Palm kernel meal regulates the expression of genes involved in the amino acid metabolism in the liver of Tibetan sheep.

BACKGROUND: Palm kernel meal (PKM) is a by-product of oil palm kernel after oil extraction, which is widely used in animal feeds due to its high energy content. This study aimed to investigate the impact of supplementing Tibetan sheep with PKM on their hepatic phenotype, oxidative stress and immune response. A total of 120 Tibetan lambs (Initial weight = 12.37 ± 0.92 kg) were randomly assigned into four groups: control group (C group, 0% PKM diet), low group (L group, 15% PKM diet), middle group (M group, 18% PKM diet), and high group (H group, 21% PKM diet) on a dry matter basis. The feeding experiment was performed for 130 d, including a 10 d adaption period. RESULTS: Results showed that the level of GSH-Px were higher in the H and M groups than in the C and L groups (P < 0.05). The levels of IgM and TNF-α were higher in the M group when compared to those on the C group (P < 0.05). The level of IgA was significantly higher in the M group than in the H group (P < 0.05). Additionally, compared with the others groups, the hepatocytes in the M group displayed a radial arrangement, forming hepatic plates that were centered around the central vein. The transcriptome results revealed that proteasome 26 S subunit, ATPase 3 (PSMC3), proteasome 26 S subunit, ATPase 5 (PSMC5), proteasome 26 S subunit ubiquitin receptor, non-ATPase 4 (PSMD4), proteasome activator subunit 1 (PSME1), acyl-CoA dehydrogenase short/branched chain (ACADSB), enoyl-CoA hydratase, short chain 1 (ECHS1), serine dehydratase (SDS), ornithine transcarbamylase (OTC), and phenylalanine hydroxylase (PAH) were the hub genes regulating the amino acid metabolism in the liver. CONCLUSIONS: In summary, dietary 18% PMK supplementation contributed to improve the hepatic phenotype, oxidative stress and immune response through regulating the expression of related genes.

Fatty Acids and Volatile Flavor Components of Adipose Tissue from Local Tibetan Sheep in Qinghai with Dietary Supplementation of Palm Kernel Meal (PKM).

Substituting traditional protein feed with palm kernel meal (PKM) in the diet of Tibetan sheep can be a cost-effective feeding strategy. To determine the impact of PKM on flavor development in different adipose tissues of Tibetan sheep, subjects were fed with 15% and 18% of PKM, while the control group received no PKM. The fatty acids and volatile compounds in the samples were then analyzed by GC-MS and HS-GC-IMS. Adding PKM to the diet significantly increased the C12:0, C14:0, C16:0 and C18:1N9 content in adipose tissues compared with the control, and most of these were associated with flavor formation (p < 0.05). The flavor compounds in the adipose tissues predominantly consisted of alcohols, ketones, acids and aldehydes. In particular, including PKM in the diet increased the proportion of ketones but decreased the proportion of alcohols, acids and aldehydes in subcutaneous and tail fat. Specifically, the proportion of acetone, acetoin monomer, 2,3-butanedione, 2-butanone monomer, 2-methyl-2-propanol, 2-methyl-2-propanol and methyl acetate increased significantly in the subcutaneous and tail fat (p < 0.05), while that of ethanol, 1-propanol monomer, butanol monomer, acetic acid monomer and acetic acid monomer decreased. Intermuscular fat exhibited variable results, mainly because the addition of PKM resulted in higher proportions of alcohols, including ethanol, 1-propanol and butanol monomer, especially at 15% PKM. In summary, the addition of PKM improved the flavor of Tibetan sheep fat and increased the amount of favorable volatile flavor compounds. This study can serve as reference for understanding the effects of dietary PKM on the adipose tissue flavor profile of Tibetan sheep.

Effect of supplementing lysins and methionine to low-protein diets on growth performance, hepatic antioxidant capacity, immune status, and glycolytic activity of tibetan sheep.

