Protein Lactylation Profiles Provide Insights into Molecular Mechanisms Underlying Metabolism in Yak.

Protein lysine lactylation, a recently discovered post-translational modification (PTM), is prevalent across tissues and cells of diverse species, serving as a regulator of glycolytic flux and biological metabolism. The yak (Bos grunniens), a species that has inhabited the Qinghai-Tibetan Plateau for millennia, has evolved intricate adaptive mechanisms to cope with the region's unique geographical and climatic conditions, exhibiting remarkable energy utilization and metabolic efficiency. Nonetheless, the specific landscape of lysine lactylation in yaks remains poorly understood. Herein, we present the first comprehensive lactylome profile of the yak, effectively identifying 421, 308, and 650 lactylated proteins in the heart, muscles, and liver, respectively. These lactylated proteins are involved in glycolysis/gluconeogenesis, the tricarboxylic acid cycle, oxidative phosphorylation, and metabolic process encompassing carbohydrates, lipids, and proteins during both anaerobic and aerobic glucose bio-oxidation, implying their crucial role in material and energy metabolism, as well as in maintaining homeostasis in yaks.

Facet-dependent transformation and toxicity of nanoscale zinc oxide in the synthetic saliva.

The nanoscale zinc oxide (n-ZnO) was used in food packages due to its superior antibacterial activity, resulting in potential intake of n-ZnO through the digestive system, wherein n-ZnO interacted with saliva. In recent, facet engineering, a technique for controlling the exposed facets, was applied to n-ZnO, whereas risk of n-ZnO with specific exposed facets in saliva was ignored. ZnO nanoflakes (ZnO-0001) and nanoneedles (ZnO-1010) with the primary exposed facets of {0001} and {1010} respectively were prepared in this study, investigating stability and toxicity of ZnO-0001 and ZnO-1010 in synthetic saliva. Both ZnO-0001 and ZnO-1010 partially transformed into amorphous Zn3(PO4)2 within 1 hr in the saliva even containing orgnaic components, forming a ZnO-Zn3(PO4)2 core-shell structure. Nevertheless, ZnO-1010 relative to ZnO-0001 would likely transform into Zn3(PO4)2, being attributed to superior dissolution of {1010} facet due to its lower vacancy formation energy (1.15 eV) than {0001} facet (3.90 eV). The toxicity of n-ZnO to Caco-2 cells was also dependent on the primary exposed facet; ZnO-0001 caused cell toxicity through oxidative stress, whereas ZnO-1010 resulted in lower cells viability than ZnO-0001 through oxidative stress and membrane damage. Density functional theory calculations illustrated that ·O2- was formed and released on {1010} facet, yet O22- instead of ·O2- was generated on {0001} facet, leading to low oxidative stress from ZnO-0001. All findings demonstrated that stability and toxicity of n-ZnO were dependent on the primary exposed facet, improving our understanding of health risk of nanomaterials.

Prevalence and risk factors of suicide attempts in young, first-episode and drug-naïve Chinese Han outpatients with psychotic major depressive disorder.

This study investigates the relationship between psychotic symptoms and suicide attempts in young first-episode, drug-naive Chinese Han outpatients diagnosed with Major Depressive Disorder (MDD). The prevalence of Psychotic Major Depressive Disorder (PMD) was found to be 8.3% among the enrolled MDD patients. The study assessed 1289 participants using various scales to evaluate the severity of clinical symptoms, including the CGI-S, the HAMD, the HAMA, and the PANSS positive subscale. Additionally, thyroid hormone and glucolipid metabolism indicators were examined. The findings indicate that among patients with PMD, 41.12% had recent suicide attempts, while 6.54% had previous suicide attempts. Patients who recently attempted suicide exhibited higher scores on the HAMA and CGI scales, along with elevated serum levels of Thyroid-Stimulating Hormone (TSH) and total cholesterol (TC), as well as higher systolic and diastolic blood pressure. Notably, TSH levels independently correlated with recent suicide attempts in PMD patients, with an impressive area under the receiver operating characteristic curve (AUROC) of 0.923. Furthermore, the subgroup of patients with previous suicide attempts displayed longer illness duration and higher HAMD scores. Duration of illness and HAMD were found to be independently associated with previous suicide attempts among PMD patients, with a combined predictive effect showing a robust AUROC of 0.910. In conclusion, this study highlights the significant prevalence of recent and previous suicide attempts among young Chinese Han outpatients with PMD. The identification of risk factors, especially the link between TSH levels and recent suicide attempts, offers valuable insights for clinicians to develop targeted interventions and preventive strategies for this vulnerable patient population.

