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Tea tree oil (TTO) plays an important role in regulating lipid metabolism and has anti-inflammatory properties. In postpartum dairy cows, dry matter intake (DMI) is dramatically decreased, resulting in lipid metabolism disorder and the systemic pro-inflammatory response. However, the effects of TTO on glucolipid metabolism and immunity in postpartum dairy cows remain uninvestigated. Therefore, this study aimed to evaluate the effects of TTO on production performance, serum biochemical indicators, and immunity in postpartum dairy cows. Our results demonstrate that DMI tended to increase (p = 0.07) in the total mixed ration (TMR) diets supplemented with 0.01% TTO/dry matter (DM) basis relative to that in the control group. The 4% fat-corrected milk (FCM) content in the 0.01% and 0.02% TTO groups showed an increase (p = 0.09) compared with that in the control. Remarkably, the levels of globulin (GLO) and immunoglobulin G (IgG) were elevated (p < 0.05) in the TMR diet supplemented with 0.02% TTO compared to those in the control group. The TTO caused no profound changes in cholesterol (CHO), triglyceride (TG), high-density lipoprotein (HDL), or low-density lipoprotein (LDL). Notably, 0.02% TTO increased (p < 0.05) the serum glucose concentration relative to that in the control group. In conclusion, our results demonstrate that TTO could improve glucolipid metabolism and enhance immunity in postpartum dairy cows. It may be a novel resolution strategy for body condition recovery and the improvement of milk performance.

Fermentation of agricultural by-products by white rot fungi is a research hotspot in the development of ruminant feed resources. The aim of this study was to investigate the potential of the nutritional value and rumen fermentation properties of white tea residue fermented at different times, using single and dual culture white rot fungal species. Phanerochaete chrysosporium, Pleurotus ostreatus, and Phanerochaete chrysosporium + Pleurotus ostreatus (dual culture) solid-state fermented white tea residue was used for 4 weeks, respectively. The crude protein content increased significantly in all treatment groups after 4 weeks. Total extractable tannin content was significantly decreased in all treatment groups (p < 0.01). P. chrysosporium and dual culture significantly reduced lignin content at 1 week. The content of NH3-N increased in each treatment group (p < 0.05). P. chrysosporium treatment can reduce the ratio of acetic to propionic and improve digestibility. Solid state fermentation of white tea residue for 1 week using P. chrysosporium was the most desirable.

Acetate is a precursor substance for fatty acid synthesis in bovine mammary epithelial cells (BMECs), and the mTOR signaling pathway plays an important role in milk fat synthesis. However, the mechanism of the regulatory effects of acetate on lipogenic genes via the mTOR signaling pathway in BMEC remains unknown. We hypothesized that acetate can enhance the expression of lipogenic genes and triglyceride (TG) production by activating the mTOR signaling pathway in BMECs. Therefore, the aim of this study was to investigate the network of acetate-regulated lipid metabolism by the mTOR signaling pathway in BMECs. These results showed that TG synthesis was elevated (p < 0.01) in BMECs with acetate treatment. The lipid droplets were increased in the acetate-treated groups compared with those in the control group through the Bodipy staining of the lipids. In addition, the fatty acid profile in BMECs treated with acetate was affected, with an elevation in the proportions of C14:0, C16:0, and C18:0. The mRNA levels of the sterol-response-element-binding protein 1 (SREBP1), stearoyl-CoA desaturase 1 (SCD1), and fatty acid synthase (FAS) genes involved in the lipogenesis and transcriptional factors were upregulated (p < 0.05) in BMECs with acetate treatment. Remarkably, the expression of acetyl-CoA carboxylase α (ACCα) and FAS rate-limiting enzymes involved in lipogenesis was upregulated in BMECs with acetate treatment. Moreover, the addition of acetate enhanced the key protein expression of S6K1, which is related to the mTOR signaling pathway. Taken together, our data suggest that TG accumulation and expression of lipogenic genes induced by acetate are associated with the activation of the mTOR signaling pathway, which provides new insights into the understanding of the molecular mechanism in the expression of mTOR-signaling-pathway-regulated lipogenic genes.

Background: Esophageal squamous cell carcinoma (ESCC) is among the most prevalent causes of cancer-related death in adults. Tumor microenvironment (TME) has been associated with therapeutic failure and lethal outcomes for patients. However, published reports on the heterogeneity and TME in ESCC are scanty. Methods: Five tumor samples and five corresponding non-malignant samples were subjected to scRNA-seq analysis. Bulk RNA sequencing data were retrieved in publicly available databases. Findings: From the scRNA-seq data, a total of 128,688 cells were enrolled for subsequent analyses. Gene expression and CNV status exhibited high heterogeneity of tumor cells. We further identified a list of tumor-specific genes and four malignant signatures, which are potential new markers for ESCC. Metabolic analysis revealed that energy supply-related pathways are pivotal in cancer metabolic reprogramming. Moreover, significant differences were found in stromal and immune cells between the esophagus normal and tumor tissues, which promoted carcinogenesis at both cellular and molecular levels in ESCC. Immune checkpoints, regarded as potential targets for immunotherapy in ESCC were significantly highly expressed in ESCC, including LAG3 and HAVCR2. Eventually, we constructed a cell-to-cell communication atlas based on cancer cells and immune cells and performed the flow cytometry, qRT-PCR, immunofluorescence, and immunohistochemistry analyses to validate the results. Interpretation: This study demonstrates a widespread reprogramming across multiple cellular elements within the TME in ESCC, particularly in transcriptional states, cellular functions, and cell-to-cell interactions. The findings offer an insight into the exploration of TME and heterogeneity in the ESCC and provide new therapeutic targets for its clinical management in the future.

