Stress adaptation in Tibetan cashmere goats is governed by inherent metabolic differences and manifested through variable cashmere phenotypes.

Tibetan cashmere goats are not only served as a valuable model for studying adaptation to hypoxia and high-altitude conditions but also playing a pivotal role in bolstering local economies through the provision of premium quality cashmere yarn. In this study, we performed an integration and network analysis of metabolomic, transcriptomic and proteomic to elucidate the role of differentially expressed genes, important metabolites, and relevant cellular and metabolic pathways between the fine (average 12.04 ± 0.03 µm of mean fiber diameter) and coarse cashmere (average 14.88 ± 0.05 µm of mean fber diameter) producing by Tibetan cashmere goats. We identified a distinction of 56 and 71 differential metabolites (DMs) between the F and C cashmere groups under positive and negative ion modes, respectively. The KEGG pathway enrichment analysis of these DMs highlighted numerous pathways predominantly involved in amino acid and protein metabolism, as indicated by the finding that the most impactful pathway was the mammalian target of rapamycin (mTOR) signalling pathway. In the F group, we identified a distinctive metabolic profile where amino acid metabolites including serine, histidine, asparagine, glutamic acid, arginine, valine, aspartic acid, tyrosine, and methionine were upregulated, while lysine, isoleucine, glutamine, tryptophan, and threonine were downregulated. The regulatory network and gene co-expression network revealed crucial genes, metabolites, and metabolic pathways. The integrative omics analysis revealed a high enrichment of several pathways, notably encompassing protein digestion and absorption, sphingolipid signalling, and the synaptic vesicle cycle. Within the sphere of our integrative analysis, DNMT3B was identified as a paramount gene, intricately associated with significant proteins such as HMCN1, CPB2, GNG12, and LRP1. Our present study delineated the molecular underpinnings governing the variations in cashmere characteristics by conducting comprehensive analyses across metabolomic, transcriptomic, and proteomic dimensions. This research provided newly insights into the mechanisms regulating cashmere traits and facilitated the advancement of selective breeding programs aimed at cultivating high-quality superfine Tibetan cashmere goats.

Narirutin Attenuates Cerebral Ischemia-Reperfusion Injury by Suppressing the TXNIP/NLRP3 Pathway.

Narirutin (Nar) is a flavonoid that is abundantly present in citrus fruits and has attracted considerable attention because of its diverse pharmacological activities and low toxicity. Here, we evaluated the preventive effects of Nar in middle cerebral artery occlusion/reperfusion (MCAO/R)-injured mice and oxygen-glucose deprivation/reperfusion (OGD/R)-injured bEnd.3 cells. Pretreatment with Nar (150 mg/kg) for 7 days effectively reduced infarct volume, improved neurological deficits, and significantly inhibited neuronal death in the hippocampus and cortex in MCAO/R-injured mice. Moreover, anti-apoptotic effects of Nar (50 µM) were observed in OGD/R-injured bEnd.3 cells. In addition, Nar pre-administration regulated blood-brain barrier function by increasing tight junction-related protein expression after MCAO/R and OGD/R injury. Nar also inhibited NOD-like receptor protein 3 (NLRP3) inflammasome activation by reducing the expression of thioredoxin-interacting protein (TXNIP) in vivo and in vitro. Taken together, these results provide new evidence for the use of Nar in the prevention and treatment of ischemic stroke.

Metabolomics reveals metabolites associated with hair follicle cycle in cashmere goats.

