Multiomics Analyses Provide New Insight into Genetic Variation of Reproductive Adaptability in Tibetan Sheep.

Domestication and artificial selection during production-oriented breeding have greatly shaped the level of genomic variability in sheep. However, the genetic variation associated with increased reproduction remains elusive. Here, two groups of samples from consecutively monotocous and polytocous sheep were collected for genome-wide association, transcriptomic, proteomic, and metabolomic analyses to explore the genetic variation in fecundity in Tibetan sheep. Genome-wide association study revealed strong associations between BMPR1B (p.Q249R) and litter size, as well as between PAPPA and lambing interval; these findings were validated in 1,130 individuals. Furthermore, we constructed the first single-cell atlas of Tibetan sheep ovary tissues and identified a specific mural granulosa cell subtype with PAPPA-specific expression and differential expression of BMPR1B between the two groups. Bulk RNA-seq indicated that BMPR1B and PAPPA expressions were similar between the two groups of sheep. 3D protein structure prediction and coimmunoprecipitation analysis indicated that mutation and mutually exclusive exons of BMPR1B are the main mechanisms for prolific Tibetan sheep. We propose that PAPPA is a key gene for stimulating ovarian follicular growth and development, and steroidogenesis. Our work reveals the genetic variation in reproductive performance in Tibetan sheep, providing insights and valuable genetic resources for the discovery of genes and regulatory mechanisms that improve reproductive success.

Longer serum phosphorus time in range associated with lower mortality risk among peritoneal dialysis patients: a multicenter retrospective cohort study.

BACKGROUND: Relationship between serum phosphorus time in range and mortality risk in peritoneal dialysis (PD) patients remains uncertain. We aimed to evaluate the association between serum phosphorus time in range and all-cause mortality in Chinese PD population. METHODS: This was a multicenter, retrospective, cohort study of 1,915 patients collected from January 2008 to October 2020 in 4 Chinese centers. Serum phosphorus time in range was estimated as the months during the first year that a patient's serum phosphorus level was within the target range (defined as 1.13-1.78 mmol/L). The primary outcome was all-cause mortality. The secondary outcomes were cardiovascular (CV) mortality and PD withdrawal. Cox proportional hazards regression model with comprehensive adjustments was used to assess the association. RESULTS: The primary outcome occurred in 249 (13.0%) PD patients over a median follow-up of 28 months. Overall, the serum phosphorus time in range was negatively associated with all-cause mortality (per 3-month increments, adjusted HR [aHR], 0.83; 95%CI: 0.75-0.92), CV mortality (per 3-month increments, aHR, 0.87; 95%CI: 0.77-0.99), and PD withdrawal (per 3-month increments, aHR, 0.89; 95%CI: 0.83-0.95). Competing-risk model showed that the relationship of serum phosphorus time in range with all-cause mortality remained stable. None of the variables including demographics, history of diabetes and CV disease, as well as several PD-related and clinical indicators modified this association. CONCLUSIONS: PD patients with longer serum phosphorus time in range in the first year was negatively associated with all-cause mortality and CV mortality. Our findings highlight the importance of maintaining serum phosphorus levels within 1.13-1.78 mmol/L for PD patients.

Plasmodium yoelii 17XL infection modified maturation and function of dendritic cells by skewing Tregs and amplificating Th17.

