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Simultaneous deep brain stimulation (DBS) and functional magnetic resonance imaging (fMRI) constitutes a powerful tool for elucidating brain functional connectivity, and exploring neuromodulatory mechanisms of DBS therapies. Previous DBS-fMRI studies could not provide full activation pattern maps due to poor MRI compatibility of the DBS electrodes, which caused obstruction of large brain areas on MRI scans. Here, we fabricate graphene fiber (GF) electrodes with high charge-injection-capacity and little-to-no MRI artifact at 9.4T. DBS-fMRI with GF electrodes at the subthalamic nucleus (STN) in Parkinsonian rats reveal robust blood-oxygenation-level-dependent responses along the basal ganglia-thalamocortical network in a frequency-dependent manner, with responses from some regions not previously detectable. This full map indicates that STN-DBS modulates both motor and non-motor pathways, possibly through orthodromic and antidromic signal propagation. With the capability for full, unbiased activation pattern mapping, DBS-fMRI using GF electrodes can provide important insights into DBS therapeutic mechanisms in various neurological disorders. Combination of fMRI and deep brain stimulation (DBS) allows for large-scale mapping of brain responses to DBS. Here the authors develop highly MRI compatible graphene fiber electrodes for full brain activation pattern mapping under DBS in Parkinsonian rats.

Similar to global trends, the incidence rate of tuberculosis (TB) in China declined from 2000 to 2018. In this study, we aimed to evaluate TB trends in northern Guizhou Province and identify risk factors associated with rifampicin-resistant (RR) and concurrent extrapulmonary TB (EPTB). We analyzed data of TB patients hospitalized in Affiliated Hospital of Zunyi Medical University from 2011 to 2018, and assessed correlations between demographic characteristics of patients and RR-TB as well as concurrent EPTB. Our results showed that numbers of new, retreated, RR-TB and concurrent EPTB cases increased gradually from 2011 to 2018. Retreated patients had the highest odds of RR-TB but a lower likelihood of concurrent EPTB compared to new patients. Patients between 21 and 40 years of age had a higher likelihood of RR-TB compared to those 20 years and younger. Female patients and patients from Bijie city as well as the Miao ethnic minority had higher odds of concurrent EPTB. In summary, our data demonstrate upward trends in new, rifampicin-resistant and concurrent extrapulmonary TB cases in northern Guizhou Province of China, which should not be overlooked especially during and post the COVID-19 pandemic because TB is a greater long-term global health threat than COVID-19.

Dynamic changes in gene and transcript expression represent a key factor in regulating the cyclical development of hair follicles. In this study, based on Nanopore sequencing (ONT-seq) data of skin tissue from three developmental stages (anagen (An), catagen (Cn), and telogen (Tn)) of Jiangnan cashmere goat hair follicles, this study presents a profile of candidate DETs implicated in cycle regulation by delineating their stage-specific expression patterns and dynamic expression trends from anagen to telogen. A large proportion of the candidate DETs were significantly enriched in functions related to fat synthesis, storage, or metabolism, with significance levels of p < 0.05 or p < 0.01. These significantly enriched DETs, which were generally upregulated from An to Cn or downregulated from Cn to Tn, support a model where accelerated intradermal fat deposition promotes the progression from An to Cn, while its subsequent decrease facilitates the transition from Cn to Tn. Concurrently, our results also suggest a potential role for dynamic changes in AS patterns in regulating the hair follicle cycle. This regulatory role of AS patterns is potentially mediated through affecting genes related to lipid synthesis/metabolism or cell structure/interaction. Notably, a broader range of fat synthesis, storage, or metabolism-related transcripts showed significant differential expression (p < 0.05) in the An vs. Cn group. Ultimately, by establishing this candidate DET profile, we aim to provide fresh perspectives for deciphering the complex molecular regulation of the hair follicle cycle and to identify new targets for genetically enhancing or molecularly breeding cashmere traits in cashmere goats.

