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.

Efficacy and safety of hyperbaric oxygen therapy in acute ischaemic stroke: a systematic review and meta-analysis.

OBJECTIVE: This study aims to evaluate the efficacy and safety of adjunctive hyperbaric oxygen therapy (HBOT) in acute ischaemic stroke (AIS) based on existing evidence. METHODS: We conducted a comprehensive search through April 15, 2023, of seven major databases for randomized controlled trials (RCTs) comparing adjunctive hyperbaric HBOT with non-HBOT (no HBOT or sham HBOT) treatments for AIS. Data extraction and assessment were independently performed by two researchers. The quality of included studies was evaluated using the tool provided by the Cochrane Collaboration. Meta-analysis was conducted using Rev Man 5.3. RESULTS: A total of 8 studies involving 493 patients were included. The meta-analysis showed no statistically significant differences between HBOT and the control group in terms of NIHSS score (MD = -1.41, 95%CI = -7.41 to 4.58), Barthel index (MD = 8.85, 95%CI = -5.84 to 23.54), TNF-α (MD = -5.78, 95%CI = -19.93 to 8.36), sICAM (MD = -308.47, 95%CI = -844.13 to 13227.19), sVCAM (MD = -122.84, 95%CI = -728.26 to 482.58), sE-selectin (MD = 0.11, 95%CI = -21.86 to 22.08), CRP (MD = -5.76, 95%CI = -15.02 to 3.51), adverse event incidence within ≤ 6 months of follow-up (OR = 0.98, 95%CI = 0.25 to 3.79). However, HBOT showed significant improvement in modified Rankin score (MD = 0.10, 95%CI = 0.03 to 0.17), and adverse event incidence at the end of treatment (OR = 0.42, 95%CI = 0.19 to 0.94) compared to the control group. CONCLUSION: While our findings do not support the routine use of HBOT for improving clinical outcomes in AIS, further research is needed to explore its potential efficacy within specific therapeutic windows and for different cerebral occlusion scenarios. Therefore, the possibility of HBOT offering clinical benefits for AIS cannot be entirely ruled out.

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.

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.

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.

Trends and Opportunities in Organic Synthesis: Global State of Research Metrics and Advances in Precision, Efficiency, and Green Chemistry.

Organic synthesis continues to drive a broad range of research advances in chemistry and related sciences. Another clear trend in organic synthesis research is the increasing desire to target improvements in the quality of life of humankind, new materials, and product specificity. Here, a landscape view of organic synthesis research is provided by analysis of the CAS Content Collection. Three emerging research directions, enzyme catalysis, photocatalysis, and green chemistry in organic synthesis, were identified and featured based on the publication trend analysis.

The fiber diameter traits of Tibetan cashmere goats are governed by the inherent differences in stress, hypoxic, and metabolic adaptations: an integrative study of proteome and transcriptome.

BACKGROUND: Tibetan cashmere goats are served as a valuable model for high altitude adaptation and hypoxia complications related studies, while the cashmere produced by these goats is an important source of income for the herders. The aim of this study was to investigate the differences in protein abundance underlying the fine (average 12.20 ± 0.03 µm of mean fiber diameter) and coarse cashmere (average 14.67 ± 0.05 µm of mean fiber diameter) producing by Tibetan cashmere goats. We systematically investigated the genetic determinants of fiber diameter by integrated analysis with proteomic and transcriptomic datasets from skin tissues of Tibetan cashmere goats. RESULTS: We identified 1980 proteins using a label-free proteomics approach. They were annotated to three different databases, while 1730 proteins were mapped to the original protein coding genes (PCGs) of the transcriptomic study. Comparative analyses of cashmere with extremely fine vs. coarse phenotypes yielded 29 differentially expressed proteins (DEPs), for instance, APOH, GANAB, AEBP1, CP, CPB2, GPR142, VTN, IMPA1, CTSZ, GLB1, and HMCN1. Functional enrichment analysis of these DEPs revealed their involvement in oxidation-reduction process, cell redox homeostasis, metabolic, PI3K-Akt, MAPK, and Wnt signaling pathways. Transcription factors enrichment analysis revealed the proteins mainly belong to NF-YB family, HMG family, CSD family. We further validated the protein abundance of four DEPs (GC, VTN, AEBP1, and GPR142) through western blot, and considered they were the most potential candidate genes for cashmere traits in Tibetan cashmere goats. CONCLUSIONS: These analyses indicated that the major biological variations underlying the difference of cashmere fiber diameter in Tibetan cashmere goats were attributed to the inherent adaptations related to metabolic, hypoxic, and stress response differences. This study provided novel insights into the breeding strategies for cashmere traits and enhance the understanding of the biological and genetic mechanisms of cashmere traits in Tibetan cashmere goats.

