Transcriptome meta-analysis reveals the hair genetic rules in six animal breeds and genes associated with wool fineness.

Wool plays an irreplaceable role in the lives of livestock and the textile industry. The variety of hair quality and shape leads to the diversity of its functions and applications, and the finer wool has a higher economic value. In this study, 10 coarse and 10 fine ordos fine wool sheep skin samples were collected for RNA-seq, and coarse and fine skin/hair follicle RNA-seq datasets of other five animal breeds were obtained from NCBI. Weighted gene co-expression network analysis showed that the common genes were clustered into eight modules. Similar gene expression patterns in sheep and rabbits with the same wool types, different gene expression patterns in animal species with different hair types, and brown modules were significantly correlated with species and breeds. GO and KEGG enrichment analyses showed that, most genes in the brown module associated with hair follicle development. Hence, gene expression patterns in skin tissues may determine hair morphology in animal. The analysis of differentially expressed genes revealed that 32 highly expressed candidate genes associated with the wool fineness of Ordos fine wool sheep. Among them, KAZALD1 (grey module), MYOC (brown module), C1QTNF6 (brown module), FOS (tan module), ITGAM, MX2, MX1, and IFI6 genes have been reported to be involved in the regulation of the hair follicle cycle or hair loss. Additionally, 12 genes, including KAZALD1, MYOC, C1QTNF6, and FOS, are differentially expressed across various animal breeds and species. The above results suggest that different sheep breeds share a similar molecular regulatory basis of wool fineness. Finally, the study provides a theoretical reference for molecular breeding of sheep breeds as well as for the investigation of the origin and evolution of animal hair.

Metabolomics reveals metabolites associated with hair follicle cycle in cashmere goats.

BACKGROUND: The hair follicle is a skin accessory organ that regulates hair development, and its activity varies on a regular basis. However, the significance of metabolites in the hair follicle cycle has long been unknown. RESULTS: Targeted metabolomics was used in this investigation to reveal the expression patterns of 1903 metabolites in cashmere goat skin during anagen to telogen. A statistical analysis was used to investigate the potential associations between metabolites and the hair follicle cycle. The findings revealed clear changes in the expression patterns of metabolites at various phases and in various feeding models. The majority of metabolites (primarily amino acids, nucleotides, their metabolites, and lipids) showed downregulated expression from anagen (An) to telogen (Tn), which was associated with gene expression, protein synthesis and transport, and cell structure, which reflected, to some extent, that the cells associated with hair follicle development are active in An and apoptotic in An-Tn. It is worth mentioning that the expression of vitamin D3 and 3,3',5-triiodo-L-thyronine decreased and then increased, which may be related to the shorter and longer duration of outdoor light, which may stimulate the hair follicle to transition from An to catagen (Cn). In the comparison of different hair follicle development stages (An, Cn, and Tn) or feeding modes (grazing and barn feeding), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that common differentially expressed metabolites (DEMs) (2'-deoxyadenosine, L-valine, 2'-deoxyuridine, riboflavin, cytidine, deoxyguanosine, L-tryptophan, and guanosine-5'-monophosphate) were enriched in ABC transporters. This finding suggested that this pathway may be involved in the hair follicle cycle. Among these DEMs, riboflavin is absorbed from food, and the expression of riboflavin and sugars (D-glucose and glycogen) in skin tissue under grazing was greater and lower than that during barn feeding, respectively, suggesting that eating patterns may also alter the hair follicle cycle. CONCLUSIONS: The expression patterns of metabolites such as sugars, lipids, amino acids, and nucleotides in skin tissue affect hair follicle growth, in which 2'-deoxyadenosine, L-valine, 2'-deoxyuridine, riboflavin, cytidine, deoxyguanosine, L-tryptophan, and guanosine-5'-monophosphate may regulate the hair follicle cycle by participating in ABC transporters. Feeding practices may regulate hair follicle cycles by influencing the amount of hormones and vitamins expressed in the skin of cashmere goats.

Comparison of different animal models for estimating genetic parameters for early growth traits and reproductive traits in Tianmu Sainuo sheep.

