to fast-spiking interneurons (FSIs) in the dorsal striatum (dSTR) (PLPNs-dSTRFSIs) mediated the hyperexcitability of FSIs and autism-like behaviors and that alterations in the PL projections to the PNs of the basolateral amygdaloid nucleus (BLA) (PLPNs-BLAPNs) mediated the hyperexcitability of PNs and anxiety-like behaviors. However, the two populations of PNs in the PL had different spatial locations, optogenetic manipulations revealed that alterations in the activity in the PL-dSTR or PL-BLA circuits led to autism- or anxiety-like behaviors, respectively. Collectively, these findings highlight that the hyperactivity of the two populations of PNs in the PL mediates autism and anxiety comorbidity through the PL-dSTR and PL-BLA circuits, which may lead to the development of new therapeutics for the autism and anxiety comorbidity.

Theoretical investigation on regulating photophysical properties and proton transfer behavior by electronegativity for near-infrared emitting styryl dyes.

Our main focus is to explore the atomic electronegativity-dependent photoinduced behavior of styryl derivatives (HBO, HBS, and HBSe). The results of structural parameter calculation by the DFT method show that the intramolecular hydrogen bonds of normal and tautomer form are strengthened and weakened, respectively, in an excited state (S1), which is conducive to the excited intramolecular proton transfer (ESIPT) process. The enhancement of excited hydrogen bond is beneficial to the ESIPT process from the aspects of infrared vibration frequency (IR), Mulliken's charge analysis, and density gradient reduction (RDG). Additionally, by determining the bond energy with the band critical point (BCP) parameter, we found that the lower the electronegativity of the atom, the larger the hydrogen bond strength at the excited state and the more likely ESIPT reaction occurs. Meanwhile, the intramolecular H-bonds O-H…N in HBO, HBS, and HBSe are enhanced with the weakened electron-withdrawing capacity of the atom (from O to S and Se). Subsequently, frontier molecular orbital (FMOs) and charge density difference (CDD) analyses essentially revealed that electron redistribution induces the ESIPT process. Low atomic electronegativity exhibits the high chemical activity of the excited state. Furthermore, to demonstrate the electronegativity-dependent ESIPT behavior of the system, we built potential energy curves (PECs) and located the transition states (TS) of proton transfer processes.

Enhanced dielectric constant and breakdown strength of sandwiched polymer nanocomposite film for excellent energy storage.

Enhanced dielectric constant and high breakdown strength offers immense promise for excellent energy storage performance, which is of critical significance in modern electronics and power systems. However, polymer nanocomposites with traditional routes have to balance between dielectric constant and breakdown strength, hence hindering substantive increases in energy density. Herein, a sandwiched polymer nanocomposite film has been constructed to take full advantage of the individual component layers. BaTiO3 nanoparticles are coated with a fluoropolymer to form core-shell structures and then introduced into a polymer as the top and the bottom layers of a sandwich film for enhancing polarization. Moreover, boron nitride nanosheets (BNNSs) in the middle layer of the sandwich film exert positive effects on the inhibition of current leakage for high breakdown resistance. The breakdown strength increases from 480 MV m-1 of the neat polymer to 580 MV m-1 of the sandwiched film. Additionally, the film exhibits a higher dielectric constant in comparison with the neat polymer. The sandwiched film displays a superior energy density (15.75 J cm-3), which is about 1.9 times that of the neat polymer. This work proposes a feasible route to achieve excellent energy storage of polymer dielectrics by synergistically introducing insulating fillers and additional dipoles in a sandwiched polymer nanocomposite film.

Simplicispira sedimenti sp. nov., isolated from a sediment of drainage ditch in winery.

