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Purpose: Radiation-induced sarcomas (RISs) have poor prognosis and lack effective treatments. Its genome and tumor microenvironment are not well characterized and need further exploration. Experimental Design: Here, we perform whole exome (WES) and mRNA sequencing (mRNA-seq) on patient with RISs and primary sarcomas (WES samples 46 vs 48, mRNA-seq samples 16 vs 8, mainly in head and neck), investigate the anti-tumor effect of PD-1 blockade in RIS-PDX models, and analyze clinical data of RIS patients treated with chemotherapy alone or combined with an anti-PD-1 antibody. Results: Compared to primary sarcomas, RISs manifested different pattern of copy number variations, significantly higher number of predicted strong MHC-binding neoantigens, and significantly increased immune cell infiltration. Clinical data showed that the combinatorial use of chemotherapy and PD-1 blockade achieved a higher overall response rate (ORR) (36.67% vs 8.00%, p = 0.003), longer overall survival (31.9 months vs 14.8 months, p = 0.014) and longer progression free survival (4.7 months vs 9.5 months, p = 0.032) in RIS patients compared to single chemotherapy. Conclusion: Elevated genomic instability and higher immune cell infiltrations was found in RISs than primary sarcomas. Moreover, higher efficacy of chemotherapy plus PD-1 blockade was observed in animal experiment and clinical practice. These evidence indicated the promising application of immune checkpoint inhibitors in the treatment of RISs.

SARS-CoV-2 variants have evolved a variety of critical mutations, leading to antigenicity changes and immune escape. The recent emerging SARS-CoV-2 Omicron variant attracted global attention due to its significant resistance to current antibody therapies and vaccines. Here, we profiled the mutations of Omicron and other various circulating SARS-CoV-2 variants in parallel by computational interface analysis and in vitro experimental assays. We identified critical mutations that lead to antigenicity changes and diminished neutralization efficiency of a panel of 14 antibodies due to diverse molecular mechanisms influencing the antigen-antibody interaction. Our study identified that Omicron exhibited extraordinary potency in immune escape compared to the other variants of concern, and explores the application of computational interface analysis in SARS-CoV-2 mutation surveillance and demonstrates its potential for the early identification of concerning variants, providing preliminary guidance for neutralizing antibody therapy.

Waste sediment generated during tunnel construction is applied to prepare synchronous grouting material, where the influences of fly ash, slag powder, and bentonite on the rheological properties (such as consistency, fluidity, setting time, drainage rate, and stone rate) are studied. The results show that adding fly ash content increases the initial consistency, setting time, and fluidity of grouting material, but also increases its drainage rate and decreases its stone rate. The addition of slag powder results in a slight increase in the setting time and fluidity of the grouting material, yet a decrease in the initial consistency value. In contrast, with the addition of bentonite, both the initial consistency and fluidity of the grouting material decrease. Finally, the optimal mix ratio of high-performance and low-cost grouting materials is fixed to be 30% fly ash, 50% slag powder, and 10% bentonite. Therefore, the fluidity of grouting material can be 170 mm, with an initial consistency of 122 mm, setting time of 1050 min, stone rate of 96.2%, drainage rate of 1.5%, and 28-day compressive strength of 8.3 MPa.

Using the structural decomposition analysis (SDA) method, we decomposed the factors affecting the increments in CO2 emissions in China's Jiangsu Province. A comparative analysis of these factors at the holistic, sectoral, and sub-sectoral levels revealed that the effects related to the province's economic growth; in particular, the transfers-out and investment effects greatly increased Jiangsu's CO2 emissions. Overall, the import and export effects increased the emissions, reflecting the deteriorating foreign trade structure from the perspective of the emissions reduction. The energy intensity reduced Jiangsu's CO2 emissions greatly, whereas the energy structure had only a slight effect, which shows the high energy efficiency and inappropriate energy structure. The technology effect had a relatively slight reducing impact on the CO2 emissions compared with the other effects, so the input and output efficiency in Jiangsu had not yet been significantly improved. On the whole, the transfers-out, investment, and export effects increased the CO2 emissions in all sectors and subsectors, whereas the other effects on the increments in Jiangsu's CO2 emissions in the sectors and industrial subsectors differed greatly. Some policy implications arising from our study results are discussed.

A framework for building EDM collaborative manufacturing system using multi-agent technology to support organizations characterized by physically distributed, enterprise-wide, heterogeneous intelligent manufacturing system over Internet is proposed. According to the characteristics of agile EDM collaborative manufacturing system(AEDMCMS), the agent technology is combined with Petri net in order to analyze the model. Based on the basic Petri Net, the definition is extended and the Agent-oriented Petri net (APN) is proposed. AEDMCM is turned into the model of Petri Net which is suitable to the analysis and optimization of manufacturing processes.

