25-hydroxycholesterol promotes proliferation and metastasis of lung adenocarcinoma cells by regulating ERß/TNFRSF17 axis.

Lung adenocarcinoma is the main type of lung cancer in women. Our previous findings have evidenced that 25-hydroxycholesterol (25-HC) promotes migration and invasion of lung adenocarcinoma cells (LAC), during which LXR as a 25-HC receptor plays an important role. Estrogen receptor beta (ERß) is a receptor of 27-hydroxycholesterol that is structurally analogous to 25-HC, but its role in the functional actions of 25-HC remained largely unknown. In this study, we demonstrated that 25-HC treatment triggered ERß expression in LAC. Knockdown of ERß inhibited 25-HC-mediated proliferation, migration and invasion, and reduced 25-HC-induced LAC metastasis in vivo. Further investigation revealed that ERß knockdown restrained the expression of TNFRSF17 (BCMA). In vivo experiments also confirmed that ERß knockdown blocked 25-HC-induced TNFRSF17 expression. TNFRSF17 knockdown also restrained 25-HC-induced proliferation, migration and invasion. Bioinformatic analysis showed that the levels of ERß and TNFRSF17 were elevated in lung adenocarcinoma, and were closely related to tumor stages and nodal metastasis status. These results suggested that 25-HC promoted the proliferation and metastasis of LAC by regulating ERß/TNFRSF17 axis.

Factors Influencing Time to First Medical Contact in Patients with Acute ST-Segment Elevation Myocardial Infarction: A Retrospective Analysis.

BACKGROUND Exploring the factors that impact the time from symptom onset to first medical contact (S2FMC) is crucial for improving outcomes in elderly patients diagnosed with acute ST-segment elevation myocardial infarction (STEMI). This study conducted a retrospective analysis on 282 patients who underwent emergency percutaneous coronary intervention (PCI) or percutaneous transluminal coronary angioplasty (PTCA) in Guangzhou City District to identify significant factors affecting S2FMC. MATERIAL AND METHODS A retrospective analysis was conducted on 282 patients with STEMI who underwent emergency percutaneous coronary intervention (PCI). Descriptive statistics, univariate and multivariate Cox regression analyses were used to identify significant factors affecting S2FMC. Additionally, interactions between risk factors were examined using multivariate logistic regression and the structural equation model (SEM). RESULTS Age (HR=0.984, 95% CI: 0.975-0.993), nature of chest pain (HR=2.561, 95% CI: 1.900-3.458), admission mode (HR=1.805, 95% CI: 1.358-2.400), and vascular characteristics (HR=1.246, 95% CI: 1.069-1.451) were independent influencing factors for S2FMC. Persistent chest tightness/pain, EMS admission, and vascular characteristics (RCADL or LCADL) played a protective role in S2FMC. Among the influencing factors, vascular characteristics (OR=1.072, 95% CI: 1.008-1.141) had an independent effect on the nature of chest pain. Meanwhile, the nature of chest pain (OR=1.148, 95% CI: 1.015-1.298) was an independent influencing factor in the admission mode. CONCLUSIONS Patients with persistent chest tightness/pain, EMS admission, and vascular characteristics (RCADL or LCADL) experienced shorter S2FMC and higher compliance rate (S2FMC ≤180 min). At the same time, age and other vascular features played an inverse role. This study proposes enhancing follow-up and monitoring measures, and shows the consequences of intermittent chest pain should not be disregarded.

Targeted and untargeted metabolomics reveals meat quality in grazing yak during different phenology periods on the Qinghai-Tibetan Plateau.

