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Adoptive cell therapy (ACT) has revolutionized the treatment of patients with cancer. The success of ACT depends largely on transferred T cell status, particularly their less-differentiated state with stem cell-like properties, which enhances ACT effectiveness. Stem cell-like memory T (TSCM) cells exhibit continuous self-renewal and multilineage differentiation similar to pluripotent stem cells. TSCM cells are promising candidates for cancer immunotherapies, whereas maintenance of a more stem-cell-like state before transfer is challenging. Here, we established a highly efficient protocol for generating CD8+ TSCM cells from peripheral blood mononuclear cells (PBMCs). The process involved activating PBMCs using anti-CD3 monoclonal antibody and RetroNectin, followed by a transient-resting culture period (24 h) and subsequent long-term expansion in vitro with interlukien-2. We report that this transient-resting culture after activation preserves CD8+ T cells in a stem memory phenotype (CD95+ CD45RA+ CCR7+) compared to the conventional culture method. Further, this approach reduces the expression of T cell immunoglobulin mucin-3, an exhaustion marker, and increases the expression of T cell factor-1, a master regulator of stemness even after long-term culture compared to the conventional culture method. In conclusion, our study presents a simplified and cost-effective method for generating and expanding CD8+ TSCM cells ex vivo. This approach streamlines the optimization of cancer immunotherapy using ACT.

ObjectivesAcademic satisfaction plays an important role in promoting the future careers of medical undergraduates. Therefore, it is of great significance to improve academic satisfaction by exploring its influencing factors. The purpose of this study was to investigate the serial multiple mediating role of life events, coping styles, anxiety, and academic satisfaction among Chinese medical students.MethodsIn this cross-sectional study, clinical medicine students from a medical university in Heilongjiang Province were surveyed using stratified random cluster sampling procedures. The questionnaires included the Adolescent Life Events Scale, the Simple Coping Style Questionnaire, the Self-rating Anxiety Scale, and the Academic Satisfaction Scale. Pearson’s correlation analysis and bootstrap analysis were used for statistical analysis.ResultsLife events were negatively related to positive coping styles and academic satisfaction and were positively related to anxiety symptoms. Positive coping styles were negatively associated with anxiety symptoms and positively associated with academic satisfaction. Anxiety symptoms were negatively associated with academic satisfaction. The serial multiple mediating role of positive coping style and anxiety in the relationship between life events and academic satisfaction was significant.ConclusionThe results showed that life events were sequentially associated with decreased positive coping styles and then increased anxiety, which resulted in reduced academic satisfaction among medical students.

Background: Although the use of anti-PD-1 antibodies has fundamentally changed traditional cancer treatment, most patients are resistant to anti-PD-1 treatment. Glucocorticoids (GCs) play an important role in tumorigenesis and tumor progression, but the role of endogenous GCs in resistance to anti-PD-1 antibody therapy remains unclear. Methods: Single cell-derived cell lines (SCDCLs) were generated from a colorectal cancer cell line (CT26) using limiting dilution. We analyzed tumor tissues from anti-PD-1 antibody-treated and untreated mice inoculated with SCDCLs via transcriptome sequencing and flow cytometry to detect pathway activity and immune cell composition changes in the tumor microenvironment. Results: Five SCDCLs were inoculated into wild-type BALB/c mice (all tumorigenic). Single-cell clone (SCC)-2 exhibited the slowest growth rates both in vivo and in vitro compared to other single-cell clones, and better long-term survival than SCC1 and CT26. Flow cytometry showed that SCC2 tumor-bearing mice exhibited significantly higher infiltration of T cells within the tumor tissue, and higher expression of PD-1 on these T cells than the other groups in vivo. However, the SCC2 group showed no response to anti-PD-1 therapy. Transcriptome analysis revealed that the SCC2 group exhibited increased expression of genes related to GC (Hsd11b1, Sgk3, Tgfbr2, and Il7r) compared to SCC2-anti-PD-1 treated tumors. Conclusions: GC pathway activation is related to resistance to anti-PD-1 therapy.

The increasing amount of massive data generated by commercial spacecraft in orbit puts forward higher and higher requirements for the stability, reliability, and computing power of computer systems for commercial aerospace data center. Data center computer systems are gradually transforming from X86 architecture and IP network model to a platform model with cloud computing and software-defined network (SDN) technology. This article proposes a new network architecture based on a unicast/multicast protocol for data interaction between the SDN and IP network. There are three main contributions of this article. The first is that the architecture proposed in this article aims to reduce end-to-end transmission latency and packet loss. The second is to improve the flexibility of system configuration and precise control when the SND controller state changes. The third is to verify the feasibility of deploying network architecture in a real data center environment.

Flexible load can optimize the load curve, which is an important means to promote renewable energy consumption. The peculiarities of electricity, heat, cooling and gas loads are analyzed in this paper, considering the fuzzy degree of human perception for water temperature, and the characteristic model of hot water load is established. Considering the fuzzy degree of human perception of ambient temperature, the characteristic model of cooling load is established by using PMV and PPD index. Meanwhile, considering four combinations of cut load, translatable load, transferable load and alternative load, and considering the coupling relationship of composite parts, different response models of load are established respectively. With the minimum cost of the system, including operation and compensation costs as the objective function, the optimization scheduling model of the regional integrated energy system is established, and the Gurobi solver is used for simulation analysis to solve the optimal output and load response curve of each piece of equipment. The results show that the load curve can be optimized, the flexible regulation ability of the regional integrated energy system can be enhanced, the energy loss of the system can be reduced, and the wind power consumption ability of the system can be increased by considering the integrated demand response.

