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.

Association of Residential Greenness Exposure with Depression Incidence in Adults 50 Years of Age and Older: Findings from the Cohort Study on Global AGEing and Adult Health (SAGE) in China.

BACKGROUND: Depression is a social and public health problem of great concern globally. Identifying and managing the factors influencing depression are crucial for preventing and decreasing the burden of depression. OBJECTIVES: Our objectives are to explore the association between residential greenness and the incidence of depression in an older Chinese population and to calculate the disease burden of depression prevented by greenness exposure. METHODS: This study was the Chinese part of the World Health Organization Study on Global AGEing and Adult Health (WHO SAGE). We collected the data of 8,481 residents ≥50 years of age in China for the period 2007-2018. Average follow-up duration was 7.00 (±2.51) years. Each participant was matched to the yearly maximum normalized difference vegetation index (NDVI) at their residential address. Incidence of depression was assessed using the Composite International Diagnostic Interview (CIDI), self-reports of depression, and/or taking depression medication. Association between greenness and depression was examined using the time-dependent Cox regression model with stratified analysis by sex, age, urbanicity, annual family income, region, smoking, drinking, and household cooking fuels. Furthermore, the prevented fraction (PF) and attributable number (AN) of depression prevented by exposure to greenness were estimated. RESULTS: Residential greenness was negatively associated with depression. Each interquartile range (IQR) increase in NDVI 500-m buffer was associated with a 40% decrease [hazard ratio (HR)=0.60; 95% confidence interval (CI): 0.37, 0.97] in the risk of depression incidence among the total participants. Subgroup analyses showed negative associations in urban residents (HR=0.32; 95% CI: 0.12, 0.86) vs. rural residents, in high-income residents (HR=0.28; 95% CI: 0.11, 0.71) vs. low-income residents, and in southern China (HR=0.50; 95% CI: 0.26, 0.95) vs. northern China. Over 8.0% (PF=8.69%; 95% CI: 1.38%, 15.40%) and 1,955,199 (95% CI: 310,492; 3,464,909) new cases of depression may be avoided by increasing greenness exposures annually across China. DISCUSSION: The findings suggest protective effects of residential greenness exposure on depression incidence in the older population, particularly among urban residents, high-income residents, and participants living in southern China. The construction of residential greenness should be included in community planning. https://doi.org/10.1289/EHP13947.

Residual networks without pooling layers improve the accuracy of genomic predictions.

KEY MESSAGE: Residual neural network genomic selection is the first GS algorithm to reach 35 layers, and its prediction accuracy surpasses previous algorithms. With the decrease in DNA sequencing costs and the development of deep learning, phenotype prediction accuracy by genomic selection (GS) continues to improve. Residual networks, a widely validated deep learning technique, are introduced to deep learning for GS. Since each locus has a different weighted impact on the phenotype, strided convolutions are more suitable for GS problems than pooling layers. Through the above technological innovations, we propose a GS deep learning algorithm, residual neural network for genomic selection (ResGS). ResGS is the first neural network to reach 35 layers in GS. In 15 cases from four public data, the prediction accuracy of ResGS is higher than that of ridge-regression best linear unbiased prediction, support vector regression, random forest, gradient boosting regressor, and deep neural network genomic prediction in most cases. ResGS performs well in dealing with gene-environment interaction. Phenotypes from other environments are imported into ResGS along with genetic data. The prediction results are much better than just providing genetic data as input, which demonstrates the effectiveness of GS multi-modal learning. Standard deviation is recommended as an auxiliary GS evaluation metric, which could improve the distribution of predicted results. Deep learning for GS, such as ResGS, is becoming more accurate in phenotype prediction.

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.

Mutual Associations of Exposure to Ambient Air Pollutants in the First 1000 Days of Life With Asthma/Wheezing in Children: Prospective Cohort Study in Guangzhou, China.