Gene network analysis reveals candidate genes related with the hair follicle development in sheep.

BACKGROUND: Merino sheep are the most famous fine wool sheep in the world. They have high wool production and excellent wool quality and have attracted worldwide attention. The fleece of the Merino sheep is composed predominantly of wool fibers grown from secondary wool follicles. Therefore, it is necessary to study the development of hair follicles to understand the mechanism of wool production. The hair follicle is a complex biological system involved in a dynamic process governed by gene regulation. The hair follicle development process is very complex and poorly understood. The purpose of our research is to identify candidate genes related to hair follicle development, provide a theoretical molecular breeding basis for the cultivation of fine wool sheep, and provide a reference for the problems of hair loss and alopecia areata that affect human beings. RESULTS: We analyzed mRNAs data in skin tissues of 18 Merino sheep at four embryonic days (E65, E85, E105 and E135) and two postnatal days (P7 and P30). G1 to G6 represent hair follicles developmental at six stages (i.e. E65 to P30). We identified 7879 differentially expressed genes (DEGs) and 12623 novel DEGs, revealed different expression patterns of these DEGs at six stages of hair follicle development, and demonstrated their complex interactions. DEGs with stage-specific expression were significantly enriched in epidermal differentiation and development, hair follicle development and hair follicle morphogenesis and were enriched in many pathways related to hair follicle development. The key genes (LAMA5, WNT10A, KRT25, SOSTDC1, ZDHHC21, FZD1, BMP7, LRP4, TGFß2, TMEM79, SOX10, ITGB4, KRT14, ITGA6, and GLI2) affecting hair follicle morphogenesis were identified by network analysis. CONCLUSION: This study provides a new reference for the molecular basis of hair follicle development and lays a foundation for further improving sheep hair follicle breeding. Candidate genes related to hair follicular development were found, which provided a theoretical basis for molecular breeding for the culture of fine wool sheep. These results are a valuable resource for biological investigations of fleece evolution in animals.

Effect of the FA2H Gene on cashmere fineness of Jiangnan cashmere goats based on transcriptome sequencing.

BACKGROUND: Cashmere goats are a heterogeneous hairy mammal. The fineness of cashmere can affect its economic value. Therefore, in this study, we used transcriptome sequencing techniques to analyze the gene expression profiles of the skin tissues of cashmere goats with different cashmere fineness. The selected candidate genes were functionally verified with the secondary hair follicle hair papillary cells of cashmere goats. RESULTS: We identified 479 DEGs, of which 238 mRNAs were up-regulated in the fine velvet group and 241 mRNA were down-regulated. Based on functional annotation and protein interaction network analysis, we found some genes that may affect the fineness of cashmere, including SOX18, SOX4, WNT5A, IGFBP4, KAP8, KRT36, and FA2H. Using qRT-PCR, Western blot, CCK-8 cell viability detection, EDU cell proliferation detection, and flow cytometry, we found that overexpression of the FA2H gene could promote the proliferation of secondary hair follicle DPCs in cashmere goats. At the same time, we proved that FA2H could regulate the expression levels of the FGF5 and BMP2 genes in DPCs. CONCLUSION: The results of this study provide a useful reference for the genetics and breeding of Jiangnan cashmere goats and goat genome annotation, and provide an experimental basis for improving cashmere quality of the cashmere goat.

Rv3737 is required for Mycobacterium tuberculosis growth in vitro and in vivo and correlates with bacterial load and disease severity in human tuberculosis.