BACKGROUND: Emerging data has suggested that Tregs, Th17, Th1 and Th2 are correlated with early immune mechanisms by controlling Plasmodium infection. Plasmodium infection appeared to impair the antigen presentation and maturation of DCs, leading to attenuation of specific cellular immune response ultimately. Hence, in this study, we aim to evaluate the relevance between DCs and Tregs/Th17 populations in the process and outcomes of infection with Plasmodium yoelii 17XL (P.y17XL). METHODS: DCs detection/analysis dynamically was performed by Tregs depletion or Th17 neutralization in P.y17XL infected BALB/c mice via flow cytometry. Then the levels of cytokines production were detected using enzyme-linked mmunosorbent assay (ELISA). RESULTS: Our results indicated that Tregs depletion or Th17 neutralization in BALB/c mice infected with P.y17XL significantly up-regulated the percentages of mDC and pDC, increased the expressions of major histocompatibility complex (MHC) class II, CD80, CD86 on DCs and the levels of IL-10/IL-12 secreted by DCs, indicating that abnormal amplification of Tregs or Th17 may damage the maturation and function of DCs during the early stage of malaria infection. Interestingly, we also found that the abnormal amplification of Th17, as well as Tregs, could inhibit the maturation of DCs. CONCLUSIONS: Tregs skewing or Th17 amplification during the early stage of malaria infection may inhibit the maturation and function of DCs by modifying the subsets of DCs, expressions of surface molecules on DCs and secretion mode of cytokines.

MiR-153-5p promotes sensibility of colorectal cancer cells to oxaliplatin via targeting Bcl-2-mediated autophagy pathway.

Oxaliplatin (L-OHP) is one of the effective chemotherapeutic drugs for colorectal cancer (CRC). Further investigation into the molecular mechanism of chemoresistance could improve outcomes for patients with colorectal cancer. Recently, microRNAs have been reported as a key in drug resistance of tumors. In this study, we aimed to investigate the effects of miR-153-5p in L-OHP-resistant CRC cells, and its underlying mechanism. Downregulation of miR-153-5p was observed in CRC cells, while upregulation of miR-153-5p enhances the chemosensitivity of CRC/L-OHP cells. The autophagy of CRC/L-OHP cells was markedly increased after exposure to L-OHP but abolished by the upregulation of miR-153-5p. Dual-luciferase reporter assays validated that Bcl-2 was a direct target of miR-153-5p. In conclusion, our data suggested that miR-153-5p was a mediator of cisplatin resistance in colorectal cancer by affecting Bcl-2-mediated autophagy, indicating a new therapeutic target for CRC treatment.

UWB/Binocular VO Fusion Algorithm Based on Adaptive Kalman Filter.

Among the existing wireless indoor positioning systems, UWB (ultra-wideband) is one of the most promising solutions. However, the single UWB positioning system is affected by factors such as non-line of sight and multipath, and the navigation accuracy will decrease. In order to make up for the shortcomings of a single UWB positioning system, this paper proposes a scheme based on binocular VO (visual odometer) and UWB sensor fusion. In this paper, the original distance measurement data of UWB and the position information of binocular VO are merged by adaptive Kalman filter, and the structural design of the fusion system and the realization of the fusion algorithm are elaborated. The experimental results show that compared with a single positioning system, the proposed data fusion method can significantly improve the positioning accuracy.

Associations of the Novel Polymorphisms of Periostin and Platelet-Derived Growth Factor Receptor-Like Genes with Egg Production Traits in Local Chinese Dagu Hens.

The periostin (POSTN) and platelet-derived growth factor receptor-like (PDGFRL) genes are implicated in regulation of hen ovarian development. In the present study, these genes were explored as possible molecular markers associated with egg production, egg weight and body weight in Chinese Dagu hens. Samples were analyzed using the PCR-single strand conformation polymorphism (PCR-SSCP) method, followed by sequencing analysis, and three novel single nucleotide polymorphisms (SNPs) were identified within the candidate genes. Among them, an A/T transversion at base position 2727 in intron 2 of POSTN gene was found to be polymorphic and named SNP A2727T; and two transitions, G/A at position 6761 and A/G at base 6839 in exon 2 of PDGFRL gene were detected and named SNPs G6761A and A6839G, respectively. For the SNP A2727T, a total of 360 Dagu hens were classified as AA and AB genotypes, allele A was found present at a higher frequency. Moreover, the AA genotype was significantly correlated with higher hen-housed egg production (HHEP) at 43, 57, and 66 weeks (wks) of age and with a higher egg weight (EW) at 30 wks (P < 0.05). For the two linked SNPs (G6761A and A6839G) in the PDGFRL fragment, the hens were typed into TT, TC and CC genotypes, with the T allele shown to be dominant. The TT genotype was correlated with higher HHEP at 57 and 66 wks of age; genotype CC associated with the highest body weight and EW at 30 and 43 wks (P < 0.05), while it was correlated with the lowest HHEP at 57 and 66 wks of age (P < 0.05). Furthermore, five haplotypes were reconstructed based on these SNPs, with the AATT haplotype associated with the highest HHEP at 43 to 66 wks of age and higher EW at 30 wks (P < 0.05). Collectively, these SNPs identified in this study might be used as a potential molecular marker favorable to genetic improvement of egg productivity in chicken breeding.