BACKGROUND: The first 1000 days of life, encompassing pregnancy and the first 2 years after birth, represent a critical period for human health development. Despite this significance, there has been limited research into the associations between mixed exposure to air pollutants during this period and the development of asthma/wheezing in children. Furthermore, the finer sensitivity window of exposure during this crucial developmental phase remains unclear. OBJECTIVE: This study aims to assess the relationships between prenatal and postnatal exposures to various ambient air pollutants (particulate matter 2.5 [PM2.5], carbon monoxide [CO], sulfur dioxide [SO2], nitrogen dioxide [NO2], and ozone [O3]) and the incidence of childhood asthma/wheezing. In addition, we aimed to pinpoint the potential sensitivity window during which air pollution exerts its effects. METHODS: We conducted a prospective birth cohort study wherein pregnant women were recruited during early pregnancy and followed up along with their children. Information regarding maternal and child characteristics was collected through questionnaires during each round of investigation. Diagnosis of asthma/wheezing was obtained from children's medical records. In addition, maternal and child exposures to air pollutants (PM2.5 CO, SO2, NO2, and O3) were evaluated using a spatiotemporal land use regression model. To estimate the mutual associations of exposure to mixed air pollutants with the risk of asthma/wheezing in children, we used the quantile g-computation model. RESULTS: In our study cohort of 3725 children, 392 (10.52%) were diagnosed with asthma/wheezing. After the follow-up period, the mean age of the children was 3.2 (SD 0.8) years, and a total of 14,982 person-years were successfully followed up for all study participants. We found that each quartile increase in exposure to mixed air pollutants (PM2.5, CO, SO2, NO2, and O3) during the second trimester of pregnancy was associated with an adjusted hazard ratio (HR) of 1.24 (95% CI 1.04-1.47). Notably, CO made the largest positive contribution (64.28%) to the mutual effect. After categorizing the exposure according to the embryonic respiratory development stages, we observed that each additional quartile of mixed exposure to air pollutants during the pseudoglandular and canalicular stages was associated with HRs of 1.24 (95% CI 1.03-1.51) and 1.23 (95% CI 1.01-1.51), respectively. Moreover, for the first year and first 2 years after birth, each quartile increment of exposure to mixed air pollutants was associated with HRs of 1.65 (95% CI 1.30-2.10) and 2.53 (95% CI 2.16-2.97), respectively. Notably, SO2 made the largest positive contribution in both phases, accounting for 50.30% and 74.70% of the association, respectively. CONCLUSIONS: Exposure to elevated levels of mixed air pollutants during the first 1000 days of life appears to elevate the risk of childhood asthma/wheezing. Specifically, the second trimester, especially during the pseudoglandular and canalicular stages, and the initial 2 years after birth emerge as crucial susceptibility windows. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-ROC-17013496; https://tinyurl.com/2ctufw8n.

Effects of long-term exposure to ambient fine particulate matter and its specific components on blood pressure and hypertension incidence.

BACKGROUND: Epidemiological evidence on the association of PM2.5 (particulate matter with aerodynamic diameter ≤ 2.5 µm) and its specific components with hypertension and blood pressure is limited. METHODS: We applied information of participants from the World Health Organization's (WHO) Study on Global Ageing and Adult Health (SAGE) to estimate the associations of long-term PM2.5 mass and its chemical components exposure with blood pressure (BP) and hypertension incidence in Chinese adults ≥ 50 years during 2007-2018. Generalized linear mixed model and Cox proportional hazard model were applied to investigate the effects of PM2.5 mass and its chemical components on the incidence of hypertension and BP, respectively. RESULTS: Each interquartile range (IQR = 16.80 µg/m3) increase in the one-year average of PM2.5 mass concentration was associated with a 17 % increase in the risk of hypertension (HR = 1.17, 95 % CI: 1.10, 1.24), and the population attributable fraction (PAF) was 23.44 % (95 % CI: 14.69 %, 31.55 %). Each IQR µg/m3 increase in PM2.5 exposure was also related to increases of systolic blood pressure (SBP) by 2.54 mmHg (95 % CI:1.99, 3.10), and of diastolic blood pressure (DBP) by 1.36 mmHg (95 % CI: 1.04, 1.68). Additionally, the chemical components of SO42-, NO3-, NH4+, OM, and BC were also positively associated with an increased risk of hypertension incidence and elevated blood pressure. CONCLUSIONS: These results indicate that long-term exposure to PM2.5 mass and its specific components may be major drivers of escalation in hypertension diseases.