The belt surface of the mine belt conveyor can cause serious wear under the condition of long-term high-load operation, which can have a negative impact on production, bring economic losses, even endanger personal safety, and cause serious production accidents. Manual detection requires a lot of manpower and material resources, and is highly dependent on empirical judgment, which is with low efficiency and security risks. Therefore, in this study, we introduce a new conveyor belt wear detection algorithm Retinex-YOLOv8-EfficientNet-NAM (RYEN algorithm) based on deep learning and machine vision technology to replace manual detection, improving detection efficiency and recognition accuracy. The wear degree of belt is reclassified and defined according to the mechanical properties and wear texture characteristics of belt with different wear degrees, and a new special data set for belt wear detection is established. Aiming at the low brightness, high noise and complex working conditions of the underground mine, Gaussian filtering and bilateral filtering are used as the central surround function of the improved Retinex algorithm, and then channel fusion is performed with the image after histogram equalization and adaptive brightness adjustment. The improved Retinex multi-image fusion algorithm is used to preprocess the collected image. EfficientNet has the performance of reasonably allocating the input resolution, network depth, and channel width, and can maximize the performance of the network with limited resources. EfficientNet is used to replace Darknet53 of YOLOv8 as the backbone of the feature extraction network, which improves the detection accuracy under limited computing resources. A lightweight attention module NAM is added to the improved network, which improves the detection speed without reducing the detection accuracy. Experimental results show that RYEN algorithm effectively maintains the smoothness of the image during the image preprocessing stage, improves the brightness and contrast of the image, and better preserves the edge information of the image. RYEN algorithm achieves a detection speed of 66FPS and an average accuracy of 98.57%. Compared with the original YOLOv8 algorithm, the accuracy of RYEN algorithm is increased by 6.4% and the speed is increased by 13.2%. In comparison experiments with similar methods, RYEN algorithm occupies less hardware resources, has strong generalization ability, good performance, and has high detection speed and accuracy.

Intestinal flora affects the maturation of the host immune system, serves as a biomarker and efficacy predictor in the immunotherapy of several cancers, and has an important role in the development of colorectal cancer (CRC). Anti-PD-1/PD-L1 antibodies have shown satisfactory results in MSI-H/dMMR CRC but performed poorly in patients with MSS/pMMR CRC. In recent years an increasing number of studies have shown that intestinal flora has an important impact on anti-PD-1/PD-L1 antibody efficacy in CRC patients. Preclinical and clinical evidence have suggested that anti-PD-1/PD-L1 antibody efficacy can be improved by altering the composition of the intestinal flora in CRC. Herein, we summarize the studies related to the influence of intestinal flora on anti-PD-1/PD-L1 antibody efficacy in CRC and discuss the potential underlying mechanism(s). We have focused on the impact of the intestinal flora on the efficacy and safety of anti-PD-1/PD-L1 antibodies in CRC and how to better utilize the intestinal flora as an adjuvant to improve the efficacy of anti-PD-1/PD-L1 antibodies. In addition, we have provided a basis for the potential of the intestinal flora as a new treatment modality and indicator for determining patient prognosis.

Gastric cancer (GC) is one of the most prominent malignancies that originate in the epithelial cells of the gastric mucosa and is one of the main causes of cancer-related mortality worldwide. New circulating biomarkers of exosomal RNA might have great potential for non-invasive early prognosis of GC. Sijunzi Decoction (SJZD) is a typical representative formula of the method of benefiting Qi and strengthening the spleen in Traditional Chinese Medicine (TCM). However, the effects and mechanism of SJZD in treating GC remain unclear. This study looked for biomarkers of exosomal RNA for early prognosis of GC, and explored the mechanism of SJZD in treating GC. A gastric cancer model with spleen deficiency syndrome was established in nude mice, and the curative effects of SJZD were investigated. Differentially expressed miRNAs in plasma and saliva exosomes were sequenced and analyzed. Potential target genes of these miRNAs were predicted and applied for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment annotation. Overlapping miRNAs in saliva and plasma samples were analyzed, and qRT-PCR was performed for verification. miR-151a-3p was selected, and qRT-PCR further determined that miR-151a-3p was downregulated in saliva and plasma exosomes from the SJZD group. The intersected miR-151a-3p target genes were predicted and enriched in the extrinsic apoptotic signaling pathways. SJZD significantly ameliorates gastric cancer with spleen deficiency syndrome in mouse models, and exosomal miRNAs, particularly miR-151-3p, might be modulated by SJZD in plasma and saliva. The exosomal miR-151-3p in saliva may serve as a non-invasive potential marker for gastric cancer diagnosis and prognosis.