Case report: Treatment of Wilson's disease by human amniotic fluid administration.

Background: Wilson's disease (WD) is not an uncommon genetic disease in clinical practice. However, the current WD therapies have limitations. The effectiveness of stem cell therapy in treating WD has yet to be verified, although a few animal studies have shown that stem cell transplantation could partially correct the abnormal metabolic phenotype of WD. In this case report, we present the therapeutic effect of human amniotic fluid containing stem cells in one WD patient. Case presentation: A 22-year-old Chinese woman was diagnosed with WD 1 year ago in 2019. The available drugs were not effective in managing the progressive neuropsychiatric symptoms. We treated the patient with pre-cultured human amniotic fluid containing stem cells. Amniotic fluid was collected from pregnant women who underwent induced labor at a gestational age of 19-26 weeks, and then, the fluid was cultured for 2 h to allow stem cell expansion. Cultured amniotic fluid that contained amniotic fluid derived stem cells (AFSC) in the range of approximately 2.8-5.5 × 104/ml was administrated by IV infusion at a rate of 50-70 drops per minute after filtration with a 300-mu nylon mesh. Before the infusion of amniotic fluid, low-molecular-weight heparin and dexamethasone were successively administrated. The patient received a total of 12 applications of amniotic fluid from different pregnant women, and the treatment interval depended on the availability of amniotic fluid. The neuropsychiatric symptoms gradually improved after the stem cell treatment. Dystonia, which included tremor, chorea, dysphagia, dysarthria, and drooling, almost disappeared after 1.5 years of follow-up. The Unified Wilson's Disease Rating Scale score of the patient decreased from 72 to 10. Brain magnetic resonance imaging (MRI) showed a reduction in the lesion area and alleviation of damage in the central nervous system, along with a partial recovery of the lesion to the normal condition. The serum ceruloplasmin level was elevated from undetectable to 30.8 mg/L, and the 24-h urinary copper excretion decreased from 171 to 37 µg. In addition, amniotic fluid transplantation also alleviates hematopoietic disorders. There were no adverse reactions during or after amniotic fluid administration. Conclusion: Amniotic fluid administration, through which stem cells were infused, significantly improves the clinical outcomes in the WD patient, and the finding may provide a novel approach for managing WD effectively.

Exploring T7 RNA polymerase-assisted CRISPR/Cas13a amplification for the detection of BNP via electrochemiluminescence sensing platform.

Brain natriuretic peptide (BNP) is considered to be an important biomarker of heart failure (HF) attracting attention. However, its low concentration and short half-life in blood lead to a low-sensitivity detection of BNP, which is a challenge that has to be overcome. In this work, we propose a highly specific, highly sensitive T7 RNA polymerase-assisted clustered regularly interspaced short palindromic repeats (CRISPR)/Cas13a system to detect BNP via an electrochemiluminescence (ECL) sensing platform and incorporate exonuclease III (Exo III)-hairpin and dumbbell-shaped hybridization chain reaction (HCR) technologies. In this detection scheme, the ECL sensing platform possesses low background signal and high sensitivity. Firstly, the T7 promoter-initiated T7 RNA polymerase acts as a signal amplification technique to generate large amounts of RNAs that can activate CRISPR/Cas13a activity. Secondly, CRISPR/Cas13a is able to trans-cleave the surrounding trigger strand to produce DNA1. Thirdly, DNA1 is involved in the co-amplification reaction of Exo III and hairpin DNA, which subsequently triggers a dumbbell-shaped HCR technology. Eventually, a large number of Ru (II) molecules are inserted into the interstitial space of the dumbbell-shaped HCR to generate a strong ECL signal. The CRISPR/Cas13a possesses outstanding specificity for a single base and increased sensitivity. The tightly conformed dumbbell-shaped HCR provides higher sensitivity than the traditional linear HCR amplification technique. Ultimately, the clever combination of several amplification reactions enables the limit of detection (LOD) as low as 3.2 fg/mL. It showed promise for clinical sample testing, with recovery rates ranging from 98.4% to 103% in 5% human serum samples. This detection method offered a valuable tool for early HF detection, emphasizing the synergy of amplification strategies and specificity conferred by CRISPR/Cas13a technology.