BACKGROUND: The hair follicle is a skin accessory organ that regulates hair development, and its activity varies on a regular basis. However, the significance of metabolites in the hair follicle cycle has long been unknown. RESULTS: Targeted metabolomics was used in this investigation to reveal the expression patterns of 1903 metabolites in cashmere goat skin during anagen to telogen. A statistical analysis was used to investigate the potential associations between metabolites and the hair follicle cycle. The findings revealed clear changes in the expression patterns of metabolites at various phases and in various feeding models. The majority of metabolites (primarily amino acids, nucleotides, their metabolites, and lipids) showed downregulated expression from anagen (An) to telogen (Tn), which was associated with gene expression, protein synthesis and transport, and cell structure, which reflected, to some extent, that the cells associated with hair follicle development are active in An and apoptotic in An-Tn. It is worth mentioning that the expression of vitamin D3 and 3,3',5-triiodo-L-thyronine decreased and then increased, which may be related to the shorter and longer duration of outdoor light, which may stimulate the hair follicle to transition from An to catagen (Cn). In the comparison of different hair follicle development stages (An, Cn, and Tn) or feeding modes (grazing and barn feeding), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that common differentially expressed metabolites (DEMs) (2'-deoxyadenosine, L-valine, 2'-deoxyuridine, riboflavin, cytidine, deoxyguanosine, L-tryptophan, and guanosine-5'-monophosphate) were enriched in ABC transporters. This finding suggested that this pathway may be involved in the hair follicle cycle. Among these DEMs, riboflavin is absorbed from food, and the expression of riboflavin and sugars (D-glucose and glycogen) in skin tissue under grazing was greater and lower than that during barn feeding, respectively, suggesting that eating patterns may also alter the hair follicle cycle. CONCLUSIONS: The expression patterns of metabolites such as sugars, lipids, amino acids, and nucleotides in skin tissue affect hair follicle growth, in which 2'-deoxyadenosine, L-valine, 2'-deoxyuridine, riboflavin, cytidine, deoxyguanosine, L-tryptophan, and guanosine-5'-monophosphate may regulate the hair follicle cycle by participating in ABC transporters. Feeding practices may regulate hair follicle cycles by influencing the amount of hormones and vitamins expressed in the skin of cashmere goats.

Regulation of cashmere fineness traits by noncoding RNA in Jiangnan cashmere goats.

BACKGROUND: Cashmere has long been used as the raw material for wool textiles. The diameter of the cashmere fibre determines its quality and economic value. However, the regulatory role of noncoding RNAs (ncRNAs) in cashmere fineness remains unclear, especially regarding the interaction between ncRNAs and coding RNAs. RESULTS: Transcriptome sequencing was used to identify the expression profiles of long noncoding RNAs (lncRNAs), circular RNAs (circRNAs) and microRNAs (miRNAs) in the skin tissues of Jiangnan cashmere goats with different cashmere fineness levels. Integration analysis of ncRNA and coding RNA was performed in combination with previous research results. The results showed that 16,437 lncRNAs, 2234 circRNAs, and 1322 miRNAs were identified in 8 skin samples of cashmere goats. A total of 403 differentially expressed (DE) lncRNAs, 62 DE circRNAs and 30 DE miRNAs were identified in the skin tissues of the fine groups (Fe) and coarse groups (Ce). We predicted the target gene of DE lncRNA, the target gene of DE miRNA and the host gene of DE circRNA. Based on functional annotation and enrichment analysis of target genes, we found that DE lncRNAs could be involved in regulating the fineness traits of cashmere. The most potential lncRNAs were MSTRG.42054.1, MSTRG.18602.3, and MSTRG.2199.13. CONCLUSIONS: The data from this study enriched the cashmere goat noncoding RNA database and helped to supplement the annotation of the goat genome. The results provided a new direction for the breeding of cashmere characters.

Expert-Level Immunofixation Electrophoresis Image Recognition based on Explainable and Generalizable Deep Learning.

BACKGROUND: Immunofixation electrophoresis (IFE) is important for diagnosis of plasma cell disorders (PCDs). Manual analysis of IFE images is time-consuming and potentially subjective. An artificial intelligence (AI) system for automatic and accurate IFE image recognition is desirable. METHODS: In total, 12 703 expert-annotated IFE images (9182 from a new IFE imaging system and 3521 from an old one) were used to develop and test an AI system that was an ensemble of 3 deep neural networks. The model takes an IFE image as input and predicts the presence of 8 basic patterns (IgA-, IgA-, IgG-, IgG-, IgM-, IgM-, light chain and ) and their combinations. Score-based class activation maps (Score-CAMs) were used for visual explanation of the models prediction. RESULTS: The AI model achieved an average accuracy, sensitivity, and specificity of 99.82, 93.17, and 99.93, respectively, for detection of the 8 basic patterns, which outperformed 4 junior experts with 1 years experience and was comparable to a senior expert with 5 years experience. The Score-CAMs gave a reasonable visual explanation of the prediction by highlighting the target aligned regions in the bands and indicating potentially unreliable predictions. When trained with only the new system images, the models performance was still higher than junior experts on both the new and old IFE systems, with average accuracy of 99.91 and 99.81, respectively. CONCLUSIONS: Our AI system achieved human-level performance in automatic recognition of IFE images, with high explainability and generalizability. It has the potential to improve the efficiency and reliability of diagnosis of PCDs.