Reducing the levels of dietary protein is an effective nutritional approach in lowering feed cost and nitrogen emissions in ruminants. The purpose of this study was to evaluate the effects of dietary Lys/Met ratio in a low protein diet (10%, dry matter basis) on the growth performance and hepatic function (antioxidant capacity, immune status, and glycolytic activity) in Tibetan lambs. Ninety two-month-old rams with an average weight of 15.37 ± 0.92 kg were randomly assigned to LP-L (dietary Lys/Met = 1:1), LP-M (dietary Lys/Met = 2:1) and LP-H (dietary Lys/Met = 3:1) treatments. The trial was conducted over 100 d, including 10 d of adaption to the diets. Hepatic phenotypes, antioxidant capacity, immune status, glycolytic activity and gene expression profiling was detected after the conclusion of the feeding trials. The results showed that the body weight was higher in the LP-L group when compared to those on the LP-M group (P < 0.05). In addition, the activities of the catalase (CAT) and glutathione peroxidase (GSH-Px) in the LP-L group were significantly increased compared with the LP-M group (P < 0.05), while the malondialdehyde (MDA) levels in LP-H group were significantly decreased (P < 0.05). Compared with LP-H group, both hepatic glycogen (P < 0.01) and lactate dehydrogenase (LDH) (P < 0.05) were significantly elevated in LP-L group. For the LP-L group, the hepatocytes were arranged radially with the central vein in the center, and hepatic plates exhibited tight arrangement. Transcriptome analysis identified 29, 179, and 129 differentially expressed genes (DEGs) between the LP-M vs. LP-L, LP-H vs. LP-M, and LP-H vs. LP-L groups, respectively (Q-values < 0.05 and |log2Fold Change| > 1). Gene Ontology (GO) and correlation analyses showed that in the LP-L group, core genes (C1QA and JUNB) enriched in oxidoreductase activity were positively correlated with antioxidant indicators, while the MYO9A core gene enriched in the immune response was positively associated with immune indicators, and core genes enriched in molecular function (PDK3 and PDP2) were positively correlated with glycolysis indicators. In summary, low-protein diet with a low Lys/Met ratio (1:1) could reduce the hepatic oxidative stress and improve the glycolytic activity by regulating the expression of related genes of Tibetan sheep.

Cyberbullying victimization and perpetration: The influence on cyberostracism and youth anxiety.

Cyberbullying is considered a major threat to adolescent anxiety. In this study, we aim to explore the simultaneous effects of cyberbullying victimization and perpetration on youth anxiety. Building on the childhood adversity model and the vulnerability-stress model, we test the model wherein cyberbullying exposure is linked with cyberostracism, which in turn is expected to be associated with an increase in anxiety. We collected data from 1115 Chinese youth aged 11-19 years based on the stratified random sampling method. Structure equation modelling was conducted in Amos 26.0 to examine the proposed theoretical model. The findings suggested that compared with cyberbullying perpetration, the experience of cyberbullying victimization led to a significantly higher risk of youth anxiety. Multiple mediation analyses revealed that the three dimensions of cyberostracism, namely cyber direct excluded, cyber indirect excluded and cyber ignored, mediated the association of cyberbullying victimization and perpetration with youth anxiety. These results indicate that cyberostracism could be a risk factor for youth anxiety, thus providing new direction regarding intervention programs to reduce anxiety symptoms in adolescents.