As the economic level of individuals rises, so too does the demand for mutton. Enhancing the breeds of mutton sheep not only boosts production efficiency and economic benefits but also fosters the sustainable growth of the mutton sheep breeding industry. Thus, this study examines the early growth and reproductive traits of Tianmu Sainuo sheep, analyzing the genetic interactions among these traits to furnish a theoretical foundation for refining breeding strategies and expediting the genetic advancement of this breed. The investigation compiled 29,966 data entries, involving 111 sires for birth weight (BWT) and 113 for other metrics. The data encompassed 10,415 BWT records from 1,633 dams, 12,753 weaning weight (WWT) records from 1,570 dams, 12,793 average daily gain (ADG) records from 1,597 dams, and 13,594 litter size (LS) records from 1,499 dams. Utilizing the GLM procedure in SAS 9.2 software, the study analyzed the non-genetic influences on lamb BWT, WWT, ADG, and LS. Concurrently, DMU software estimated the variance components across various animal models for each trait. Employing the Akaike Information Criterion (AIC) and likelihood ratio test (LRT), six models were tested, incorporating or excluding maternal inheritance and environmental impacts, to identify the optimal model for deriving genetic parameters. The findings reveal that birth year (BY), birth quarter (BQ), birth type (BT), age of mother (AM), and birth sex (BS) exerted significant impacts on BWT, WWT, and ADG (p < 0.01). Additionally, BQ and AM significantly influenced LS (p < 0.01). The most accurate genetic evaluation model determined the heritability of BWT, WWT, ADG, and LS to be 0.0695, 0.0849, 0.0777, and 0.1252, respectively.

Stress adaptation in Tibetan cashmere goats is governed by inherent metabolic differences and manifested through variable cashmere phenotypes.

Tibetan cashmere goats are not only served as a valuable model for studying adaptation to hypoxia and high-altitude conditions but also playing a pivotal role in bolstering local economies through the provision of premium quality cashmere yarn. In this study, we performed an integration and network analysis of metabolomic, transcriptomic and proteomic to elucidate the role of differentially expressed genes, important metabolites, and relevant cellular and metabolic pathways between the fine (average 12.04 ± 0.03 µm of mean fiber diameter) and coarse cashmere (average 14.88 ± 0.05 µm of mean fber diameter) producing by Tibetan cashmere goats. We identified a distinction of 56 and 71 differential metabolites (DMs) between the F and C cashmere groups under positive and negative ion modes, respectively. The KEGG pathway enrichment analysis of these DMs highlighted numerous pathways predominantly involved in amino acid and protein metabolism, as indicated by the finding that the most impactful pathway was the mammalian target of rapamycin (mTOR) signalling pathway. In the F group, we identified a distinctive metabolic profile where amino acid metabolites including serine, histidine, asparagine, glutamic acid, arginine, valine, aspartic acid, tyrosine, and methionine were upregulated, while lysine, isoleucine, glutamine, tryptophan, and threonine were downregulated. The regulatory network and gene co-expression network revealed crucial genes, metabolites, and metabolic pathways. The integrative omics analysis revealed a high enrichment of several pathways, notably encompassing protein digestion and absorption, sphingolipid signalling, and the synaptic vesicle cycle. Within the sphere of our integrative analysis, DNMT3B was identified as a paramount gene, intricately associated with significant proteins such as HMCN1, CPB2, GNG12, and LRP1. Our present study delineated the molecular underpinnings governing the variations in cashmere characteristics by conducting comprehensive analyses across metabolomic, transcriptomic, and proteomic dimensions. This research provided newly insights into the mechanisms regulating cashmere traits and facilitated the advancement of selective breeding programs aimed at cultivating high-quality superfine Tibetan cashmere goats.

Regulation of cashmere fineness traits by noncoding RNA in Jiangnan cashmere goats.

BACKGROUND: Cashmere has long been used as the raw material for wool textiles. The diameter of the cashmere fibre determines its quality and economic value. However, the regulatory role of noncoding RNAs (ncRNAs) in cashmere fineness remains unclear, especially regarding the interaction between ncRNAs and coding RNAs. RESULTS: Transcriptome sequencing was used to identify the expression profiles of long noncoding RNAs (lncRNAs), circular RNAs (circRNAs) and microRNAs (miRNAs) in the skin tissues of Jiangnan cashmere goats with different cashmere fineness levels. Integration analysis of ncRNA and coding RNA was performed in combination with previous research results. The results showed that 16,437 lncRNAs, 2234 circRNAs, and 1322 miRNAs were identified in 8 skin samples of cashmere goats. A total of 403 differentially expressed (DE) lncRNAs, 62 DE circRNAs and 30 DE miRNAs were identified in the skin tissues of the fine groups (Fe) and coarse groups (Ce). We predicted the target gene of DE lncRNA, the target gene of DE miRNA and the host gene of DE circRNA. Based on functional annotation and enrichment analysis of target genes, we found that DE lncRNAs could be involved in regulating the fineness traits of cashmere. The most potential lncRNAs were MSTRG.42054.1, MSTRG.18602.3, and MSTRG.2199.13. CONCLUSIONS: The data from this study enriched the cashmere goat noncoding RNA database and helped to supplement the annotation of the goat genome. The results provided a new direction for the breeding of cashmere characters.

