Feedback control strategy of networked multi-LSRMs system with semi-Markov topology switching and time delay.

This paper studies the networked control system (NCS) with semi-Markov topology switching and network delay. The time delays of the system are considered in the measurement and control channels. The control channel is between the controller and the actuator, the measurement channel is between the sensor and the controller. The topology switching and the transition process among modes are described by semi-Markov sojourn-time probability density function and Markov transition probability matrix respectively. The mean square stability conditions for the networked multi-LSRMs system are obtained by constructing a new Lyapunov function. To ensure the σ-error mean square stability of the closed loop system, a state feedback controller is designed by combining the variation technique of inequalities and Lyapunov stability theory. Finally, several experiments results verify the effectiveness and rationality of the proposed control strategy.

Adipocyte Rnf20 ablation increases the fast-twitch fibers of skeletal muscle via lysophosphatidylcholine 16:0.

Both adipose tissue and skeletal muscle are highly dynamic tissues and interact at the metabolic and hormonal levels in response to internal and external stress, and they coordinate in maintaining whole-body metabolic homeostasis. In our previous study, we revealed that adipocyte-specific Rnf20 knockout mice (ASKO mice) exhibited lower fat mass but higher lean mass, providing a good model for investigating the adipose-muscle crosstalk and exploring the effect of the adipocyte Rnf20 gene on the physiology and metabolism of skeletal muscle. Here, we confirmed that ASKO mice exhibited the significantly increased body weight and gastrocnemius muscle weight. Fiber-type switching in the soleus muscle of ASKO mice was observed, as evidenced by the increased number of fast-twitch fibers and decreased number of slow-twitch fibers. Serum metabolites with significant alteration in abundance were identified by metabolomic analysis and the elevated lysophosphatidylcholine 16:0 [LysoPC (16:0)] was observed in ASKO mice. In addition, lipidome analysis of gonadal white adipose tissue revealed a significant increase in LysoPCs and LysoPC (16:0) in ASKO mice. Furthermore, knockdown of Rnf20 gene in 3T3-L1 cells significantly increased the secretion of LysoPC, suggesting that LysoPC might be a critical metabolite in the adipose-muscle crosstalk of ASKO mice. Furthermore, in vitro study demonstrated that LysoPC (16:0) could induce the expression of fast-twitch muscle fibers related genes in differentiated C2C12 cells, indicating its potential role in adipose-muscle crosstalk. Taken together, these findings not only expand our understanding of the biological functions of Rnf20 gene in systemic lipid metabolism, but also provide insight into adipose tissue dysfunction-induced physiological alterations in skeletal muscle.

Distinct Transcriptional Responses of Skeletal Muscle to Short-Term Cold Exposure in Tibetan Pigs and Bama Pigs.

Piglets are susceptible to cold, and piglet death caused by cold stress leads to economic losses in the pig industry in cold areas. Skeletal muscle plays a key role in adaptive thermogenesis in mammals, but the related mechanism in pigs is unclear. In this study, cold-tolerant Tibetan pigs and cold-sensitive Bama pigs were subjected to either a cold environment (4 °C) or a room temperature environment (25 °C) for 3 days. The biceps femoris (BF) and longissimus dorsi muscle (LDM) were collected for phenotypic analysis, and the BF was used for genome-wide transcriptional profiling. Our results showed that Tibetan pigs had a higher body temperature than Bama pigs upon cold stimulation. RNA-seq data indicated a stronger transcriptional response in the skeletal muscle of Tibetan pigs upon cold stimulation, as more differentially expressed genes (DEGs) were identified with the same criteria (p < 0.05 and fold change > 2). In addition, distinct pathway signaling patterns in skeletal muscle upon cold exposure were found between the breeds of pigs. Mitochondrial beta-oxidation-related genes and pathways were significantly upregulated in Tibetan pigs, indicating that Tibetan pigs may use fatty acids as the primary fuel source to protect against cold. However, the significant upregulation of inflammatory response- and glycolysis-related genes and pathways in the skeletal muscle of Bama pigs suggested that these pigs may use glucose as the primary fuel source in cold environments. Together, our study revealed the distinct transcriptional responses of skeletal muscle to cold stimulation in Tibetan pigs and Bama pigs and provided novel insights for future investigation of the cold adaptation mechanism in pigs.