The increasing demand for achieving high-efficiency and high-quality medium-thick aluminium alloy welded structures, especially for large scale aerospace components, presents an urgent challenge to the conventional TIG arc welding process. This work proposed a novel double-pulsed variable polarity tungsten inert gas (DP-VPTIG) arc, in which the variable polarity square wave current was simultaneously modulated into ultrasonic frequency (20–80 kHz) and low frequency (0.5–10 Hz) pulses. Full penetration welds of 6 mm thick AA2219 aluminum alloy were successfully obtained by using this process. The microstructure and mechanical properties of the weld produced by DP-VPTIG arc were investigated, taking the conventional VPTIG arc as a comparative study. Results show that the microstructure of weld zone by DP-VPTIG arc showed an alternating distribution of fine equiaxed grain band and slightly coarse equiaxed grain band. Compared to VPTIG arc, the grain structure was effectively refined in the weld zone with DP-VPTIG arc, showing a significant reduction of average grain size by 51.2% along transverse section and 61.3% along longitudinal section. The morphology of α-Al+θ-CuAl2 eutectics transformed from continuously distributed netlike shape to separately distributed granular shape, and segregation of Cu solute element was obviously improved. The average microhardness of weld zone was increased by about 8.7% and 5.6% along transverse section and along longitudinal section. The tensile properties of ultimate tensile strength, yield strength and elongation were increased by 6.6%, 10.6% and 20.5%, respectively. The results provide a valuable basis for improving welding efficiency and joint quality through a hybrid pulsed arc.

Purpose To make a propensity-score matching analysis on the clinical application of gastric-jejunum pouch anastomosis (GJPA) and continuous jejunal pouch and residual stomach anastomosis combined with jejunal lateral anastomosis (Contin-L). Methods The clinic data of 287 patients who received distal gastrectomy from January 2015 to January 2019 were collected retrospectively. The enrolled patients were divided into the GJPA group and the Contin-L group according to the reconstruction method used. Clinical data and operation complications were analyzed. Results Compared with Contin-L group, the duration of digestive tract reconstruction in the GJPA group was shorter, and the overall cost in the GJPA group was lower. No obvious intergroup differences were found in other intraoperative data, early surgical outcomes, incidence rates of reflux gastritis, anastomotic ulcer, postoperative nutritional and hematological indicators. The postoperative subjective feelings in the GJPA group were similar with those in the Contin-L groups. Conclusion Addition of jejunal lateral anastomosis is not necessary for GJPA following distal gastrectomy.

Abstract Background Fiber, as the main product of cotton, provides main raw material for the textile industry. Many key factors have been revealed a significant role in fiber cell development including Myb proteins, phytohormones, fatty acid metabolites, and epigenetic modifications. DNA methylation is one of the important epigenetic modifications to regulate plant development and responses to abiotic or biotic stimuli. In general, DNA methylation consisting of 5mC and 6mA regulates the chromatin structure and gene transcription to affect plant development, however, the detailed role and underlying mechanism of DNA methylation in the fiber development of cotton are yet vague. Results Here, systematical study of the 5mC and 6mA DNA methylation profiles during the fiber initiation period of Xu142 and its glabrous mutant Xu142fl represented a clear alteration of global DNA methylation associated with fiber cell initiation. Then, the genome-wide identification of genes responsible for methylation regulation at the fifth carbon of cytosine and the sixth carbon of adenine of DNA was operated in Gossypium hirsutum. As a result, 13, 10, 6, and 17 genes were identified for 5mC methylation, 5mC demethylation, 6mA methylation, and 6mA demethylation, respectively. We then investigated the tissue expression pattern of all these genes, and some genes showed higher expression levels in fiber initiation, among which some displayed a significant change in transcription between Xu142 and Xu142fl. The possible interaction between histone acetylation and DNA methylation in fiber initiation through in vitro culture was studied by dot blot, and the results showed that repressed histone deacetylation by Trichostatin A (TSA) inhibited the global DNA methylation, and some causal genes (e. g., GhDMT13, GhDAMT2, GhALKBH12, GhDM7) were also identified. Conclusions In this study, all the findings indicated the interplay between histone acetylation and DNA methylation, supporting their important roles and providing precious clues for the epigenetic modifications associated with DNA methylation in the fiber development of cotton.

A design method of a phononic crystal structure with a local effect is introduced, and the mechanism and influencing factors (elastic modulus, density, local layer thickness) of the bandgap are analyzed. The finite element method is used to calculate the eigenfrequency. The first bandgap width accounts for more than 98% of the frequency below 20 000 Hz. Two kinds of materials with different wave velocities are arranged periodically to form a two-dimensional local effect structure. Due to the influence of the local effect, when the elastic wave propagates in the local layer, the wave propagation will be restrained, and the eigenfrequency spectrum presents a series of discrete energy levels. The material parameters and structural parameters of the transmission layer have a great influence on the bandgap. The first bandgap is an ultra-wide low frequency bandgap, and the bandgap frequency ranges from 238 to 18857 Hz. This periodic structure with the local effect has great potential application value in noise and vibration suppression.

In this study, arc and friction stir hybrid welding (AFSHW) was proposed to weld aluminum-steel dissimilar metals in attempt to realize high quality joining. Firstly, an interlayer was produced on galvanized steel by using bypass current-metal inert gas welding (BC-MIG), and then an aluminium plate was jointed via Friction stir lap welding (FSLW). The effects of tool pin length and FSLW times on the microstructure and mechanical properties of dissimilar joints were fully investigated by means of Optical Microscopy (OM), Scanning Electron Microscope (SEM), Electron Backscatter Diffraction (EBSD), and mechanical testing. The results show that as pin length increased, joint strength tended to increase and then decrease, and the tensile failure partially occurred at aluminium base metal. However, with additional number of FSLW, joint strength would be reduced, which was attributed to attenuated dislocation density and strain concertation in dissimilar joint. The research outcomes will provide a new welding method to obtain sound Al-Fe dissimilar metal joint, and benefit to a better understanding of Al-Fe joining mechanism.