Effect of extremely low-frequency electromagnetic radiation on pregnancy outcome: A meta-analysis.

Extremely low-frequency electromagnetic radiation (ELF-EMF) are generated by electrical devices and power systems (1 to 300 Hz). Although several studies have demonstrated that ELF-EMF may beassociated with an increased risk of adverse pregnancy outcomes, other studies have shown no evidence of associations. This meta-analysis was conducted to assess the effect of extremely low frequency electromagnetic radiation on pregnancy outcomes. The following electronic bibliographic databases were searched to identify relevant studies: PubMed, Web Of Science, Cochrane library, Embase, EBSCO. In addition, the manual retrieval of relevant references was conducted as a supplement. Select all eligible studies published from Database construction library to March 10, 2021. Search type for queue research on influence of electromagnetic field radiation on pregnancy results. Data were screened and extracted independently by two researchers. Review Manager 5.3 software was used for the meta-analysis. There was no significant increase in the risk of miscarriage, stillbirth, birth defects and preterm delivery in the pregnant women who lived near the electromagnetic fields compared with the control group. Conclusions: No correlation has been found between maternal ELF-EMF exposure and miscarriage, stillbirth, neonatal birth defects and preterm delivery, while the effects on small gestational age and low birth weight are still uncertain. Related research with high-quality large samples and different regions are still needed for further verification.

Autophagy promotes GSDME-mediated pyroptosis via intrinsic and extrinsic apoptotic pathways in cobalt chloride-induced hypoxia reoxygenation-acute kidney injury.

Cobalt is a transition element that abundantly exists in the environment. Besides direct hypoxia stress, cobalt ions indirectly induce hypoxia-reoxygenation injury (HRI), the main cause of acute kidney injury (AKI), a life-threatening clinical syndrome characterized by the necrosis of the proximal tubular epithelial cells (PTECs) and inflammation. Pyroptosis, a type of inflammatory programmed cell death, might play an essential role in HRI-AKI. However, whether pyroptosis is involved in cobalt chloride (CoCl2)-induced HRI-AKI remains unknown. Autophagy is a cellular biological process maintaining cell homeostasis that is involved in cell damage in AKI, yet the underlying regulatory mechanism of autophagy on pyroptosis has not been fully understood. In this study, the in vitro and in vivo models of CoCl2-induced HRI-AKI were established with HK-2 cell line and C57BL/6J mouse. Pyroptosis-related markers were detected with western blotting and immunofluorescence assays, and results showed that gasdermin E (GSDME)-mediated pyroptosis was involved in the cell damage in HRI-AKI. Specific chemical inhibitors of caspase 3, caspase 8, and caspase 9 significantly inhibited GSDME-mediated pyroptosis, verifying that GSDME-mediated pyroptosis was induced via the activation of caspase 3/8/9. The western blotting and immunofluorescence assays were adopted to detect the accumulation of the autophagosomes, and results suggested that HRI increased the autophagic level. The effects of autophagy on apoptosis and pyroptosis were evaluated using lentivirus transfection assays to knock down autophagy-specific genes atg5 and fip200, and results demonstrated that autophagy induced GSDME-mediated pyroptosis via apoptotic pathways in HRI-AKI. Our results revealed the involvement of GSDME-mediated pyroptosis in CoCl2-induced HRI-AKI and promoted the understanding of the regulatory mechanism of GSDME cleavage. Our study might provide a potential therapeutic target for HRI-AKI, and will be helpful for the risk evaluation of cobalt exposure.

Changes of T lymphocyte subsets in patients with HIV-negative symptomatic neurosyphilis.