Background: Depression is prevalent in patients with all stages of CKD and is associated with adverse outcome. Abnormally elevated GFR, or hyperfiltration, may play a crucial role in the initiation and progression of CKD. However, the association between depression and hyperfiltration is not known. The aim of this study is to investigate the relationship between depression and hyperfiltration. Methods: This was an observational cross-sectional study. A total of 3,716 volunteers (1,303 males and 2,413 females) aged 40–75 years without CKD from a community in China were included for the study. Depressive symptoms and the presence of a minor or major depressive episode were assessed with the 9-item Patient Health Questionnaire (PHQ-9) and Diagnostic and Statistical Manual of Mental Disorders (4th edition)-based structured interview, respectively. Results: The mean age of the participants in the present study was 53.8 ± 9.0 years. 115 participants had clinically relevant depression, and 122 participants had a minor or major depressive episode. In a multivariable logistic regression analysis adjusted for potential confounders, the association between clinically relevant depression and renal hyperfiltration remained significant in men but not in women. As compared with men without depression (PHQ

Abstract Salmonella is a pathogenic bacterium contributing to food poisoning and acute infectious intestinal disease. The traditional standard detection method is based on the principle of liquid phase enrichment and has a low sensitivity on targeted bacteria. We previously developed a visual immunosensor technique for efficient detection and isolation of Salmonella by applying fluorescent nanobioprobes on a specially-designed cellulose-based swab. In this study, a whole-sample solid-phase enrichment assay (WSEA) was established by optimization of the enrichment medium using response surface methodology (RSM), a powerful statistical tool for regression analysis. The optimal formula was determined as: 0.60% polyvalent poly peptone, 0.40% buffered peptone water, 0.09% ferric citrate amine, 0.24% sodium hyposulfite, 0.035% cystine, 0.01 µg mL−1 super absorbing polymer, 0.011% sodium deoxycholate, 15.00 µg mL−1 ethyl green and 30.00 µg mL−1 sodium selenite. Using this formula, Salmonella was visualized with naked eyes by relying on the indication of black spots formed on the swab. The analytic sensitivity of the assay was determined as 101 cells mL−1 with a concentration of interfering bacteria (Escherichia coli) at 105 cells mL−1. This optimized formula was confirmed with 4006 patients’ fecal samples, in which the positive rate was 0.42% by the conventional culture-based method and 2.12% by WSEA. The optimized formulation on solid phase enrichment by RSM allows relatively quick, low-cost, and large-scale detection of Salmonella, and could be used in grassroots medical institutions.

Background/Purpose: Experience in procedures combining left atrial appendage (LAA) closure (LAAC) and catheter ablation (CA) was scarce in Chinese nonvalvular atrial fibrillation (AF) patients with high risks for stroke and bleeding. We aimed to investigate the efficacy and safety of the combination therapy with LAAC and AF CA in a single procedure based on the multicenter data and medium-term follow-up results. Methods: A total of 122 AF patients with a mean CHA2DS2-VASc score of 4.3 ± 1.4 and HAS-BLED score of 3.3 ± 1.0 were enrolled. The Watchman (n = 83) devices were implanted either before or after AF ablations in the same procedure, while the Amplatzer Cardiac Plug (ACP, n = 39) devices were implanted immediately after CA. AF recurrence and transesophageal echocardiography results were evaluated. Results: All devices were successfully implanted and acute complete LAA occlusions were achieved in 115 (94.3%) of patients. Neither acute nor chronic peri-device leaks greater than 5 mm were detected. Oral anticoagulation was held in all patients but two with asymptomatic device-related thrombi, which were resolved after prolonged anticoagulation. AF-free success rate without antiarrhythmic drugs was 76.2% after a mean follow-up of 11.5 ± 6.8 months. No serious complications were observed during the follow-up. Conclusion: The combination therapy with LAAC and AF ablation in a single procedure was efficacious and safe in the Chinese symptomatic AF population with high risk for stroke and bleeding. Keywords: Atrial fibrillation, Catheter ablation, Left atrial appendage closure, Oral anticoagulation

In cloud architectures, the microservice model divides an application into a set of loosely coupled and collaborative fine-grained services. As a lightweight virtualization technology, the container supports the encapsulation and deployment of microservice applications. Despite a large number of solutions and implementations, there remain open issues that have not been completely addressed in the deployment and management of the microservice containers. An effective method for container resource scheduling not only satisfies the service requirements of users but also reduces the running overhead and ensures the performance of the cluster. In this paper, a multi-objective optimization model for the container-based microservice scheduling is established, and an ant colony algorithm is proposed to solve the scheduling problem. Our algorithm considers not only the utilization of computing and storage resources of the physical nodes but also the number of microservice requests and the failure rate of the physical nodes. Our algorithm uses the quality evaluation function of the feasible solutions to ensure the validity of pheromone updating and combines multi-objective heuristic information to improve the selection probability of the optimal path. By comparing with other related algorithms, the experimental results show that the proposed optimization algorithm achieves better results in the optimization of cluster service reliability, cluster load balancing, and network transmission overhead.