Effect of tocilizumab plus corticosteroid on clinical outcome in patients hospitalized with severe fever with thrombocytopenia syndrome: A randomized clinical trial.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging viral hemorrhagic fever with high fatality rates. The blockade of pro-inflammatory cytokines presents a promising therapeutic strategy. METHODS: We conducted a randomized clinical trial at the 154th hospital, Xinyang, Henan Province. Eligible patients with severe SFTS disease were randomly assigned in a 1:2 ratio to receive either a single intravenous infusion of tocilizumab plus usual care; or usual care only. The primary outcome was the clinical status of death/survival at day 14, while secondary outcomes included improvement from baseline in liver and kidney damage and time required for hospital discharge. The efficacy of tocilizumab plus corticosteroid was compared to those receiving corticosteroid alone. The trial is registered with the Chinese Clinical Trial Registry website (ChiCTR2300076317). RESULTS: 63 eligible patients were assigned to the tocilizumab group and 126 to the control group. The addition of tocilizumab to usual care was associated with a reduced death rate (9.5%) compared to those received only usual care (23.0%), with an adjusted hazard ratio (aHR) of 0.37 (95% confidence interval [CI], 0.15 to 0.91, P = 0.029). Combination therapy of tocilizumab and corticosteroids was associated with a significantly reduced fatality (aHR, 0.21; 95% CI, 0.08 to 0.56; P = 0.002) compared to those receiving corticosteroids alone. CONCLUSIONS: A significant benefit of reducing fatality in severe SFTS patients was observed by using tocilizumab. A combined therapy of tocilizumab plus corticosteroids was recommended for the therapy of severe SFTS.

Insights into the effects of saline forage on the meat quality of Tibetan sheep by metabolome and multivariate analysis.

This work aimed to investigate how two different types of forage (saline and alkaline) impact the meat quality and muscle metabolism of Tibetan sheep. An integrative multi-omics analysis of meat quality and different metabolites was performed using untargeted and targeted metabolomics approaches. The research results indicated that GG grass (saline and alkaline forage) possessed superior characteristics in terms of apparent quality and secondary metabolite content compared with HG grass (Non saline alkali forage), regardless of the targeted metabolites or non-targeted ones. Simultaneously, under stress conditions, the carbohydrates-rich salt-alkali grass play a significant role in slowing down the decline in pH, increasing the unsaturated fatty acid content and reducing the thawing loss in Tibetan sheep. This study provides an understanding of the impact of different salt-alkali grass on the quality of Tibetan sheep meat, while providing a scientific basis for the future development of salt-alkali livestock industry.

A low bleeding risk thrombolytic agent: citPA5.

AIMS: Alteplase is a cornerstone thrombolytic agent in clinical practice, but presents a potential bleeding risk. Stroke patients need pre-screening to exclude hemorrhagic stroke before using Alteplase. In this study, we develop a new thrombolytic agent citPA5, characterized by an enhanced safety profile and minimal bleeding tendency. METHODS AND RESULTS: A clot lysis agent, named citPA5, is developed based on rtPA with point mutations to completely suppress its proteolytic activity in the absence of fibrin. In the presence of fibrin, citPA5 exhibited significantly higher fibrinolytic activity (a 15.8-fold increase of kcat/Km). Furthermore, citPA5 showed resistance to endogenous fibrinolysis inhibitor, PAI-1, resulting in enhanced potency. In a series of safety evaluation experiments, including thrombelastography (TEG) assay, mice tail bleeding assay, and a murine intracerebral hemorrhage (ICH) model, citPA5 did not cause systemic bleeding or worsen intracerebral hemorrhage compared to Alteplase. This highlights the low risk of bleeding associated with citPA5. Finally, we found that citPA5 effectively improved cerebral blood flow and reduced infarct volume in a carotid embolism-induced stroke (CES) model. CONCLUSIONS: This clot lysis agent, citPA5, not only exhibits a low risk of bleeding but also demonstrates highly effective thrombolysis capabilities. As a result, citPA5 shows great potential for administration prior to the classification of stroke types, making it possible for use in ambulances at the onset of stroke when symptoms are identified. The findings presented in this study also suggest that this strategy could be applied to develop a new generation of fibrinolytic drugs that offer greater safety and specificity in targeting fibrin.

Integrated metabolome and microbiome analysis reveals the effect of rumen-protected sulfur-containing amino acids on the meat quality of Tibetan sheep meat.