Yak meat is more popular among consumers because of its high nutritional value, but little attention has been paid to its meat quality, which is affected by different phenology periods grass. We hypothesized that seasonal variations in grass composition influenced the ruminal bacteria community, and eventually affected the meat quality of yaks. This study aims to investigate the relationship of meat quality in grazing yak as well as the key rumen bacteria using targeted and untargeted metabolomics and 16S rRNA during different phenology periods. The main three altered metabolic pathways in grazing yak, including amino acids biosynthesis, glutathione metabolism, and fatty acids biosynthesis, were found in the grass period (GP) group compared to the regreen period (RP) and hay period (HP) groups. The GP group had higher concentrations of flavor amino acids (FAA), polyunsaturated fatty acids (PUFA), and a lower ratio of n-6/n-3 compared with the RP group. Correlation analysis results showed that Rikenellaceae_RC9_gut_group was positively correlated with fatty acids and lipid metabolites, which might be involved in lipid metabolism. Pediococcus had a positive correlation with biological peptides, which could be involved in the metabolism of bioactive compounds. In conclusion, grass in different phenology periods was associated with modified amino acids and fatty acids composition of yak meat as well as altered regulation of biological pathways, which was correlated with changes in rumen bacterial communities.

Low Pneumoperitoneum Pressure Reduces Gas Embolism During Laparoscopic Liver Resection: A Randomized Controlled Trial.

OBJECTIVE: To compare the effect of low and standard pneumoperitoneal pressure (PP) on the occurrence of gas embolism during laparoscopic liver resection (LLR). BACKGROUND: LLR has an increased risk of gas embolism. Although animal studies have shown that low PP reduces the occurrence of gas embolism, clinical evidence is lacking. METHODS: This parallel, dual-arm, double-blind, randomized controlled trial included 141 patients undergoing elective LLR. Patients were randomized into standard ("S," 15 mm Hg; n = 70) or low ("L," 10 mm Hg; n = 71) PP groups. Severe gas embolism (≥ grade 3, based on the Schmandra microbubble method) was detected using transesophageal echocardiography and recorded as the primary outcome. Intraoperative vital signs and postoperative recovery profiles were also evaluated. RESULTS: Fewer severe gas embolism cases (n = 29, 40.8% vs n = 47, 67.1%, P = 0.003), fewer abrupt decreases in end-tidal carbon dioxide partial pressure, shorter severe gas embolism duration, less peripheral oxygen saturation reduction, and fewer increases in heart rate and lactate during gas embolization episodes was found in group L than in group S. Moreover, a higher arterial partial pressure of oxygen and peripheral oxygen saturation were observed, and fewer fluids and vasoactive drugs were administered in group L than in group S. In both groups, the distensibility index of the inferior vena cava negatively correlated with central venous pressure throughout LLR, and a comparable quality of recovery was observed. CONCLUSIONS: Low PP reduced the incidence and duration of severe gas embolism and achieved steadier hemodynamics and vital signs during LLR. Therefore, a low PP strategy can be considered a valuable choice for the future LLR.

Integrative analysis identifies cancer cell-intrinsic RARRES1 as a predictor of prognosis and immune response in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with poor prognosis and limited treatment options. Although immune checkpoint inhibitors (ICIs) have been proven to improve outcomes in TNBC patients, the potential mechanisms and markers that determine the therapeutic response to ICIs remains uncertain. Revealing the relationship and interaction between cancer cells and tumor microenvironment (TME) could be helpful in predicting treatment efficacy and developing novel therapeutic agents. By analyzing single-cell RNA sequencing dataset, we comprehensively profiled cell types and subpopulations as well as identified their signatures in the TME of TNBC. We also proposed a method for quantitatively assessment of the TME immune profile and provided a framework for identifying cancer cell-intrinsic features associated with TME through integrated analysis. Using integrative analyses, RARRES1 was identified as a TME-associated gene, whose expression was positively correlated with prognosis and response to ICIs in TNBC. In conclusion, this study characterized the heterogeneity of cellular components in TME of TNBC patients, and brought new insights into the relationship between cancer cells and TME. In addition, RARRES1 was identified as a potential predictor of prognosis and response to ICIs in TNBC.

Effects of the alpine meadow in different phenological periods on rumen fermentation and gastrointestinal tract bacteria community in grazing yak on the Qinghai-Tibetan Plateau.