Apparent Treatment-Resistant Hypertension in the First Year Associated With Cardiovascular Mortality in Peritoneal Dialysis Patients.

BACKGROUND: Few reports have focused on the association between apparent treatment-resistant hypertension (aTRH) and cardiovascular (CV) mortality in peritoneal dialysis (PD) population, thus we conducted this retrospective cohort to explore it. METHODS: This was a retrospective cohort study conducted from January 2011 to January 2020 with PD patients in 4 Chinese dialysis centers. aTRH was defined according to the American College of Cardiology and American Heart Association guidelines. aTRH duration was calculated as the total number of months when patients met the diagnostic criteria in the first PD year. The primary outcome was CV mortality, and the secondary outcomes were CV events, all-cause mortality, combined endpoint (all-cause mortality and transferred to hemodialysis [HD]), and PD withdrawal (all-cause mortality, transferred to HD, and kidney transplantation). Cox proportional hazards models were used to assess the association. RESULTS: A total of 1,422 patients were finally included in the analysis. During a median follow-up period of 26 months, 83 (5.8%) PD patients incurred CV mortality. The prevalence of aTRH was 24.1%, 19.9%, and 24.6% at 0, 3, and 12 months after PD initiation, respectively. Overall, aTRH duration in the first PD year positively associated with CV mortality (per 3 months increment, adjusted hazards ratio [HR], 1.29; 95% confidence interval 1.10, 1.53; P = 0.002). After categorized, those with aTRH duration more than 6 months presented the highest adjusted HR of 2.92. Similar results were found for secondary outcomes, except for the CV event. CONCLUSIONS: Longer aTRH duration in the first PD year is associated with higher CV mortality and worse long-term clinical outcomes. Larger studies are warranted to confirm these findings. CLINICAL TRIALS REGISTRATION: There is no clinical trial registration for this retrospective study.

Effects of direct oral anticoagulants vs. vitamin K antagonists on acute kidney injury in patients with atrial fibrillation: A systematic review.

Background: Patients with atrial fibrillation (AF) are routinely prescribed oral anticoagulants to prevent thromboembolism. Concerns regarding the efficacy and safety of oral anticoagulants, such as vitamin K antagonists (VKA) and direct oral anticoagulants (DOACs), arise for patients with non-valvular atrial fibrillation (NVAF) because of their widespread use in clinical practice. Even though there have been an abundance of studies on this topic, it is still not clear if DOAC users with NVAF have a lower risk of acute kidney injury (AKI) than warfarin users. Methods and results: We conducted electronic searches in PubMed, Embase, and the Cochrane Library to identify relevant studies for this systematic review. We included randomized clinical trials and observational studies that reported on the incidence rate, hazard ratio (HR), and 95% confidence interval (95% CI) of AKI in patients using oral anticoagulants. This systemic review included six observational studies and four randomized clinical trials (RCT). The overall results showed that DOACs were associated with a lower AKI risk than warfarin. However, for NVAF patients with severe renal dysfunction, DOACs may not have a reduced risk of AKI compared to warfarin. Conclusion: The overall results suggest that, except for edoxaban, patients using DOACs may experience a reduced risk of AKI. However, it is uncertain whether this is also the case for patients with severe renal dysfunction. Further research is needed to confirm the effect of DOACs on this population.