Simultaneous determination of 58 glucocorticoid residues in milk by ultra-high performance liquid chromatography-tandem mass spectrometry.

Abuse of glucocorticoid veterinary drugs in dairy industry can potentially threat milk safety and consequently influence human health. Here a reliable method for determination of 58 glucocorticoid drug residues in milk was established by combining solid phase extraction with ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The analytes were extracted with acetonitrile and cleanup with EMR-Lipid lipid removal column. The analytes were chromatographically separated using Poroshell EC-C18 column and acquired by electrospray ionization with multiple-reaction monitoring (MRM) mode. The limit of quantification (S/N ≥ 10) ranged from 0.2 to 2.0 µg/kg and the limit of detection (S/N ≥ 3) ranged from 0.1 to 1.0 µg/kg. Average recoveries were from 71% to 113%, the relative standard deviations (RSDs) were less than 15%, and the correlation coefficients (R2) of calibration curves exceeded 0.99. The method was applied to detect twenty milk products obtained from local supermarkets including ten pasteurized milk and ten UHT milk. Two endogenous glucocorticoids, i.e. hydrocortisone and cortisone were detected but not exceed the maximum residue limits (MRLs).

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.

Ambient PM2.5 and cardiopulmonary mortality in the oldest-old people in China: A national time-stratified case-crossover study.

BACKGROUND: Evidence on the associations of fine particulate matter (PM2.5) with cardiopulmonary mortality in the oldest-old (aged 80+ years) people remains limited. METHODS: We conducted a time-stratified case-crossover study of 1,475,459 deaths from cardiopulmonary diseases in China to estimate the associations between short-term exposure to ambient PM2.5 and cardiopulmonary mortality among the oldest-old people. FINDINGS: Each 10 µg/m3 increase in PM2.5 concentration (6-day moving average [lag05]) was associated with higher mortality from cardiopulmonary diseases (excess risks [ERs] = 1.69%, 95% confidence interval [CI]: 1.54%, 1.84%), cardiovascular diseases (ER = 1.72%, 95% CI: 1.54%, 1.90%), and respiratory diseases (ER = 1.62%, 95% CI: 1.33%, 1.91%). Compared to the other groups, females (ER = 1.94%, 95% CI: 1.73%, 2.15%) (p for difference test = 0.043) and those aged 95-99 years (ER = 2.31%, 95% CI: 1.61%, 3.02%) (aged 80-85 years old was the reference, p for difference test = 0.770) presented greater mortality risks. We found 14 specific cardiopulmonary causes associated with PM2.5, out of which emphysema (ER = 3.20%, 95% CI: 1.57%, 4.86%) had the largest association. Out of the total deaths, 6.27% (attributable fraction [AF], 95% CI: 5.72%, 6.82%) were ascribed to short-term PM2.5 exposure. CONCLUSIONS: This study provides evidence of PM2.5-induced cardiopulmonary mortality and calls for targeted prevention actions for the oldest-old people. FUNDING: This work was supported by the National Key Research and Development Program of China, the National Natural Science Foundation of China, the Foreign Expert Program of the Ministry of Science and Technology, the Natural Science Foundation of Guangdong, China, and the Science and Technology Program of Guangzhou.

A transformer-based genomic prediction method fused with knowledge-guided module.