DNA methylation-based profiling of horse archaeological remains for age-at-death and castration.

Age profiling of archaeological bone assemblages can inform on past animal management practices, but is limited by the fragmentary nature of the fossil record and the lack of universal skeletal markers for age. DNA methylation clocks offer new, albeit challenging, alternatives for estimating the age-at-death of ancient individuals. Here, we take advantage of the availability of a DNA methylation clock based on 31,836 CpG sites and dental age markers in horses to assess age predictions in 84 ancient remains. We evaluate our approach using whole-genome sequencing data and develop a capture assay providing reliable estimates for only a fraction of the cost. We also leverage DNA methylation patterns to assess castration practice in the past. Our work opens for a deeper characterization of past husbandry and ritual practices and holds the potential to reveal age mortality profiles in ancient societies, once extended to human remains.

Fecal Microbiota Was Reshaped in UCP1 Knock-In Pigs via the Adipose-Liver-Gut Axis and Contributed to Less Fat Deposition.

The relationship between the host gut microbiota and obesity has been well documented in humans and mice; however, few studies reported the association between the gut microbiota and fat deposition in pigs. In a previous study, we generated uncoupling protein 1 (UCP1) knock-in pigs (UCP1 pigs), which exhibited a lower fat deposition phenotype. Whether the gut microbiota was reshaped in these pigs and whether the reshaped gut microbiota contributes to the lower fat content remain unknown. Here, we revealed that the fecal microbiota composition and metabolites were significantly altered under both chow diet (CD) and high-fat/high-cholesterol (HFHC) diet conditions in UCP1 pigs compared to those in wild-type (WT) pigs. The abundance of Oscillospira and Coprococcus and the level of metabolite hyodeoxycholic acid (HDCA) from feces were observed to be significantly increased in UCP1 pigs. An association analysis revealed that Oscillospira and Coprococcus were significantly negatively related to backfat thickness. In addition, after fecal microbiota transplantation (FMT), the mice that were orally gavaged with feces from UCP1 pigs exhibited less fat deposition under both CD and high-fat diet (HFD) conditions, suggesting that the fecal microbes of UCP1 pigs participate in regulating host lipid metabolism. Consistently, HDCA-treated mice also exhibited reduced fat content. Mechanistically, we found that UCP1 expression in white adipose tissue alters the gut microbiota via the adipose-liver-gut axis in pigs. Our study provides new data concerning the cross talk between host genetic variations and the gut microbiota and paves the way for the potential application of microbes or their metabolites in the regulation of fat deposition in pigs. IMPORTANCE This article investigated the effect of the ectopic expression of UCP1 on the regulation of fecal microbiota composition and metabolites and which alters the fat deposition phenotype. Bacteria, including Oscillospira and Coprococcus, and the metabolite HDCA were found to be significantly increased in feces of UCP1 pigs and had a negative relationship with backfat thickness. Mice with fecal microbiota transplantation phenocopied the UCP1 pigs under both CD and HFD conditions, suggesting that the fecal microbes of UCP1 pigs participate in regulating host lipid metabolism. Our study provides new data regarding the cross talk between host genetic variations and the gut microbiota and paves the way for the potential application of microbes or their metabolic production in the regulation of fat deposition in pigs.

CTRP1 prevents high fat diet-induced obesity and improves glucose homeostasis in obese and STZ-induced diabetic mice.