Introduction: This study investigated the effects of rumen-protected sulfur-containing amino acids (RPSAA) on the rumen and jejunal microbiota as well as on the metabolites and meat quality of the longissimus lumborum (LL) in Tibetan sheep. Methods: By combining 16S rDNA sequencing with UHPLC-Q-TOF MS and Pearson correlation analysis, the relationship between gastrointestinal microbiota, muscle metabolites and meat quality was identified. Results: The results showed that feeding RPSAA can increase the carcass weight, abdominal fat thickness (AP-2 group), and back fat thickness (AP-2 and AP-3 group) of Tibetan sheep. The water holding capacity (WHC), texture, and shear force (SF) of LL in the two groups also increased although the fatty acids content and brightness (L*) value significantly decreased in the AP-2 group. Metabolomics and correlation analysis further showed that RPSAA could significantly influence the metabolites in purine metabolism, thereby affecting L* and SF. In addition, RPSAA was beneficial for the fermentation of the rumen and jejunum. In both groups, the abundance of Prevotella 1, Lachnospiraceae NK3A20 group, Prevotella UCG-003, Lachnospiraceae ND3007 group in the rumen as well as the abundance of Eubacterium nodatum group and Mogibacterium group in the jejunum increased. In contrast, that of Turicibacter pathogens in the jejunum was reduced. The above microorganisms could regulate meat quality by regulating the metabolites (inosine, hypoxanthine, linoleic acid, palmitic acid, etc.) in purine and fatty acids metabolism. Discussion: Overall, reducing the levels of crude proteins in the diet and feeding RPSAA is likely to improve the carcass quality of Tibetan sheep, with the addition of RPMET (AP-2) yielding the best edible quality, possibly due to its ability to influence the gastrointestinal microbiota to subsequently regulate muscle metabolites.

Electronic and magnetic properties of transition-metal-doped monolayer B2S2 within GGA + U framework.

Considering the significant role of magnetism induction in two-dimensional (2D) semiconductor materials, we systematically investigate the effects of various dopants from the 3d and 4d transition metal (TM) series, including Ti, V, Mn, Fe, Co, Ni, Cu, Zn, Zr, Nb, Mo, Ru, Rh, Pd, Ag and Cd, on the electronic and magnetic properties of monolayer B2S2 through first-principles calculations. The calculated formation energies indicate that substitutional doping at the B site with various TM atoms could be achieved under S-rich growth conditions. What matters is that with the exception of systems doped with Cu, Tc, and Ag elements, which exhibit non-magnetic semiconductor properties, all other doped systems demonstrate magnetism. Specifically, the Cr-, Ni- and Pd-doped monolayers are magnetic half-metals, while the rest are magnetic semiconductors. We have also performed calculations of magnetic couplings between two TM atoms with an impurity concentration of 3.12%, revealing the prevalence of weak magnetic coupling in the majority of the magnetic systems examined. Moreover, the monolayers doped with Cr, Zr and Pd atoms exhibit ferromagnetic ground states. These findings strongly support the high potential for inducing magnetism in the B2S2 monolayer through B-site doping.

The impact of different levels of wheat diets on hepatic oxidative stress, immune response, and lipid metabolism in Tibetan sheep (Ovis aries).