OBJECTIVES: The host immune response could be an imperative factor in the pathogenesis of neurosyphilis, but the role of T lymphocyte subsets remains unclear. In the present study, we assessed the CD4+ T and CD8+ T cell subsets in the peripheral blood of patients with HIV-negative symptomatic neurosyphilis and then explored the clinical application value of neurosyphilis. METHODS: In total, 24 patients with HIV-negative symptomatic neurosyphilis and 22 patients with syphilis/non-neurosyphilis were included in this study and cerebrospinal fluid (CSF) and blood samples were obtained. Th1, Th2, Th17, Th9, CD8+IFN-γ+, CD8+IL-4+, CD8+IL-9+, and CD8+IL-17 + cells were identified by flow cytometry. RESULTS: The levels of CD8+IFN-γ+ were significantly increased in the peripheral blood of neurosyphilis patients compared to that in syphilis/non-neurosyphilis patients, but it was opposite to Th2, Th9, CD8+IL-4+, CD8+IL-9+, and CD8+IL-17 + cells. Dendritic cells (DCs) of neurosyphilis matured by T. pallidum induced the development of a combination of IFN-γ-producing Th1 cells. The number of CD8+IL-17 + cells was significantly correlated with the CSF RPR and CSF TPPA levels. ROC curve analysis revealed that the number of CD8+IFN-γ+ cells could be a potential biomarker for neurosyphilis from non-neurosyphilis/syphilis. CONCLUSIONS: High expression of CD8+IFN-γ+ cells and low expression of CD8+IL-17 + cells in patients with symptomatic neurosyphilis, which explains the pathogenesis of symptomatic neurosyphilis, meanwhile CD8+IFN-γ+ cells may be a better indicator in classifying symptomatic neurosyphilis from non-neurosyphilis/syphilis among patients without HIV infection.

A new single-urea-bound 3,5-dimethylphenylcarbamoylated ß-cyclodextrin chiral stationary phase and its enhanced separation performance in normal-phase liquid chromatography.

A new single-urea-bound chiral stationary phase based on 3,5-dimethylphenylcarbamoylated ß-cyclodextrin was prepared through the Staudinger reaction of mono (6A -azido-6A -deoxy)-per(3,5-dimethylphenylcarbamoylated) ß-cyclodextrin and 3-aminopropyl silica gel under CO2 atmosphere. The new phase exhibited good enantioseparation performance for 33 analytes using normal-phase HPLC conditions; 19 of them were baseline separated. Effects of structure of analytes, alcoholic modifiers, and acidic/basic additives on separation performances of this new cyclodextrin chiral stationary phase have been studied in detail. The results showed that the retention and resolution of acidic and basic analytes on the CSP were greatly affected by the additives. Peak symmetry for some analytes could be improved by simultaneously adding acidic and basic additives to the mobile phase. This work expands the potential applications of the cyclodextrin-based chiral stationary phases in the normal-phase HPLC.

General Strategy for Rapid Production of Low-Dimensional All-Inorganic CsPbBr3 Perovskite Nanocrystals with Controlled Dimensionalities and Sizes.

Currently, all-inorganic CsPbX3 (X = Br, I, Cl) perovskite nanocrystals (NCs) are shining stars with exciting potential applications in optoelectronic devices such as solar cells, light-emitting diodes, lasers, and photodetectors, due to their superior performance in comparison to their organic-inorganic hybrid counterparts. In the present work, we report a general strategy based on a microwave technique for the rapid production of low-dimensional all-inorganic CsPbBr3 perovskite NCs with tunable morphologies within minutes. The effect of the key parameters such as the introduced ligands, solvents, and PbBr2 precursors and microwave powers as well as the irradiation times on the production of perovskite NCs was systematically investigated, which allowed their growth with tunable dimensionalities and sizes. As a proof of concept, the ratio of OA to OAm as well as the concentration of PbBr2 precursor played important roles in triggering the anisotropic growth of the perovskite NCs, favoring their growth into 1D/2D single-crystalline nanostructures. Meanwhile, their sizes could be tailored by controlling the microwave powers and irradiation times. The mechanism for the tunable growth of perovskite NCs is discussed.