Epigenomics Analysis of the Suppression Role of SIRT1 via H3K9 Deacetylation in Preadipocyte Differentiation.

Sirtuin 1 (SIRT1) overexpression significantly inhibits lipid deposition during yak intramuscular preadipocyte (YIMA) differentiation; however, the regulatory mechanism remains unknown. We elucidated the role of SIRT1 in YIMA differentiation using lentivirus-mediated downregulation technology and conducted mRNA-seq and ChIP-seq assays using H3K9ac antibodies after SIRT1 overexpression in order to reveal SIRT1 targets during YIMA adipogenesis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed in order to identify the functional annotation of common genes. In addition, a potential target of SIRT1 was selected to verify its effects on the differentiation and proliferation of YIMAs. SIRT1 interfered with lipid deposition and promoted YIMA differentiation. In total, 143,518 specific peaks were identified after SIRT1 overexpression, where genes associated with downregulation peaks were enriched in transcription, gene expression, lipid-related processes, and classical lipid-related pathways. The H3K9ac signal in the whole genome promoter region (2 kb upstream and downstream of the transcription start site (TSS)) was weakened, and the peaks were distributed across all gene functional regions. Genes that lost signals in their TSS region or gene body region were enriched in both biological processes and pathways associated with lipogenesis. The ChIP-seq results revealed 714 common differential genes in mRNA-seq, which were enriched in "MAPK signaling", "lipid and atherosclerosis", "mTOR signaling", and "FoxO signaling" pathways. A total of 445 genes were downregulated in both their H3K9ac signals and mRNA expression, and one of their most significantly enriched pathways was FoxO signaling. Nine genes (FBP2, FPGT, HSD17B11, KCNJ15, MAP3K20, SLC5A3, TRIM23, ZCCHC10, and ZMYM1) lost the H3K9ac signal in their TSS regions and had low mRNA expression, and three genes (KCNJ15, TGM3, and TRIM54) had low expression but lost their H3K9ac signal in the gene body region. The interference of TRIM23 significantly inhibited fat deposition during preadipocyte differentiation and promoted cell proliferation by increasing S-phase cell numbers. The present study provides new insights into the molecular mechanism of intramuscular fat content deposition and the epigenetic role of SIRT1 in adipocyte differentiation.

Optimized core-shell lanthanide nanoparticles with ultrabright Ce3+-modulated second near-infrared emission for "lighting" plants.

Second near-infrared (NIR-II, 1000-1700 nm) photon-mediated fluorescence imaging has attracted extensive interest in the field of bioimaging. However, NIR-II fluorescent nanoprobes competent for plant imaging have been rarely developed. Herein, lanthanide-doped nanoparticle (LDNP) optimal core-shell structure and ultrabright NIR-II emission were developed for "lighting" plants. The Ce3+-doped active shell coated on the NaErF4:Tm core enables dual-mode red upconversion (UC) and NIR-II downconversion (DC) emission of LDNPs upon 980 nm laser excitation. Under the optimized doping content, the intensities of red UC and NIR-II DC emission were respectively boosted by 5- and 19-fold those of the core nanoparticles, which endowed LDNPs with ideal NIR-II emissive capabilities for optical imaging of plants. Significantly, the NIR-II fluorescent signal affords much higher signal-to-noise rate than the red UC. LDNPs were modified with polyethyleneimine to enable outstanding hydrophilicty and facilitate their uptake by plants. Arabidopsis thaliana and Nicotiana benthamiana were chosen as plant models for NIR-II imaging studies. The toxic effect of LDNPs after being transported into Brassica rapa chinensis was systematically studied on mice. The NIR-II imaging strategy offers a promising method for studying the uptake and transport of nanoparticles in plants.