Case report: A HIV-negative hemodialysis patient positive for pANCA with severe pneumocystis pneumonia: A case report and review of literature.

RATIONALE: Pneumocystis pneumonia (PCP) is an opportunistic fungal infection that occurs in people with impaired or suppressed immunity such as patients with human immunodeficiency virus or organ transplant. However, the incidence and characteristics of PCP in the population with long-term hemodialysis is poorly described in the literature. PATIENT CONCERNS: We present a case of a 50-year-old female patient being transferred to our hospital in February 2022 with a 20-day history of cough and tight breath. She received amoxicillin and cephalosporin anti-infection treatment successively in local hospital but no significant improvement in symptoms. She had a 2-year history of hemodialysis and no relevant transplantation and human immunodeficiency virus infection. She was diagnosed as ANCA associated vasculitis (AAV) and given oral prednisone acetate (20 mg/day) and methotrexate (2.5 mg/week) half a year ago. DIAGNOSES: Based on the patient's medical history, Lung computerized tomography image, the Next generation sequencing report, the patient was diagnosed with renal failure, anti-neutrophil cytoplasmic antibody associated vasculitis, and Pneumocystis pneumonia. INTERVENTIONS: The dosage of immunosuppressant was reduced due to leucocyte dripping and fever, and antibiotic and antifungal treatment were also given. The patient's lung condition was getting worse and noninvasive ventilator was required to maintain blood oxygen. Blood filtration is used to remove toxins. Ganciclovir and trimethoprim-sulfamethoxazole was used based on the next generation sequencing report. OUTCOMES: The patient died of respiratory failure. LESSONS: The risk of PCP in hemodialysis patients may be higher than that in ordinary population, and the prognosis of patients with immunosuppression may be worse. Dynamic assessment of vasculitis activity is necessary for hemodialysis patients with AAV because infections may obscure lung symptoms of AAV. It is not recommended that hemodialysis patients with long-term immunosuppression should reduce or stop the dosage of immunosuppressive drugs during the treatment because it may aggravate the condition of PCP. There is still no clear conclusion on whether hemodialysis patients need preventive medicine, but the identification of risk factors and early diagnosis and treatment are important for the prognosis of PCP on hemodialysis population.

High-dose insulin and dexamethasone combined with radiotherapy in endometrial stromal sarcoma recurring with multiple metastases: A case report.

RATIONALE: Endometrial stromal sarcoma (ESS) is a rare malignant tumor. There is insufficient data supporting the efficiency of current treatments in multiple metastatic settings, and novel therapeutic options for ESS are considered an area of high unmet clinical need. PATIENT CONCERNS: We report the case of a 28-year-old woman who was diagnosed with ESS after undergoing total hysterectomy and left adnexectomy at another hospital. Two years later, the disease recurred, with multiple abdominal cavities and lung metastases. The patient was treated with a variety of chemotherapeutic drugs, including tyrosine kinase inhibitors, at the same hospital; however, none of them inhibited disease progression. DIAGNOSES: Computed tomography (CT) revealed multiple masses in the abdominal and pelvic cavities and multiple pulmonary nodules. Ultrasound-guided biopsy was performed and the tumor tissue was histologically confirmed after treatment. INTERVENTIONS: Insulin 300-400 IU was administrated by intravenous infusion in 10% glucose (500 mL) with disodium adenosine triphosphate 60 mg, coenzyme A 100 units, 10% potassium chloride 5 mL and 25% magnesium sulfate 5 mL. Dexamethasone (20-25 mg/d) was diluted with 10 mL of 2% lidocaine and then intraperitoneally injected after ascites draw. After 9 months, the patient was referred to another center for radiotherapy. OUTCOMES: CT images tomography showed recurrent pelvic masses, and multiple abdominal cavity and lung metastases gradually shrunk with treatment. Histological biopsy revealed growth arrest of tumor cells. The patient experienced for 3-years survival. LESSONS: High-dose insulin and dexamethasone combined with radiotherapy provides a novel and promising option for patients with multiple ESS metastases.