Risk Factors for Major Amputation in Diabetic Foot Ulcer Patients.

BACKGROUND: The purpose of our study was to identify the new and the more specific risk factors for major amputation in patients with diabetic foot ulcer (DFU). METHODS: We used data from the Electronic Medical Record (EMR) database of our hospital from February 2014 to July 2020. Patients with DFU and amputation were included in the study. The logistic regression model was adjusted for demographic characteristics and related comorbidities between major and minor amputation groups. RESULTS: Among 3654 patients with DFU, 363 (9.9%) were amputated. Patients with major versus minor amputation, in multivariable logistic regression models, major amputation independent factors included previous amputation history (odds ratio [OR] 2.31 [95% CI 1.17-4.53], p = 0.02), smoking (2.58 [1.31-5.07], p = 0.01), coronary artery disease (CAD) (2.67 [1.35-5.29], p = 0.03), ankle brachial index (ABI) <0.4 (15.77 [7.51-33.13], p < 0.01), Wagner 5 (5.50 [1.89-16.01], p < 0.01), activated partial thromboplastin time (APTT) (1.23 [1.03-1.48], p = 0.01), glycosylated hemoglobin A1c (HbA1c) (1.23 [1.03-1.48], p = 0.03), hemoglobin (Hb) (0.98 [0.96-1.00], p = 0.01), plasma albumin (ALB) (0.88 [0.81-0.95], p < 0.01) and white blood cell (WBC) (1.10 [1.04-1.16], p < 0.01). CONCLUSION: Major amputation was associated with previous amputation history, smoking, CAD, Wagner 5, ABI <0.4, HbA1c, Hb, ALB, WBC, and APTT might be a new independent factor. In view of these factors, early prevention and guidance promptly orientated by multidisciplinary is of great significance to reduce the disability rate and economic burden.

Cost of Diabetic Foot Ulcer Management in China: A 7-Year Single-Center Retrospective Review.

BACKGROUND: The cost of care for diabetic foot ulcers has became a global economic burden. The study aimed to analyze diabetic foot ulcer cost changes over time and to identify factors associated with these variables, so as to strengthen and improve the management of diabetic foot ulcers. METHODS: We retrospectively analyzed the data in the electronic medical record system of our wound treatment center. The homepage of the system was queried using the national clinical version 2.0 disease diagnosis code (ICD-10), the data of patient's basic information were exported. Through the statistics and analysis of these data, the socioeconomic changes and possible risk factors of diabetic foot ulcers management in recent years were obtained. RESULTS: There were 3654 patients included in the study, an average of 522 per year. The total cost per patient increased from ¥15,535.58 in 2014 to ¥42,040.60 in 2020, with an average of ¥21,826.91. The average length of stay between 14.29 days and 31.4 days from 2014 to 2020, with an average of 18.10 days. Besides, the average incidence of peripheral arterial disease in diabetic foot ulcers patients admitted was as high as 81.9%, and the average amputation rate was 9.9%. The study reflected the total cost and length of stay of diabetic foot patients increased significantly from 2014 to 2020, which were related to age (>85 years), gender (male), peripheral arterial disease, amputation (P < 0.05). CONCLUSION: A heavy cost from diabetic foot ulcers and its complications was significantly increased yearly, which was related to older age, co-morbidity, amputation and duration of hospitalization. The prevention and treatment of diabetic foot ulcers have a long way to go, early comprehensive prevention and multi-disciplinary cooperation may still be an effective way.

Circular RNA circ_0124644 exacerbates the ox-LDL-induced endothelial injury in human vascular endothelial cells through regulating PAPP-A by acting as a sponge of miR-149-5p.