Improvement in surface-enhanced Raman spectroscopy from cubic SiC semiconductor nanowhiskers by adjustment of energy levels.

Enhanced reproducible Raman signals of the 4-MBA molecule were observed on the surface of semiconducting SiC nanowhiskers (SiCNWs) by surface-enhanced Raman spectroscopy (SERS). The SERS enhancement was further tuned and boosted by doping with B. Theoretical calculations were performed to unravel the mechanism of the SERS enhancement and it was found that the SERS effect was strongly associated with the energy level structure between the substrate and analyte. Appropriate energy level matching facilitated the charge transfer process during laser illumination, enhancing the SERS signal. This proposed mechanism was verified through multiple control experiments.

[The value of multi-slice spiral computed tomography portography in assessing severity of liver cirrhosis and predicting episode risks of hepatic encephalopathy].

OBJECTIVE: To explore the clinical value of multi-slice spiral computed tomography portography (MSCTP) in assessing severity of liver cirrhosis and predicting episode risks of hepatic encephalopathy (HE). METHODS: Eighty-six patients with liver cirrhosis who were hospitalized in the Department of Gastroenterology at the Affiliated Hospital of Yan'an University were included in the study.All patients underwent 64-slice MSCTP to grade the portal vein anatomy.The West Haven criteria were used for semi-quantitative assessment of each patient's mental state.The Child-Pugh grading system was used to assess the extent of cirrhosis.Comparison of measurement data between multiple groups was made by one-way ANOVA analysis, and comparison of such between two groups was made by the Mann-Whitney U test, Ranked data were compared with the rank-sum test, and count data were compared by the Chi-Square test.Correlation analysis was performed with Spearman's correlation test. RESULTS: Comparison of the HE grade III group and the HE grade I group showed significant differences between the two in the diameters of left gastric vein, the splenic vein, the intrahepatic left portal vein and the intrahepatic right portal vein (P less than 0.05).Comparison of the Child-Pugh grade C group and the Child-Pugh grade A group showed significant differences between the two in diameters of the left gastric vein, the splenic vein, the intrahepatic left portal vein and the intrahepatic right portal vein (P less than 0.05).The diameters of the main portal vein were not significantly different between the ChildPugh grades and HE classifications (P more than 0.05).The results of MSCTP did show significant differences between different HE classifications in patients with liver cirrhosis and the rate of formation of portal vein thrombosis and fistulas of the hepatic artery-portal vein (P less than 0.05), .but no significant differences with the esophageal and gastric varices, varicose veins around the esophagus, and periumbilical varicose veins (P more than 0.05).HE classification was significantly correlated with formation of portal vein thrombosis and fistula of the hepatic artery-portal vein (r=0.687, P less than 0.05 and r=0.565, P less than 0.05, respectively).MSCTP grading (grade 1:n=35, grade 2:n=36, grade 3:n=15) was not correlated with the Child-Pugh grade (grade A:n=36, grade B:n=32, grade C:n=18) (Z=-0.135, P more than 0.05).Incidence of HE was significantly different among the different MSCTP grades (grade 1:0%(0), grade 2:33.3% (12/36), grade 3:66.7% (10/15); x2=26.468, P less than 0.05).The MSCTP grade was significantly correlated with the episode risks of HE (r=0.552, P less than 0.05). CONCLUSION: MSCTP may be valuable for assessing severity of liver cirrhosis and for predicting episode risks of HE; however, future studies with larger sample numbers is required for validation of our findings.

Shikonin reactivates TSGs GADD45B and PPP3CC to block NSCLC cell proliferation and migration through JNK/P38/MAPK signaling pathways.