BACKGROUND: In this study, we investigated the effects of alpine meadow in different phenological periods on ruminal fermentation, serum biochemical indices, and gastrointestinal tract microbes in grazing yak on the Qinghai-Tibetan Plateau. A total of eighteen female freely grazing yaks with an average age of 3 years old and a body weight of 130 ± 19 kg were selected. According to the plant phenological periods, yaks were randomly allocated to one of three treatments: (1) regreen periods group (RP, n = 6); (2) grassy periods group (GP, n = 6); and (3) hay periods group (HP, n = 6). At the end of the experiment, the blood, rumen fluids, and rectal contents were collected to perform further analysis. RESULTS: The concentrations of total volatile fatty acid (TVFA), acetate, glucose (GLU), triglyceride (TG), cholesterol (CHO), high density lipoprotein (HDL), and low density lipoprotein (LDL) were higher in the GP group than in the HP group (P < 0.05). However, compared with the RP and GP groups, the HP group had higher concentrations of isobutyrate, isovalerate, valerate, and creatinine (CREA) (P < 0.05). The abundance of Prevotella in the rumen, and the abundances of Rikenellaceae_RC9_gut_group, Eubacterium_coprostanoligenes_group, and Prevotellaceae_UCG-004 in the gut were higher in the GP group compared with the HP group (P < 0.05). The HP had higher abundance of Eubacterium_coprostanoligenes_group in the rumen as well as the abundances of Romboutsia and Arthrobacter in the gut compared with the RP and GP groups (P < 0.05). CONCLUSIONS: Based on the results of rumen fermentation, serum biochemical, differential biomarkers, and function prediction, the carbohydrate digestion of grazing yak would be higher with the alpine meadow regreen and grassy due to the gastrointestinal tract microbes. However, the risk of microbe disorders and host inflammation in grazing yak were higher with the alpine meadow wither.

IUPHAR ECR review: The cGAS-STING pathway: Novel functions beyond innate immune and emerging therapeutic opportunities.

Stimulator of interferon genes (STING) is a crucial innate immune sensor responsible for distinguishing pathogens and cytosolic DNA, mediating innate immune signaling pathways to defend the host. Recent studies have revealed additional regulatory functions of STING beyond its innate immune-related activities, including the regulation of cellular metabolism, DNA repair, cellular senescence, autophagy and various cell deaths. These findings highlight the broader implications of STING in cellular physiology beyond its role in innate immunity. Currently, approximately 10 STING agonists have entered the clinical stage. Unlike inhibitors, which have a maximum inhibition limit, agonists have the potential for infinite amplification. STING signaling is a complex process that requires precise regulation of STING to ensure balanced immune responses and prevent detrimental autoinflammation. Recent research on the structural mechanism of STING autoinhibition and its negative regulation by adaptor protein complex 1 (AP-1) provides valuable insights into its different effects under physiological and pathological conditions, offering a new perspective for developing immune regulatory drugs. Herein, we present a comprehensive overview of the regulatory functions and molecular mechanisms of STING beyond innate immune regulation, along with updated details of its structural mechanisms. We discuss the implications of these complex regulations in various diseases, emphasizing the importance and feasibility of targeting the immunity-dependent or immunity-independent functions of STING. Moreover, we highlight the current trend in drug development and key points for clinical research, basic research, and translational research related to STING.

The characteristics and influencing factors of farmland soil microplastic in Hetao Irrigation District, China.