Chemokines are a class of small cytokines or signaling proteins that are secreted by cells. Owing to their ability to induce directional chemotaxis of nearby responding cells, they are called chemotactic cytokines. Chemokines and chemokine receptors have now been shown to influence many cellular functions, including survival, adhesion, invasion, and proliferation, and regulate chemokine levels. Most malignant tumors express one or more chemokine receptors. The CXC subgroup of chemokine receptors, CXCR3, is mainly expressed on the surface of activated T cells, B cells, and natural killer cells, and plays an essential role in infection, autoimmune diseases, and tumor immunity by binding to specific receptors on target cell membranes to induce targeted migration and immune responses. It is vital to treat infections, autoimmune diseases, and tumors. CXCR3 and its ligands, CXCL9, CXCL10, and CXCL11, are closely associated with the development and progression of many tumors. With the elucidation of its mechanism of action, CXCR3 is expected to become a new indicator for evaluating the prognosis of patients with tumors and a new target for clinical tumor immunotherapy. This article reviews the significance and mechanism of action of the chemokine receptor CXCR3 and its specific ligands in tumor development.

Increasing eutrophication and climate change have led to heavy cyanobacterial blooms in water diversion sources (e.g., lakes, reservoirs), which can potentially cause algae-bearing water to spread to downstream to an urban river network via diversion channels. Defining the extent of cyanobacterial blooms in an urban river network has become a novel concern in urban river management. In this paper, we investigated the physicochemical and algae community characteristics of a small, closed, urban river network, JiangXinZhou (JXZ), in the Lake Taihu basin. We propose a novel indicator, resource use efficiency (RUE), for defining the extent of cyanobacterial blooms in JXZ, whose recreational drinking water comes entirely from outside diversion sources. The results show that the JXZ's aquatic habitat conditions (mean water temperature, total nitrogen concentration, total phosphorus concentration, and nitrogen to phosphorus ratio) are highly suitable for the proliferation of cyanobacterial biomass during the high-water period. The RUE was used for calculation and shows a strong relationship with algae density, which means that it can be used as an index to define the degree of urban river cyanobacterial blooms. The findings indicate that the risk of cyanobacterial bloom is absent when the RUE is less than 46.81; blooms appear in the water bodies when the RUE reaches up to 106.68. This work provides theoretical support for the sustainable use of regional water resources.

Cervical cancer is a top lethal cancer for women worldwide. Although screening and vaccination programs are available in many countries, resulting in the decline of new cases, this is not true for developing countries where there are many new cases and related deaths. Cancer immunotherapy through adaptive cell therapy (ACT) has been applied in clinics, but now much attention is focused on autogenic tumor-infiltrating lymphocyte (TIL)-based therapy, which has shown more specificity and better ability to inhibit tumor growth. Data from melanoma and cervical cancers confirm that tumor-specific T cells in TILs can be expanded for more specific and effective ACT. Moreover, TILs are derived from individual patients and are ready to home back to kill tumor cells after patient infusion, aligning well with personalized and precision medicine. In addition to therapy, TIL cell types and numbers are good indicators of host immune response to the tumor, and thus they have significant values in prognosis. Because of the special relationship with human papillomavirus (HPV) infection, cervical cancer has some specialties in TIL-based prognosis and therapy. In this review, we summarize the recent advances in the prognostic significance of TILs and TIL-based therapy for cervical cancer and discuss related perspectives.

Background and Objective: The preferred treatment for Cholangiocarcinoma (CCA) patients is surgery. Approximately, 35% of patients can undergo surgical resection in clinic. Biomarkers for CCA need to be identified for diagnosis, treatment, or prognosis prediction of this disease. Y-box binding protein-1 (YBOX-1) is highly correlated with tumor progression and poor overall survival in many malignancies. The prognostic value of YBOX-1 overexpression in CCA remains unclear. We examined the expression of YBOX-1 in resected tissue in CCA patients and studied the effect of YBOX-1 in CCA migration and invasion in vitro and in vivo. Methods: Expression of YBOX-1 in the tissue of 91 CCA patients was investigated by immunohistochemistry. The effects of YBOX-1 on migration, invasion, and proliferation in CCA cell lines were assessed by short hairpin RNA lentivirus or overexpression plasmid transfection. Results: A total of 55 (60.4%) of CCA cancerous tissues showed strongly positive YBOX-1 cytoplasmic staining. The strongly positive expression of YBOX-1 was close to early recurrence and poor overall survival by Kaplan–Meier analyses. Knockdown of YBOX-1 reduced migration and invasion in CCA cells and proliferation of tumor in xenotransplantation nude mice. Overexpression of YBOX-1 promoted migration and invasion in CCA cells and proliferation of tumor in xenotransplantation nude mice. Conclusion: YBOX-1 is correlated with early recurrence and poor overall survival in CCA. YBOX-1 may be a factor of predicting poor prognosis and overall survival.