Transcriptional and open chromatin analysis of bovine skeletal muscle development by single-cell sequencing.

Skeletal muscle is a complex heterogeneous tissue and characterizing its cellular heterogeneity and transcriptional and epigenetic signatures are important for understanding the details of its ontogeny. In our study, we applied scRNA-seq and scATAC-seq to investigate the cell types, molecular features, transcriptional and epigenetic regulation, and patterns of developing bovine skeletal muscle from gestational, lactational and adult stages. Detailed molecular analyses were used to dissect cellular heterogeneity, and we deduced the differentiation trajectory of myogenic cells and uncovered their dynamic gene expression profiles. SCENIC analysis was performed to demonstrate key regulons during cell fate decisions. We explored the future expression states of these heterogeneous cells by RNA velocity analysis and found extensive networks of intercellular communication using the toolkit CellChat. Moreover, the transcriptomic and chromatin accessibility modalities were confirmed to be highly concordant, and integrative analysis of chromatin accessibility and gene expression revealed key transcriptional regulators acting during myogenesis. In bovine skeletal muscle, by scRNA-seq and scATAC-seq analysis, different cell types such as adipocytes, endothelial cells, fibroblasts, lymphocytes, monocytes, pericyte cells and eight skeletal myogenic subpopulations were identified at the three developmental stages. The pseudotime trajectory exhibited a distinct sequential ordering for these myogenic subpopulations and eight distinct gene clusters were observed according to their expression pattern. Moreover, specifically expressed TFs (such as MSC, MYF5, MYOD1, FOXP3, ESRRA, BACH1, SIX2 and ATF4) associated with muscle development were predicted, and likely future transcriptional states of individual cells and the developmental dynamics of differentiation among neighbouring cells were predicted. CellChat analysis on the scRNA-seq data set then classified many ligand-receptor pairs among these cell clusters, which were further categorized into significant signalling pathways, including BMP, IGF, WNT, MSTN, ANGPTL, TGFB, TNF, VEGF and FGF. Finally, scRNA-seq and scATAC-seq results were successfully integrated to reveal a series of specifically expressed TFs that are likely to be candidates for the promotion of cell fate transition during bovine skeletal muscle development. Overall, our results outline a single-cell dynamic chromatin/transcriptional landscape for normal bovine skeletal muscle development; these provide an important resource for understanding the structure and function of mammalian skeletal muscle, which will promote research into its biology.

Diversified land conversion deepens understanding of impacts of rapid rubber plantation expansion on plant diversity in the tropics.

Understanding the status and changes of plant diversity in rubber (Hevea brasiliensis) plantations is essential for sustainable plantation management in the context of rapid rubber expansion in the tropics, but remains very limited at the continental scale. In this study, we investigated plant diversity from 10-meter quadrats in 240 different rubber plantations in the six countries of the Great Mekong Subregion (GMS)-where nearly half of the world's rubber plantations are located-and analyzed the influence of original land cover types and stand age on plant diversity using Landsat and Sentinel-2 satellite imagery since the late 1980s. The results indicate that the average plant species richness of rubber plantations is 28.69 ± 7.35 (1061 species in total, of which 11.22 % are invasive), approximating half the species richness of tropical forests but roughly double that of the intensively managed croplands. Time-series satellite imagery analysis revealed that rubber plantations were primarily established in place of cropland (RPC, 37.72 %), old rubber plantations (RPORP, 27.63 %), and tropical forests (RPTF, 24.12 %). Plant species richness in RPTF (34.02 ± 7.62) was significantly (p < 0.001) higher than that in RPORP (26.41 ± 7.02) and RPC (26.34 ± 5.37). More importantly, species richness can be maintained for the duration of the 30-year economic cycle, and the number of invasive species decreases as the stand ages. Given diverse land conversions and changes in stand age, the total loss of species richness due to rapid rubber expansion in the GMS was 7.29 %, which is far below the traditional estimates that only consider tropical forest conversion. In general, maintaining higher species richness at the earliest stages of cultivation has significant implications for biodiversity conservation in rubber plantations.