Genomic prediction (GP) uses single nucleotide polymorphisms (SNPs) to establish associations between markers and phenotypes. Selection of early individuals by genomic estimated breeding value shortens the generation interval and speeds up the breeding process. Recently, methods based on deep learning (DL) have gained great attention in the field of GP. In this study, we explore the application of Transformer-based structures to GP and develop a novel deep-learning model named GPformer. GPformer obtains a global view by gleaning beneficial information from all relevant SNPs regardless of the physical distance between SNPs. Comprehensive experimental results on five different crop datasets show that GPformer outperforms ridge regression-based linear unbiased prediction (RR-BLUP), support vector regression (SVR), light gradient boosting machine (LightGBM) and deep neural network genomic prediction (DNNGP) in terms of mean absolute error, Pearson's correlation coefficient and the proposed metric consistent index. Furthermore, we introduce a knowledge-guided module (KGM) to extract genome-wide association studies-based information, which is fused into GPformer as prior knowledge. KGM is very flexible and can be plugged into any DL network. Ablation studies of KGM on three datasets illustrate the efficiency of KGM adequately. Moreover, GPformer is robust and stable to hyperparameters and can generalize to each phenotype of every dataset, which is suitable for practical application scenarios.

Regulation of secondary hair follicle cycle in cashmere goats by miR-877-3p targeting IGFBP5 gene.

Cashmere, a highly valuable animal product derived from cashmere goats, holds significant economic importance. MiRNAs serve as crucial regulators in the developmental processes of mammalian hair follicles. Understanding the regulation of miRNAs during the hair follicle cycle is essential for enhancing cashmere quality. In this investigation, we employed high-throughput sequencing technology to analyze the expression profiles of miRNAs in the secondary hair follicles of Jiangnan cashmere goats at different stages. Through bioinformatics analysis, we identified differentially expressed miRNAs (DE miRNAs). The regulatory relationships between miRNAs and their target genes were verified using multiple techniques, including RT-qPCR, western blot, Dual-Luciferase Reporter, and CKK-8 assays. Our findings revealed the presence of 193 DE miRNAs during various stages of the hair follicle cycle in Jiangnan cashmere goats. Based on the previously obtained mRNA data, the target genes of DE miRNA were predicted, and 1,472 negative regulatory relationships between DE miRNAs and target genes were obtained. Notably, the expression of chi-miR-877-3p was down-regulated during the telogen (Tn) phase compared to the anagen (An) and catagen (Cn) phases, while the IGFBP5 gene exhibited up-regulation. Further validation experiments confirmed that overexpression of chi-miR-877-3p in dermal papilla cells suppressed IGFBP5 gene expression and facilitated cell proliferation. The results of this study provide novel insights for analyzing the hair follicle cycle.

Cashmere goats, known for their diverse range of animal products including delectable meat, soft sheepskin, and high-quality natural fiber, offer an excellent opportunity to explore hair regeneration as they represent a heterogenous fur mammal. MicroRNAs (miRNAs) are small non-coding RNA molecules encoded by approximately 3% of mammalian genes. Remarkably, they have the ability to regulate around 30% of protein-coding genes. Given that a single miRNA can target multiple genes, they exert control over various biological functions such as metabolism, growth, development, and immunity. In this study, we found that miR-877-3p is able to regulate the expression of insulin-like growth factor binding protein 5 (IGFBP5), a key gene involved in the development of the hair follicle cycle. Investigating the regulatory role of miRNAs in the hair follicle cycle of cashmere goats provides a novel perspective for unraveling the mechanisms underlying hair follicle growth and development in mammals.

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.

Drivers of plateau adaptability in cashmere goats revealed by genomic and transcriptomic analyses.