Abstract Attributable to its late diagnosis, early metastasis, and poor prognosis, pancreatic cancer remains one of the most lethal diseases worldwide. Unlike other solid tumors, pancreatic cancer harbors ample stromal cells and abundant extracellular matrix but lacks vascularization, resulting in persistent and severe hypoxia within the tumor. Hypoxic microenvironment has extensive effects on biological behaviors or malignant phenotypes of pancreatic cancer, including metabolic reprogramming, cancer stemness, invasion and metastasis, and pathological angiogenesis, which synergistically contribute to development and therapeutic resistance of pancreatic cancer. Through various mechanisms including but not confined to maintenance of redox homeostasis, activation of autophagy, epigenetic regulation, and those induced by hypoxia-inducible factors, intratumoral hypoxia drives the above biological processes in pancreatic cancer. Recognizing the pivotal roles of hypoxia in pancreatic cancer progression and therapies, hypoxia-based antitumoral strategies have been continuously developed over the recent years, some of which have been applied in clinical trials to evaluate their efficacy and safety in combinatory therapies for patients with pancreatic cancer. In this review, we discuss the molecular mechanisms underlying hypoxia-induced aggressive and therapeutically resistant phenotypes in both pancreatic cancerous and stromal cells. Additionally, we focus more on innovative therapies targeting the tumor hypoxic microenvironment itself, which hold great potential to overcome the resistance to chemotherapy and radiotherapy and to enhance antitumor efficacy and reduce toxicity to normal tissues.

With the rapid development of the power grid, the high penetration of new energy sources and the diversity of loads have further aggravated the uncertainty of “source-load”, which has brought huge challenges to the peak shaving of the power grid. In order to ensure the reliable operation of the power system during the electricity peak, this paper combines the IoT technology to propose a flexible control strategy for controllable large industrial loads that considers the interrupt priority. Firstly, the perception and fusion framework of large industrial load information is constructed based on the IoT technology. After that, the improved TOPSIS method is adopted to establish the evaluation model of the adjustable potentials of large industrial loads and the load interruption priority is further divided. Finally, a three-stage rolling regulation model for controllable large industrial loads to participate in the deep peak shaving of the power grid is constructed to achieve the goal of bidirectional peak shaving on the power generation side and the demand side. The case uses an improved IEEE 30-node system for simulation. As the simulation results show, the method proposed in this paper can not only take the cost of peak load regulation into account, but also effectively achieve the goal of ‘peak shaving and valley filling’.

Manning’s roughness coefficient(n) is considered a key parameter in a one-dimensional (1D) hydrodynamic model. However, it is highly variable and time- and site- dependent. Further, identifying proper n values is not easy, especially in plain looped river network areas. Therefore, a more systematic approach is needed. This study proposes a coupled optimization-simulation model to systematically estimate the spatial distribution of n values. The particle swarm optimization (PSO) algorithm and InfoWorks Integrated Catchment Modelling (ICM) software were integrated to solve the objective function and hydraulic process, respectively. Crisscrossing rivers were partitioned into river reaches that were each assumed to have a uniform and constant Manning’s roughness coefficient according to their network topology and cross-section variation. In addition, a sensitivity analysis was implemented to determine the weights of measured data from different gauging stations, and a large difference in the spatial distribution of the sensitivity index illustrated the importance of identifying the weights of multiple stations. Then, a systematic approach was applied to estimate the n values in the Changshu Grand Polder Area (CGPA), which is crisscrossed by 150 rivers, under the water diversion stage. The calculation statistics and efficiency indicated that the proposed method performs well for model calibration.

The bandgap (BG) of a phononic crystal (PnC) can suppress the propagation of elastic waves and has great potential in suppressing vibration. In this paper, a new type of multi-BG PnC is studied, which has many BGs in the low frequency. The eigenfrequency and displacement vector field distribution of the structure are calculated using the finite element method, and the influence of geometric parameters and material parameters on the first BG is analyzed. In addition, the BG ratio is defined to describe the coverage ability of multiple BGs in the reference frequency range. The results show that there are many flat bands in the dispersion curve of the structure. The BG covers almost all frequencies below 4000 Hz. In the range of 0–4000 Hz, the BG width accounts for more than 95% coverage, which can effectively suppress the propagation of elastic waves in the low frequency.

Background: Stone recurrence is a major problem limiting the effects of surgical treatment for hepatolithiasis. It was showed that hyperplasia of perihilar liver may compress the hepatic portal and cause deficient bile flow because of compressed hilar bile duct, thereby leading to the formation of bile stasis and precipitating stone recurrence. This retrospective study aimed to evaluate the efficiency of perihilar hepatectomy for hepatolithiasis with compressed hilar bile duct induced by perihilar hyperplasia of liver. Methods: 135 patients with compressed hilar bile duct induced by hypertrophied perihilar liver were included in this study from January 2011 to July 2016. Among these patients, 77 underwent conventional operation procedure (control group) and 58 underwent conventional operation procedure added by perihilar hepatectomy (perihilar hepatectomy group). Clinical data containing preoperative data, intraoperative data, operation complications, and short-term and long-term outcomes were collected. Results: The demographic and disease-related characteristics of the two groups were comparable. The two groups were not remarkably different in operation-related characteristics. The incidence of bile leakage in the perihilar hepatectomy group was substantially higher than that in the control group. Other postoperative complications were not remarkably different between the two groups. In the long-term postoperative follow-up period, the incidence of the recurrence of stones and cholangitis in the control group was considerably higher than that in the perihilar hepatectomy group. Conclusions: Based on conventional operation procedure, additional perihilar hepatectomy is a reliable intervention with definite clinical effects for hepatolithiasis with compressed hilar bile duct induced by hypertrophied perihilar liver.