The development of e-commerce has ushered in a golden age. E-commerce product reviews are remarks initiated by online shopping users to evaluate the quality and service of the products they purchase; these reviews help consumers learn the reality of the product. The sentiment polarity of e-commerce product reviews is the best way to obtain customer feedback on products. Therefore, sentiment analysis of product reviews on e-commerce platforms is greatly significant. However, the challenges of sentiment analysis of Chinese e-commerce product reviews lie in dimension mapping, disambiguation of sentiment words, and polysemy of Chinese words. To solve the above problems, this paper proposes a sentiment analysis model ERNIE-BiLSTM-Att (EBLA). Here, the dynamic word vector generated using the Enhanced Representation through Knowledge Integration (ERNIE) word embedding model is input into the Bidirectional Long Short-term Memory (BiLSTM) to extract text features. Then, the Attention Mechanism (Att) is used to optimize the weight of the hidden layer. Finally, softmax is used as the output layer for sentiment classification. The experimental results on the JD.com Chinese e-commerce product review dataset show that the proposed model achieves more than 0.87 in precision, recall, and F1 values, which is superior to classic deep learning models proposed by other researchers; it has strong practicability in sentiment analysis of Chinese e-commerce product reviews.

Premature damage to heavy-duty pavement has been found to be significantly caused by the vehicle–highway alignment interaction, especially in mountainous regions. This phenomenon was further verified by field pavement damage investigations and field tests. In order to elucidate the potential mechanism of this interaction, it is important to address the vehicle dynamic loads generated by the interaction between vehicle and pavement. Based on this, the paper realizes a new method of vehicle dynamic load prediction using data mining techniques, namely artificial neural network (ANN) and support vector machine (SVM)). The data, including dynamic loads and highway geometric characteristics, were collected by a wheel force transducer (WFT) and global positioning system (GPS), respectively. The coefficient of determination (R2) and root mean square error (RMSE) were used to evaluate the performance of the prediction models. The results showed that the proposed dynamic load prediction model established by ANN was better than that by SVM. Moreover, the model implied that dynamic loads were highly correlated with curvature and longitudinal grade, and furthermore, curvature was found to have a larger effect. The proposed dynamic load prediction technique provides a feasible and rapid approach to identify pavement damage under complex vehicle–highway alignment interactions.

Improving the life service for the elderly is a topic of great concern to the government and society. This paper explores the influence of net attention on social work service satisfaction of the elderly. This paper studies and analyzes the current situation of the elderly’s net attention and social satisfaction, constructs the index system of social service satisfaction through the sample data of 17 districts and counties in A province, and establishes a multilayer linear model to analyze the influencing factors of social service satisfaction, and empirically analyzes the feasibility of the proposed model’s rationality and effectiveness. The structure shows that the scores of elderly people’s satisfaction with public services in all regions of A province are higher than 60 points, and the biggest difference of standard deviation of each region is 3.91 points. Public service expenditure has a negative effect on social service satisfaction, but population density, geographical location, and per capita GDP have no obvious effect. The regression coefficient of public service expenditure is -0.099134, which can reduce the score of social service satisfaction. Elderly participation in public welfare activities, elderly awareness of government, and elderly participation in government can improve the social service satisfaction score.

Twenty-four healthy castrated male Holstein growing cattle, with similar body weight (301 ± 11.5 kg), were enrolled in this study and randomly allocated into two groups (12/pen). Holstein growing cattle in the LPT (low NFC/NDF pelleted TMR) group were fed basal pelleted TMR with a low NFC/NDF ratio (NFC/NDF = 1.07), while the HPT (high NFC/NDF pelleted TMR) group were fed with a high NFC/NDF ratio diet (NFC/NDF = 1.71). The results showed that: (1) Body measurements were found to be increased for the LPT group (p < 0.05); compared with the HPT group, feed intake to gain ratio and feed cost in the LPT group were decreased by 12.24% and 15.35%, respectively (p < 0.01). Compared with the HPT group, the LPT group tended to increase chest girth. (2) Digestibility of DM and NDF in the LPT group was higher (p < 0.05) than in the HPT group, being increased by 3.41% and 4.26%, respectively, and increased digestibility of ADF in the LPT group was significant (p < 0.01). (3) The daily feed consumption of NDF in the LPT group was higher than that in the HPT group and the daily rumination time and chewing time in the LPT group were longer than that in the HPT group (p < 0.05). (4) Compared with the LPT group, the parameter of pH, microbial protein and acetate: propionate (p < 0.05) in the HPT group were decreased by 8.57%, 12.46% and 23.71%, respectively. In contrast, the concentration of total volatile fatty acids, acetate and propionate were higher (p < 0.05) in the HPT group, and increased by 13.49%, 19.59% and 52.70%, respectively. (5) Compared with the LPT group, rumen fluid in the HPT group diet up-regulated the mRNA expression levels of BRECs pro-inflammatory factor IL-1β and TNF-α (p < 0.05), and meanwhile, up-regulated the mRNA expression levels of BRECs pro-inflammatory factor IL-6 (p < 0.01); compared with the LPT group, rumen fluid in the HPT group diet up-regulated the mRNA expression levels of CCL28 and CCL20 (p < 0.05) chemokines in CCL types of BRECs; in addition, compared with the LPT group, rumen fluid in the HPT group up-regulated the mRNA expression levels of CXCL2, CXCL3, CXCL9 and CXCL14 chemokines in CXCL types of BRECs (p < 0.01), and the mRNA expression levels of the CXCL5 chemokine tended to be increased (p = 0.06).