BACKGROUND: The adaptive evolution of plateau indigenous animals is a current research focus. However, phenotypic adaptation is complex and may involve the interactions between multiple genes or pathways, many of which remain unclear. As a kind of livestock with important economic value, cashmere goat has a high ability of plateau adaptation, which provides us with good materials for studying the molecular regulation mechanism of animal plateau adaptation. RESULTS: In this study, 32 Jiangnan (J) and 32 Tibetan (T) cashmere goats were sequenced at an average of 10. Phylogenetic, population structure, and linkage disequilibrium analyses showed that natural selection or domestication has resulted in obvious differences in genome structure between the two breeds. Subsequently, 553 J vs. T and 608 T vs. J potential selected genes (PSGs) were screened. These PSGs showed potential relationships with various phenotypes, including myocardial development and activity (LOC106502520, ATP2A2, LOC102181869, LOC106502520, MYL2, ISL1, and LOC102181869 genes), pigmentation (MITF and KITLG genes), hair follicles/hair growth (YAP1, POGLUT1, AAK1, HES1, WNT1, PRKAA1, TNKS, WNT5A, VAX2, RSPO4, CSNK1G1, PHLPP2, CHRM2, PDGFRB, PRKAA1, MAP2K1, IRS1, LPAR1, PTEN, PRLR, IBSP, CCNE2, CHAD, ITGB7, TEK, JAK2, and FGF21 genes), and carcinogenesis (UBE2R2, PIGU, DIABLO, NOL4L, STK3, MAP4, ADGRG1, CDC25A, DSG3, LEPR, PRKAA1, IKBKB, and ABCG2 genes). Phenotypic analysis showed that Tibetan cashmere goats has finer cashmere than Jiangnan cashmere goats, which may allow cashmere goats to better adapt to the cold environment in the Tibetan plateau. Meanwhile, KRTs and KAPs expression in Jiangnan cashmere goat skin was significantly lower than in Tibetan cashmere goat. CONCLUSIONS: The mutations in these PSGs maybe closely related to the plateau adaptation ability of cashmere goats. In addition, the expression differences of KRTs and KAPs may directly determine phenotypic differences in cashmere fineness between the two breeds. In conclusion, this study provide a reference for further studying plateau adaptive mechanism in animals and goat breeding.

Joint Effects of Long-Term Exposure to Ambient Fine Particulate Matter and Ozone on Asthmatic Symptoms: Prospective Cohort Study.

BACKGROUND: The associations of long-term exposure to air pollutants in the presence of asthmatic symptoms remain inconclusive and the joint effects of air pollutants as a mixture are unclear. OBJECTIVE: We aimed to investigate the individual and joint associations of long-term exposure to ambient fine particulate matter (PM2.5) and daily 8-hour maximum ozone concentrations (MDA8 O3) in the presence of asthmatic symptoms in Chinese adults. METHODS: Data were derived from the World Health Organization Study on Global Ageing and Adult Health (WHO SAGE) cohort study among adults aged 50 years or older, which was implemented in 1 municipality and 7 provinces across China during 2007-2018. Annual average MDA8 O3 and PM2.5 at individual residential addresses were estimated by an iterative random forest model and a satellite-based spatiotemporal model, respectively. Participants who were diagnosed with asthma by a doctor or taking asthma-related therapies or experiencing related conditions within the past 12 months were recorded as having asthmatic symptoms. The individual associations of PM2.5 and MDA8 O3 with asthmatic symptoms were estimated by a Cox proportional hazards regression model, and the joint association was estimated by a quantile g-computation model. A series of subgroup analyses was applied to examine the potential modifications of some characteristics. We also calculated the population-attributable fraction (PAF) of asthmatic symptoms attributed to PM2.5 and MDA8 O3. RESULTS: A total of 8490 adults older than 50 years were included, and the average follow-up duration was 6.9 years. During the follow-up periods, 586 (6.9%) participants reported asthmatic symptoms. Individual effect analyses showed that the risk of asthmatic symptoms was positively associated with MDA8 O3 (hazard ratio [HR] 1.12, 95% CI 1.01-1.24, for per quantile) and PM2.5 (HR 1.18, 95% CI 1.05-1.31, for per quantile). Joint effect analyses showed that per equal quantile increment of MDA8 O3 and PM2.5 was associated with an 18% (HR 1.18, 95% CI 1.05-1.33) increase in the risk of asthmatic symptoms, and PM2.5 contributed more (68%) in the joint effects. The individual PAFs of asthmatic symptoms attributable to PM2.5 and MDA8 O3 were 2.86% (95% CI 0.17%-5.50%) and 4.83% (95% CI 1.42%-7.25%), respectively, while the joint PAF of asthmatic symptoms attributable to exposure mixture was 4.32% (95% CI 1.10%-7.46%). The joint associations were greater in participants with obesity, in urban areas, with lower family income, and who used unclean household cooking fuel. CONCLUSIONS: Long-term exposure to PM2.5 and MDA8 O3 may individually and jointly increase the risk of asthmatic symptoms, and the joint effects were smaller than the sum of individual effects. These findings informed the importance of joint associations of long-term exposure to air pollutants with asthma.