Single-cell transcriptome analysis and in vitro differentiation of testicular cells reveal novel insights into male sterility of the interspecific hybrid cattle-yak.

BACKGROUND: Interspecific hybridization plays vital roles in enriching animal diversity, while male hybrid sterility (MHS) of the offspring commonly suffered from spermatogenic arrest constitutes the postzygotic reproductive isolation. Cattle-yak, the hybrid offspring of cattle (Bos taurus) and yak (Bos grunniens) can serve as an ideal MHS animal model. Although meiotic arrest was found to contribute to MHS of cattle-yak, yet the cellular characteristics and developmental potentials of male germline cell in pubertal cattle-yak remain to be systematically investigated. RESULTS: Single-cell RNA-seq analysis of germline and niche cell types in pubertal testis of cattle-yak and yak indicated that dynamic gene expression of developmental germ cells was terminated at late primary spermatocyte (meiotic arrest) and abnormal components of niche cell in pubertal cattle-yak. Further in vitro proliferation and differentially expressed gene (DEG) analysis of specific type of cells revealed that undifferentiated spermatogonia of cattle-yak exhibited defects in viability and proliferation/differentiation potentials. CONCLUSION: Comparative scRNA-seq and in vitro proliferation analysis of testicular cells indicated that not only meiotic arrest contributed to MHS of cattle-yak. Spermatogenic arrest of cattle-yak may originate from the differentiation stage of undifferentiated spermatogonia and niche cells of cattle-yak may provide an adverse microenvironment for spermatogenesis.

Modeling the resistive viscoelasticity of conductive polymer composites for sensor usage.

With the development of fully printed electronics, soft sensors are in demand in various fields, such as wearable electronics, soft machines, etc. Most soft resistive sensors are made of conductive elements dispersed in a viscoelastic polymer binder, exhibiting resistive viscoelastic behavior. The resistance of soft resistive sensors is time-dependent due to the viscoelastic response of polymer binder and structural rearrangement of the conductive pathway. In this paper, experiments and theoretical modeling are used to study the resistive viscoelastic behavior of printed silver wires. The printed silver wire belongs to conductive polymer composites (CPCs) consisting of conductive silver-nanoparticle pathways in an elastic polymer binder. Based on tunneling theory, a multi-branch model is developed to capture the resistance variation of the printed silver wire under mechanical loading. Our experiment-validated model uses only a single set of parameters to predict the resistive relaxation behaviors of CPCs under different strain and different loading rates. Moreover, we demonstrated this numerical model could describe the resistance response under complex loading conditions, such as cyclic loading, similar to the sensor's working condition. The multi-branch model can be extended to any other soft resistive sensor, such as a strain sensor, and provide a new avenue to calibrate these soft sensors.

Functional study and epigenetic targets analyses of SIRT1 in intramuscular preadipocytes via ChIP-seq and mRNA-seq.