BACKGROUND: Compared with corn, wheat contains higher crude protein, amino acids concentration. However, wheat contains a mass of anti-nutritional factors, resulting in increased of the digesta viscosity and impaired the intestinal function in ruminant. OBJECTIVE: This study aimed to investigate the effects of substitution of different amounts of wheat for corn on hepatic metabolism in the Tibetan lamb. METHODS: Ninety Tibetan lambs (Body weight = 12.37 ± 0.92 kg) were randomly assigned to three groups: 0% wheat diet (Control), 10% wheat diet (Low group), and 15% wheat diet (High group). The feeding trial lasted for 130 d, including a 10 d adaption period. Hepatic gene expression profiling was performed via RNA sequencing after the conclusion of the feeding trials. RESULTS: Results showed that greater level of glutathione peroxidase levels in L group compared with those of the C and H groups (P < 0.05). The immune indexes, including interleukin-1ß (IL-1ß), immunoglobulin A (IgA), and IgM were also elevated in L group compared with the other groups (P < 0.05). Compared with H group, the hepatocytes were arranged radially, and hepatic plates anastomosed with each other to form a labyrinth-like structure in L group. Transcriptomic analysis showed 872 differentially expressed genes (DEG) between H and L group, of which 755 were down-regulated and 117 were up-regulated. Through Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, 32 pathways were significantly enriched (Q-value < 0.05), such as the cAMP signaling pathway, Th1 and Th2 cell differentiation, leukocyte transendothelial migration, platelet activation and adipocytokine signaling pathway. Additionally, the expression of comment DEGs were verified via quantitative reverse-transcription polymerase chain reaction. CONCLUSION: In summary, our findings suggest that wheat can be supplemented up to 10% in Tibetan sheep, contributing to improve the hepatic oxidative stress, immune response and lipid metabolism through regulating the expression of related genes.

Fat deposition, fatty acid profiles, antioxidant capacity and differentially expressed genes in subcutaneous fat of Tibetan sheep fed wheat-based diets with and without xylanase supplementation.

Xylanase, an exogenous enzyme that plays an essential role in energy metabolism by hydrolysing xylan into xylose, has been shown to positively influence nutrient digestion and utilisation in ruminants. The objective of this study was to evaluate the effects of xylanase supplementation on the back-fat thickness, fatty acid profiles, antioxidant capacity, and differentially expressed genes (DEGs) in the subcutaneous fat of Tibetan sheep. Sixty three-month-old rams with an average weight of 19.35 ± 2.18 kg were randomly assigned to control (no enzyme added, WH group) and xylanase (0.2% of diet on a dry matter basis, WE group) treatments. The experiment was conducted over 97 d, including 7 d of adaption to the diets. The results showed that xylanase supplementation in the diet increased adipocyte volume of subcutaneous fat (p < 0.05), shown by hematoxylin and eosin (H&E) staining. Gas chromatography showed greater concentrations of C14:0 and C16:0 in the subcutaneous fat of controls compared with the enzyme-treated group (p < 0.05), while opposite trend was seen for the absolute contents of C18:1n9t, C20:1, C18:2n6c, C18:3, and C18:3n3 (p < 0.05). Compared with controls, supplementation with xylanase increased the activity of T-AOC significantly (p < 0.05). Transcriptomic analysis showed the presence of 1630 DEGs between the two groups, of which 1023 were up-regulated and 607 were down-regulated, with enrichment in 4833 Gene Ontology terms, and significant enrichment in 31 terms (p < 0.05). The common DEGs were enriched in 295 pathways and significantly enriched in 26 pathways. Additionally, the expression of lipid-related genes, including fatty acid synthase, superoxide dismutase, fatty acid binding protein 5, carnitine palmytoyltransferase 1 A, and peroxisome proliferator-activated receptor A were verified via quantitative reverse-transcription polymerase chain reaction. In conclusion, dietary xylanase supplementation was found to reduce subcutaneous fat deposition in Tibetan sheep, likely through modulating the expression of lipid-related genes.

Effects of dietary wheat supplementation levels on growth performance, rumen bacterial community and fermentation parameters in Chinese Tibetan Sheep.