Applying Rituximab During the Conditioning Regimen Prevents Epstein-Barr Virus Infection Following Allogeneic Hematopoietic Stem Cell Transplant in a Children's Cohort: A Retrospective Case-Control Study.

INTRODUCTION: Since hematopoietic stem cell transplant (HSCT) is an important therapy for malignant and non-malignant pediatric diseases, improving transplant-related mortality remains a challenge. Currently, rituximab, a monoclonal antibody of anti-CD20, is widely used for several post-HSCT complications. However, few studies have focused on the application of rituximab before HSCT. METHODS: We conducted a retrospective case-control study from January 2019 to July 2021 to determine this effect in a single center. Forty-eight patients were included in the rituximab group, with a one-to-one ratio matched to the control group. RESULTS: Both the occurrence rate and cumulative incidence rate of Epstein-Barr virus (EBV) infection were significantly lower in the rituximab group than in the without-rituximab group (10.4% vs. 33.3%, p = 0.014 and 12.2% vs. 39.3% p = 0.0026, respectively). Furthermore, without the application of rituximab was identified as a risk factor for post-HSCT EBV infection via both univariate [hazard ratio (HR) = 4.17, 95%CI (1.52-11.43), p = 0.005] and multivariate analyses [HR = 4.65, 95%CI (1.66-13.0), p = 0.003]. Although the overall survival (OS) probability of the rituximab group was comparable to the without-rituximab group, a markedly improved OS of the rituximab group was found in the malignant disease subgroup (78.9% vs. 42.1%, p = 0.032). The outcomes of graft-versus-host disease, neutrophil and platelet engraftment, other viral infections, and the reconstitution of lymphocytes showed no significant differences between the two groups. CONCLUSIONS: The administration of rituximab before HSCT may prevent EBV infection following HSCT.

Methylation Levels in the Promoter Region of FHIT and PIAS1 Genes Associated with Mastitis Resistance in Xinjiang Brown Cattle.

Mastitis causes serious economic losses in the dairy industry, but there are no effective treatments or preventive measures. In this study, the ZRANB3, PIAS1, ACTR3, LPCAT2, MGAT5, and SLC37A2 genes in Xinjiang brown cattle, which are associated with mastitis resistance, were identified using a GWAS. Pyrosequencing analysis showed that the promoter methylation levels of the FHIT and PIAS1 genes in the mastitis group were higher and lower, respectively, than those in the healthy group (65.97 ± 19.82% and 58.00 ± 23.52%). However, the methylation level of the PIAS1 gene promoter region in the mastitis group was lower than that in the healthy group (11.48 ± 4.12% and 12.17 ± 4.25%). Meanwhile, the methylation levels of CpG3, CpG5, CpG8, and CpG15 in the promoter region of the FHIT and PIAS1 genes in the mastitis group were significantly higher than those in the healthy group (p < 0.01), respectively. RT-qPCR showed that the expression levels of the FHIT and PIAS1 genes were significantly higher in the healthy group than those in the mastitis group (p < 0.01). Correlation analysis showed that the promoter methylation level of the FHIT gene was negatively correlated with its expression. Hence, increased methylation in the promoter of the FHIT gene reduces the mastitis resistance in Xinjiang brown cattle. Finally, this study provides a reference for the molecular-marker-assisted selection of mastitis resistance in dairy cattle.

Transcriptome analysis reveals genes associated with wool fineness in merinos.