BACKGROUND: Shikonin, a natural naphthoquinone compound extracted from the Chinese traditional herbal medicine "Lithospermum erythrorhizon", possesses antitumor activity against various cancer types. Tumor-suppressor genes (TSGs) negatively regulate cell growth, proliferation, and differentiation, thereby inhibiting tumor formation. However, the molecular mechanism of action of shikonin on TSGs in non-small-cell lung cancer (NSCLC) remains unclear. METHODS: The inhibitory effect of shikonin on the proliferation and migration abilities of lung cancer cells were measured by Cell Counting Kit 8 (CCK8) and wound healing assays. The alteration of genes by shikonin treatment was detected by mRNA high-throughput sequencing and further confirmed by qPCR and western blotting experiments. The dominant functions of the upregulated genes were analyzed by GO and KEGG profiling. RESULTS: Shikonin inhibited the proliferation and migration of A549 and H1299 NSCLC cells in a dose-dependent manner. mRNA high-throughput sequencing revealed a total of 1794 upregulated genes in shikonin-treated NSCLC cells. Moreover, bioinformatic analysis of GO and KEGG profiling revealed that the up-regulated genes were mostly involved in the JNK/P38/MAPK signaling pathway, among which the expression of GADD45B and PPP3CC was significantly enhanced. Finally, we confirmed that GADD45B and PPP3CC were indeed upregulated in JNK/P38/MAPK pathway. CONCLUSIONS: Taken together, these results suggested that shikonin might affect the expression of GADD45B and PPP3CC through the JNK/P38/MAPK pathway, therefore exerting an inhibitory effect on the proliferation and migration of cancer cells. To our knowledge, this is the first study reporting the role of shikonin in upregulating TSGs to activate the JNK/P38/MAPK signaling pathways in NSCLC.

Transcriptome meta-analysis reveals the hair genetic rules in six animal breeds and genes associated with wool fineness.

Wool plays an irreplaceable role in the lives of livestock and the textile industry. The variety of hair quality and shape leads to the diversity of its functions and applications, and the finer wool has a higher economic value. In this study, 10 coarse and 10 fine ordos fine wool sheep skin samples were collected for RNA-seq, and coarse and fine skin/hair follicle RNA-seq datasets of other five animal breeds were obtained from NCBI. Weighted gene co-expression network analysis showed that the common genes were clustered into eight modules. Similar gene expression patterns in sheep and rabbits with the same wool types, different gene expression patterns in animal species with different hair types, and brown modules were significantly correlated with species and breeds. GO and KEGG enrichment analyses showed that, most genes in the brown module associated with hair follicle development. Hence, gene expression patterns in skin tissues may determine hair morphology in animal. The analysis of differentially expressed genes revealed that 32 highly expressed candidate genes associated with the wool fineness of Ordos fine wool sheep. Among them, KAZALD1 (grey module), MYOC (brown module), C1QTNF6 (brown module), FOS (tan module), ITGAM, MX2, MX1, and IFI6 genes have been reported to be involved in the regulation of the hair follicle cycle or hair loss. Additionally, 12 genes, including KAZALD1, MYOC, C1QTNF6, and FOS, are differentially expressed across various animal breeds and species. The above results suggest that different sheep breeds share a similar molecular regulatory basis of wool fineness. Finally, the study provides a theoretical reference for molecular breeding of sheep breeds as well as for the investigation of the origin and evolution of animal hair.

Diabetes and vascular mild cognitive impairment among Chinese ≥50 years: A cross-sectional study with 2020 participants.

BACKGROUND: With the decline of cognitive function in vascular cognitive impairment, the burden on the family and society will increase. Therefore, early identification of vascular mild cognitive impairment (VaMCI) is crucial. The focus of early identification of VaMCI is on the attention of risk factors. Therefore, this study aimed to investigate the relationship between diabetes and VaMCI among the Chinese, hoping to predict the risk of VaMCI by diabetes and to move the identification of vascular cognitive impairment forward. METHODS: We collected data from seven clinical centers and nine communities in China. All participants were over 50 years of age and had cognitive complaints. We collected basic information of the participants, and cognitive function was professionally assessed by the Montreal Cognitive Assessment scale. Finally, logistic regression analysis was used to analyze the correlation between each factor and VaMCI. RESULTS: A total of 2020 participants were included, including 1140 participants with VaMCI and 880 participants with normal cognition. In univariate logistic regression analysis, age, heavy smoking, and diabetes had a positive correlation with VaMCI. At the same time, being married, high education, and light smoking had a negative correlation with VaMCI. After correction, only diabetes (OR = 1.04, 95% CI: 1.01-1.09, p = 0.05) had a positive correlation with VaMCI, and high education (OR = 0.60, 95% CI:.45-.81, p = 0.001) had a negative correlation with VaMCI. CONCLUSION: In our study, we found that diabetes had a positive correlation with VaMCI, and high education had a negative correlation with VaMCI. Therefore, early identification and timely intervention of diabetes may reduce the risk of VaMCI and achieve early prevention of VaMCI.