BACKGROUND: C1q/tumor necrosis factor-related protein 1 (CTRP1) is an adipokine secreted by adipose tissue, related to chondrocyte proliferation, inflammation, and glucose homeostasis. However, the therapeutic effects on metabolic disorders and the underlying mechanism were unclear. Here, we investigated the functions and mechanisms of CTRP1 in treating obesity and diabetes. METHODS: The plasmid containing human CTRP1 was delivered to mice by hydrodynamic injection, which sustained expression of CTRP1 in the liver and high protein level in the blood. High-fat diet (HFD) fed mice and STZ-induced diabetes model were used to study the effects of CTRP1 on obesity, glucose homeostasis, insulin resistance, and hepatic lipid accumulation. The lipid accumulation in liver and adipose tissue, glucose tolerance, insulin sensitivity, food intake, and energy expenditure were detected by H&E staining, Oil-Red O staining, glucose tolerance test, insulin tolerance test, and metabolic cage, respectively. The metabolic-related genes and signal pathways were determined using qPCR and western blotting. RESULTS: With high blood circulation, CTRP1 prevented obesity, hyperglycemia, insulin resistance, and fatty liver in HFD-fed mice. CTRP1 also improved glucose metabolism and insulin resistance in obese and STZ-induced diabetic mice. The metabolic cage study revealed that CTRP1 reduced food intake and enhanced energy expenditure. The mechanistic study demonstrated that CTRP1 upregulated the protein level of leptin in blood, thermogenic gene expression in brown adipose tissue, and the gene expression responsible for lipolysis and glycolysis in white adipose tissue (WAT). CTRP1 also downregulated the expression of inflammatory genes in WAT. Overexpression of CTRP1 activated AMPK and PI3K/Akt signaling pathways and inhibited ERK signaling pathway. CONCLUSION: These results demonstrate that CTRP1 could improve glucose homeostasis and prevent HFD-induced obesity and fatty liver through upregulating the energy expenditure and reducing food intake, suggesting CTRP1 may serve as a promising target for treating metabolic diseases.

Networked control strategy of dual linear switched reluctance motors based time delay tracking system.

To reduce the influence of time delay on the tracking performance of a direct-drive motion control system, this paper concentrates on stability analysis and cooperative position tracking control issues for the dual linear switched reluctance motors (LSRMs) system with network-induced time delays. The closed-loop network control system (NCS) is constructed by modeling random and bounded network-induced time delays existing in forward and feedback channels as a discrete-time Markov chain. Incremental time delay information is introduced in Lyapunov functional analysis to satisfy the high-precision movement of master and secondary motors and improve the system control performance. The time delay compensation method is proposed to compensate for the damage to the networked control system caused by random delay. With Lyapunov stability theory and LMI are applied, stability and stabilization conditions with less computational complexity and low conservatism are obtained based on incremental time delay information insertion. Finally, the numerical simulation and the experimental platform of the motor control system are built. Simulation and experiment results demonstrate that the networked control strategy can compensate the negative impact of delay on the tracking performance of LSRMs based motion control system.

N, P, O co-doped carbon filling into carbon nitride microtubes to promote photocatalytic hydrogen production.

Carbon nitride (CN) as the photocatalytic hydrogen production catalyst has attracted great attentions but suffering from a poor performance due to the unsatisfied energy band gap and the low separation efficiency of photogenerated carriers. Herein, we create a simple method to construct a novel CN-based photocatalyst, i.e., the N, P, O co-doped carbon filled CN microtube, which presents a narrow band gap, a high separation efficiency of photogenerated carriers, and a good stability. In this novel structure, the tubular morphology of CN ensures a narrow band gap, and the N, P, O co-doped carbon facilitates the transfer of photogenerated electrons. Coupling these two further reduces the energy band gap and improves the separation efficiency. For the photocatalytic hydrogen evolution under the visible light, the optimal sample presents an ultrahigh hydrogen evolution rate of 1149.71 µmol g-1 h-1 ranking at the top level, which is 112.60 times that of traditional bulk CN. In addition, it also has a high reusability and good stability after four cycle experiments. This study has provided a new viewpoint to design or develop the high-efficient photocatalysts for hydrogen production.