Idiopathic pulmonary fibrosis (IPF) can severely disrupt lung function, leading to fatal consequences, and there is currently a lack of specific therapeutic drugs. Bergenin is an isocoumarin compound with lots of biological functions including antioxidant activity. This study evaluated the potential beneficial effects of bergenin on pulmonary fibrosis and investigated the possible mechanisms. We found that bergenin alleviated bleomycin-induced pulmonary fibrosis by relieving oxidative stress, reducing the deposition of the extracellular matrix (ECM) and inhibiting the formation of myofibroblasts. Furthermore, we showed that bergenin could induce phosphorylation and expression of p62 and activation of Nrf2, Nrf2 was required for bergenin-induced p62 upregulation, and p62 knockdown reduced bergenin-induced Nrf2 activity. More importantly, knockdown of Nrf2 or p62 could abrogate the antioxidant activity of bergenin and the inhibition effect of bergenin on TGF-β-induced ECM deposition and myofibroblast differentiation. Thereby, a regulatory loop is formed between p62 and Nrf2, which is an important target for bergenin aimed at treating pulmonary fibrosis.

Background/Aims: The aim of the study was to investigate clinicopathological characteristics, the role of immunosuppressive therapy and renal outcome in IgA nephropathy (IgAN) patients with hyperuricemia. Methods: 206 biopsy-proven primary IgAN patients were included between January 2010 and December 2015, and divided into two groups: patients without hyperuricemia (n=122), and patients with hyperuricemia (n=84). The clinicopathological features, response, renal outcome and safety were recorded. In univariate and multivariate models, hyperuricemia-associated pathological factors were analyzed. Results: The patients with hyperuricemia presented higher systolic blood pressure, worse kidney function and more severe time-averaged proteinuria. Proportions of glomerulosclerosis, segmental glomerulosclerosis, tubular atrophy/interstitial fibrosis, lymphocytes and monocytes infiltration were higher, while the proportion of segmental adhesion was lower in patients with hyperuricemia. By multivariate logistic regression analysis, only tubular atrophy/interstitial fibrosis (T1∼2) (HR=3.969, 95% CI=1.439−10.945, P=0.008) was significantly associated with hyperuricemia. For hyperuricemic patients, the response rate to therapy and renal survival rate were significantly higher in patients that received RAS blockade in combination with immunosuppressive therapy. After RAS blockade treatment, renal survival in the patients with hyperuricemia was worse compared with the patients without hyperuricemia. Conclusion: Hyperuricemic IgAN patients presented more severe clinical features. Tubulointerstitial injury could be a pathological feature closely related to hyperuricemia in IgAN. Immunosuppressive therapy and RAS blockade could reduce proteinuria and improve renal outcome in IgAN patients with hyperuricemia.

Background/Aims: Previous studies imply that telocytes may have a protective effect on fibrosis in various organs, including the liver, colon, and heart. The effect of telocytes on renal fibrosis remains unknown. Herein, this study was designed to investigate the effect of telocytes on renal fibrosis and the potential mechanisms involved. Methods: In a unilateral ureteral obstruction (UUO)-induced renal fibrosis model, telocytes were injected via the tail vein every other day for 10 days. The degree of renal damage and fibrosis was determined using histological assessment. The expression of collagen I, fibronectin, epithelial-mesenchymal transition markers, and Smad2/3 phosphorylation was examined by western blot analyses. Real-time PCR and enzyme-linked immunosorbent assay were performed in vivo to detect the levels of transforming growth factor (TGF)-β1 and various growth factors. Results: Telocytes attenuated renal fibrosis, as evidenced by reduced interstitial collagen accumulation, decreased expression of fibronectin and collagen I, upregulation of E-cadherin, and downregulation of α-smooth muscle actin. Furthermore, telocytes decreased serum TGF-β1 levels, suppressed Smad2/3 phosphorylation, and increased the expression of hepatocyte growth factor (HGF) in rat kidney tissue following UUO. Blockage of HGF counteracted the protective effect of telocytes on UUO-treated kidneys. Through the detection of HGF mRNA levels in vitro, we found that telocytes had no effect on HGF expression compared with renal fibroblasts. Conclusion: Telocytes attenuated UUO-induced renal fibrosis in rats, likely through enhancing the expression of HGF in an indirect manner.