A Gram-stain-negative, motile (by single polar flagellum) and rod-shaped bacterium, designated W1-6T, was isolated from a sediment of drainage ditch in winery in Guiyang, south-western China. Strain W1-6T showed the highest 16S rRNA gene sequence similarities with the type strain of Acidovorax wautersii (98.1%) and Simplicispira lacusdiani (97.9%). Phylogenetic analysis based on 16S rRNA gene sequences showed that strain W1-6T was placed adjacent to the members of the genus Simplicispira and formed a separat subclade. Cells showed oxidase and catalase negative reactions. The only respiratory quinone detected was ubiquinone-8 (Q-8). Summed feature 3 (C16:1 ω7c and/or C16:1 ω6c), C16:0 and summed feature 8 (C18:1 ω7c and/or C18:1 ω6c) were predominant cellular fatty acids (> 10%) of strain W1-6T. Diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and five unidentified phospholipids were found in the polar lipid extraction. The genomic DNA G + C content was 65.6%. Strain W1-6T shared the highest digital DNA-DNA hybridization [dDDH, (27.6%)] and average nucleotide identity [ANI (84.3%)] values with the type strain of S. lacusdiani. The dDDH and ANI values were below the cutoff level (dDDH 70%; ANI 95-96%) for species delineation. The polyphasic characteristics indicated that the strain W1-6T represents a novel species of the genus Simplicispira, for which the name Simplicispira sedimenti sp. nov. is proposed. The type strain is W1-6T (= CGMCC 1.16274T = NBRC 115624T).

Father support breastfeeding self-efficacy positively affects exclusive breastfeeding at 6 weeks postpartum and its influencing factors in Southeast China: a multi-centre, cross-sectional study.

BACKGROUND: The exclusive breastfeeding condition in China is not optimism now. Maternal breastfeeding self-efficacy stands as a pivotal factor influencing exclusive breastfeeding. Interestingly, studies have suggested that father support breastfeeding self-efficacy is a pivotal mediator in infant breastfeeding. Thus, the current research aimed to investigate the association between father support breastfeeding self-efficacy and exclusive breastfeeding at six weeks postpartum, and the influencing factors of father support breastfeeding self-efficacy. METHODS: This research was structured as a multi-centre cross-sectional study, involving 328 fathers, whose partners were six weeks postpartum, and recruited from two public hospitals in Southeast China. Self-designed demographic questionnaires, namely, Father Support Breastfeeding Self-Efficacy Scale-Short Form, Breastfeeding Knowledge Questionnaire, Positive Affect Scale and the 14-item Fatigue Scale, were applied. Descriptive statistics, Chi-square test, logistic regression univariate analysis and multiple linear regression were used to analyse data. RESULTS: Results indicate a significant difference between the infant feeding methods at six weeks postpartum and fathers with different levels of support breastfeeding self-efficacy (p < 0.05). Particularly, father support breastfeeding self-efficacy positively affected exclusive breastfeeding at six weeks postpartum after adjusting all the demographic characteristics of fathers (OR: 2.407; 95% CI: 1.017-4.121). Moreover, results show that the significant influencing factors of father support breastfeeding self-efficacy include breastfeeding knowledge, fatigue, positive affect, successfully experienced helping mothers to breastfeed, spousal relationships and companionship time. CONCLUSIONS: High-level father support breastfeeding self-efficacy effectively increased exclusive breastfeeding rate at six weeks postpartum. To enhance the exclusive breastfeeding rate, nurses or midwives can endeavour to design educational programmes or take supportive interventions customised for fathers, such as enhancing their breastfeeding knowledge education, reducing fatigue and mobilising positive emotions, thereby bolstering paternal self-efficacy in breastfeeding.

The Causal Relationship between Plasma Myeloperoxidase Levels and Respiratory Tract Infections: A Bidirectional Mendelian Randomization Study.

Background: Observational researches reported the underlying correlation of plasma myeloperoxidase (MPO) concentration with respiratory tract infections (RTIs), but their causality remained unclear. Here, we examined the cause-effect relation between plasma MPO levels and RTIs. Materials and Methods: Datasets of plasma MPO levels were from the Folkersen et al. study (n = 21,758) and INTERVAL study (n = 3,301). Summarized data for upper respiratory tract infection (URTI) (2,795 cases and 483,689 controls) and lower respiratory tract infection (LRTI) in the intensive care unit (ICU) (585 cases and 430,780 controls) were from the UK Biobank database. The primary method for Mendelian randomization (MR) analysis was the inverse variance weighted approach, with MR-Egger and weighted median methods as supplements. Cochrane's Q test, MR-Egger intercept test, MR pleiotropy residual sum and outliers global test, funnel plots, and leave-one-out analysis were used for sensitivity analysis. Results: We found that plasma MPO levels were positively associated with URTI (odds ratio (OR) = 1.135; 95% confidence interval (CI) = 1.011-1.274; P=0.032) and LRTI (ICU) (OR = 1.323; 95% CI = 1.006-1.739; P=0.045). The consistent impact direction is shown when additional plasma MPO level genome-wide association study datasets are used (URTI: OR = 1.158; 95% CI = 1.072-1.251; P < 0.001; LRTI (ICU): OR = 1.216; 95% CI = 1.020-1.450; P=0.030). There was no evidence of a causal effect of URTI and LRTI (ICU) on plasma MPO concentration in the reverse analysis (P > 0.050). The sensitivity analysis revealed no violations of MR presumptions. Conclusions: Plasma MPO levels may causally affect the risks of URTI and LRTI (ICU). In contrast, the causal role of URTI and LRTI (ICU) on plasma MPO concentration was not supported in our MR analysis. Further studies are needed to identify the relationship between RTIs and plasma MPO levels.