A single-nucleotide mutation within the TBX3 enhancer increased body size in Chinese horses.

Chinese ponies are endemic to the mountainous areas of southwestern China and were first reported in the archaeological record at the Royal Tomb of Zhongshan King, Mancheng, dated to approximately ∼2,100 YBP.1 Previous work has started uncovering the genetic basis of size variation in western ponies and horses, revealing a limited number of loci, including HMGA2,2LCORL/NCAPG,3ZFAT, and LASP1.4,5 Whether the same genetic pathways also drive the small body size of Chinese ponies, which show striking anatomical differences to Shetland ponies,6 remains unclear.2,7 To test this, we combined whole-genome sequences of 187 horses across China. Statistical analyses revealed top association between genetic variation at the T-box transcription factor 3 (TBX3) and the body size. Fine-scale analysis across an extended population of 189 ponies and 574 horses narrowed down the association to one A/G SNP at an enhancer region upstream of the TBX3 (ECA8:20,644,555, p = 2.34e-39). Luciferase assays confirmed the single-nucleotide G mutation upregulating TBX3 expression, and enhancer-knockout mice exhibited shorter limbs than wild-type littermates (p < 0.01). Re-analysis of ancient DNA data showed that the G allele, which is most frequent in modern horses, first occurred some ∼2,300 years ago and rose in frequency since. This supports selection for larger size in Asia from approximately the beginning of the Chinese Empire. Overall, this study characterized the causal regulatory mutation underlying small body size in Chinese ponies and revealed size as one of the main selection targets of past Chinese breeders.

RNF20 affects porcine adipocyte differentiation via regulation of mitotic clonal expansion.

OBJECTIVES: RNF20 is recognized as a main E3 ligase for monoubiquitination of histone H2B at lysine 120 (H2Bub). The critical role of RNF20 and H2Bub in various molecular events, such as DNA replication, RNA transcription, and DNA damage response, has been widely investigated and documented. However, its role in porcine adipogenesis remains unknown. In this study, we aimed to clarify the effect of RNF20 on porcine preadipocyte differentiation. MATERIALS AND METHODS: Backfat tissues from fat-type pigs (Bama and Meishan) and lean-type pigs (Yorkshire and Landrace) were collected to detect the expression level of RNF20. Preadipocytes were isolated from Bama piglets and induced to differentiation. Small interfering RNAs were applied to deplete RNF20. Oil Red O staining, quantitative real-time PCR, RNA-seq, Western blot analysis, and EdU assays were performed to study the regulatory mechanism of RNF20 during adipogenesis. RESULTS: We found that the expression levels of RNF20 and H2Bub were significantly higher in backfat tissues from fat-type pigs than in those from lean-type pigs. Consistently, the significantly induced expression of RNF20 and H2Bub was also observed in porcine differentiated adipocytes. In addition, knockdown of RNF20 greatly inhibited porcine adipogenesis, as evidenced by dramatically decreased lipid droplet formation and lower expression levels of adipogenic transcription masters in RNF20 knockdown cells. Mechanistically, the depletion of RNF20 decreases the cell proliferation and the level of p-C/EBPß via the Ras-Raf-MEK1/2-ERK1/2 cascade pathway at the mitotic clonal expansion phase and therefore suppresses cell differentiation. CONCLUSIONS: Our results demonstrate that RNF20 is required for porcine preadipocyte differentiation.

Factors Influencing the Prognosis of Patients with Intra-Abdominal Infection and Its Value in Assessing Prognosis.