Abstract Pancreatic cancer is currently one of the most lethal diseases. In recent years, increasing evidence has shown that reprogrammed metabolism may play a critical role in the carcinogenesis, progression, treatment and prognosis of pancreatic cancer. Affected by internal or external factors, pancreatic cancer cells adopt extensively distinct metabolic processes to meet their demand for growth. Rewired glucose, amino acid and lipid metabolism and metabolic crosstalk within the tumor microenvironment contribute to unlimited pancreatic tumor progression. In addition, the metabolic reprogramming involved in pancreatic cancer resistance is also closely related to chemotherapy, radiotherapy and immunotherapy, and results in a poor prognosis. Reflective of the key role of metabolism, the number of preclinical and clinical trials about metabolism-targeted therapies for pancreatic cancer is increasing. The poor prognosis of pancreatic cancer patients might be largely improved after employing therapies that regulate metabolism. Thus, investigations of metabolism not only benefit the understanding of carcinogenesis and cancer progression but also provide new insights for treatments against pancreatic cancer.

Abstract Pancreatic cancer is an aggressive and malignant tumor with an exceedingly high mortality rate. The quality of life and survival rates of pancreatic cancer patients with metastasis are poor compared with those without metastasis. Thus far, no effective treatment strategy has been established for metastatic pancreatic cancer patients. Therefore, an appropriate therapeutic method based on the elimination of metastatic pancreatic cancer is critical to improve patient outcome. Tumor-targeted vaccines have been widely discussed in recent studies and enabled important breakthroughs in the treatment of pancreatic cancer by preventing the escape of tumor cells from immune surveillance and activating the immune system to eliminate cancer cells. T cells can be activated by the stimulation of tumor-targeted vaccines, but to mount an effective immune response, both immune checkpoint inhibitors and positive costimulatory molecules are required. In this review, we discuss potential tumor-targeted vaccines that can target pancreatic cancer, elaborate the probably appropriate combination of vaccines therapy and evaluate the underlying benefits as well as obstacles in the current therapy for metastatic pancreatic cancer.

Background: Pancreatic cancer (PC) is a highly aggressive gastrointestinal tumor and has a poor prognosis. Evaluating the prognosis validly is urgent for PC patients. In this study, we utilized the RNA-sequencing (RNA-seq) profiles and DNA methylation expression data comprehensively to develop and validate a prognostic signature in patients with PC.Methods: The integrated analysis of RNA-seq, DNA methylation expression profiles, and relevant clinical information was performed to select four DNA methylation-driven genes. Then, a prognostic signature was established by the univariate, multivariate Cox, and least absolute shrinkage and selection operator (LASSO) regression analyses in The Cancer Genome Atlas (TCGA) dataset. GSE62452 cohort was utilized for external validation. Finally, a nomogram model was set up and evaluated by calibration curves.Results: Nine DNA methylation-driven genes that were related to overall survival (OS) were identified. After multivariate Cox and LASSO regression analyses, four of these genes (RIC3, MBOAT2, SEZ6L, and OAS2) were selected to establish the predictive signature. The PC patients were stratified into two groups according to the median risk score, of which the low-risk group displayed a prominently favorable OS compared with the high-risk group, whether in the training (p < 0.001) or validation (p < 0.01) cohort. Then, the univariate and multivariate Cox regression analyses showed that age, grade, risk score, and the number of positive lymph nodes were significantly associated with OS in PC patients. Therefore, we used these clinical variables to construct a nomogram; and its performance in predicting the 1-, 2-, and 3-year OS of patients with PC was assessed via calibration curves.Conclusion: A prognostic risk score signature was built with the four alternative DNA methylation-driven genes. Furthermore, in combination with the risk score, age, grade, and the number of positive lymph nodes, a nomogram was established for conveniently predicting the individualized prognosis of PC patients.

In order to reduce the influence of abnormal data on load forecasting effects and further improve the training efficiency of forecasting models when adding new samples to historical data set, an ultra-short-term load dynamic forecasting method considering abnormal data reconstruction based on model incremental training is proposed in this paper. Firstly, aiming at the abnormal data in ultra-short-term load forecasting, a load abnormal data processing method based on isolation forests and conditional adversarial generative network (IF-CGAN) is proposed. The isolation forest algorithm is used to accurately eliminate the abnormal data points, and a conditional generative adversarial network (CGAN) is constructed to interpolate the abnormal points. The load-influencing factors are taken as the condition constraints of the CGAN, and the weighted loss function is introduced to improve the reconstruction accuracy of abnormal data. Secondly, aiming at the problem of low model training efficiency caused by the new samples in the historical data set, a model incremental training method based on a bidirectional long short-term memory network (Bi-LSTM) is proposed. The historical data are used to train the Bi-LSTM, and the transfer learning is introduced to process the incremental data set to realize the adaptive and rapid adjustment of the model weight and improve the model training efficiency. Finally, the real power grid load data of a region in eastern China are used for simulation analysis. The calculation results show that the proposed method can reconstruct the abnormal data more accurately and improve the accuracy and efficiency of ultra-short-term load forecasting.

Objective To compare the surgical effects and long-term efficacy of hand-assisted laparoscopic surgery (HALS) and open surgery (OS) in radical gastrectomy for advanced distal gastric cancer. Methods One hundred twenty-four patients who were admitted to the Department of Gastrointestinal Surgery of the West War Zone General Hospital from May 2008 to April 2012 were randomly divided into a HALS group (n = 62) and an OS group (n = 62). After surgery, 113 patients were followed up for 5 and 8 years, and 11 patients were lost to follow-up. The 5- and 8-year overall survival and disease-free survival rates of the two groups were compared and analyzed. Results The 5- and 8-year overall survival rates were 31.90% and 18.40% in the HALS group and 32.50% and 18.60% in the OS group, respectively. The 5- and 8-year disease-free survival rates were 21.50% and 13.00% in the HALS group and 21.90% and 13.10% in the OS group, respectively. No significant differences were found. Conclusion Hand-assisted laparoscopic radical gastrectomy for advanced distal gastric cancer has the advantages of less severe trauma, less intraoperative blood loss, more rapid postoperative recovery, and equivalent long-term efficacy compared with OS.