BACKGROUND: Rv3737 is the sole homologue of multifunctional transporter ThrE in Mycobacterium tuberculosis (Mtb). In this study, we aimed to investigate whether this transporter participates in vitro and in vivo survival of Mtb. METHODS: To characterize the role of Rv3737, we constructed and characterized a Mtb H37RvΔRv3737. This strain was evaluated for altered growth rate and macrophage survival using a cell model of infection. In addition, the comparative analysis was conducted to determine the association between Rv3737 mRNA expression and disease severity in active pulmonary TB patients. RESULTS: The H37RvΔRv3737 strain exhibited significantly slow growth rate compared to H37Rv-WT strain in standard culture medium. Additionally, the survival rate of H37Rv-WT strain in macrophages was 2 folds higher than that of H37RvΔRv3737 at 72 h. A significantly higher level of TNF-α and IL-6 mRNA expression was observed in macrophages infected with H37RvΔRv3737 as compared to H37Rv-WT. Of note, Rv3737 expression was significantly increased in clinical Mtb isolates than H37Rv-WT. The relative expression level of Rv3737 was positively correlated with lung cavity number of TB patients. Similarly, the higher Rv3737 mRNA level resulted in lower C(t) value by Xpert MTB/RIF assay, demonstrating that a positive correlation between Rv3737 expression and bacterial load in TB patients. CONCLUSIONS: Our data takes the lead in demonstrate that the threonine transporter Rv3737 is required for in vitro growth and survival of bacteria inside macrophages. In addition, the expression level of Rv3737 may be associated with bacterial load and disease severity in pulmonary tuberculosis patients.

Thiazolidinedione-Based Structure Modification of Celastrol Provides Thiazolidinedione-Conjugated Derivatives as Potent Agents against Non-Small-Cell Lung Cancer Cells through a Mitochondria-Mediated Apoptotic Pathway.

In order to improve the potential of celastrol against non-small-cell lung cancer cells, the privileged structure, thiazolidinedione, was introduced into its C-20 carboxylic group with acetylpiperazine as a linker, and the thiazolidinedione-conjugated compounds 10a-10t were prepared. The target compounds were evaluated for their cytotoxic activities against the A549 cell line, and the results showed that most of the compounds 10a-10t displayed improved potency over celastrol, and compound 10b exhibited significant activity against the A549 cell line, with an IC50 value of 0.08 µM, which was 13.8-fold more potent than celastrol (IC50 = 1.10 µM). The mechanistic studies suggested that 10b could induce A549 cell apoptosis, as evidenced by Hoechst 33342 staining and annexin V-FITC/propidium iodide dual staining assays. Western blot analysis suggested that compound 10b could upregulate Bax expression, downregulate Bcl-2 expression, and activate the mitochondria-mediated apoptotic pathway. Furthermore, compound 10b could effectively inhibit tumor growth when tested in an A549 cell xenograft mouse model. Collectively, compound 10b is worthy of further investigation to support the discovery of effective agents against non-small-cell lung cancer.

Integrated analysis of lncRNAs and mRNAs by RNA-Seq in secondary hair follicle development and cycling (anagen, catagen and telogen) of Jiangnan cashmere goat (Capra hircus).