Microplastic pollution, a major global concern, has garnered increasing attention in agricultural ecosystem research. China's Hetao Irrigation District, vital for grain production in the Yellow River Basin, lacks sufficient research on microplastic pollution of agricultural soils. This study, based on a detailed background investigation and testing of 47 samples, is the first to elucidate the characteristics and potential influencing factors of microplastics in the Hetao Irrigation District. The abundance of microplastics in the farmland soil ranged from 1810 to 86331 items/kg, with 90% measuring below 180 µm and mainly in film and fragment forms. Predominant polymers were polyethylene (PE, 43.0%) and polyamide (PA, 27.8%). Key pollution influencers were identified as agricultural inputs, with low-density polyethylene (LDPE) being the most extensively used plastic type. The carbonyl index and hydroxyl indices of the detected LDPE microplastics ranged from 0.041 to 0.96 and 0.092 to 1.20, respectively. The study highlights the significance of mulching management and agronomic practices in shaping microplastic characteristics. Potential pollution sources include agricultural inputs, irrigation equipment, domestic waste, and tire wear. Proposed effective strategies include responsible plastic use, robust waste management, and irrigation system upgrades, establishing a foundation for future ecological risk assessments and effective management approaches in the Hetao Irrigation District. ENVIRONMENTAL IMPLICATION: The harmful substances studied in this paper are microplastics, which are widely distributed in the environment and have potential ecological risks. This study is the first to investigate the characteristics of microplastics in farmland soil within the Hetao Irrigation Area, a region that is of critical importance to agricultural production in the Yellow River Basin of China. The study provides comprehensive insights into the factors influencing the characteristics of microplastics and speculates on their sources. These findings offer a novel perspective on the assessment of microplastic contamination in the area and provide valuable recommendations for prevention and control measures.

Age at menopause is inversely related to the prevalence of common gynecologic cancers: a study based on NHANES.

Background: The fluctuation or even loss of estrogen level caused by menopause in women, and most gynecological cancers often occur before and after menopause, so the age of menopause may be related to the occurrence of gynecological cancer. Aim: To investigate whether the age at menopause is independently associated with the incidence of gynecological cancers and to analyze the possible influencing factors. Methods: We selected the NHANES public database to conduct the study, and by excluding relevant influencing factors, we finally included 5706 NHANES participants who had full data on age at menopause and the occurrence of gynecologic cancers to analyze the relationship between the amount of age at menopause and gynecologic cancers based on univariate or multifactorial logistic regression analysis. Further, the relationship between age at menopause and the prevalence of different gynecologic cancers was investigated, and changes in the prevalence of different gynecologic cancers by age at menopause subgroups were observed. Finally, other relevant factors affecting the prevalence of gynecologic cancers were further investigated by subgroup analysis as well as subcluster analysis. Results: Univariate logistic regression analysis between age at menopause and gynecologic tumor prevalence revealed a negative association between age at menopause and the prevalence of common gynecologic cancers ovarian and cervical cancer, and after adjusting for the effects of covariates, a higher risk of gynecologic tumors was found with statistically significant differences at earlier age at menopause. The regression results showed a negative association between age at menopause and gynecologic cancer prevalence in cervical and ovarian cancer patients (P<0.01,P<0.01). Cervical cancer (OR: 0.91, 95% CI: 0.87,0.94) and ovarian cancer (OR: 0.90, 95% CI: 0.86, 0.95) were more prevalent among those with younger age at menopause. Conclusion: Age at menopause is negatively associated with the prevalence of cervical and ovarian cancers, and the earlier the age at menopause, the greater the risk of developing gynecological cancers.

Evaluation of the Longissimus Thoracis et Lumborum Muscle Quality of Chaka and Tibetan Sheep and the Analysis of Possible Mechanisms Regulating Meat Quality.

This study aimed to comprehensively evaluate the characteristics in the longissimus thoracis et lumborum (LTL) muscle of Chaka (CK) sheep and Tibetan (TB) sheep, and transcriptomics-metabolomics association analysis was used to find the possible genes, differential metabolites, and significant differential metabolic pathways that lead to meat quality differences. Based on the researched results, the nutritional quality of meat, including the contents of ether extract (11.95% vs. 10.56%), unsaturated fatty acid (51.20% vs. 47.69%), and polyunsaturated fatty acid (5.71% vs. 3.97%), were better in TB sheep than in CK sheep, while the CK sheep has better muscle fiber characteristics, such as the total number (62 vs. 45) and muscle fiber density (1426.54 mm2 vs. 1158.77 mm2) and flavor. Omics research has shown that the key differential metabolites and metabolic pathways were dominated by amino acid metabolism, particularly the glutathione metabolism, taurine and hypotaurine metabolism, and lipid metabolism-related pathways, such as glycerophospholipid metabolism and the sphingolipid signaling pathway. The intermediate metabolite sn-Glycerol 3-phosphoethanolamine played a key role in determining sheep meat quality, which was regulated by GPAT2, PLPP2, AGPAT1, PNPLA2, and GPAT4 and correlated with meat color, texture, and flavor. Overall, these results will provide effective information and more evidence to support further exploration of valuable biomarkers of meat quality.