The SIRT1 epigenetic regulator is involved in hepatic lipid homoeostasis. However, the role of SIRT1 in regulating intramuscular fat deposition as well as the pathways and potential epigenetic targets involved remain unknown. Herein, we investigate SIRT1 function, its genome-wide epigenetic target profile, and transcriptomic changes under SIRT1 overexpression during yak intramuscular preadipocytes differentiation. To this end, we analysed the relationship between SIRT1 and intramuscular fat content as well as lipid metabolism-related genes in longissimus dorsi tissue. We found that SIRT1 expression negatively correlates with intramuscular fat content as well as with the expression of genes related to lipid synthesis, while positively correlating with that of fatty acid oxidation-involved genes. SIRT1 overexpression in intramuscular preadipocytes significantly reduced adipose differentiation marker expression, intracellular triacylglycerol content, and lipid deposition. Chromatin immunoprecipitation coupled with high-throughput sequencing of H3K4ac (a known direct target of SIRT1) and high-throughput mRNA sequencing results revealed that SIRT1 may regulate intramuscular fat deposition via three potential new transcription factors (NRF1, NKX3.1, and EGR1) and four genes (MAPK1, RXRA, AGPAT1, and HADH) implicated in protein processing within the endoplasmic reticulum pathway and the MAPK signalling pathway in yaks. Our study provides novel insights into the role of SIRT1 in regulating yak intramuscular fat deposition and may help clarify the mechanistic determinants of yak meat characteristics.

DNA methylome of primary spermatocyte reveals epigenetic dysregulation associated with male sterility of cattleyak.

DNA cytosine methylation modification in the germline is of particular importance since it is a highly heritable epigenetic mark. Although cytosine methylation has been analyzed at the genome-scale for several mammalian species, our knowledge of DNA methylation patterns and the mechanisms underlying male hybrid sterility is still limited in domestic animals such as cattleyak. Here we for the first time show the genome-wide and single-base resolution landscape of methylcytosines (mC) in the primary spermatocyte (PSC) genome of yak with normal spermatogenesis and the inter-specific hybrid cattleyak with male infertility. A comparative investigation revealed that widespread differences are observed in the composition and patterning of DNA cytosine methylation between the two methylomes. Global CG or non-CG DNA methylation levels, as well as the number of mC sites, are increased in cattleyak compared to yak. Notably, the DNA methylome in cattleyak PSC exhibits promoter hypermethylation of meiosis-specific genes and piRNA pathway genes with respect to yak. Furthermore, major retrotransposonson classes are predominantly hypermethylated in cattleyak while those are fully hypomethylated in yak. KEGG pathway enrichment indicates Rap1 signaling and MAPK pathways may play potential roles in the spermatogenic arrest of cattleyak. Our present study not only provides valuable insights into distinct features of the cattleyak PSC methylome but also paves the way toward elucidating the complex, yet highly coordinated epigenetic modification during male germline development for inter-specific hybrid animals.

Emotion Context Insensitivity is generalized in individuals with major depressive disorder but not in those with subclinical depression.

BACKGROUND: Depressed individuals experience deficits in emotional reactivity. One well-established theory is the Emotion Context Insensitivity (ECI) theory. To better understand impairments in emotional reactivity, we investigated whether the ECI theory is applicable to anticipatory, consummatory, and remembered affect, in both clinical and subclinical depression. METHODS: Participants were divided into four groups: Major Depressive Disorder Group (MDD, N = 60), Control Group for MDD (ControlMDD, N = 50), Subclinical Depression Group (SD, N = 56), and Control Group for SD (ControlSD, N = 56). The Hamilton Depression Rating Scale and the Beck Depression Inventory were used to assess the severity of depression and anhedonia symptoms. The Monetary Incentive Delay Task evaluated participants' affective responses towards monetary stimuli. RESULTS: The MDD group was more insensitive to both monetary reward and loss across most types of affect than was the control group. Compared with the controls, the SD group exhibited lower reactivity in anticipatory positive affect but enhanced reactivity in consummatory positive, anticipatory, and remembered negative affect. LIMITATIONS: Emotional affect was evaluated by subjective ratings, which may lack objectivity. Additionally, laboratory settings and monetary rewards used in this study may cause the results less generalized to daily life and to other types of rewards. CONCLUSION: The pattern of emotional reactivity in the MDD group was partly consistent with the ECI theory, whereas the SD group showed greater arousal and instability of emotional reactions. These different patterns could facilitate the understanding of emotional reactivity and develop further treatments across the course of depression.