Sixty castrated male Haimen white growing goats with an initial age of 100 days old and similar body weight (16 ± 1.5 kg) were selected and randomly allocated into five groups with three replicates in each group with four goats in each pen (5 m × 3.2 m). Goats in the control group (CG) were fed a basal pelleted total mixed ration supplemented with 30% alfalfa hay pellet, while experimental treatments (G6, G12, G18, or G24) were supplemented with four levels (6%, 12%, 18%, or 24%) of GBLR replacing alfalfa hay pellet in the diet, separately. Results showed that (1) the final body weight, average daily gain, and average feed intake of G18 was significantly higher (p < 0.05) than CG; in contrast, the feed conversion ratio of G18 was significantly lower than CG and G12 (p < 0.05); the feed cost per head per day of CG was significantly higher (p < 0.05) than that of G18 and G24, and exhibited obvious linearly decrease (p = 0.04) with increasing GBLR supplementation; and apparent total-tract digestibility of DM and NDF in GBLR treatments were significantly higher (p < 0.05) than CG; (2) alanine transaminase (ALT) concentration in the G18 group was significantly lower (p < 0.05) than those in the control group; aspartate transaminase (AST) concentration in the G24 was significantly lower (p < 0.05) than those in the control group, and an increase in dietary level of GBLR tended to result in a linear decrease (p = 0.09) in the concentration of serum AST; (3) the concentration of malondialdehyde (MDA) demonstrated a tendency to decrease (p = 0.06) linearly with increasing GBLR supplementation; however, glutathione peroxidase (GSH-PX) activity in G12 was significantly higher (p < 0.05) than CG, G6, and G24; in addition, superoxide dismutase (SOD) activity in G18 was significantly higher (p < 0.05) than CG and G6; concentration of immunoglobulin M (IgM), immunoglobulin G (IgG), and immunoglobulin A (IgA) were not affected by GBLR, but increasing dietary GBLR showed a tendency (p = 0.08) to linearly increase the IgG concentration; the content of interleukin 4 (IL4) was significantly higher (p < 0.05) in G12, G18, and G24 than that in CG and G6; (4) There were similar NH3-N, pH, TVFA, and butyrate for goats fed different levels of GBLR supplementation; the C2 (p = 0.07) and acetate: propionate (p = 0.06) demonstrated a tendency to increase linearly with increasing level of GBLR supplementation, separately; however, it was observed that concentration of propionate showed a tendency to decrease (p = 0.08) linearly in response to GBLR supplementation; and (5) Increasing dietary GBLR tended to linearly enhance the lightness (L*) (p = 0.07) and yellowness (b*) (p = 0.09) values of longissimus dorsi muscles; the redness (a*) value in G18 was significantly higher than that in CG (p < 0.05).

Bacillus megaterium is an ideal microecologics in the feed industry. BM1259 was already isolated from chicken manure and the whole-genome sequencing was also analyzed in our previous study. However, few studies concentrated on dietary supplementation with BM1259 in young ruminants and especially its effect on Holstein bull calves have not been reported. Hence, this experiment was conducted with the aim to evaluate the effects of BM1259 on growth performance, nutrient digestibility, rumen fermentation, and blood biochemical parameters in Holstein bull calves. Twenty-four healthy Holstein bull calves with the initial age of 90 days old and a similar body weight (115 ± 6.5 kg) were selected and randomly allocated into two groups with one Holstein bull calf in each pen (2.5 m × 2.2 m). Holstein bull calves in the control group (COG) were fed a basal total mixed ration (TMR), while experimental treatments (BMG) were fed with the TMR diet supplemented with 12 g/head/day of BM1259 powder (1 × 1010 cfu/g) separately. Results showed that (1) the average daily gain and dry matter intake of the BMG were significantly higher than those of the COG (p < 0.01), increased by 12.5% and 8.79%, respectively, during the 4–8 weeks after the addition of 12 g/head/day of BM1259; from 0 to 8 weeks, ADG (p < 0.05) and DMI (p < 0.05) in the BMG were significantly higher than those in the COG, increased by 14.9% and 6.04%, respectively. (2) At the end of the fourth week, the apparent digestibility of crude protein and neutral detergent fiber in the BMG was significantly higher than that in the COG (p < 0.05), increased by 5.97% and 6.70%, respectively; at the end of the eighth week, the apparent digestibility of crude protein and neutral detergent fiber was significantly higher than that of the COG (p < 0.01), increased by 5.88% and 10.26%, respectively. (3) At the end of the eighth week, the rumen fluid pH (p < 0.05), MCP (p < 0.05), and acetate (p < 0.05) in the BMG were significantly higher than those in the COG, increased by 9.03%, 19.68%, and 12.74%, respectively; at the end of the fourth and eighth week, NH3-N concentration in the BMG was significantly lower than that in the COG, with a decrease of 21.81% and 16.40%, respectively. (4) At the end of the fourth (p < 0.05) and eighth week (p < 0.05), the glutamate content of the rumen fluid of the Holstein bull calves in the BMG was significantly higher than that in the COG, increased by 13.21% and 14.32%, respectively; at the end of the fourth week, the contents of glutamate in the serum (p < 0.05), urine (p < 0.05), and feces (p < 0.05) of the Holstein bull calves in the BMG were significantly lower than those in the COG, decreased by 25.76%, 33.87%, and 9.23%, respectively; at the end of the eighth week, the contents of glutamate in the serum, urine, and feces of the Holstein bull calves in the BMG were significantly lower than those in the COG (p < 0.01), decreased by 26.69%, 27.94%, and 11.11%, respectively. (5) After adding 12 g/head/day of BM1259, the urine ammonia–nitrogen content of the BMG was extremely significantly lower than that of the COG at the end of the fourth and eighth week (p < 0.01), decreased by 54.60% and 40.31%, respectively. (6) After adding 12 g/head/day of BM1259, there was no significant effect on the level of blood biochemical parameters of the Holstein bull calves. This study demonstrates that BM1259 can be applied as a potential microecologics to improve growth performance, nutrient digestibility, rumen fermentation, and nitrogen utilization in Holstein bull calves.