Comparison of different animal models for estimating genetic parameters for early growth traits and reproductive traits in Tianmu Sainuo sheep.

As the economic level of individuals rises, so too does the demand for mutton. Enhancing the breeds of mutton sheep not only boosts production efficiency and economic benefits but also fosters the sustainable growth of the mutton sheep breeding industry. Thus, this study examines the early growth and reproductive traits of Tianmu Sainuo sheep, analyzing the genetic interactions among these traits to furnish a theoretical foundation for refining breeding strategies and expediting the genetic advancement of this breed. The investigation compiled 29,966 data entries, involving 111 sires for birth weight (BWT) and 113 for other metrics. The data encompassed 10,415 BWT records from 1,633 dams, 12,753 weaning weight (WWT) records from 1,570 dams, 12,793 average daily gain (ADG) records from 1,597 dams, and 13,594 litter size (LS) records from 1,499 dams. Utilizing the GLM procedure in SAS 9.2 software, the study analyzed the non-genetic influences on lamb BWT, WWT, ADG, and LS. Concurrently, DMU software estimated the variance components across various animal models for each trait. Employing the Akaike Information Criterion (AIC) and likelihood ratio test (LRT), six models were tested, incorporating or excluding maternal inheritance and environmental impacts, to identify the optimal model for deriving genetic parameters. The findings reveal that birth year (BY), birth quarter (BQ), birth type (BT), age of mother (AM), and birth sex (BS) exerted significant impacts on BWT, WWT, and ADG (p < 0.01). Additionally, BQ and AM significantly influenced LS (p < 0.01). The most accurate genetic evaluation model determined the heritability of BWT, WWT, ADG, and LS to be 0.0695, 0.0849, 0.0777, and 0.1252, respectively.

Transpiration rates decline under limited moisture supply along hillslopes in a humid karst terrain.

Topographic positions can mediate subsurface water availability, but its effects on tree transpiration are controversial. In humid karst regions, climax forests are usually not limited by moisture supply, even at the summit, through absorbing water from deep layers. However, little is known on the transpiration pattern and its limiting factor on the shrubland widely distributed along the karst hillslopes. In the current study, Rhus chinensis, a widely spread constructive species in natural restoration was selected. Meteorological factors, 0-300 cm soil-epikarst moisture, sap flow, and root water uptake were studied during an entire growing season to assess how hillslope positions affected transpiration. We found the mean water content in uphill was only around 60 % of that in downhill, indicating a contrasting water supply along the slope. However, there were no significant differences in the xylem isotopic composition and lc-excess which suggested the similar water uptake strategies in both uphill and downhill. R. chinensis primarily relied on the soil water rather than epikarst water (groundwater) along the hillslope because of the MixSIAR model results and more negative lc-excess values (-13.18 ‰). R. chinensis exhibited decreases of nearly half in the transpiration rate and amount in uphill compared to those in downhill. In downhill with sufficient water availability, transpiration followed the variation in atmospheric water demand. In uphill, a poor moisture supply limited tree transpiration and its response to atmospheric water demand. Our findings revealed that the early successional species did not entirely depend on atmospheric water demand, absorbing deep epikarst water as the mature forest. The transpiration rates of those species declined by nearly half to adapt to the water-limited environment along the hillslope in the humid karst region. This study can contribute to the evaluation of eco-hydrological functions during natural restoration.

Bioinformatics analysis and identification of upregulated tumor suppressor genes associated with suppressing colon cancer progression by curcumin treatment.