The objective of this study was to evaluate various wheat supplementation levels on rumen microbiota and fermentation parameter in Tibetan sheep. A total of ninety ram with an average 12.37 ± 0.92 kg at the age of 2 months were randomly allocated to three treatments: 0% wheat diet (CW, N = 30), 10% wheat diet (LW, N = 30), and 15% wheat diet (HW, N = 30) on a dry matter basis. The experiment was conducted over a period of 127 days, including 7 days of adaption to the diets. Our results showed that sheep fed 10% wheat exhibited optimal average daily gain and feed gain ratio compared with HW group (p < 0.05). The serum alkaline phosphatase concentration was the lowest when fed the 10% wheat diet (p < 0.05), whereas serum aspartate aminotransferase concentration was the highest (p < 0.05). Both acetate and propionate increased with increase in dietary wheat ratio (p < 0.05), while a greater decrease in concentrations of NH3 -N was observed (p < 0.05). In rumen fluid, 3413 OTUs were obtained with 97% consistency. Phylum Firmicutes was the predominant bacteria and accounted for 49.04%. The CW groups supported significantly increased the abundance of Bacteroidetes (p < 0.05), as compared with the HW group. The abundance of Bacteroidales_UCG-001, Ruminococcus, and Mitsuokella possessed a higher relative abundance in HW group (p < 0.05). No differences in the bacterial community and fermentation parameters were observed between the sheep fed 0% and 10% wheat (p > 0.05). Ruminal bacterial community structure was significantly correlated with isobutyrite (r2 = 0.4878, p = 0.035) and valerate (r2 = 0.4878, p = 0.013). In conclusion, supplementation of 10% wheat in diet promoted the average daily gain and never altered microbial community structure and fermentation pattern, which can be effectively replace partial corn in Chinese Tibetan Sheep.

Insight into the differences of meat quality between Qinghai white Tibetan sheep and black Tibetan sheep from the perspective of metabolomics and rumen microbiota.

The purpose of this study was to investigate the differences in meat quality between two local breeds of Tibetan sheep, the White Tibetan sheep and the Black Tibetan sheep in Qinghai, and to search for metabolic mechanisms that produce meat quality differences by analyzing differential metabolites and key rumen microorganisms. The meat quality results showed that one breed, SG73, was superior to the other (WG). Further investigation identified differences in the composition of muscle metabolites and rumen microorganisms between the two Tibetan sheep breeds. It also regulates muscle tenderness, water retention, fat content and the composition and content of AA and FA through two major metabolic pathways, AA metabolism and carbohydrate metabolism. These findings could be beneficial for the development of breeding strategies for Tibetan sheep in Qinghai in the future.

From disinfectants to antibiotics: Enhanced biosafety of quaternary ammonium compounds by chemical modification.

The excessive use of quaternary ammonium compounds (QACs) following the COVID-19 pandemic has raised substantial concerns regarding their biosafety. Overuse of QACs has been associated with chronic biological adverse effects, including genotoxicity or carcinogenicity. In particular, inadvertent intravascular administration or oral ingestion of QACs can lead to fatal acute toxicity. To enhance the biosafety and antimicrobial efficacy of QACs, this study reports a new series of QACs, termed as PACs, with the alkyl chain of benzalkonium substituted by a phthalocyanine moiety. Firstly, the rigid phthalocyanine moiety enhances the selectivity of QACs to bacteria over human cells and reduces alkyl chain's entropic penalty of binding to bacterial membranes. Furthermore, phthalocyanine neutralizes hemolysis and cytotoxicity of QACs by binding with albumin in plasma. Our experimental results demonstrate that PACs inherit the optical properties of phthalocyanine and validate the broad-spectrum antibacterial activity of PACs in vitro. Moreover, the intravascular administration of the most potent PAC, PAC1a, significantly reduced bacterial burden and ameliorated inflammation level in a bacteria-induced septic mouse model. This study presents a new strategy to improve the antimicrobial efficacy and biosafety of QACs, thus expanding their range of applications to the treatment of systemic infections.

Exploring the effects of palm kernel meal feeding on the meat quality and rumen microorganisms of Qinghai Tibetan sheep.