Tumor-responsive nanomedicine based on Ce3+-modulated up-/downconversion dual-mode emission for NIR-II imaging-guided dynamic therapy.

Chemodynamic therapy (CDT) and photodynamic therapy (PDT) based on intratumoral generation of reactive oxygen species (ROS) have been playing crucial roles in conquering tumors. However, the above therapeutic methods are still constrained by the overexpressed tumor glutathione (GSH) and intrinsic tumor resistance to conventional organic photosensitizers. Herein, lanthanide-doped nanoparticles (LDNPs) were coated with inorganic bimetallic copper and manganese silicate nanospheres (CMSNs) and modified with sodium alginate (SA) for second near-infrared (NIR-II, 1000-1700 nm) imaging-guided CDT and PDT. Interestingly, cross-relaxation (CR) pathways between Ce3+ and Ho3+ and CR between Ce3+ and Er3+ are fully exploited to enable dual-mode upconversion (UC) and NIR-II downconversion (DC) emissions of LDNPs under 980 nm laser excitation. UC emission can induce CMSNs to produce toxic singlet oxygen (1O2) for PDT, and the released Mn2+ and Cu+ ions caused by GSH-induced degradation of CMSNs can react with endogenous H2O2 to produce hydroxyl radical (˙OH) for CDT. Significantly, the ultrabright NIR-II DC emission endows the systems with exceptional optical imaging capabilities. All results affirm the potency of such an "all in one" theranostic nanomedicine integrating PDT, CDT and remarkable NIR-II imaging abilities accompanied by the function of modulating tumor microenvironment in cancer theranostics.

Learning Ability and Hippocampal Transcriptome Responses to Early and Later Life Environmental Complexities in Dual-Purpose Chicks.

In this study, we hypothesized that complex early-life environments enhance the learning ability and the hippocampal plasticity when the individual is faced with future life challenges. Chicks were divided into a barren environment group (BG), a litter materials group (LG), and a perches and litter materials group (PLG) until 31 days of age, and then their learning abilities were tested following further rearing in barren environments for 22 days. In response to the future life challenge, the learning ability showed no differences among the three groups. In the hippocampal KEGG pathways, the LG chicks showed the downregulation of neural-related genes neuronal growth regulator 1 (NEGR1) and neurexins (NRXN1) in the cell adhesion molecules pathway compared to the BG (p < 0.05). Immune-related genes TLR2 in Malaria and Legionellosis and IL-18 and IL18R1 in the TNF signaling pathway were upregulated in the LG compared to in the BG (p < 0.05). Compared to the BG, the PLG displayed upregulated TLR2A in Malaria (p < 0.05). The PLG showed upregulated neural-related gene, i.e., neuronal acetylcholine receptor subunit alpha-7-like (CHRNA8) in the nicotine addiction pathway and secretagogin (SCGN) gene expression, as compared to the LG (p < 0.05). In conclusion, early-life environmental complexities had limited effects on the learning ability in response to a future life challenge. Early-life perches and litter materials can improve neural- and immune-related gene expression and functional pathways in the hippocampus of chicks.

Influence of salinity on the heterogeneous catalytic ozonation process: Implications to treatment of high salinity wastewater.

The heterogeneous catalytic ozonation process is a promising treatment option for high salinity reverse osmosis concentrate (ROC) however the influence of salts on the catalyst performance is not well understood. In this work, we investigate the effect of salts on the performance of the catalytic ozonation process for treatment of synthetic ROC using a commercially available Fe-loaded Al2O3 catalyst. Our results show that the presence of salts influences the rate and extent of degradation of organic compounds present in the synthetic ROC when subjected to the heterogeneous catalytic ozonation process. Scavenging of aqueous O3 by chloride ions and/or transformation of organics (particularly humics) to more hydrophobic form as a result of charge shielding between adjacent functional groups and/or intramolecular binding by cations inhibits the bulk oxidation of organics to a measurable extent. While the scavenging of aqueous hydroxyl radicals at the salt concentrations investigated here was minimal, the accumulation of chloride ions in the electric double layer near the catalyst surface, particularly when pH< pHpzc, results in more significant scavenging of surface associated hydroxyl radicals. Overall, the presence of salts (particularly chloride ions) has a significant influence on the performance of both conventional and catalytic ozonation processes with some scope to mitigate this effect through appropriate choice of catalyst.