PURPOSE: To explore the distribution of pathogenic bacteria in patients with intra-abdominal infection, to clarify the independent factors that affect the prognosis of patients with intra-abdominal infection and its evaluation value for prognosis. PATIENTS AND METHODS: The pathogens, underlying diseases, and related clinical data of patients with intra-abdominal infection from January 2012 to December 2019 in our hospital were retrospectively collected and the APACHE II score was calculated. The patients were divided into survival group and death group according to the prognosis, and the index between the two groups was compared. Spearman correlation analysis was used to evaluate the correlation between each index and prognosis, multivariate logistic regression analysis was used to screen the independent prognostic factors. RESULTS: Spearman correlation analysis showed that ALB level was negatively correlated with prognosis, age and APACHE II score were positively correlated with prognosis. Logistic regression analysis showed that age, ALB level, and APACHE II score were independent prognostic factors. The formula of age combined ALB level and APACHE II score was Y = X1-3.6X2 + 6.5X3 (X1 was the age, X2 was the ALB level and X3 was the APACHE II score), Y was positively correlated with poor prognosis, and the optimal cutoff value was Y = 40.96. CONCLUSION: Age, ALB level, and APACHE II score are independent factors that influencing the prognosis of patients with intra-abdominal infection, and the combination of age, ALB level, and APACHE II score can better assess the prognosis of patients with intra-abdominal infection.

Primary visual cortex of the brain is associated with optic nerve head changes in neuromyelitis optica spectrum disorders.

OBJECTIVE: To explore the association between the primary visual cortex in the brain and optic nerve head changes, ONH, (structural thickness and microvascular changes) in neuromyelitis optica spectrum disorder (NMOSD). METHODS: Nineteen patients who were aquaporin-4 (AQP-4) seropositive NMOSD patients and twenty-two healthy controls (HC) were enrolled for this cross-sectional study. Optical coherence tomographic angiography (OCT-A) was used to image and measure the capillaries density (RPC, radial peripapillary capillaries) and structural thickness (pRNFL, peripapillary retinal nerve fiber layer) around the optic nerve head. A resting-state functional magnetic resonance imaging was used to image and evaluate the gray matter volume (GMV) and functional connectivity (FC) the brain of each participant. We assessed the primary visual cortex (lingual gyrus, calcarine sulcus and thalamus) of the brain. RESULTS: Changes in RPC density showed a significant association (P < 0.05) with FC of the right lingual gyrus, bilateral calcarine gyrus and left thalamus respectively. pRNFL thickness showed significant association with FC of the right lingual gyrus (Rho = 0.374, P = 0.016), right calcarine gyrus (Rho = 0.355, P = 0.023) and left thalamus (Rho = 0.376, P = 0.015) respectively. CONCLUSIONS: Visual impairment, structural and microvascular changes around optic nerve head is associated with the functional visual networks in NMOSD. Our report suggests that structural and microvascular changes around the ONH reflect the changes in the primary visual cortex of the brain.

Rnf20 deficiency in adipocyte impairs adipose tissue development and thermogenesis.

RNF20, an E3 ligase critical for monoubiquitination of histone H2B at lysine 120 (H2Bub), has been implicated in the regulation of various cellar processes; however, its physiological roles in adipocytes remain poorly characterized. Here, we report that the adipocyte-specific knockout of Rnf20 (ASKO) in mice led to progressive fat loss, organomegaly and hyperinsulinemia. Despite signs of hyperinsulinemia, normal insulin sensitivity and improved glucose tolerance were observed in the young and aged CD-fed ASKO mice. In addition, high-fat diet-fed ASKO mice developed severe liver steatosis. Moreover, we observed that the ASKO mice were extremely sensitive to a cold environment due to decreased expression levels of brown adipose tissue (BAT) selective genes, including uncoupling protein 1 (Ucp1), and impaired mitochondrial functions. Significantly decreased levels of peroxisome proliferator-activated receptor gamma (Pparγ) were observed in the gonadal white adipose tissues (gWAT) from the ASKO mice, suggesting that Rnf20 regulates adipogenesis, at least in part, through Pparγ. Rosiglitazone-treated ASKO mice exhibited increased fat mass compared to that of the non-treated ASKO mice. Collectively, our results illustrate the critical role of RNF20 in control of white and brown adipose tissue development and physiological function.