Palm kernel meal (PKM) has been shown to be a high-quality protein source in ruminant feeds. This study focused on the effects of feed, supplemented with different amounts of PKM (ZL-0 as blank group, and ZL-15, ZL-18, and ZL-21 as treatment group), on the quality and flavor profile of Tibetan sheep meat. Furthermore, the deposition of beneficial metabolites in Tibetan sheep and the composition of rumen microorganisms on underlying regulatory mechanisms of meat quality were studied based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry as well as 16S rDNA sequencing. The results of the study showed that Tibetan sheep in the ZL-18 group exhibited superior eating quality and flavor profile while depositing more protein and fat relative to the other groups. The ZL-18 group also changed significantly in terms of the concentration and metabolic pathways of meat metabolites, as revealed by metabolomics. Metabolomics and correlation analyses finally showed that PKM feed mainly affected carbohydrate metabolism in muscle, which in turn affects meat pH, tenderness, and flavor. In addition, 18% of PKM increased the abundance of Christensenellaceae R-7 group, Ruminococcaceae UCG-013, Lachnospiraceae UCG-002, and Family XIII AD3011 group in the rumen but decreased the abundance of Prevotella 1; the above bacteria groups regulate meat quality by regulating rumen metabolites (succinic acid, DL-glutamic acid, etc.). Overall, the addition of PKM may improve the quality and flavor of the meat by affecting muscle metabolism and microorganisms in the rumen.

Albumin-based drug carrier targeting urokinase receptor for cancer therapy.

Urokinase plasminogen activator receptor (uPAR) is a key participant in extracellular proteolysis, tissue remodeling and cell motility. uPAR overexpresses in most solid tumors and several hematologic malignancies, but has low levels on normal tissues, thus is advocated as a molecular target for cancer therapy. One of the obstacles for the evaluation of uPAR targeting agents in preclinical study is the species specificity, where targeting agents for human uPAR  usually not bind to murine uPAR. Here, we develop a targeting agent that binds to both murine and human uPAR. This targeting agent is genetically fused to human serum albumin, a commonly used drug carrier, and the final construct is named as uPAR targeting carrier (uPARTC). uPARTC binds specifically to uPAR-overexpressing 293T/huPAR and 293T/muPAR as demonstrated by flow cytometry. A cytotoxic compound, celastrol, is embedded into uPARTC non-covalently. The resulting macromolecular complex show effective proliferation inhibition on both murine and human uPAR overexpressing cells, and exhibit potent antitumor efficacy on hepatoma H22-bearing mice. This work demonstrates that uPARTC is a promising tumor targeting drug carrier, which address the species-specificity challenge of uPAR targeting agents and can be used to load other cytotoxic compounds.

RNA-Seq revealed the effect of adding different proportions of wheat diet on fat metabolism of Tibetan lamb.

The objective of this study was to evaluate the effect of the level of wheat substitution for corn on the fat metabolism of Tibetan lamb. A total of 90 Tibetan lambs [body weight (BW) of 19.78 ± 2.45 kg] were arranged with three substitution levels of wheat: WC (100 % corn), WL (10 % wheat substitution for corn), and WH (15 % wheat substitution for corn) on a dry matter basis. After the experiment, cry section technology was used to scrutinize the subcutaneous adipose tissue morphology, and genes related to fat metabolism were excavated using high-throughput sequencing technology. According to the study results, fat diameter and fat biovolume of the WL and WH groups were less than the WC group. A total of 506 differentially expressed genes (DEGs) were identified by RNA sequencing (RNA-Seq) technology. Compared with the WC group, 66 DEGs were upregulated and 59 DEGs were downregulated in the WL group, and 179 DEGs were upregulated and 269 DEGs were downregulated in the WH group. The top 20 DEGs were analyzed by Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathway, indicating significant differences in the fat metabolism pathway. Five DEGs were randomly screened for quantitative reverse transcription-polymerase chain reaction (qRT-PCR) verification, and the results were consistent with the RNA-Seq results, which proved the accuracy of sequencing. In summary, with the increase in the proportion of supplemental wheat, the fat cells became smaller, and the genes related to fat decomposition were significantly upregulated.

A Data-Driven Model for Automated Chinese Word Segmentation and POS Tagging.