Reproductive and growth traits are key economic traits in sheep. This study aims to identify key single nucleotide polymorphisms (SNPs) and candidate genes associated with reproductive and growth traits in Tianmu polytocous sheep through a genome-wide association study (GWAS). The findings are expected to provide both a theoretical foundation for molecular breeding in this breed and novel insights into the genetic basis of ovine reproductive and growth performance. This study took 483 adult Tianmu polytocous ewes as the research subjects, collected their lambing records, measured their phenotypic values of growth traits (3 weight and 11 body size traits), and collected their blood samples for whole-genome resequencing to identify SNPs in the Tianmu polytocous sheep genome. The results identified a total of 9,499,019 (3× coverage) and 27,413,216 (30× coverage) high-quality SNPs in the Tianmu polytocous sheep genome. Subsequently, the association analysis between SNPs and reproductive and growth traits was conducted using a mixed linear model. A total of 92, 66, 18, 28, 6, 42, 3, 3, 6, 1, 12, 3, 22, 8, 6, and 3 SNPs were found associated with litter size at first parity, litter size at second parity, litter size at third parity, litter size at fourth parity, birth weight, weaning weight, body height, withers height, body length, head length, head width, cannon bone circumference, forelimb height, chest girth, chest depth, and withers width, respectively. Further, based on SNP annotation, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, candidate genes associated with the reproductive and growth traits were identified. Among these genes, 11 LOC, DEPTOR, GNG12, GRM7, PTH, PTH2R, WWOX, INHA, and NRG3 are candidate genes associated with litter size at first parity or litter size at third parity. These genes are involved in the G protein-coupled receptor signaling pathway, G protein-coupled receptor activity, ovarian tissue development, and hormone secretion. Additionally, TFRC and NTN1 are candidate genes associated with birth weight, while five UGT1A and CASR are candidate genes associated with weaning weight. These candidate genes are primarily involved in lipid metabolism. Finally, the following genes were identified as candidates associated with specific traits: DLG2, TMEM126A, and TMEM126B with body height; DSCAM and SCN8A with body length; BARX1 with cannon bone circumference; four LOC genes with forelimb height; EPHA4 with chest depth; and MRS2 with withers width.

To identify molecular markers associated with wool traits in fine-wool sheep, we examined genetic polymorphisms in the NOTCH2 and CD1A genes in 944 Subo Merino sheep in this study. Subsequently, we performed association analyses between mutation sites in the NOTCH2 and CD1A genes and wool traits using SAS 9.4 software, followed by linkage disequilibrium (LD) analysis of different mutation sites using Haploview 4.2 software. Additionally, bioinformatics tools were employed to predict the potential impacts of missense mutations on protein secondary and tertiary structures. Finally, quantitative PCR (qPCR) was used to assess the expression levels of the NOTCH2 and CD1A genes. Genetic analysis revealed six polymorphic sites in NOTCH2 and CD1A, all of which were missense mutations. Two SNPs in NOTCH2 (SNP1 and SNP2) showed significant associations with the coefficient of variation of fibre diameter, and SNP1 was also associated with greasy fleece weight. Four SNPs in CD1A (SNP3–SNP6) were significantly associated with fibre diameter standard deviation, and SNP3, SNP4, and SNP5 were additionally associated with crimp number. LD analysis revealed that SNP3, SNP4, and SNP5 were closely linked. Bioinformatics analysis indicated that the mutations caused alterations in the secondary and tertiary structures of the NOTCH2 and CD1A proteins. qPCR results showed that the CD1A gene was highly expressed in the fine wool fibre group compared with the ultra-fine wool fibre group. In conclusion, this study revealed a genetic association between NOTCH2 and CD1A and wool traits. The results are expected to provide a theoretical foundation for breeding wool traits in Subo Merino sheep, thereby enhancing the economic value of fine wool.