DjFARP Contributes to the Regeneration and Maintenance of the Brain through Activation of DjRac1 in Dugesia japonica.

FERM, RhoGEF, and Pleckstrin domain protein (FARP) mediated RhoGTPase pathways are involved in diverse biological processes, such as neuronal development and tumorigenesis. However, little is known about their role in neural regeneration. We uncovered for the first time that FARP-Rac1 signaling plays an important role in neural regeneration in Dugesia japonica, a planarian that possesses unparalleled regenerative capacities. The planarian FARP homolog DjFARP was primarily expressed in both intact and regenerating brain and pharynx tissue. Functional studies suggested that downregulation of DjFARP with dsRNA in Dugesia japonica led to smaller brain sizes, defects in brain lateral branches, and loss of cholinergic, GABAergic, and dopaminergic neurons in both intact and regenerating animals. Moreover, the Rho GTPase DjRac1 was shown to play a similar role in neural regeneration and maintenance. Rac1 activation assay showed that DjFARP acts as a guanine nucleotide exchange factor (GEF) for DjRac1. Together, these findings indicate that the brain defects seen in DjFARP knockdown animals may be attributable to DjRac1 inactivation. In conclusion, our study demonstrated that DjFARP-DjRac1 signaling was required for the maintenance and proper regeneration of the brain in Dugesia japonica.

A modified primary culture method of rat pulmonary vein smooth muscle cells.

BACKGROUND: Although the pressure of pulmonary vein increases before pulmonary artery in pulmonary hypertension due to left heart disease (PH-LHD), only a few studies have assessed pulmonary vein smooth muscle cells (PVSMCs) because of the lack of a simple and feasible isolation method. METHODS: In this study, we introduced a simple method to obtain PVSMCs. Primary pulmonary veins were removed by puncture needle cannula guidance. Then, PVSMCs were cultured by the tissue explant method and purified by the differential adhesion method. The cells were characterized by hematoxylin-eosin (HE) staining, immunohistochemistry, western blotting, and immunofluorescence to observe the morphology and verify the expression of alpha-smooth muscle actin (α-SMA). RESULTS: The HE staining results showed that the pulmonary vein media was thinner than the pulmonary artery, the intima and adventitia of the pulmonary vein were removed by this method, and the obtained cells with good activity exhibited morphological characteristics of smooth muscle cells. In addition, higher α-SMA expression was observed in the cells obtained by our isolation method than in the traditional method. CONCLUSION: This study established a simple and feasible method to isolate and culture PVSMCs that might facilitate the cytological experiments for PH-LHD.

Mitigation of greenhouse gas emissions and improved yield by plastic mulching in rice production.

Soil mulching technologies are effective practices which alleviate non-point source pollution and carbon emissions, while ensuring grain production security and increasing water productivity. However, the lack of comprehensive understanding of the impacts of mulching technologies on rice fields has hindered progress in global implementation due to the varying environments and application conditions under which they are implemented. This study conducted a meta-analysis based on 2412 groups of field experiment data from 313 studies to evaluate the effects of soil mulching methods on rice production, greenhouse gas (GHG) emissions and water use efficiency. The results show that plastic mulching, straw mulching and no mulching (PM, SM and NM) have reduced CH4 emissions (68.8 %, 61.4 % and 57.2 %), increased N2O emissions (84.8 %, 89.1 % and 96.6 %), reduced global warming potentials (50.7 %, 47.5 % and 46.8 %) and improved water use efficiency (50.2 %, 40.9 % and 34.0 %) compared with continuous flooding irrigation. However, PM increased rice yield (1.6 %), while SM and NM decreased yield (4.3 % and 9.2 %). Furthermore, analysis using random forest models revealed that rice yield, GHG emissions and WUE response to soil mulching were related to climate, soil properties, fertilizer and rice varieties. Our findings can guide the implementation of plastic mulching technology in priority areas, contribute to agricultural carbon neutrality and support the development of practical guidelines for farmers.