Clinical outcomes following direct anterior approach during total hip arthroplasty without hip extension: a retrospective comparative study.

BACKGROUND: Traditional total hip arthroplasty (THA) using the direct anterior approach (DAA) requires a hip extension. This study aimed to compare the clinical outcomes of patients undergoing THA with DAA using either the no hip extension (NHE) or the traditional hip extension (THE) strategy. METHODS: A retrospective analysis of demographics, clinical and radiological outcomes, and occurrence of complications was performed using data from 123 patients treated between January 2020 and November 2021. The patients were categorised into two groups: NHE (84 patients) and THE (39 patients). RESULTS: The NHE group exhibited shorter operative time and had more male participants with higher ages. Comparable outcomes were observed in the visual analogue scale, Harris Hip, and Oxford Hip scores at the final follow-up. Furthermore, complications were observed in the NHE and THE groups, including two and one greater trochanteric fractures and three and one transfusions, respectively. CONCLUSIONS: Compared to the THE, employing the NHE strategy during THA with DAA in elderly and young female patients resulted in comparable clinical outcomes with several advantages, such as favourable surgical time. The NHE method also exhibited good safety and effectiveness. Therefore, the NHE strategy may be a favourable option for elderly and young female patients.

Preliminary Screening and Study of Key Gene Expression in Endometrial Window Period.

Background: Implantation is a highly coordinated event involving both embryonic and endometrial participation. The endometrium expresses a complex array of proteins during the menstrual cycle many of which help to define a period of receptivity collectively known as the "window of implantation." Objective: Using high-throughput RNA sequencing technology analysis to find differentially expressed genes before and after the endometrial window, and search for key marker genes of the membrane implantation window. Design: This was a retrospective study. Setting: This study was performed in the Department of Obstetrics and Gynecology, Taizhou People's Hospital. Participants: Fifty patients with repeated implantation failure in in vitro fertilization were selected and were divided into (1) the normal window group (36 cases); (2) the window forward group (8 cases); and (3) the window backward group (6 cases) based on endometrial biopsy findings. Interventions: Using RNA sequencing technology combined with biological information analysis tools to analyze the differentially-expressed genes in 9 samples. Gene Ontology databases were used for the functional annotation of these differentially-expressed genes. Kyoto Encyclopedia of Genes and Genomes analysis was used to draw a signal path diagram. Primary Outcome Measures: (1) Screening of differentially-expressed genes and (2) functional analysis of the differential genes. Results: A total of 22 differentially-expressed genes related to endometrial receptivity were obtained by transcriptome sequencing. Seven of the 22 differentially-expressed genes have been shown to have a close relationship with the endometrial receptive window period. Further, it was proved that the Wnt signaling pathway and mitogen-activated protein kinase signaling pathway were closely related to endometrial receptivity. Conclusions: The present study identified a series of key genes and pathways that may be involved in the endometrial window period, providing an experimental and theoretical basis for exploring the personalized embryo transfer program.

Effect of structured pelvic floor muscle training on pelvic floor muscle contraction and treatment of pelvic organ prolapse in postpartum women: ultrasound and clinical evaluations.