BACKGROUND: Among the world's finest natural fiber composites is derived from the secondary hair follicles (SHFs) of cashmere goats yield one of the world's best natural fibres. Their development and cycling are characterized by photoperiodism with diverse, well-orchestrated stimulatory and inhibitory signals. Long non-coding RNA (lncRNAs) and mRNAs play important roles in hair follicle (HF) development. However, not many studies have explored their specific functions in cashmere development and cycling. This study detected mRNAs and lncRNAs with their candidate genes and related pathways in SHF development and cycling of cashmere goat. We utilized RNA sequencing (RNA-Seq) and bioinformatics analysis on lncRNA and mRNA expressions in goat hair follicles to discover candidate genes and metabolic pathways that could affect development and cycling (anagen, catagen, and telogen). RESULTS: We identified 228 differentially expressed (DE) mRNAs and 256 DE lncRNA. For mRNAs, catagen and anagen had 16 upregulated and 35 downregulated DEGs, catagen and telogen had 18 upregulated and 9 downregulated DEGs and telogen and anagen had 52 upregulated and 98 downregulated DEGs. LncRNA witnessed 22 upregulated and 39 downregulated DEGs for catagen and anagen, 36 upregulated and 29 downregulated DEGs for catagen and telogen as well as 66 upregulated and 97 downregulated DEGs for telogen and anagen. Several key genes, including MSTRG.5451.2, MSTRG.45465.3, MSTRG.11609.2, CHST1, SH3BP4, CDKN1A, GAREM1, GSK-3ß, DEFB103A KRTAP9-2, YAP1, S100A7A, FA2H, LOC102190037, LOC102179090, LOC102173866, KRT2, KRT39, FAM167A, FAT4 and EGFL6 were shown to be potentially important in hair follicle development and cycling. They were related to, WNT/ß-catenin, mTORC1, ERK/MAPK, Hedgehog, TGFß, NFkB/p38MAPK, caspase-1, and interleukin (IL)-1a signaling pathways. CONCLUSION: This work adds to existing understanding of the regulation of HF development and cycling in cashmere goats via lncRNAs and mRNAs. It also serves as theoretical foundation for future SHF research in cashmere goats.

Comprehensive transcriptome and methylome analysis delineates the biological basis of hair follicle development and wool-related traits in Merino sheep.

BACKGROUND: Characterization of the molecular mechanisms underlying hair follicle development is of paramount importance in the genetic improvement of wool-related traits in sheep and skin-related traits in humans. The Merino is the most important breed of fine-wooled sheep in the world. In this study, we systematically investigated the complexity of sheep hair follicle development by integrating transcriptome and methylome datasets from Merino sheep skin. RESULTS: We analysed 72 sequence datasets, including DNA methylome and the whole transcriptome of four gene types, i.e. protein-coding genes (PCGs), lncRNAs, circRNAs, and miRNAs, across four embryonic days (E65, E85, E105, and E135) and two postnatal days (P7 and P30) from the skin tissue of 18 Merino sheep. We revealed distinct expression profiles of these four gene types across six hair follicle developmental stages, and demonstrated their complex interactions with DNA methylation. PCGs with stage-specific expression or regulated by stage-specific lncRNAs, circRNAs, and miRNAs were significantly enriched in epithelial differentiation and hair follicle morphogenesis. Regulatory network and gene co-expression analyses identified key transcripts controlling hair follicle development. We further predicted transcriptional factors (e.g. KLF4, LEF1, HOXC13, RBPJ, VDR, RARA, and STAT3) with stage-specific involvement in hair follicle morphogenesis. Through integrating these stage-specific genomic features with results from genome-wide association studies (GWAS) of five wool-related traits in 7135 Merino sheep, we detected developmental stages and genes that were relevant with wool-related traits in sheep. For instance, genes that were specifically upregulated at E105 were significantly associated with most of wool-related traits. A phenome-wide association study (PheWAS) demonstrated that candidate genes of wool-related traits (e.g. SPHK1, GHR, PPP1R27, CSRP2, EEF1A2, and PTPN1) in sheep were also significantly associated with dermatological, metabolic, and immune traits in humans. CONCLUSIONS: Our study provides novel insights into the molecular basis of hair follicle morphogenesis and will serve as a foundation to improve breeding for wool traits in sheep. It also indicates the importance of studying gene expression in the normal development of organs in understanding the genetic architecture of economically important traits in livestock. The datasets generated here are useful resources for functionally annotating the sheep genome, and for elucidating early skin development in mammals, including humans.

Integration of a single-step genome-wide association study with a multi-tissue transcriptome analysis provides novel insights into the genetic basis of wool and weight traits in sheep.