Genetic diversity and selection of Tibetan sheep breeds revealed by whole-genome resequencing.

OBJECTIVE: This study aimed to elucidate the underlying gene regions responsible for productive, phenotypic or adaptive traits in different ecological types of Tibetan sheep and the discovery of important genes encoding valuable traits. METHODS: We used whole-genome resequencing to explore the genetic relationships, phylogenetic tree, and population genetic structure analysis. In addition, we identified 28 representative Tibetan sheep single-nucleotide polymorphisms (SNPs) and genomic selective sweep regions with different traits in Tibetan sheep by fixation index (Fst) and the nucleotide diversity (θπ) ratio. RESULTS: The genetic relationships analysis showed that each breed partitioned into its own clades and had close genetic relationships. We also identified many potential breed-specific selective sweep regions, including genes associated with hypoxic adaptability (MTOR, TRHDE, PDK1, PTPN9, TMTC2, SOX9, EPAS1, PDGFD, SOCS3, TGFBR3), coat color (MITF, MC1R, ERCC2, TCF25, ITCH, TYR, RALY, KIT), wool traits (COL4A2, ERC2, NOTCH2, ROCK1, FGF5, SOX9), and horn phenotypes (RXFP2). In particular, a horn-related gene, RXFP2, showed the four most significantly associated SNP loci (g. 29481646 A>G, g. 29469024 T>C, g. 29462010 C>T, g. 29461968 C>T) and haplotypes. CONCLUSION: This finding demonstrates the potential for genetic markers in future molecular breeding programs to improve selection for horn phenotypes. The results will facilitate the understanding of the genetic basis of production and adaptive unique traits in Chinese indigenous Tibetan sheep taxa and offer a reference for the molecular breeding of Tibetan sheep.

Genome-wide identification of candidate copy number polymorphism genes associated with complex traits of Tibetan-sheep.

Copy number variation (CNV) is a genetic structural polymorphism important for phenotypic diversity and important economic traits of livestock breeds, and it plays an important role in the desired genetic variation. This study used whole genome sequencing to detect the CNV variation in the genome of 6 local Tibetan sheep groups. We detected 69,166 CNV events and 7230 copy number variable regions (CNVRs) after merging the overlapping CNVs, accounting for 2.72% of the reference genome. The CNVR length detected ranged from 1.1 to 1693.5 Kb, with a total length of 118.69 Mb and an average length of 16.42 Kb per CNVR. Functional GO cluster analysis showed that the CNVR genes were mainly involved in sensory perception systems, response to stimulus, and signal transduction. Through CNVR-based Vst analysis, we found that the CACNA2D3 and CTBP1 genes related to hypoxia adaptation, the HTR1A gene related to coat color, and the TRNAS-GGA and PIK3C3 genes related to body weight were all strongly selected. The findings of our study will contribute novel insights into the genetic structural variation underlying hypoxia adaptation and economically important traits in Tibetan sheep.

Vascular Disruptive Hydrogel Platform for Enhanced Chemotherapy and Anti-Angiogenesis through Alleviation of Immune Surveillance.

Patients undergoing immunotherapy always exhibit a low-response rate due to tumor heterogeneity and immune surveillance in the tumor. Angiogenesis plays an important role in affecting the status of tumor-infiltrated lymphocytes by inducing hypoxia and acidosis microenvironment, suggesting its synergistic potential in immunotherapy. However, the antitumor efficacy of singular anti-angiogenesis therapy often suffers from failure in the clinic due to the compensatory pro-angiogenesis signaling pathway. In this work, classic injectable thermosensitive PLGA-PEG-PLGA copolymer was used to construct a platform to co-deliver CA4P (vascular disruptive agent) and EPI for inducing immunogenic cell death of cancer cells by targeting the tumor immune microenvironment. Investigation of 4T1 tumor-bearing mouse models suggests that local administration of injectable V+E@Gel could significantly inhibit the proliferation of cancer cells and prolong the survival rate of 4T1 tumor-bearing mouse models. Histological analysis further indicates that V+E@Gel could effectively inhibit tumor angiogenesis and metastasis by down-regulating the expression of CD34, CD31, MTA1 and TGF-ß. Moreover, due to the sustained release kinetics of V+E@Gel, its local administration relieves the immune surveillance in tumor tissues and thus induces a robust and long-lasting specific antitumor immune response. Overall, this work provides a new treatment strategy through the mediation of the tumor immune microenvironment by vascular disruption to fulfill enhanced chemotherapy and immunotherapy.