Abstract Background Autologous tumor-infiltrating lymphocytes (Tils) immunotherapy is a promising treatment in patients with advanced hepatocellular cancer. Although Tils treatment has shown great promise, their persistence and the efficacy after adoptive-transfer are insufficient and remain a challenge. Studies have demonstrated that IL-15 and Akt inhibitor can regulate T cell differentiation and memory. Here, we constructed S-15 (Super human IL-15), a fusion protein consisting of human IL-15, the sushi domain of the IL-15 receptor α chain and human IgG-Fc. Herein we compared the effects of S-15 with IL-2 or in combination with Akti on the expansion and activation of Tils. Methods Hepatocellular cancer tissues were obtained from 6 patients, Tils were expanded using IL-2, IL-2/S-15, IL-2/Akti or in combination IL-2/S-15/Akti. At day 10, anti-CD3 antibody was added to the culture media and expanded to day 25. The composition, exhaustion and T-cell differentiation markers (CD45RA/CCR7) were analyzed by flow cytometry. Results We found that IL-2/S-15/Akti expanded Tils and showed the highest percentage of central memory CD45RA−CCR7+ phenotype prior to anti-CD3 antibody activation and after anti-CD3 antibody activation. T cells cultured with IL-2/S-15/Akti exhibited a mixture of CD4+, CD8+, and CD3+CD4−CD8− T cells; S-15 in combination with Akt inhibitor downregulated the expression of PD-1+Tim-3+ on Tils and decreased the Tregs in Tils. Additionally, the Tils expanded in the presence of the Akt inhibitor and S-15 showed enhanced antitumor activity as indicated by the increase in IFN-γ producing tumor infiltrating CD8+ T cells and without comprising the Tils expansion. Conclusion Our study elucidates that IL-2/S-15/Akti expanded Tils and represent a viable source for the cellular therapy for patients with hepatocellular cancer.

In the green pepper harvesting robot, the color of green pepper is similar to that of leaves, which makes it difficult to recognize the green pepper target. In order to solve this problem, a green pepper recognition method based on least-squares support vector machine optimized by the improved particle swarm optimization (IPSO-LSSVM) is proposed in this paper. Firstly, the green pepper images are segmented by K-Means method under the Lab color space, and the segmentation images of the target and background are obtained. The processed green pepper image was divided into training and testing samples. Then, the shape and texture features of green pepper targets are extracted separately from the training sample using the hu invariant moment and Tamura texture feature. Meanwhile, in order to reduce the complexity of data calculations and improve the efficiency, the extracted feature vectors are normalized. The feature vector is used as the input eigenvector of the least-squares support vector machine (LSSVM). The particle swarm optimization algorithm is used to obtain the optimal regularization parameter and the kernel function width. In order to maintain the particle activity, the mutation strategy is introduced to improve the particle swarm optimization algorithm. The experimental results show that the recognition rate of IPSO-LSSVM is higher than that of other methods, and the recognition accuracy is 89.04%. It could meet the requirements of green pepper identification.

The paper analyses and studies the classification and characteristics of Internet of Things (IoT) information, and discusses the construction and application of Hadoop Cloud Platform. This paper mainly carries out from two aspects. One is to design the system architecture of the Open Platform for Data Simulation Resources of the IoT and design the key modules. A platform for data simulation resources of the IoT is built to provide the running environment and external services for the sensor data simulation model established. On the other hand, it is the key method to study the simulation data model based on IoT sensors. That is, based on the research environment of the IoT built by the existing laboratories, collect the data of sensors, analyze and study the characteristics of sensors in the IoT, and design the key algorithms for data simulation. This paper presents two key models for sensor data modeling: the Long Short-term Memory (LSTM) prediction model and the Support Vector Machine (SVM) model based on IoT data, which are suitable for different data volumes. Extensive simulations are executed to validate the remarkable nature in Hadoop platform, in terms of prediction accuracy and training efficiency under different working condition.

Pancreatic cancer (PC) is a highly malignant tumor in the digestive system. Both long noncoding RNAs (lncRNAs) and autophagy play vital roles in the development and progress of PC. Here, we constructed a prognostic risk score system based on the expression profile of autophagy-associated lncRNAs for prognostic prediction in PC patients. Firstly, we extracted the expression profile of lncRNA and clinical information from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. The autophagy-associated genes were from The Human Autophagy Database. Through Cox regression and survival analysis, we screened out seven autophagy-associated lncRNAs and built the risk score system in which the patients with PC were distinguished into high- and low-risk groups in both training and validation datasets. PCA plot displayed distinct discrimination, and risk score system displayed independently predictive value for PC patient survival time by multivariate Cox regression. Then, we built a lncRNA and mRNA co-expression network via Cytoscape and Sankey diagram. Finally, we analyzed the function of lncRNAs in high- and low-risk groups by gene set enrichment analysis (GSEA). The results showed that autophagy and metabolism might make significant effects on PC patients of low-risk groups. Taken together, our study provides a new insight to understand the role of autophagy-associated lncRNAs and finds novel therapeutic and prognostic targets in PC.