Gdf11 gene transfer prevents high fat diet-induced obesity and improves metabolic homeostasis in obese and STZ-induced diabetic mice.

BACKGROUND: The growth differentiation factor 11 (GDF11) was shown to reverse age-related hypertrophy on cardiomyocytes and considered as anti-aging rejuvenation factor. The role of GDF11 in regulating metabolic homeostasis is unclear. In this study, we investigated the functions of GDF11 in regulating metabolic homeostasis and energy balance. METHODS: Using a hydrodynamic injection approach, plasmids carrying a mouse Gdf11 gene were delivered into mice and generated the sustained Gdf11 expression in the liver and its protein level in the blood. High fat diet (HFD)-induced obesity was employed to examine the impacts of Gdf11 gene transfer on HFD-induced adiposity, hyperglycemia, insulin resistance, and hepatic lipid accumulation. The impacts of GDF11 on metabolic homeostasis of obese and diabetic mice were examined using HFD-induced obese and STZ-induced diabetic models. RESULTS: Gdf11 gene transfer alleviates HFD-induced obesity, hyperglycemia, insulin resistance, and fatty liver development. In obese and STZ-induced diabetic mice, Gdf11 gene transfer restores glucose metabolism and improves insulin resistance. Mechanism study reveals that Gdf11 gene transfer increases the energy expenditure of mice, upregulates the expression of genes responsible for thermoregulation in brown adipose tissue, downregulates the expression of inflammatory genes in white adipose tissue and those involved in hepatic lipid and glucose metabolism. Overexpression of GDF11 also activates TGF-ß/Smad2, PI3K/AKT/FoxO1, and AMPK signaling pathways in white adipose tissue. CONCLUSIONS: These results demonstrate that GDF11 plays an important role in regulating metabolic homeostasis and energy balance and could be a target for pharmacological intervention to treat metabolic disease.

Transcriptional Response of Subcutaneous White Adipose Tissue to Acute Cold Exposure in Mice.

Beige adipose tissue has been considered to have potential applications in combating obesity and its related metabolic diseases. However, the mechanisms of acute cold-stimulated beige formation still remain largely unknown. Here, transcriptional analysis of acute cold-stimulated (4 °C for 4 h) subcutaneous white adipose tissue (sWAT) was conducted to determine the molecular signatures that might be involved in beige formation. Histological analysis confirmed the appearance of beige adipocytes in acute cold-treated sWAT. The RNA-sequencing data revealed that 714 genes were differentially expressed (p-value < 0.05 and fold change > 2), in which 221 genes were upregulated and 493 genes were downregulated. Gene Ontology (GO) analyses showed that the upregulated genes were enriched in the GO terms related to lipid metabolic process, fatty acid metabolic process, lipid oxidation, fatty acid oxidation, etc. In contrast, downregulated genes were assigned the GO terms of regulation of immune response, regulation of response to stimulus, defense response, etc. The expressions of some browning candidate genes were validated in cold-treated sWAT and 3T3-L1 cell browning differentiation. In summary, our results illustrated the transcriptional response of sWAT to acute cold exposure and identified the genes, including Acad11, Cyp2e1, Plin5, and Pdk2, involved in beige adipocyte formation in mice.

Adipocyte-specific disruption of ATPase copper transporting α in mice accelerates lipoatrophy.