Hair/wool usually plays an important role in maintaining animal physiological activities, and the economic value of wool cannot be ignored. At present, people set higher demands on wool fineness. Hence, improving wool fineness is the concern of fine wool sheep breeding. Using RNA-Seq to screen the potential candidate genes that associate with wool fineness can provide theoretical references for fine-wool sheep breeding, and also provide us new ideas for further understand the molecular regulation mechanism of hair growth. In this study, we compared the expression pattern difference of genome-wide genes between the skin transcriptomes of Subo and Chinese Merinos. The results showed that, 16 candidate differentially expressed genes (DEGs) (Included: CACNA1S, GP5, LOC101102392, HSF5, SLITRK2, LOC101104661, CREB3L4, COL1A1, PTPRR, SFRP4, LOC443220, COL6A6, COL6A5, LAMA1, LOC114115342 and LOC101116863 genes) that may associate with wool fineness were screened, and these genes were located in signaling pathways that regulate hair follicle development, cycle or hair growth. It is worth noting that, among the 16 DEGs, COL1A1 gene has the highest expression level in Merino skins, and the fold change of LOC101116863 gene is the highest, and the structures of these two genes are both highly conserved in different species. In conclusion, we speculate that these two genes may play a key role in regulating wool fineness and respectively have similar and conserved functions in different species.

Gender-specific effects of oxidative balance score on the prevalence of diabetes in the US population from NHANES.

Background: The relationship between oxidative balance score (OBS) and diabetes remains poorly understood and may be gender-specific. We conducted a cross-sectional study to investigate the complex association between OBS and diabetes among US adults. Methods: Overall, 5,233 participants were included in this cross-sectional study. The exposure variable was OBS, composed of scores for 20 dietary and lifestyle factors. Multivariable logistic regression, subgroup analysis, and restricted cubic spline (RCS) regression were applied to examine the relationship between OBS and diabetes. Results: Compared to the lowest OBS quartile group (Q1), the multivariable-adjusted odds ratio (OR) (95% confidence interval (CI) for the highest OBS quartile group (Q4) was 0.602 (0.372-0.974) (p for trend = 0.007), and for the highest lifestyle, the OBS quartile group was 0.386 (0.223-0.667) (p for trend < 0.001). Moreover, gender effects were found between OBS and diabetes (p for interaction = 0.044). RCS showed an inverted-U relationship between OBS and diabetes in women (p for non-linear = 6e-04) and a linear relationship between OBS and diabetes in men. Conclusions: In summary, high OBS was negatively associated with diabetes risk in a gender-dependent manner.

Avatrombopag for the treatment of thrombocytopenia in children's patients following allogeneic hematopoietic stem-cell transplantation: A pilot study.

Thrombocytopenia following allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a common and life-threatening complication. Thus, new prevention and treatment strategies for post-HSCT thrombocytopenia are urgently required. In recent studies, thrombopoietin receptor agonists (TPO-RA) for treating post-HSCT thrombocytopenia indicated efficiency and safety. The improved effect of post-HSCT thrombocytopenia in adults was found in the administration of avatrombopag which was a new TPO-RA. However, there was no relevant study in the children's cohort. Herein, we retrospectively analyzed the effect of avatrombopag in post-HSCT thrombocytopenia in children. As a result, the overall response rate (ORR) and complete response rate (CRR) were 91% and 78%, respectively. Furthermore, both cumulative ORR and CRR were significantly lower in the poor graft function (PGF)/secondary failure of platelet recovery (SFPR) group compared to the engraftment-promotion group (86.7% vs. 100%, p = 0.002 and 65.0% vs. 100%, p < 0.001, respectively). Achieving OR required a median of 16 days in the PGF/SFPR group while 7 days in the engraftment-promotion group (p = 0.003). Grade III-IV acute graft vs. host disease and inadequate megakaryocytes were identified as risk factors of CRR only in univariate analysis (p = 0.03 and p = 0.01, respectively). No severe adverse events were documented. Conclusively, avatrombopag is an alternatively efficient and safe agent for treating post-HSCT thrombocytopenia in children.