In this study, 944 Subo Merino sheep, a high-quality fine wool breed, were selected as research subjects. The SNP typing of the FAT3 gene was performed using the Fluidigm BiomarkTM HD system, and 11 missense mutation sites were identified. The analysis of population polymorphism of single-nucleotide polymorphisms was conducted. It is noteworthy that a substantial strong linkage disequilibrium was identified between SNP 5 and SNP 6 (r2 > 0.8). The association between SNPs of the FAT3 gene and wool traits showed that multiple SNPs were significantly correlated with several different wool traits (p < 0.05). Furthermore, the investigation delved into the impact of the FAT3 gene on wool fiber through the utilization of quantitative polymerase chain reaction (qPCR), which yielded findings that this gene was notably expressed in fine wool fiber (FW) (p < 0.001). To predict the subcellular localization and protein transmembrane structure of FAT3, we employed the PSORT II Prediction and TMHMM online software. It was determined that the protein contains a transmembrane domain. This study provides molecular markers for the improvement of the selection and breeding of ultrafine-wool sheep and offers experimental evidence for accelerating the genetic breeding of sheep.

With economic development and improved living standards, the demand for mutton and wool continues to grow, and improving the production performance and genetic potential of sheep breeds has become the key to promoting the high-quality development of the sheep industry. Thus, this study analyzes the influencing factors of the early production traits of Yunnan semi-fine wool sheep, optimizes the genetic evaluation model, and relies on accurate genetic parameter estimation to provide a theoretical basis for formulating a scientific and efficient breeding strategy for this breed. Data were collected from the Laishishan and Xiaohai breeding farms in Qiaojia, Yunnan, covering production records of the core flock from 2018 to 2022. Using the GLM procedure in SAS 9.4 software, this study analyzed the non-genetic influences on early production traits in Yunnan semi-fine wool sheep. Concurrently, Danish Milk Unit 5 (DMU 5) 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 the genetic parameters. The results show that the birth year, dam age, sex, flock and litter size significantly affect both the Birth Weight (BWT) and Weaning Weight (WWT) (p < 0.01). Additionally, the birth month was found to exert a significant effect on Birth Weight (BWT) (p < 0.01), the weaning month has a significant effect on the Weaning Weight (WWT) (p < 0.05). No significant effects of farm location were observed on either trait (p > 0.05). The most accurate genetic evaluation model determined the heritability of the Birth Weight (BWT) and Weaning Weight (WWT) as 0.3123 and 0.3471. From a production perspective, improving lamb birth, Weaning Weight (WWT), feed composition, and maternal nutrition during gestation is vital for breeding efficiency. This study not only identified the optimal animal models for early growth traits in Yunnan semi-fine wool sheep, offering a precise basis for estimating genetic parameters but also provides theoretical guidance for genetic selection and breed improvement in this population.

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.

Large-scale brain activity mapping is important for understanding the neural basis of behaviour. Electrocorticograms (ECoGs) have high spatiotemporal resolution, bandwidth, and signal quality. However, the invasiveness and surgical risks of electrode array implantation limit its application scope. We developed an ultrathin, flexible shape-changing electrode array (SCEA) for large-scale ECoG mapping with minimal invasiveness. SCEAs were inserted into cortical surfaces in compressed states through small openings in the skull or dura and fully expanded to cover large cortical areas. MRI and histological studies on rats proved the minimal invasiveness of the implantation process and the high chronic biocompatibility of the SCEAs. High-quality micro-ECoG activities mapped with SCEAs from male rodent brains during seizures and canine brains during the emergence period revealed the spatiotemporal organization of different brain states with resolution and bandwidth that cannot be achieved using existing noninvasive techniques. The biocompatibility and ability to map large-scale physiological and pathological cortical activities with high spatiotemporal resolution, bandwidth, and signal quality in a minimally invasive manner offer SCEAs as a superior tool for applications ranging from fundamental brain research to brain-machine interfaces. The invasiveness of extensive craniotomy hinders large-scale cortex mapping. Here, the authors developed a flexible, shape-changing electrode array which enables minimally invasive implantation and achieves high spatiotemporal resolution brain mapping.

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.