Comparative transcriptome analysis of winter yaks in plateau and plain.

The yak is an important source for the people living and ecological environment in the Qinghai-Tibet Plateau. In every winter, many domestic yaks will lose bodyweight or dead under cold and food scarcity. Moving the plateau yaks to farm in the plain is a useful approach to reduce their environmental stress and gain more production. In this study, we measured growth, slaughter and beef quality traits every month and sequenced mRNA expression levels of muscles of two groups yaks living in plateau and plain respectively. We found there is significant difference (p-value <0.01) in the third (60 days), fourth (90 days), fifth (120 days) and sixth (150 days) weights between subpopulations in the plateau and plain. We identified 540 different expressed genes (DEGs) including 123 known genes and 417 unknown genes. Using the weighted correlation network analysis (WGCNA) to build a co-express network, the modules were strong relative to weight traits. The findings highlighted the underlying way and a relative network to yield a new view about gene expression between the yaks living plateau and plain.

Genome-Wide DNA Methylation and Hydroxymethylation Changes Revealed Epigenetic Regulation of Neuromodulation and Myelination in Yak Hypothalamus.

Both 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) are important epigenetic modifications in neurodevelopment. However, there is little research examining the genome-wide patterns of 5mC and 5hmC in brain regions of animals under natural high-altitude conditions. We used oxidative reduced representation bisulfite sequencing (oxRRBS) to determine the 5mC and 5hmC sites in the brain, brainstem, cerebellum, and hypothalamus of yak and cattle. We reported the first map of genome-wide DNA methylation and hydroxymethylation in the brain, brainstem, cerebellum, and hypothalamus of yak (living at high altitudes) and cattle. Overall, we found striking differences in 5mC and 5hmC between the hypothalamus and other brain regions in both yak and cattle. Genome-wide profiling revealed that 5mC level decreased and 5hmC level increased in the hypothalamus than in other regions. Furthermore, we identified differentially methylated regions (DMRs) and differentially hydroxymethylated regions (DhMRs), most of which overlapped with each other. Interestingly, transcriptome results for these brain regions also showed distinctive gene levels in the hypothalamus. Finally, differentially expressed genes (DEGs) regulated by DMRs and DhMRs may play important roles in neuromodulation and myelination. Overall, our results suggested that mediation of 5mC and 5hmC on epigenetic regulation may broadly impact the development of hypothalamus and its biological functions.

Whole-Transcriptome Analysis of Yak and Cattle Heart Tissues Reveals Regulatory Pathways Associated With High-Altitude Adaptation.