In subacute rumen acidosis (SARA), the rumen epithelium is frequently attacked by endotoxin (LPS), which is caused by the lysis of dead Gram-negative bacteria. However, the rumen epithelium innate immune system can actively respond to the infection. Previous studies have demonstrated that tea tree oil (TTO) has good bactericidal and anti-inflammatory effects. Therefore, the aim of this study was to investigate the effect of TTO on the expression of genes involved in the inflammatory cytokines in goat rumen epithelial cells (GRECs) triggered by LPS. Our study shows that rumen epithelial cells isolated from goat rumen tissue can be cultured in vitro in 0.25% trypsin for a long time. These cells were identified as epithelial cells by the expression of cytokeratin 18, monocarboxylate transporter 4 (MCT4), Na[+]/H[+] hydrogen exchanger 1 (NHE1), putative anion transporter 1 (PAT1), vH+ ATPase B subunit (vH+ ATPase), and anion exchanger 2 (AE2). The mRNA expression of IL-1β, IL-6, TNF-α, TLR-2, NF-κB, CXCL6 and CXCL8 genes was significantly increased when LPS was used compared to untreated controls. In addition, mRNA expression of IL-1β, IL-6, TNF-α, TLR-2, NF-κB, CXCL8, CXCL6 and interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) genes was also significantly higher in the LPS group compared to the 0.05% TTO group. However, the expression of IL-1β, IL-6, TNF-α, TLR-2, CXCL6 and IFIT3 genes was significantly lower in the LPS and 0.05% TTO group compared to the 1 μg/mL LPS group. These results suggest that TTO can inhibit LPS-induced inflammatory cytokines expression in GRECs.

Material anisotropy significantly impacts the mechanical behaviors of asphalt pavements. However, most current asphalt pavement design methods treat the material properties only as isotropic, which could significantly skew the mechanical behaviors. There is a need to evaluate the impact of material anisotropy on pavement mechanical behaviors. In this study, we first developed a new and efficient 3-dimensional finite element (FE) model of anisotropic material. Then, the feasibility of the proposed FE model was verified using field data collected with a falling weight deflectometer. Finally, using this model, the contributions of each layer anisotropy to the mechanical properties were determined. The results showed that the mechanical behaviors were more sensitive to the orthotropy than to the transverse isotropy of the material. The all-layer orthotropy was the most unfavorable combination. In addition, the subgrade orthotropy showed the most significant effect on increasing the surface deflection and compressive strain of the subgrade top (by about 10%). Based on the study results, we recommend that the homogeneity degree of the filling subgrade should be strictly controlled to ensure adequate pavement capacity and anti-rutting performance during construction.

This paper focuses on the pricing problem of a two-stage closed-loop supply chain (CLSC) considering the cross-channel recycling and channel preference based on a single manufacturer and a single traditional retailer. The pricing decision problem raises from the manufacturer’s direct sales and the retailer’s retailing including recycling. Managers need to focus on intelligible management considering consumer channel preferences, cross-channel recovery and pricing strategies. According to game theory, centralized and decentralized CLSC decision models are used to provide an efficient solution to managers for the pricing problem. The centralized model consists of differential and uniform pricing strategy and the decentralized model consists of manufacturer-led Stackelberg, retailer-led Stackelberg and Nash equilibrium game, respectively. The impact of cross-channel recycling rate and channel preference on pricing and profitability in a two-stage CLSC system is explained elaborately in this study. The results show that cross-channel recovery rates and consumer channel preferences have a direct significant impact on pricing strategies including profit allocation decisions in CLSC. It demonstrated that different channel preferences leading to different pricing strategies and decision for manufacturers and retailers choices. Manufacturer’s pricing decreases when channel preferences are constant and cross-channel recovery rates increase. Retailer’s pricing remains stable as the cross-channel recovery rate has less affected on it. Furthermore, if the cross-channel recovery rates increase, then the manufacturers pricing decreases and retailers pricing increases. This information will be a helpful guideline for the manager to select suitable pricing strategies based on the company scenario.