Genetic Polymorphisms of IGF1 and IGF1R Genes and Their Effects on Growth Traits in Hulun Buir Sheep.

The identification of candidate genes and genetic variations associated with growth traits is important for sheep breeding. Insulin like growth factor 1 (IGF1) and insulin like growth factor 1 receptor (IGF1R) are well-accepted candidate genes that affect animal growth and development. The current study attempted to assess the association between IGF1 and IGF1R genetic polymorphisms and growth traits in Hulun Buir sheep. To achieve this goal, we first identified three and ten single nucleotide polymorphisms (SNPs) in exons of IGF1 and IGF1R in Hulun Buir sheep and then constructed six haplotypes of IGF1R based on linkage disequilibrium, respectively. Association studies were performed between SNPs and haplotypes of IGF1 and IGF1R with twelve growth traits in a population encompassing 229 Hulun Buir sheep using a general linear model. Our result indicated three SNPs in IGF1 were significantly associated with four growth traits (p < 0.05). In IGF1R, three SNPs and two haplotype blocks were significantly associated with twelve growth traits (p < 0.05). The combined haplotype H5H5 and H5H6 in IGF1R showed the strong association with 12 superior growth traits in Hulun Buir sheep (p < 0.05). In conclusion, we identified SNPs and haplotype combinations associated with the growth traits, which provided genetic resources for marker-assisted selection (MAS) in Hulun Buir sheep breeding.

Identification of SSTR5 Gene Polymorphisms and Their Association With Growth Traits in Hulun Buir Sheep.

The aim of this study was to locate SSTR5 polymorphisms and evaluate their association with growth traits in Hulun Buir sheep. The study followed up 884 Hulun Buir sheep from birth to 16 months of age, which were born in the same pasture and the same year, and a consistent grazing management strategy was maintained. The birth weight (BRW) was recorded at birth, and body weight (BW), body height (BH), body length (BL), chest circumference (ChC), chest depth (ChD), chest width (ChW), hip width (HW), and cannon circumference (CaC) were measured at 4 and 9 months of age. BW, BH, BL, ChD, HW, and CaC were also recorded at 16 months of age. Based on the growth traits, 233 sheep were selected as experimental animals. Sanger sequencing was performed, and seven single-nucleotide polymorphisms (SNPs) were identified. Association analyses of the SNPs and the growth traits were then conducted. Seven SNPs of the SSTR5 exhibited moderate polymorphism (0.25

Effects of vitamin D with or without calcium on pathological ossification: A retrospective clinical study.

Vitamin D protects against the development and severity of several rheumatic diseases. However, the effect of vitamin D on the pathological ossification associated with rheumatic diseases remains unknown. The present retrospective study analyzed the clinical outcomes of vitamin D without calcium compared with vitamin D with calcium on pathological ossification in joints and ligaments. Data were collected from patients who were diagnosed with osteoarthritis, rheumatoid arthritis or spondylarthritis, and the presence of pathological ossification in joints or ligaments was confirmed by X-ray, computed tomography or magnetic resonance imaging examination. A total of 2,965 patients aged 18-75 years old were included, among who, 1,725 were included in the vitamin D alone group and 1,240 in the vitamin D with calcium group. Vitamin D was administered intramuscularly (300,000 IU) once every 7-10 days, 4-6 times in total. Patients who ingested an oral calcium supplement (1,000 mg/day; ≥5 days/week) were considered the vitamin D with calcium group. The clinical outcome was evaluated based on the imaging changes of pathological ossification, which were classified as alleviation, aggravation and unchanged. The bone mineral density (BMD) was determined, and the calcium concentration in the serum and urine was measured. The results revealed that vitamin D alone alleviated pathological ossification, while vitamin D combined with calcium aggravated pathological ossification in the majority of patients (P<0.0001) independent of disease type and patient age. BMD measurements demonstrated a decreasing trend in the vitamin D alone group, whereas they exhibited an increasing trend in the vitamin D combined with calcium group. The urine calcium concentration increased after vitamin D treatment alone. Therefore, it was concluded that vitamin D exerted both pro-resorptive and anti-resorptive actions on pathological ossification. The bidirectional action of vitamin D on bone metabolism may depend on exogenous calcium supplementation.