AIMS/HYPOTHESIS: ATPase copper transporting α (ATP7A), also known as Menkes disease protein, is a P-type ATPase that transports copper across cell membranes. The critical role of ATP7A-mediated copper homeostasis has been well recognised in various organs, such as the intestine, macrophages and the nervous system. However, the importance of adipocyte ATP7A-mediated copper homeostasis on fat metabolism is not well understood. Here, we sought to reveal the contribution of adipose ATP7A to whole-body fat metabolism in mice. METHODS: We generated adipocyte-specific Atp7a-knockout (ASKO) mice using the Cre/loxP system, with Cre expression driven by the adiponectin promoter. ASKO mice and littermate control mice were aged on a chow diet or fed with a high-fat diet (HFD); body weight, fat mass, and glucose and insulin metabolism were analysed. Histological analysis, transmission electron microscopy and RNA-sequencing (RNA-Seq) analysis of white adipose tissue (WAT) were used to understand the physiological and molecular changes associated with loss of copper homeostasis in adipocytes. RESULTS: Significantly increased copper concentrations were observed in adipose tissues of ASKO mice compared with control mice. Aged or HFD-fed ASKO mice manifested a lipoatrophic phenotype characterised by a progressive generalised loss of WAT. Dysfunction of adipose tissues in these ASKO mice was confirmed by decreased levels of both serum leptin and adiponectin and increased levels of triacylglycerol and insulin. Systemic metabolism was also impaired in these mice, as evidenced by a pronounced glucose intolerance, insulin resistance and hepatic steatosis. Moreover, we demonstrate a significant induction of lipolysis and DNA-damage signalling pathways in gonadal WAT from aged and HFD-fed ASKO mice. In vitro studies suggest that copper overload is responsible for increased lipolysis and DNA damage. CONCLUSIONS/INTERPRETATION: Our results show a previously unappreciated role of adipocyte Atp7a in the regulation of ageing-related metabolic disease and identify new metallophysiologies in whole-body fat metabolism. DATA AVAILABILITY: The datasets generated during the current study are available in the Genome Sequence Archive in BIG Data Center, Beijing Institute of Genomics (BIG), Chinese Academy of Sciences, under accession number CRA001769 (http://bigd.big.ac.cn/gsa).

EPAS1 Gain-of-Function Mutation Contributes to High-Altitude Adaptation in Tibetan Horses.

High altitude represents some of the most extreme environments worldwide. The genetic changes underlying adaptation to such environments have been recently identified in multiple animals but remain unknown in horses. Here, we sequence the complete genome of 138 domestic horses encompassing a whole altitudinal range across China to uncover the genetic basis for adaptation to high-altitude hypoxia. Our genome data set includes 65 lowland animals across ten Chinese native breeds, 61 horses living at least 3,300 m above sea level across seven locations along Qinghai-Tibetan Plateau, as well as 7 Thoroughbred and 5 Przewalski's horses added for comparison. We find that Tibetan horses do not descend from Przewalski's horses but were most likely introduced from a distinct horse lineage, following the emergence of pastoral nomadism in Northwestern China ∼3,700 years ago. We identify that the endothelial PAS domain protein 1 gene (EPAS1, also HIF2A) shows the strongest signature for positive selection in the Tibetan horse genome. Two missense mutations at this locus appear strongly associated with blood physiological parameters facilitating blood circulation as well as oxygen transportation and consumption in hypoxic conditions. Functional validation through protein mutagenesis shows that these mutations increase EPAS1 stability and its hetero dimerization affinity to ARNT (HIF1B). Our study demonstrates that missense mutations in the EPAS1 gene provided key evolutionary molecular adaptation to Tibetan horses living in high-altitude hypoxic environments. It reveals possible targets for genomic selection programs aimed at increasing hypoxia tolerance in livestock and provides a textbook example of evolutionary convergence across independent mammal lineages.

Adipose lipidomics and RNA-Seq analysis revealed the enhanced mitochondrial function in UCP1 knock-in pigs.