Rumen Microbiome Reveals the Differential Response of CO2 and CH4 Emissions of Yaks to Feeding Regimes on the Qinghai-Tibet Plateau.

Shifts in feeding regimes are important factors affecting greenhouse gas (GHG) emissions from livestock farming. However, the quantitative values and associated drivers of GHG emissions from yaks (Bos grunniens) following shifts in feeding regimes have yet to be fully described. In this study, we aimed to investigate CH4 and CO2 emissions differences of yaks under different feeding regimes and their potential microbial mechanisms. Using static breathing chamber and Picarro G2508 gas concentration analyzer, we measured the CO2 and CH4 emissions from yaks under traditional grazing (TG) and warm-grazing and cold-indoor feeding (WGCF) regimes. Microbial inventories from the ruminal fluid of the yaks were determined via Illumina 16S rRNA and ITS sequencing. Results showed that implementing the TG regime in yaks decreased their CO2 and CH4 emissions compared to the WGCF regime. The alpha diversity of ruminal archaeal community was higher in the TG regime than in the WGCF regime. The beta diversity showed that significant differences in the rumen microbial composition of the TG regime and the WGCF regime. Changes in the rumen microbiota of the yaks were driven by differences in dietary nutritional parameters. The relative abundances of the phyla Neocallimastigomycota and Euryarchaeota and the functional genera Prevotella, Ruminococcus, Orpinomyces, and Methanobrevibacter were significantly higher in the WGCF regime than in the TG regime. CO2 and CH4 emissions from yaks differed mainly because of the enrichment relationship of functional H2- and CO2-producing microorganisms, hydrogen-consuming microbiota, and hydrogenotrophic methanogenic microbiota. Our results provided a view that it is ecologically important to develop GHG emissions reduction strategies for yaks on the Qinghai-Tibet Plateau based on traditional grazing regime.

Comparative Analysis of the Composition of Fatty Acids and Metabolites between Black Tibetan and Chaka Sheep on the Qinghai-Tibet Plateau.

The objective of this study was to investigate and compare fatty acids and metabolites in the longissimus dorsi muscle between Black Tibetan and Chaka sheep grazing in a highly saline environment. A total of eight castrated sheep (14 months old) with similar body weights (25 ± 2.2 kg) were selected. The experimental treatments included Black Tibetan (BT) and Chaka sheep (CK) groups, and each group had four replications. The experiment lasted for 20 months. All sheep grazed in a highly saline environment for the whole experimental period and had free access to water. The results showed that the diameter (42.23 vs. 51.46 µm), perimeter (131.78 vs. 166.14 µm), and area of muscle fibers (1328.74 vs. 1998.64 µm2) were smaller in Chaka sheep than in Black Tibetan sheep. The ash content in the longissimus dorsi was lower in Chaka sheep than in Black Tibetan sheep (p = 0.010), and the contents of dry matter (DM), ether extract (EE), and crude protein (CP) in the longissimus dorsi showed no differences (p > 0.05). For fatty acids, the proportions of C10:0, C15:0, and tC18:1 in the longissimus dorsi were higher in Chaka sheep than in Black Tibetan sheep (p < 0.05). However, all other individual fatty acids were similar among treatments, including saturated fatty acids (SFAs), unsaturated fatty acids (UFAs), monounsaturated fatty acids (MUFAs), polyunsaturated fatty acids (PUFAs), and the ratios of n-6 PUFAs to n-3 PUFAs and PUFAs to SFAs (p > 0.05). A total of 65 biomarkers were identified between the two breeds of sheep. Among these metabolites, 40 metabolic biomarkers were upregulated in the CK group compared to the BT group, and 25 metabolites were downregulated. The main metabolites include 30 organic acids, 9 amino acids, 5 peptides, 4 amides, 3 adenosines, 2 amines, and other compounds. Based on KEGG analysis, eight pathways, namely, fatty acid biosynthesis, purine metabolism, the biosynthesis of unsaturated fatty acids, renin secretion, the regulation of lipolysis in adipocytes, neuroactive ligand−receptor interaction, the cGMP-PKG signaling pathway, and the cAMP signaling pathway, were identified as significantly different pathways. According to the results on fatty acids and metabolites, upregulated organic acid and fatty acid biosynthesis increased the meat quality of Chaka sheep.