Integrated Strategies of Diverse Feature Selection Methods Identify Aging-Based Reliable Gene Signatures for Ischemic Cardiomyopathy.

Objective: Ischemic cardiomyopathy (ICM) is a major cardiovascular state associated with prominently increased morbidity and mortality. Our purpose was to detect reliable gene signatures for ICM through integrated feature selection strategies. Methods: Transcriptome profiles of ICM were curated from the GEO project. Classification models, including least absolute shrinkage and selection operator (LASSO), support vector machine (SVM), and random forest, were adopted for identifying candidate ICM-specific genes for ICM. Immune cell infiltrates were estimated using the CIBERSORT method. Expressions of candidate genes were verified in ICM and healthy myocardial tissues via Western blotting. JC-1 staining, flow cytometry, and TUNEL staining were presented in hypoxia/reoxygenation (H/R)-stimulated H9C2 cells with TRMT5 deficiency. Results: Following the integration of three feature selection methods, we identified seven candidate ICM-specific genes including ASPN, TRMT5, LUM, FCN3, CNN1, PCNT, and HOPX. ROC curves confirmed the excellent diagnostic efficacy of this combination of previous candidate genes in ICM. Most of them presented prominent interactions with immune cell infiltrates. Their deregulations were confirmed in ICM than healthy myocardial tissues. TRMT5 expressions were remarkedly upregulated in H/R-stimulated H9C2 cells. TRMT5 deficiency enhanced mitochondrial membrane potential and reduced apoptosis in H/R-exposed H9C2 cells. Conclusion: Collectively, our findings identified reliable gene signatures through combination strategies of diverse feature selection methods, which facilitated the early detection of ICM and revealed the underlying mechanisms.

Hypokalemia Duration in the First Year Associated with Subsequent Peritoneal Dialysis-Associated Peritonitis: A Multicenter Retrospective Cohort Study.

BACKGROUND: The association of hypokalemia (LK) with peritoneal dialysis-associated peritonitis (PDAP) risk remains uncertain. Here, we calculated LK duration in the first PD year and evaluated its association with PDAP. METHODS: A multicenter, retrospective, incident cohort study of 1633 participants was conducted from January 2008 to October 2020 in China. The duration of LK and severe hypokalemia (SLK) was calculated as the total number of months that a patient's serum potassium (SK) level was less than 3.5 or 3.0 mEq/L during the first PD year. The study outcome was the risk of subsequent PDAP started in the second year and later. Cox proportional hazards models and competing risk models were used to assess the association. RESULTS: The subsequent PDAP occurred in 420 (25.7%) participants during a median of 28 months of follow-up. Overall, LK duration in the first year was positively associated with a subsequent PDAP risk (per 3-month increments, adjusted HR, 1.13; 95%CI: 1.05-1.23). After categorization, patients with LK duration longer than 6 months had the highest adjusted HR of 1.53 (p = 0.005 vs. those without LK) for subsequent PDAP risk. A similar trend was also found for SLK duration. In a competing risk model, a similar trend was also observed. None of the variables, including demographic and PD characteristics, diabetes history, and several clinical measurements, significantly modified this association. The causative organisms of PDAP were similar to those previously reported. CONCLUSIONS: PD patients with longer LK duration in the first year had a higher subsequent PDAP risk.