BACKGROUND: Genetic improvement of wool and growth traits is a major goal in the sheep industry, but their underlying genetic architecture remains elusive. To improve our understanding of these mechanisms, we conducted a weighted single-step genome-wide association study (WssGWAS) and then integrated the results with large-scale transcriptome data for five wool traits and one growth trait in Merino sheep: mean fibre diameter (MFD), coefficient of variation of the fibre diameter (CVFD), crimp number (CN), mean staple length (MSL), greasy fleece weight (GFW), and live weight (LW). RESULTS: Our dataset comprised 7135 individuals with phenotype data, among which 1217 had high-density (HD) genotype data (n = 372,534). The genotypes of 707 of these animals were imputed from the Illumina Ovine single nucleotide polymorphism (SNP) 54 BeadChip to the HD Array. The heritability of these traits ranged from 0.05 (CVFD) to 0.36 (MFD), and between-trait genetic correlations ranged from - 0.44 (CN vs. LW) to 0.77 (GFW vs. LW). By integrating the GWAS signals with RNA-seq data from 500 samples (representing 87 tissue types from 16 animals), we detected tissues that were relevant to each of the six traits, e.g. liver, muscle and the gastrointestinal (GI) tract were the most relevant tissues for LW, and leukocytes and macrophages were the most relevant cells for CN. For the six traits, 54 quantitative trait loci (QTL) were identified covering 81 candidate genes on 21 ovine autosomes. Multiple candidate genes showed strong tissue-specific expression, e.g. BNC1 (associated with MFD) and CHRNB1 (LW) were specifically expressed in skin and muscle, respectively. By conducting phenome-wide association studies (PheWAS) in humans, we found that orthologues of several of these candidate genes were significantly (FDR < 0.05) associated with similar traits in humans, e.g. BNC1 was significantly associated with MFD in sheep and with hair colour in humans, and CHRNB1 was significantly associated with LW in sheep and with body mass index in humans. CONCLUSIONS: Our findings provide novel insights into the biological and genetic mechanisms underlying wool and growth traits, and thus will contribute to the genetic improvement and gene mapping of complex traits in sheep.

Study of microRNA Expression Profile in Different Regions of Ram Epididymis.

The regional expression of epididymal genes provides a guarantee for sperm maturation. As a class of endogenous non-coding small RNAs, microRNAs (miRNAs) play an important role in spermatogenesis, maturation and fertilization. Currently, the regulatory role of miRNA in the epididymis is poorly understood. Here, transcriptome sequencing was used to analyse miRNA expression profiles in three regions of the epididymis of rams, including caput, corpus and cauda. The results showed that there were 13 known miRNAs between the caput and corpus controls, 29 between the caput and cauda and 22 differences between the corpus and cauda. Based on the analysis of miRNA target genes by GO and KEGG, a negative regulation network of miRNA-mRNA was constructed in which let-7, miR-541-5p, miR-133b and miR-150 may play an important regulatory role in the maturation regulation of ram epididymal sperm. This research provides a reference for studying the regulation mechanism of sperm maturation in male epididymis and improving semen quality and male reproductive performance.

Soft and MRI Compatible Neural Electrodes from Carbon Nanotube Fibers.

Soft and magnetic resonance imaging (MRI) compatible neural electrodes enable stable chronic electrophysiological measurements and anatomical or functional MRI studies of the entire brain without electrode interference with MRI images. These properties are important for many studies, ranging from a fundamental neurophysiological study of functional MRI signals to a chronic neuromodulatory effect investigation of therapeutic deep brain stimulation. Here we develop soft and MRI compatible neural electrodes using carbon nanotube (CNT) fibers with a diameter from 20 µm down to 5 µm. The CNT fiber electrodes demonstrate excellent interfacial electrochemical properties and greatly reduced MRI artifacts than PtIr electrodes under a 7.0 T MRI scanner. With a shuttle-assisted implantation strategy, we show that the soft CNT fiber electrodes can precisely target specific brain regions and record high-quality single-unit neural signals. Significantly, they are capable of continuously detecting and isolating single neuronal units from rats for up to 4-5 months without electrode repositioning, with greatly reduced brain inflammatory responses as compared to their stiff metal counterparts. In addition, we show that due to their high tensile strength, the CNT fiber electrodes can be retracted controllably postinsertion, which provides an effective and convenient way to do multidepth recording or potentially selecting cells with particular response properties. The chronic recording stability and MRI compatibility, together with their small size, provide the CNT fiber electrodes unique research capabilities for both basic and applied neuroscience studies.

Production of Formamides from CO and Amines Induced by Porphyrin Rhodium(II) Metalloradical.