Abstract Background Neoadjuvant chemoradiation is not recommended as an approach for treatment of esophageal squamous cell carcinoma due to its significant postoperative mortality. However, it is assumed the combination of neoadjuvant chemoradiation with minimally invasive esophagectomy (MIE) may reduce postoperative mortality, which can revive preoperative chemoradiation. No randomized controlled studies comparing neoadjuvant chemoradiation plus MIE with neoadjuvant chemotherapy plus MIE have been performed so far. The present trial is initiated to obtain valid information whether neoadjuvant chemoradiation plus MIE yields better survival without worse postoperative morbidity and mortality in the treatment of locally advanced resectable esophageal squamous cell carcinoma(cT3-4aN0-1M0). Methods/design CMISG1701 is a multicenter, prospective, randomized, phase III clinical trial, investigating the safety and efficacy of neoadjuvant chemoradiation plus MIE compared with neoadjuvant chemotherapy plus MIE. Patients with locally advanced resectable esophageal squamous cell carcinoma (cT3-4aN0-1M0) are eligible for the study. A total of 264 patients are randomly assigned to neoadjuvant chemoradiation (arm A) or neoadjuvant chemotherapy (arm B) with a 1:1 allocation ratio. The primary outcome is overall survival assessed with a minimum follow-up of 36 months. Secondary outcomes are progression-free survival, recurrence-free survival, postoperative pathologic stage, treatment-related complications, postoperative mortality as well as quality of life. Discussion The objective of this trial is to identify the superior protocol with regard to patient survival, treatment morbidity/mortality and quality of life between neoadjuvant chemoradiation plus MIE and neoadjuvant chemotherapy plus MIE. Trial registration NCT03001596 (December 17, 2016).

This experiment was conducted to study the effects of dietary alfalfa flavonoids extraction supplemental level on growth performance, organ development and blood biochemical indexes of Yangzhou geese at the age of 28 to 70 days. Two hundred and forty 21-day-old healthy male geese with similar body weight were randomly distributed into 4 groups with 6 replicates per group and 10 geese per replicate. Geese in the control group were fed a basal diet and the others in the experimental groups (groups 1, 2, and 3) were fed experimental diets supplemented with 150, 300 and 450 mg/kg alfalfa flavonoids extraction (the concentration of it was 81%), respectively. The experiment had 7 days for pre-test and 42 days for formal test. The results showed that the final body weight and average daily intake of group 2 were significantly higher than those of other groups (P 0.05). Pre-slaughter live weight, carcass weight, slaughter rate, semi-eviscerated weight, semi-eviscerated rate, eviscerated weight, eviscerated rate, leg muscle weight and leg muscle rate had no significant difference between each group (P > 0.05). The breast muscle weight and ratio of each test group were significantly higher than those in the control group (P 0.05). Spleen weight in test groups was significantly higher than that in the control group (P 0.05). Alanine aminotransferase and aspartate transaminase (AST) in groups 2 and 3 were higher than those in the group 1 and control group but not obvious (P > 0.05) and alkaline phosphatase (ALP) in groups 1 and 2 was higher than that in the control group and group 3 (P > 0.05). It is concluded that alfalfa flavonoids extraction added in dietary feed improve the growth performance, organ development and blood biochemical indexes of Yangzhou geese. It is concluded that 300 mg/kg supplemental level of the dietary alfalfa flavonoids extraction is optimal in this experiment.

Since the effect of intermediate principal stress on the strength of pavement materials is not entirely clear so far, a proprietary true triaxial apparatus was developed to simulate the spatial status of principal stresses to conduct compressive strength tests on different gradations of AC-13, different cement contents of cement-stabilized macadam. With the same minimum principal stress, the triaxial compressive strengths of cube specimens under different intermediate principal stresses were compared. The results indicate that, as the intermediate principal stress increases, the compressive strength of the specimen increases and then decreases; different gradations of AC-13 do not show much difference in triaxial compressive strength while different cement contents of cement-stabilized macadam indicate considerable difference. Analysis results suggest significant effect of intermediate principal stress on the compressive strength of pavement materials: for AC-13, the coarser the gradation, the greater the effect of intermediate principal strength on its strength; for cement-stabilized Macadam, the higher the cement content, the greater the effect of intermediate principal stress. Strength model analysis results suggest that Double-Shear-Corner Model is more suitable to characterize cement-stabilized macadam’s strength performance compared to the Mohr–Coulomb model and Double-Shear Model.

To expand the armamentarium of treatment for chronic kidney disease (CKD), we explored the utility of boosting endogenously synthesized N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP), which is augmented by inhibition of the angiotensin converting enzyme. Male BALB/c mice underwent unilateral ureteral ligation (UUO) or sham operation and received exogenously administered Ac-SDKP delivered via a subcutaneous osmotic minipump or Captopril treatment by oral gavage. Seven days after UUO, there were significant reductions in the expression of both collagen 1 and collagen 3 in kidneys treated with Ac-SDKP or Captopril, and there was a trend towards reductions in collagen IV, α-SMA, and MCP-1 versus control. However, no significant attenuation of interstitial injury or macrophage infiltration was observed. These findings are in contrary to observations in other models and underscore the fact that a longer treatment time frame may be required to yield anti-inflammatory effects in BALB/c mice treated with Ac-SDKP compared to untreated mice. Finding an effective treatment regimen for CKD requires fine-tuning of pharmacologic protocols.