Chinese natural language processing tasks often require the solution of Chinese word segmentation and POS tagging problems. Traditional Chinese word segmentation and POS tagging methods mainly use simple matching algorithms based on lexicons and rules. The simple matching or statistical analysis requires manual word segmentation followed by POS tagging, which leads to the inability to meet the practical requirements for label prediction accuracy. With the continuous development of deep learning technology, data-driven machine learning models provide new opportunities for automated Chinese word segmentation and POS tagging. Therefore, a data-driven automated Chinese word segmentation and POS tagging model is proposed in order to address the above problems. Firstly, the main idea and overall framework of the proposed automated model are outlined, and the tagging strategy and neural network language model used are described. Secondly, two main optimisations are made on the input side of the model: (1) the use of word2Vec for the representation of text features, thus representing the text as a distributed word vector; and (2) the use of an improved AlexNet for efficient encoding of long-range word, and the addition of an attention mechanism to the model. Finally, on the output side, an additional auxiliary loss function was designed to optimise the Chinese text based on its frequency. The experimental results show that the proposed model can significantly improve the accuracy and operational efficiency of Chinese word segmentation and POS tagging compared with other existing models, thus verifying its effectiveness and advancement.

Performance Optimization of Surface Plasmon Resonance Imaging Sensor Network Based on the Multi-Objective Optimization Algorithm.

In this work, we report performance optimization of a wireless sensor network (WSN) based on the plain silver surface plasmon resonance imaging (SPRi) sensor. At the sensor node level, we established the refractive index-thickness models for both gold and silver in the sensor and calculated the depth-width ratio (DWR) and penetration depth (PD) values of the sensor of different gold and silver thicknesses by the Jones transfer matrix and Kriging interpolation. We optimized the DWR and PD simultaneously by using the multi-objective optimization genetic algorithm (MOGA). In the following performance optimization of WSN, we simultaneously optimized the transmission success rate and information dimension with the number of nodes and transmission failure rate of the sensor node as variables by the same algorithm. By calculating the information dimension and the transmission success rate of each Pareto optimal solution, we obtained the number of nodes and transmission failure probability of the node available for practical deployment of WSN. The above results indicate that the Pareto optimal solution set obtained from MOGA can help to provide the best solution for the optimization of some certain performance parameters and also assist us in making the trade-off decision in the structure design and network deployment if optimal values of all the performance parameters can be obtained simultaneously.

Metabolomics approach reveals high energy diet improves the quality and enhances the flavor of black Tibetan sheep meat by altering the composition of rumen microbiota.

This study aims to determine the impact of dietary energy levels on rumen microbial composition and its relationship to the quality of Black Tibetan sheep meat by applying metabolomics and Pearson's correlation analyses. For this purpose, UHPLC-QTOF-MS was used to identify the metabolome, whereas 16S rDNA sequencing was used to detect the rumen microbiota. Eventually, we observed that the high energy diet group (HS) improved the carcass quality of Black Tibetan sheep and fat deposition in the longissimus lumborum (LL) compared to the medium energy diet group (MS). However, HS considerably increased the texture, water holding capacity (WHC), and volatile flavor of the LL when compared to that of MS and the low energy diet group (LS). Metabolomics and correlation analyses revealed that dietary energy levels mainly affected the metabolism of carbohydrates and lipids of the LL, which consequently influenced the content of volatile flavor compounds (VOCs) and fats. Furthermore, HS increased the abundance of Quinella, Ruminococcus 2, (Eubacterium) coprostanoligenes, and Succinivibrionaceae UCG-001, all of which participate in the carbohydrate metabolism in rumen and thus influence the metabolite levels (stachyose, isomaltose, etc.) in the LL. Overall, a high-energy diet is desirable for the production of Black Tibetan sheep mutton because it improves the mouthfeel and flavor of meat by altering the composition of rumen microbiota, which influences the metabolism in the LL.