OBJECTIVES: The purpose of this study is to examine the impact of structured pelvic floor muscle training (PFMT) on pelvic floor muscle (PFM) contraction and the treatment of pelvic organ prolapse (POP) in postpartum women. METHODS: Sixty patients who volunteered for a PFMT assessment at 6-8 weeks after delivery were included in this retrospective analysis. For 5 weeks, all patients had structured PFMT, which included supervised daily pelvic muscle contractions, biofeedback therapy, and electrical stimulation. The main outcomes were POP stage assessed by POP quantification (POP-Q), pelvic organ position and hiatus area (HA) assessed by transperineal ultrasound, PFM contraction assessed by Modified Oxford scale (MOS), surface electromyography (EMG), and sensation of PFM graded using visual analog scale (VAS). RESULTS: Structured PFMT was associated with better POP-Q scores in Aa, Ba, C, and D (p values were 0.01, 0.001, 0.017, and 0.001 separately). The bladder neck at rest and maximum Valsalva, the cervix position and HA at maximum Valsalva in transperineal ultrasound were significantly better than before (p values were 0.031, < 0.001, 0.043, and < 0.001 separately). PFM contraction assessed by MOS, EMG, and PFM VAS score were significantly improved (all p values were < 0.001). However, no significant improvement was observed in POP-Q stage. CONCLUSIONS: Structured PFMT can increase PFM function in postpartum women but cannot modify the POP-Q stage. Transperineal ultrasonography is a useful method for evaluating therapy efficacy objectively. More randomized controlled trials are needed before definitive conclusions can be drawn about the effect of structured PFMT on POP in postpartum women.

Mechanism of dexmedetomidine protection against cisplatin induced acute kidney injury in rats.

OBJECTIVE: This study explored the molecular mechanisms by which dexmedetomidine (Dex) alleviates cisplatin (CP)-induced acute kidney injury (AKI) in rats. METHODS: CP-induced AKI models were established, and Dex was intraperitoneally injected at different concentrations into rats in the model groups. Subsequently, rats were assigned to the control, CP, CP + Dex 10 µg/kg, and CP + Dex 25 µg/kg groups. After weighing the kidneys of the rats, the kidney arterial resistive index was calculated, and CP-induced AKI was evaluated. In addition, four serum biochemical indices were measured: histopathological damage in rat kidneys was detected; levels of inflammatory factors, interleukin (IL)-1ß, IL-18, IL-6, and tumor necrosis factor alpha, in kidney tissue homogenate of rats were assessed through enzyme-linked immunosorbent assay (ELISA); and levels of NLRP-3, caspase-1, cleaved caspase-1, gasdermin D (GSDMD), and GSDMD-N in kidney tissues of rats were determined via western blotting. RESULTS: Dex treatment reduced nephromegaly and serum clinical marker upregulation caused by CP-induced AKI. In addition, hematoxylin and eosin staining revealed that Dex treatment relieved CP-induced kidney tissue injury in AKI rats. ELISA analyses demonstrated that Dex treatment reduced the upregulated levels of proinflammatory cytokines in the kidney tissue of AKI rats induced by CP, thereby alleviating kidney tissue injury. Western blotting indicated that Dex alleviated CP-induced AKI by inhibiting pyroptosis mediated by NLRP-3 and caspase-1. CONCLUSION: Dex protected rats from CP-induced AKI, and the mechanism may be related to NLRP-3/Caspase-1-mediated pyroptosis.

Effects of the Interaction between Rumen Microbiota Density-VFAs-Hepatic Gluconeogenesis on the Adaptability of Tibetan Sheep to Plateau.

During the adaptive evolution of animals, the host and its gut microbiota co-adapt to different elevations. Currently, there are few reports on the rumen microbiota-hepato-intestinal axis of Tibetan sheep at different altitudes. Therefore, the purpose of this study was to explore the regulatory effect of rumen microorganism-volatile fatty acids (VFAs)-VFAs transporter gene interactions on the key enzymes and genes related to gluconeogenesis in Tibetan sheep. The rumen fermentation parameters, rumen microbial densities, liver gluconeogenesis activity and related genes were determined and analyzed using gas chromatography, RT-qPCR and other research methods. Correlation analysis revealed a reciprocal relationship among rumen microflora-VFAs-hepatic gluconeogenesis in Tibetan sheep at different altitudes. Among the microbiota, Ruminococcus flavefaciens (R. flavefaciens), Ruminococcus albus (R. albus), Fibrobactersuccinogenes and Ruminobacter amylophilus (R. amylophilus) were significantly correlated with propionic acid (p < 0.05), while propionic acid was significantly correlated with the transport genes monocarboxylate transporter 4 (MCT4) and anion exchanger 2 (AE2) (p < 0.05). Propionic acid was significantly correlated with key enzymes such as pyruvate carboxylase, phosphoenolpyruvic acid carboxylase and glucose (Glu) in the gluconeogenesis pathway (p < 0.05). Additionally, the expressions of these genes were significantly correlated with those of the related genes, namely, forkhead box protein O1 (FOXO1) and mitochondrial phosphoenolpyruvate carboxykinase 2 (PCK2) (p < 0.05). The results showed that rumen microbiota densities differed at different altitudes, and the metabolically produced VFA contents differed, which led to adaptive changes in the key enzyme activities of gluconeogenesis and the expressions of related genes.