Service mode and dynamic network interfere techniques are analyzed. An elastohydrodynamic lubrication oil thickness theory of rolling bearing type planetary friction transmission mechanism system based on web is presented.Elastohydrodynamic lubrication theory is adopted in rolling bearing type planetary friction transmission mechanism in this paper. Research indicates that elastohydrodynamic oil file lubrication can be realized while mechanical parts with connection between points or lines run under certain conditions. At the same time, surface disrepair of the parts has relation to lubrication state. Minimal oil film thickness formula is deduced based on the elastohydrodynamic lubrication theory. It is a part of He’nan Scientific Committee science and technology research projects 《research on collaborative design and manufacturing technique in gear manufacturing based on network and multi-Agent》

A framework for building network-based EDM CAPP system using intelligent technology to support organizations characterized by physically distributed, enterprise-wide, heterogeneous intelligent manufacturing system over Internet is proposed. Expert system theory is introduced. Rule-Based reasoning and Case-Based reasoning method are introduced to reason EDM method. Genetic Algorithm is applied to optimize EDM technological parameter. Fuzzy reasoning algorithm is applied to select technological data. Artificial Neural Network is applied to forecast technological effect. Internet environment and Technological knowledge database modules are introduced. Instances are also introduced to testify feasibility.

Elastohydrodynamic lubrication theory is adopted in rolling bearing type planetary friction transmission mechanism in this paper. Operation performance and using life-span are improved. Minimal oil film thickness formula is deduced based on the elastohydrodynamic lubrication theory. Relationship curve between minimal oil film thickness and rotate speed is presented. Variation law between minimal oil film thickness and work parameters is given.

Heparin is well known to suppress vascular smooth muscle cell (VSMC) proliferation, and attempts to exploit this therapeutically have led to recognition of multiple pathways for heparin's anti-mitogenic actions. At low concentrations (ca. 1 µg · ml−1), these suppressive effects may reflect physiological activities of endogenous heparan sulfates, and appear to be rapid responses to extracellular or cell surface-associated heparin. Because heparin has been shown to influence expression of caveolin proteins, and caveolae/lipid rafts are critical structures modulating cell signaling, we examined the effect of heparin on signaling involving cholesterol-rich membrane microdomains. The VSMC line PAC-1 activates the MAP kinase Erk in response to the cholesterol-sequestering agents methyl-β-cyclodextrin and nystatin. This follows a temporal sequence that involves Ras-GTP activation of MEK, and is independent of PKC, Src, and PI3 kinase. However, ligand-independent phosphorylation of the EGF receptor (EGFR) by removal of cholesterol precedes Ras activation, and the EGFR kinase inhibitor AG1478 blocks Erk phosphorylation, supporting occurrence of the signaling sequence EGFR-Ras-MEK-Erk. Phosphorylation of EGFR occurs predominantly in caveolin-rich microdomains as identified by Western blotting of fractions from density gradient centrifugation of membranes prepared under detergent-free conditions. In these situations, heparin inhibits phosphorylation of EGFR on the Src-dependent site Tyr845, but not the autophosphorylation of Tyr1173, and decreases Ras activation and Erk phosphorylation. We conclude that heparin can suppress Erk signaling in VSMC with effects on site-specific phosphorylation of EGFR localized in caveolin-enriched lipid rafts. J. Cell. Physiol. 211: 205–212, 2007. © 2007 Wiley-Liss, Inc.

Type 1 diabetes (T1D) is an insulin-dependent diabetes because of insufficient insulin pro‐ duction by the pancreatic islet β cells. Although the pathogenic mechanism of T1D is not yet completely clear, the current view of T1D pathogenesis is that under certain genetic back‐ ground, exogenous and/or endogenous factors trigger autoimmunity against islet β cells in the pancreas causing β cell damage and subsequent insufficiency of insulin production [1, 2]. About two decades ago, it was first demonstrated that T cells specific to β cell antigens were activated and participated in the pathogenesis of T1D [3, 4]. A great deal of work fol‐ lowing these reports in both animal models and humans has provided convincing data fur‐ ther supporting T1D is a T cell-mediated autoimmune disease. On the other hand, the evidence showing that majority of T1D patients have high titers of autoantibodies against islet β cells [5, 6] suggests that self-reactive B cells must also be involved in the autoimmune process. The role of B cells in the pathogenesis of T1D was further supported by the recent research and clinical data demonstrating B cell depletion by anti-CD20 antibodies delayed the disease process.