BACKGROUND: The yak (Bos grunniens) is an important livestock species that can survive the extremely cold, harsh, and oxygen-poor conditions of the Qinghai-Tibetan Plateau and provide meat, milk, and transportation for the Tibetans living there. However, the regulatory network that drive this hypoxic adaptation remain elusive. RESULTS: The heart tissues from LeiRoqi (LWQY) yak and their related cattle (Bos Taurus) breeds, which are two native cattle breeds located in high altitude (HAC) and low altitude (LAC) regions, respectively, were collected for RNA sequencing. A total of 178 co-differentially expressed protein-coding transcripts (co-DETs) were discovered in each of the LAC-vs-LWQY and LAC-vs-HAC comparison groups, including NFATC2, NFATC1, ENPP2, ACSL4, BAD, and many other genes whose functions were reported to be associated with the immune-system, endocrine-system, and lipid metabolism. Two and 230 lncRNA transcripts were differentially expressed in the LAC-vs-LWQY and LAC-vs-HAC comparisons' respectively, but no lncRNA transcripts that were co-differentially expressed. Among the 58 miRNAs that were co-differentially expressed, 18 were up-regulated and 40 were down-regulated. In addition, 640 (501 up-regulated and 139 down-regulated) and 152 (152 up-regulated and one down-regulated) circRNAs showed differential expression in LAC-vs-LWQY and LAC-vs-HAC comparison groups, respectively, and 53 up-regulated co-differentially expressed circRNAs were shared. Multiple co-DETs, which are the targets of miRNAs/lncRNAs, are significantly enriched in high-altitude adaptation related processes, such as, T cell receptor signaling, VEGF signaling, and cAMP signaling. A competing endogenous RNA (ceRNA) network was constructed by integrating the competing relationships among co-differentially expressed mRNAs, miRNAs, lncRNAs and circRNAs. Furthermore, the hypoxic adaptation related ceRNA network was constructed, and the six mRNAs (MAPKAPK3, PXN, NFATC2, ATP7A, DIAPH1, and F2R), the eight miRNAs (including miR-195), and 15 circRNAs (including novel-circ-017096 and novel-circ-018073) are proposed as novel and promising candidates for regulation of hypoxic adaptation in the heart. CONCLUSION: In conclusion, the data recorded in the present study provides new insights into the molecular network of high-altitude adaptation along with more detailed information of protein-coding transcripts and non-coding transcripts involved in this physiological process, the detailed mechanisms behind how these transcripts "crosstalk" with each other during the plateau adaptation are worthy of future research efforts.

A study of the correlation between M2 macrophages and lymph node metastasis of colorectal carcinoma.

BACKGROUND: Lymph node metastasis is a major prognostic sign of colorectal carcinoma and an important indicator for individualized treatment. M2 macrophages play a key role in carcinogenesis and tumor development by enhancing invasiveness and promoting lymph node metastasis. The purpose of this study was to investigate the effect of CD163-positive M2 macrophages on lymph node metastasis in colorectal carcinoma. METHODS: Postoperative lymph node tissues were obtained from 120 patients with colorectal carcinoma who underwent radical surgery in the First Affiliated Hospital of Jinzhou Medical University between December 2019 and May 2020. We detected the expression of the CD163 protein in lymph nodes using immunohistochemistry. Furthermore, the relationships between M2 macrophages identified by expression of CD163 and lymph node metastasis were analyzed using the independent sample t-test and Chi-square test. RESULTS: M2 macrophages were increased in metastatic lymph nodes and non-metastatic lymph nodes adjacent to the cancer. The M2 macrophage count was higher in patients with macro-metastases than in patients with micro-metastases. CONCLUSIONS: The presence of M2 macrophages represents an important indicator for lymph node metastasis in colorectal carcinoma and may be a potential marker for its prediction. Thus, M2 macrophage localization might offer a new target for the comprehensive treatment of colorectal carcinoma.

Removal of roosters alters the domestic phenotype and microbial and genetic profile of hens.

Hens are raised apart from roosters in modern poultry production, a substantial change from their natural social structure. We compared productivity, injuries, behavior, physiology, microbiome and transcriptome of hens housed with (R+) or without (R-) roosters to quantify the effects of this change in social structure. Hens were raised free-range from 70 to 280 days when 30 birds per treatment were assigned to battery cages until Day 315 (R+C vs. R-C), while 30 birds per treatment remained in free-range pens (R+F vs. R-F). Response to a novel environment and object, behavioral time budgets, cecum microbiome, blood composition and transcriptomic sequencing of thigh muscle and spleen were analyzed. Hens housed without roosters showed better survival, consumed less food, produced more eggs and had better feed conversion. R+F hens clustered around the rooster and were less mobile in the novel environment and object tests. R+F hens displayed the richest microbiome, and the presence of roosters resulted in differentially expressed genes related to muscle development, cellular processes, environmental information processing and immune function. Removing roosters from housed hens intensified desirable characteristics favored by domestication probably operating by deprivation of mating behavior and reduced fear, along with altered microbial and genetic function.