Tumor suppressor genes (TSGs) are commonly downregulated in colon cancer and play a negative role in tumorigenesis and cancer progression by affecting genomic integrity, the cell cycle, and cell proliferation. Curcumin (CUR), a Chinese herb-derived phytochemical, exerts antitumor effects on colon cancer. However, it remains unclear whether CUR exerts its antitumor effects by reactivating TSGs in colon cancer. Here, we demonstrated that CUR inhibited HT29 and HCT116 proliferation and migration by cell-counting kit-8, colony-formation, and wound-healing assays. Furthermore, the comprehensive bioinformatics analysis of mRNA sequencing revealed that 3,505 genes were significantly upregulated in response to CUR in HCT116 cells. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses showed that the most upregulated genes were enriched in cancer pathways containing 37 TSGs. Five (ARHGEF12, APAF1, VHL, CEBPA, and CASP8) of the 37 upregulated TSGs were randomly selected for real-time fluorescence polymerase chain reaction and the verification results showed that these five genes were significantly reactivated after CUR treatment, suggesting that TSGs are related to CUR-mediated colon cancer inhibition. ARHGEF12 is a newly identified TSG and a potential therapeutic target for colon cancer. Furthermore, molecular docking was performed to predict the binding sites of CUR and ARHGEF12, suggesting that CUR can prevent colon cancer cell invasion and metastasis by inhibiting ARHGEF12 and RhoA binding. In conclusion, the present study reveals that CUR inhibits colon cancer cell proliferation and migration by reactivating TSGs, revealing a new mechanism and potential target for colon cancer treatment.

Natural Shikonin Potentially Alters Intestinal Flora to Alleviate Acute Inflammation.

Shikonin, derived from the herb Lithospermum erythrorhizon (Purple Cromwell), is extensively utilized in traditional Chinese medicine as an anti-inflammatory agent; however, its effect on the intestinal flora is not yet known. Herein, we demonstrate that, compared to a blank control group, the intragastric administration of shikonin suppressed the swelling rate of ears in a mouse model of acute inflammation in a dose-dependent manner via animal experiments; furthermore, the 20 mg/kg shikonin treatment exhibited the highest inhibitory effect. In formal animal experimentation, we discovered that the inhibitory effect of shikonin with 20 mg/kg on inflammation was closely linked to the intestinal flora, whereby the microbiota phylum was altered in feces through a 16S rDNA sequencing analysis, implying that shikonin improves gut microbiota structures and compositions to counteract inflammation. Notably, using a real-time quantitative polymerase chain reaction (RT-qPCR), a Western blotting assay, and an immunohistochemistry (IHC) assay, we found that inflammatory cytokines such as TNF-α, IL-6, and IL-1ß reduced in both the shikonin-administration group and the positive control group than those in the blank control group, as expected. To the best of our knowledge, this is the first study to outline the underlying mechanism through which shikonin acts on gut microbes to alleviate acute inflammation, providing an alternative mechanism for shikonin to become a preventive agent in countering inflammation.

Ultrathin hierarchical hydrogel-carbon nanocomposite for highly stretchable fast-response water-proof wearable humidity sensors.

Wearable humidity sensors play an important role in human health monitoring. However, challenges persist in realizing high performance wearable humidity sensors with fast response and good stretchability and durability. Here we report wearable humidity sensors employing an ultrathin micro-nano hierarchical hydrogel-carbon nanocomposite. The nanocomposite is synthesized on polydimethylsiloxane (PDMS) films via a facile two-step solvent-free approach, which creates a hierarchical architecture consisting of periodic microscale wrinkles and vapor-deposited nanoporous hydrogel-candle-soot nanocoating. The hierarchical surface topography results in a significantly enlarged specific surface area (>107 times that of planar hydrogel), which along with the ultrathin hydrogel endow the sensor with high sensitivity and a fast response/recovery (13/0.48 s) over a wide humidity range (11-96%). Owing to the wrinkle structure and interpenetrating network between the hydrogel and PDMS, the sensor is stable and durable against repeated 180° bending, 100% strain, and even scratching. Furthermore, encapsulation of the sensor imparts excellent resistance to water, sweat, and bacteria without influencing its performance. The sensor is then successfully used to monitor different human respiratory behaviors and skin humidity in real time. The reported method is convenient and cost-effective, which could bring exciting new opportunities in the fabrication of next-generation wearable humidity sensors.