AIMS: To further explore the mechanisms of apoptosis in mononephrectomized rats with renal lymph circulation disorder. METHODS: Animals were divided into three groups: rats with left renal lymph ligation and right nephrectomy (KL), rats with only right nephrectomy (KN) and sham-operated rats (sham). 24-h proteinuria and serum creatinine level were monitored. Indexes of oxidative stress were measured. Renal apoptosis was examined. Further biochemical analysis was provided using real-time PCR, western blot and Elisa techniques. RESULTS: Our results showed that renal lymphatic ligation induced renal tubular epithelial cell apoptosis and aggravated renal dysfunction in mononephrectomized rats. In addition, renal lymphatic ligation increased the activities of caspase-3, caspase-8 and caspase-9. Further investigation of mechanisms showed that renal lymphatic ligation up-regulated Fas expression, increased the ratio of Bax/Bcl-2, and also increased the levels of reactive oxygen species (ROS), malondialdehyde (MDA) while reducing superoxide dismutase (SOD) activity. CONCLUSION: These results indicated that disturbance of renal lymphatic circulation might lead to tubular epithelial cell apoptosis through activation of intrinsic and extrinsic apoptotic pathways, suggestive of an essential role of renal lymphatic circulation in the maintenance of tubular integrity and function.

Type 2 diabetes mellitus (T2DM) is characterized by a chronic low-grade inflammatory state. Toll-like receptor 4 (TLR4) is a critical mediator of innate immunity. Polymorphisms in TLR4 gene have been shown to be associated with impaired inflammatory response. Here, we investigated the association of TLR4 polymorphisms with T2DM. Four TLR4 polymorphisms (+986A/G, +1196C/T, +3725G/C, and +11367G/C) were genotyped in a total number of 822 T2DM patients and 835 healthy controls. Results showed that the +986A/G and +1196C/T polymorphisms did not exist in the Han Chinese population. The prevalence of TLR4 +3725GC and CC genotypes were significantly decreased in T2DM cases than in controls (odds ratio (OR) = 0.62, 95 % confidence interval (CI) = 0.50-0.78, p = 3.48 × 10(-5), and OR = 0.36, 95 % CI = 0.22-0.59, p = 1.55 × 10(-5), respectively). Also, the frequency of TLR4 +3725C allele was significantly lower in T2DM patients (p = 2.46 × 10(-9)). When analyzing the TLR4 +11367G/C polymorphism, the +11367CC genotype revealed lower numbers in patients compared to healthy controls (OR = 0.46, 95 % CI = 0.27-0.78, p = 0.0032). Analysis of the clinical features on the control subjects demonstrated no correlations between these TLR4 polymorphisms and sex, age, body mass index, etc. (p > 0.05). In conclusion, these data indicate that TLR4 +3725G/C and +11367G/C polymorphisms may be novel protective factors against T2DM in the Chinese population.

The present study was designed to identify the changes in microvesicle-dipeptidyl peptidase-IV (DPP IV) levels in human urine and serum, and to determine whether there were correlations with the severity of diabetic kidney disease (DKD). A total of 127 patients with type 2 diabetes mellitus (T2DM) were divided into three groups according to the urinary albumin/ creatinine ratio (UACR): microalbuminuria group ( n = 50); macroalbuminuria group ( n = 34) and normoalbuminuria group ( n = 43), and 34 age- and sex-matched non-diabetic healthy subjects were selected as controls. Microvesicle-bound DPP IV and free urinary DPP IV were separated by a filtra-centrifugation method. The total microvesicles were captured by a specific monoclonal antibody, AD-1. DPP IV activity was determined by measuring the cleavage of chromogenic free 4-nitroaniline from Gly-Pro-p-nitroanilide at 405 nm with an ELISA plate reader. DPP IV protein levels were determined by ELISA and Western blot. Our results showed that the microvesicle-bound type was the major form of DPP IV in urine; the urinary microvesicle-DPP IV excretion of each T2DM group was significantly higher compared with controls. The urinary microvesicle-DPP IV level was positively correlated with UACR in patients with T2DM. These findings suggest that the urinary level of microvesicle-bound DPP IV is associated with the severity of DKD.

Lipin1, a lately indentified adipokine, may link obesity with insulin resistance and diabetes. The present study aimed to investigate the changes and significance of lipin1 expression and lipin1-AMPK signaling in diet-induced hepatic insulin resistance.24 4-week-old Male Wistar rats were randomly divided into 2 groups: (1) control group (CO), (2) high-fat diet group (HF). Insulin sensitivity was evaluated by hyperinsulinemic-euglycemic clamp technique. The mRNA levels of α1 and α2 subunit of AMPKα as well as Lipin1 were measured using Real-time RT-PCR. The activities of AMPKα and Akt were evaluated by detection of p-AMPKα (Thr-172) and p-Akt (ser473) by Western blot.After treatment of 4 months, HF group showed significantly increased levels of body weight, fasting plasma glucose and insulin levels; Plasma and liver total cholesterol (TC), triglycerides (TG) levels were also markedly elevated; Lipin1 expression at both mRNA and protein levels were significantly deceased. Compared with CO group, the mRNA and protein levels of AMPKα1 and AMPKα2 were not changed, whereas the p-AMPK (Thr-172) and p-AKT (ser473) levels in liver were significantly decreased in HF group.These findings indicated that the decrease in lipin1 expression and AMPKα activation may contribute to hepatic insulin resistance in diet-induced obese rats.