Genome-wide analysis of CNVs in three populations of Tibetan sheep using whole-genome resequencing.

Copy number variation (CNV), an important source of genomic structural variation, can disturb genetic structure, dosage, regulation and expression, and is associated with phenotypic diversity and adaptation to local environments in mammals. In the present study, 24 resequencing datasets were used to characterize CNVs in three ecotypic populations of Tibetan sheep and assess CNVs related to domestication and adaptation in Qinghai-Tibetan Plateau. A total of 87,832 CNV events accounting for 0.3% of the sheep genome were detected. After merging the overlapping CNVs, 2777 CNV regions (CNVRs) were obtained, among which 1098 CNVRs were shared by the three populations. The average length of these CNVRs was more than 3 kb, and duplication events were more frequent than deletions. Functional analysis showed that the shared CNVRs were significantly enriched in 56 GO terms and 18 KEGG pathways that were mainly concerned with ABC transporters, olfactory transduction and oxygen transport. Moreover, 188 CNVRs overlapped with 97 quantitative trait loci (QTLs), such as growth and carcass QTLs, immunoglobulin QTLs, milk yield QTLs and fecal egg counts QTLs. PCDH15, APP and GRID2 overlapped with body weight QTLs. Furthermore, Vst analysis showed that RUNX1, LOC101104348, LOC105604082 and PAG11 were highly divergent between Highland-type Tibetan Sheep (HTS) and Valley-type Tibetan sheep (VTS), and RUNX1 and LOC101111988 were significantly differentiated between VTS and Oura-type Tibetan sheep (OTS). The duplication of RUNX1 may facilitate the hypoxia adaptation of OTS and HTS in Qinghai-Tibetan Plateau, which deserves further research in detail. In conclusion, for the first time, we represented the genome-wide distribution characteristics of CNVs in Tibetan sheep by resequencing, and provided a valuable genetic variation resource, which will facilitate the elucidation of the genetic basis underlying the distinct phenotypic traits and local adaptation of Tibetan sheep.

The Gut Microbiota Determines the High-Altitude Adaptability of Tibetan Wild Asses (Equus kiang) in Qinghai-Tibet Plateau.

It was acknowledged long ago that microorganisms have played critical roles in animal evolution. Tibetan wild asses (TWA, Equus kiang) are the only wild perissodactyls on the Qinghai-Tibet Plateau (QTP) and the first national protected animals; however, knowledge about the relationships between their gut microbiota and the host's adaptability remains poorly understood. Herein, 16S rRNA and meta-genomic sequencing approaches were employed to investigate the gut microbiota-host associations in TWA and were compared against those of the co-resident livestock of yak (Bos grunnies) and Tibetan sheep (Ovis aries). Results revealed that the gut microbiota of yak and Tibetan sheep underwent convergent evolution. By contrast, the intestinal microflora of TWA diverged in a direction enabling the host to subsist on sparse and low-quality forage. Meanwhile, high microbial diversity (Shannon and Chao1 indices), cellulolytic activity, and abundant indicator species such as Spirochaetes, Bacteroidetes, Prevotella_1, and Treponema_2 supported forage digestion and short-chain fatty acid production in the gut of TWA. Meanwhile, the enterotype identification analysis showed that TWA shifted their enterotype in response to low-quality forage for a better utilization of forage nitrogen and short-chain fatty acid production. Metagenomic analysis revealed that plant biomass degrading microbial consortia, genes, and enzymes like the cellulolytic strains (Prevotella ruminicola, Ruminococcus flavefaciens, Ruminococcus albus, Butyrivibrio fibrisolvens, and Ruminobacter amylophilus), as well as carbohydrate metabolism genes (GH43, GH3, GH31, GH5, and GH10) and enzymes (ß-glucosidase, xylanase, and ß-xylosidase, etc.) had a significantly higher enrichment in TWA. Our results indicate that gut microbiota can improve the adaptability of TWA through plant biomass degradation and energy maintenance by the functions of gut microbiota in the face of nutritional deficiencies and also provide a strong rationale for understanding the roles of gut microbiota in the adaptation of QTP wildlife when facing harsh feeding environments.