microRNA Temporal-Specific Expression Profiles Reveal longissimus dorsi Muscle Development in Tianzhu White Yak.

As a class of regulatory factors, microRNAs (miRNAs) play an important role in regulating normal muscle development and fat deposition. Muscle and adipose tissues, as major components of the animal organism, are also economically important traits in livestock production. However, the effect of miRNA expression profiles on the development of muscle and adipose tissues in yak is currently unknown. In this study, we performed RNA sequencing (RNA-Seq) on Tianzhu white yak longissimus dorsi muscle tissue obtained from calves (6 months of age, M6, n = 6) and young (30 months of age, M30, n = 6) and adult yak (54 months of age, M54, n = 6) to identify which miRNAs are differentially expressed and to investigate their temporal expression profiles, establishing a regulatory network of miRNAs associated with the development of muscle and adipose. The results showed that 1191 miRNAs and 22061 mRNAs were screened across the three stages, of which the numbers of differentially expressed miRNAs (DE miRNAs) and differentially expressed mRNAs (DE mRNAs) were 225 and 450, respectively. The expression levels of the nine DE miRNAs were confirmed using a reverse transcription quantitative PCR (RT-qPCR) assay, and the trend of the assay results was generally consistent with the trend of the transcriptome profiles. Based on the expression trend, DE miRNAs were categorized into eight different expression patterns. Regarding the expression of DE miRNAs in sub-trends Profile 1 and Profile 2 (p < 0.05), the gene expression patterns were upregulated (87 DE miRNAs). Gene ontology (GO) and Kyoto Encyclopedia of Genes Genomes (KEGG) analyses showed that the identified DE miRNAs and DE mRNAs were enriched in pathway entries associated with muscle and intramuscular fat (IMF) growth and development. On this basis, we constructed a DE miRNA-mRNA interaction network. We found that some DE mRNAs of interest overlapped with miRNA target genes, such as ACSL3, FOXO3, FBXO30, FGFBP4, TSKU, MYH10 (muscle development), ACOX1, FADS2, EIF4E2, SCD1, EL0VL5, and ACACB (intramuscular fat deposition). These results provide a valuable resource for further studies on the molecular mechanisms of muscle tissue development in yak and also lay a foundation for investigating the interactions between genes and miRNAs.

Mutations in the FOXO3 Gene and Their Effects on Meat Traits in Gannan Yaks.

The FOXO3 gene, a prominent member of the FOXO family, has been identified as a potential quantitative trait locus for muscle atrophy and lipid metabolism in livestock. It is also considered a promising candidate gene for meat quality traits such as Warner-Bratzler shear force (WBSF) and water holding capacity (WHC). The aim of this study was to identify sequence mutations in the FOXO3 gene of yaks and to analyze the association of genotypes and haplotypes with meat traits such as WBSF and WHC. Quantitative reverse-transcriptase PCR (RT-qPCR) was applied to determine the expression levels of FOXO3 in yak tissues, with the results revealing a high expression in the yak longissimus dorsi muscle. Exons of the FOXO3 gene were then sequenced in 572 yaks using hybrid pool sequencing. Five single nucleotide polymorphisms were identified. Additionally, four effective haplotypes and four combined haplotypes were constructed. Two mutations of the FOXO3 gene, namely C>G at exon g.636 and A>G at exon g.1296, were associated with cooked meat percentage (CMP) (p < 0.05) and WBSF (p < 0.05), respectively. Furthermore, the WBSF of the H2H3 haplotype combination was significantly lower than that of other combinations (p < 0.05). The findings of this study suggest that genetic variations in FOXO3 could be a promising biomarker for improving yak meat traits.