Uncoupling protein 1 (UCP1) plays a key role in nonshivering thermogenesis and is involved in the pathogenesis of obesity. In a previous study, we generated adipocyte-specific UCP1 knock-in (UCP1-KI) pigs, which exhibited improved thermoregulatory ability and decreased fat deposition. To investigate whether UCP1 knock-in alters the lipid composition of adipose tissues, lipidomics of inguinal subcutaneous white adipose tissue (iWAT) and backfat from 6-month-old cold-treated UCP1-KI pigs and wild-type (WT) pigs were profiled. In addition, genome-wide RNA-sequencing of iWAT was performed to further study the genetic basis for lipid alterations. The results showed that iWAT and backfat from UCP1-KI pigs exhibited distinct lipidomic profiles, as the mild lipid alteration was observed in backfat of UCP1 knock-in pigs. Inguinal WAT from UCP1-KI pigs contained significantly decreased total triacylglycerol (p < 0.05), together with the downregulation of genes involved in fatty acid metabolism, suggesting the decreased lipogenesis in iWAT of UCP1-KI pigs. Significantly increased levels of total sphingolipids (p<0.05) were also observed in iWAT from UCP1-KI pigs. Notably, two mitochondrial-specific lipid species, cardiolipin CL72:8 (18:2) and CL74:9 (18:2), were found to be dramatically increased in iWAT from UCP1-KI pigs, suggesting enhanced mitochondrial function. This observation was further supported by the significant upregulation of numerous mitochondrial-related genes and significantly increased number of large mitochondria and mitochondrial cristae in iWAT of UCP1-KI pigs. Taken together, these data illustrate the specific role of UCP1 in lipid metabolism of fat tissues in pigs and provide new data for characterization of fat traits in UCP1-KI pigs.

Genome-wide detection of copy number variation in Chinese indigenous sheep using an ovine high-density 600 K SNP array.

Copy number variants (CNVs) represent a form of genomic structural variation underlying phenotypic diversity. In this study, we used the Illumina Ovine SNP 600 K BeadChip array for genome-wide detection of CNVs in 48 Chinese Tan sheep. A total of 1,296 CNV regions (CNVRs), ranging from 1.2 kb to 2.3 Mb in length, were detected, representing approximately 4.7% of the entire ovine genome (Oar_v3.1). We combined our findings with five existing CNVR reports to generate a composite genome-wide dataset of 4,321 CNVRs, which revealed 556 (43%) novel CNVRs. Subsequently, ten novel CNVRs were randomly chosen for further quantitative real-time PCR (qPCR) confirmation, and eight were successfully validated. Gene functional enrichment revealed that these CNVRs cluster into Gene Ontology (GO) categories of homeobox and embryonic skeletal system morphogenesis. One CNVR overlapping with the homeobox transcription factor DLX3 and previously shown to be associated with curly hair in sheep was identified as the candidate CNV for the special curly fleece phenotype in Tan sheep. We constructed a Chinese indigenous sheep genomic CNV map based on the Illumina Ovine SNP 600 K BeadChip array, providing an important addition to published sheep CNVs, which will be helpful for future investigations of the genomic structural variations underlying traits of interest in sheep.

Collaborative Tracking Control of Dual Linear Switched Reluctance Machines Over Communication Network With Time Delays.

This paper investigates the collaborative tracking control for dual linear switched reluctance machines (LSRMs) over a communication network with random time delays. Considering the spatio-temporal constraint relationship of the dual LSRMs in complex industrial processes, the collaborative tracking control scheme is proposed based on the networked motion control method. The stability conditions and the controller design method for the networked dual LSRMs are obtained from the two motors relative position error by using Lyapunov theory and delay systems approach. Four different allocation schemes combined with two kinds of external control signals are applied onto the collaborative tracking control experiment platform of the dual LSRMs to validate the effectiveness of the proposed method. The maximum steady-state relative position error within 0.104 mm can be achieved under the constant absolute position reference input signal of 3 mm, and the maximum absolute relative position error within ±0.46 mm can be achieved under the sinusoidal reference of 8 mm amplitude and 0.2 Hz.