The Response of Ruminal Microbiota and Metabolites to Different Dietary Protein Levels in Tibetan Sheep on the Qinghai-Tibetan Plateau.

Ruminal microbiota and metabolites play crucial roles in animal health and productivity. Exploring the dynamic changes and interactions between microbial community composition and metabolites is important for understanding ruminal nutrition and metabolism. Tibetan sheep (Ovis aries) are an important livestock resource on the Qinghai-Tibetan Plateau (QTP), and the effects of various dietary protein levels on ruminal microbiota and metabolites are still unknown. The aim of this study was to investigate the response of ruminal microbiota and metabolites to different levels of dietary protein in Tibetan sheep. Three diets with different protein levels (low protein 10.1%, medium protein 12.1%, and high protein 14.1%) were fed to Tibetan sheep. 16S rRNA gene sequencing and gas chromatography coupled with time-of-flight mass spectrometry (GC-TOF-MS) were used to study the profile changes in each group of ruminal microbes and metabolites, as well as the potential interaction between them. The rumen microbiota in all groups was dominated by the phyla Bacteroidetes and Firmicutes regardless of the dietary protein level. At the genus level, Prevotella_1, Rikenellaceae_RC9_gut_group and Prevotellaceae_UCG-001 were dominant. Under the same forage-to-concentrate ratio condition, the difference in the dietary protein levels had no significant impact on the bacterial alpha diversity index and relative abundance of the major phyla and genera in Tibetan sheep. Rumen metabolomics analysis revealed that dietary protein levels altered the concentrations of ruminal amino acids, carbohydrates and organic acids, and significantly affected tryptophan metabolism (p < 0.05). Correlation analysis of the microbiota and metabolites revealed positive and negative regulatory mechanisms. Overall, this study provides detailed information on rumen microorganisms and ruminal metabolites under different levels of dietary protein, which could be helpful in subsequent research for regulating animal nutrition and metabolism through nutritional interventions.

The early diagnoses and treatment of anti-Yo antibody-mediated paraneoplastic cerebellar degeneration in a patient with breast cancer: a case report.

Background: Paraneoplastic cerebellar degeneration (PCD) is a relatively rare complication among patients with cancers with nonmetastatic tumor manifestation, including breast cancer. A breast cancer diagnosis is usually made several months (or even years) after the onset of neurological symptoms. Case Description: In this study, we describe the early diagnosis and treatment of PCD in one patient with breast cancer. The patient's first symptom was unsteady gait, followed by dizziness and dysarthria of explosive speech. Subacute progressive ataxia symptoms, weight loss, normal imaging findings, and a lack of evidence of infection combined to lead to clinical diagnosis of PCD, and further confirmed by positron emission tomography-computed tomography (PET-CT), positive anti-Yo antibodies and core needle biopsy. Immunosuppressant therapy consisting of intravenous immunoglobulin (IVIG) and high-dose corticosteroids was effective. The patient underwent modified radical mastectomy and 2 cycles of chemotherapy, and the result suggested that treatment of the primary tumor also improved the neurological symptoms to a certain extent. At 1-year follow-up, there was no evidence of recurrence, and the patient's neurological symptoms were stable. Conclusions: Once PCD was suspected, without clear physical findings or symptoms, PET-CT should be performed for a systemic evaluation for an occult malignancy. Even if the diagnosis and treatment were timely, expectations for prognosis should not be too high.