The modulatory roles of numerous circular RNAs (circRNAs) have been exposited in atherosclerosis (AS). Our study paid attention to the function of circRNA_ 0124644 (circ_0124644) in AS development, as well as its functional mechanism. The AS cell model was established by the treatment of oxidized low-density lipoprotein (ox-LDL) to human vascular endothelial cells (HUVECs). Cell proliferation and cycle were severally measured by Cell Counting Kit-8 (CCK-8) and cell cycle detection kit. The examination of apoptosis rate was executed through flow cytometry. Western blot was exploited for detecting the associated proteins. The expression levels of circ_0124644 and microRNA-149-5p (miR-149-5p) and pregnancy-associated plasma protein-A (PAPP-A) were assayed using quantitative real-time polymerase chain reaction. The combination of targets was validated via the dual-luciferase reporter assay, RNA immunoprecipitation (RIP), and RNA pull-down assay. Clonal capacity was analyzed using colony formation assay. Ox-LDL restrained HUVECs proliferation and cycle, but facilitated apoptosis. Circ_0124644 expression was increased, while miR-149-5p was downregulated in ox-LDL-treated HUVECs. Besides, circ_0124644 served as a molecular sponge of miR-149-5p and intensified the ox-LDL-induced HUVECs injury by sponging miR-149-5p. PAPP-A was a target of miR-149-5p and miR-149-5p could mitigate the HUVECs injury caused by ox-LDL through inhibiting PAPP-A. Moreover, PAPP-A was positively regulated by circ_0124644 via the miR-149-5p. In this report, we concluded the promoted role of circ_0124644 in the ox-LDL-induced endothelial injury of HUVECs via the miR-149-5p/PAPP-A axis with an emphasis on its diagnostic and therapeutic values in AS.

Timing of Exercise Affects Glycemic Control in Type 2 Diabetes Patients Treated with Metformin.

OBJECTIVE: The purpose of the study was to examine the acute effects of the timing of exercise on the glycemic control during and after exercise in T2D. METHODS: This study included 26 T2D patients (14 women and 12 men) who were treated with metformin. All patients were tested on four occasions: metformin administration alone (Metf), high-intensity interval training (HIIT) performed at 30 minutes (EX30), 60 minutes (EX60), and 90 minutes (EX90) postbreakfast, respectively. Glucose, insulin, and superoxide dismutase (SOD) activity were examined. RESULTS: Glucose decreased significantly after the exercise in EX30, EX60, and EX90. Compared with Metf, the decline in glucose immediately after the exercise was larger in EX30 (-2.58 mmol/L; 95% CI, -3.36 to -1.79 mmol/L; p < 0.001), EX60 (-2.13 mmol/L; 95% CI, -2.91 to -1.34 mmol/L; p < 0.001), and EX90 (-1.87 mmol/L; 95% CI, -2.65 to -1.08 mmol/L; p < 0.001), respectively. Compared with Metf, the decrease in insulin was larger in EX30 and EX60 (both p < 0.001). CONCLUSIONS: Timing of exercise is a factor to consider when prescribing exercise for T2D patients treated with metformin. This trial is registered with ChiCTR-IOR-16008469 on 13 May 2016.

[CLINICAL APPLICATION OF AXIAL LOAD MECHANICAL TESTING IN REMOVING EXTERNAL FIXATOR AFTER TIBIA AND FIBULA FRACTURES SURGERY].

OBJECTIVE: To explore the efficacy and safety of the axial load mechanical testing for removing external fixator. METHODS: Between January 2014 and August 2015, 27 patients with tibia and fibula fractures caused by trauma underwent an external fixation. Of 27 patients, 21 were male and 6 were female with the average age of 45 years (range, 19-63 years), including 7 cases of closed fracture and 20 cases of open fracture. X-ray film results showed spiral unstable fracture in 4 cases and comminuted unstable fracture in 23 cases. All patients underwent an external fixation. Bone nonunion occurred in 3 cases because of infection, and bone nonunion combined with bone defect occurred in 1 case, who received tibial osteotomy lengthening surgery. When X-ray film showed continuity high density callus formation at fracture site, axial load mechanical test was performed. If the axial load ratio of external fixator was less than 10%, the external fixator was removed. RESULTS: At 21-85 weeks after external fixation (mean, 44 weeks), axial load mechanical test was performed. The results showed that the axial load ratio of external fixation was less than 10% in 26 cases, and the external fixator was removed; at 6 weeks after removal of external fixator, the patients could endure full load and return to work, without re-fracture. The axial load ratio was 14% in 1 case at 85 weeks, and the X-ray film result showed that fracture did not completely heal with angular deformity; re-fracture occurred after removing external fixator, and intramedullary fixation was used. CONCLUSIONS: External fixator axial load mechanical testing may objectively reveal and quantitatively evaluate fracture healing, so it is safe and reliable to use for guiding the external fixator removal.