The orbital occupancy, as the origin of Hund's rule coupling, provides critical information in understanding the multiorbital iron-based superconductors. The one-unit-cell (1UC) FeSe thin film on a SrTiO3 substrate with superconductive Tc above 60 K has been reported with unique electronic structures as well as orbital occupancy. In this paper, we present the x-ray absorption spectroscopy and resonant inelastic x-ray scattering (RIXS) study of the FeSe/STO thin films of different thicknesses. Together with the atomic multiplet simulation analysis, the FeSe/STO thin films (from 1UC to 10UC) are shown with the pure 3d6 electronic configuration which is identical to the bulk FeSe. Moreover, 1UC FeSe/STO is found to be distinctively more persistent in hosting the 3d6 configuration other than the thicker films under the oxidization process. The robustness of the 3d6 in 1UC FeSe/STO is discussed as a result of charge transfer from the substrate, as well as a mechanism to maintain the high-Tc superconductivity. Finally, our research calls for a further high-resolution RIXS study of the pristine superconductive 1UC FeSe/STO thin film.

The recent discovery of spin-triplet superconductivity emerging from a nonmagnetic parent state in UTe2 has stimulated great interest in the underlying mechanism of Cooper pairing. Experimental characterization of short-range electronic and magnetic correlations is vital to understanding these phenomena. Here we use resonant inelastic x-ray scattering (RIXS), x-ray absorption spectroscopy (XAS), and atomic-multiplet-based modeling to shed light on the active debate between 5f26d1-based models with singlet crystal field states versus 5f3-based models that predict atomic Kramers doublets and much greater 5f itinerancy. The XAS and RIXS data are found to agree strongly with predictions for a 5f26d1-like valence electron configuration with weak intradimer magnetic correlations, and provide a context for interpreting recent investigations of the electronic structure and superconducting pairing mechanism.

Bone marrow-derived mesenchymal stem cells (BM-MSCs) have recently shown promise as a therapeutic tool in various types of chronic kidney disease (CKD) models. However, the mechanism of action is incompletely understood. As renal prognosis in CKD is largely determined by the degree of renal tubular injury that correlates with residual proteinuria, we hypothesized that BM-MSCs may exert modulatory effects on renal tubular inflammation and epithelial-to-mesenchymal transition (EMT) under a protein-overloaded milieu. Using a co-culture model of human proximal tubular epithelial cells (PTECs) and BM-MSCs, we showed that concomitant stimulation of BM-MSCs by albumin excess was a prerequisite for them to attenuate albumin-induced IL-6, IL-8, TNF-α, CCL-2, CCL-5 overexpression in PTECs, which was partly mediated via deactivation of tubular NF-κB signaling. In addition, albumin induced tubular EMT, as shown by E-cadherin loss and α-SMA, FN and collagen IV overexpression, was also prevented by BM-MSC co-culture. Albumin-overloaded BM-MSCs per se retained their tri-lineage differentiation capacity and overexpressed hepatocyte growth factor (HGF) and TNFα-stimulating gene (TSG)-6 via P38 and NF-κB signaling. Albumin-induced tubular CCL-2, CCL-5 and TNF-α overexpression were suppressed by recombinant HGF treatment, while the upregulation of α-SMA, FN and collagen IV was attenuated by recombinant TSG-6. Neutralizing HGF and TSG-6 abolished the anti-inflammatory and anti-EMT effects of BM-MSC co-culture in albumin-induced PTECs, respectively. In vivo, albumin-overloaded mice treated with mouse BM-MSCs had markedly reduced BUN, tubular CCL-2 and CCL-5 expression, α-SMA and collagen IV accumulation independent of changes in proteinuria. These data suggest anti-inflammatory and anti-fibrotic roles of BM-MSCs on renal tubular cells under a protein overloaded condition, probably mediated via the paracrine action of HGF and TSG-6.

Biased random walk has been studied extensively over the past decade especially in the transport and communication networks communities. The mean first passage time (MFPT) of a biased random walk is an important performance indicator in those domains. While the fundamental matrix approach gives precise solution to MFPT, the computation is expensive and the solution lacks interpretability. Other approaches based on the Mean Field Theory relate MFPT to the node degree alone. However, nodes with the same degree may have very different local weight distribution, which may result in vastly different MFPT. We derive an approximate bound to the MFPT of biased random walk with short relaxation time on complex network where the biases are controlled by arbitrarily assigned node weights. We show that the MFPT of a node in this general case is closely related to not only its node degree, but also its local weight distribution. The MFPTs obtained from computer simulations also agree with the new theoretical analysis. Our result enables fast estimation of MFPT, which is useful especially to differentiate between nodes that have very different local node weight distribution even though they share the same node degrees.