It is of fundamental importance to transform carbon monoxide (CO) to petrochemical feedstocks and fine chemicals. Many strategies built on the activation of C≡O bond by π-back bonding from the transition metal center were developed during the past decades. Herein, a new CO activation method, in which the CO was converted to the active acyl-like metalloradical, [(por)Rh(CO)]• (por = porphyrin), was reported. The reactivity of [(por)Rh(CO)]• and other rhodium porphyrin compounds, such as (por)RhCHO and (por)RhC(O)NH nPr, and corresponding mechanism studies were conducted experimentally and computationally and inspired the design of a new conversion system featuring 100% atom economy that promotes carbonylation of amines to formamides using porphyrin rhodium(II) metalloradical. Following this radical based pathway, the carbonylations of a series of primary and secondary aliphatic amines were examined, and turnover numbers up to 224 were obtained.

Association analysis of polymorphisms in six keratin genes with wool traits in sheep.

OBJECTIVE: The purpose of this study was to investigate the genetic effects of six keratin (KRT) genes on the wool traits of 418 Chinese Merino (Xinjiang type) (CMXT) individuals. METHODS: To explore the effects and association of six KRT genes on sheep wool traits, The polymerase chain reaction-based single-strand conformation polymorphism (PCR-SSCP), DNA sequencing, and the gene pyramiding effect methods were used. RESULTS: We report 20 mutation sites (single-nucleotide polymorphisms) within the six KRT genes, in which twelve induced silent mutations; five induced missense mutations and resulted in Ile→Thr, Glu→Asp, Gly→Ala, Ala→Ser, Se→His; two were nonsense mutations and one was a same-sense mutation. Association analysis showed that two genotypes of the KRT31 gene were significantly associated with fiber diameter (p<0.05); three genotypes of the KRT36 gene were significantly associated with wool fineness score and fiber diameter (p<0.05), three genotypes of the KRT38 gene were significantly associated with the number of crimps (p< 0.05); and three genotypes of the KRT85 gene were significantly associated with wool crimps score, body size, and fiber diameter (p<0.05). Analysis of the gene pyramiding effect between the different genotypes of the gene loci KRT36, KRT38, and KRT85, each genotype in a gene locus was combined with all the genotypes of another two gene loci and formed the different three loci combinations, indicated a total of 26 types of possible combined genotypes in the analyzed population. Compared with the other combined genotypes, the combinations CC-GG-II, CC-HH-IJ, CC-HH-JJ, DD-HH-JJ, CC-GH-IJ, and CC-GH-JJ at gene loci KRT36, KRT38, and KRT85, respectively, had a greater effect on wool traits (p<0.05). CONCLUSION: Our results indicate that the mutation loci of KRT31, KRT36, KRT38, and KRT85 genes, as well as the combinations at gene loci KRT36, KRT38, and KRT85 in CMXT have significant effects on wool traits, suggesting that these genes are important candidate genes for wool traits, which will contribute to sheep breeding and provide a molecular basis for improved wool quality in sheep.

Graphene Encapsulated Copper Microwires as Highly MRI Compatible Neural Electrodes.

Magnetic resonance imaging (MRI) compatible neural electrodes are important for combining high-resolution electrophysiological measurements with more global MRI mapping of brain activity, which is critical for fundamental neuroscience studies, as well as clinical evaluation and monitoring. Copper is a favorable material to use in MRI because it has magnetic susceptibility close to water and tissues. However, the cytotoxicity of copper precludes its direct implantation for neural recording. Here, we overcome this limitation by developing a graphene encapsulated copper (G-Cu) microelectrode. The toxicity of copper is largely eliminated, as evidenced by the in vitro cell tests and in vivo histology studies. Local field potentials and single-unit spikes were recorded from rodent brains with the G-Cu microelectrodes. Notably, the G-Cu microelectrodes show no image artifacts in a 7.0 T MRI scanner, indicating minimal magnetic field distortion in their vicinity. This high MRI compatibility of our G-Cu probes would open up new opportunities for fundamental brain activity studies and clinical applications requiring continuous MRI and electrophysiological recordings.

WITHDRAWN:Identification of Polymorphisms and Association of Five KAP Genes with Sheep Wool Traits.

Ahead of Print article withdrawn by publisher.