BACKGROUND:Chronic pain has been associated with alterations in brain structure and function that appear dependent on pain phenotype. Functional connectivity (FC) data on chronic back pain (CBP) is limited and based on heterogeneous pain populations. We hypothesize that failed back surgery syndrome (FBSS) patients being considered for spinal cord stimulation (SCS) therapy have altered resting state (RS) FC cross-network patterns that 1) specifically involve emotion and reward/aversion functions and 2) are related to pain scores. METHODS:RS functional MRI (fMRI) scans were obtained for 10 FBSS patients who are being considered for but who have not yet undergone implantation of a permanent SCS device and 12 healthy age-matched controls. Seven RS networks were analyzed including the striatum (STM). The Wilcoxon signed-rank test evaluated differences in cross-network FC strength (FCS). Differences in periaqueductal grey (PAG) FC were assessed with seed-based analysis. RESULTS:Cross-network FCS was decreased (p

With the change of the network communication environment in vehicular ad hoc networks (VANETs) of a smart city, vehicles may encounter security threats such as eavesdropping, positioning, and tracking, so appropriate anonymity protection is required. Based on the certificateless cryptosystem and group signature ideas, this paper proposes a certificateless group signature anonymous authentication scheme for the VANETs of a smart city. In this scheme, it can implement the process of adding, signing, verifying, and revoking group members only by simple multiplication of the elliptic curve and synchronization factor technology, which shortens the length of the signature and improves the efficiency of the signature. From the proofs of correctness and security, we know that it does not only has anonymity and traceability of the group signature scheme but also has unforgeability and forward security. According to the performance verification, this scheme has lower calculation overhead and higher authentication efficiency.

For the repair level and spare parts stocking problems, generally METRIC type methods and Level of repair analysis (LORA) are used separately. Since LORA does not consider the availability of capital goods, solving LORA and spare parts stocking problems sequentially may lead to suboptimal solutions. On these considerations, this study presents a joint optimization method to minimize the service logistics cost under the constraints of system availability. Maintenance capability factor and maintenance decisions are introduced into the joint optimization model to express the influence of multiple failure modes on repair level and spare parts stocking. Thus, we establish the bridge relationship between LORA and METRIC models. The joint optimization model is solved by an improved iterative algorithm, and a typical fleet system is taken as an example to verify the correctness and effectiveness of the model and the algorithm. Compared with the optimization of spare parts inventory and maintenance level independently, the joint optimization method could effectively reduce the service logistic system cost.

Abstract Background T lymphocytes play an indispensably important role in clearing virus and tumor antigen. There is little knowledge about impacts of inhibitory molecules with cytokine on tumor-infiltrating CD4+ T-cells in the presence of gastric cancer (GC). This study investigated the distribution of tumor-infiltrating T-cells subset and the differentiation as well as inhibitory phenotype of T-cells from blood and tissues of GC patients. Materials and methods Patients with GC diagnosed on the basis of pre-operative staging and laparotomy findings were approached for enrollment between 2014 and 2015 at the Affiliated Cancer Hospital of Zhengzhou University, China. Phenotypic analysis based on isolation of tumor-infiltrating lymphocytes and intracellular IFN-γ staining assay is conducted. Statistical analysis is performed to show significance. Results The results showed that the percentage of CD4+ T-cells among CD3+ cells in tumors was significantly higher than that in the matched paraneoplastic tissue. CD4+ CD25high CD127low regulatory T-cells (Tregs), PD-1+, Tim-3+, and PD-1+ Tim-3+ cells were up-regulated on tumor infiltrating T-cells from patients with GC compared to their expressions on corresponding peripheral blood and peritumoral T-cells. Blockades of PD-1+ and Tim-3+ were effective in restoring tumor infiltrating T-cells’ production of interferon-gamma (IFN-γ). Combined PD-1+ and Tim-3+ inhibition had a synergistic effect on IFN-γ secretion by CD4+ T-cells. Conclusion The results suggested that the composition, inhibitors, and location of the immune infiltrate should be considered when evaluating antitumor immunotherapy. A new insight into the mechanisms underlying T cell dysfunction is provided.

Several models have been proposed to explain the emergence of sex chromosomes. Here, through comparative genomics and mutant analysis, Harkess et al. show that linked but separate genes on the Y chromosome are responsible for sex determination in Asparagus, supporting a two-gene model for sex chromosome evolution.

Chronic pain affects 50% of adults with sickle cell disease (SCD). Although central sensitization is thought to contribute to the pathogenesis of this chronic pain, no studies have examined differences in functional connectivity of the brain between patients with SCD with and without chronic pain. We performed an observational cohort study using resting-state functional MRI (rsfMRI) of the brain on adults with SCD with and without chronic pain. We tested the hypothesis that, compared to those without chronic pain, those with chronic pain would have differences in functional connectivity between the periaqueductal grey (PAG) and other regions of the brain. Twenty-two adults with SCD, 15 with chronic pain and 7 without chronic pain, as well as 10 African-American controls, underwent rsfMRI of the brain. When SCD patients with chronic pain were compared to those without chronic pain, significant differences in connectivity were noted between the PAG and 9 regions of the brain, including several in the default mode network, a network involved in introspection that has been implicated in other chronic pain syndromes. Changes in functional connectivity between patients with SCD with and without chronic pain suggest a mechanism for chronic pain that involves neuro-plastic changes to the brain.

The first-line chemotherapies for patients with unresectable pancreatic cancer (PC) are 5-fluorouracil (5-FU) and gemcitabine therapy. However, due to chemoresistance the prognosis of patients with PC has not been significantly improved. Mitochondria are essential organelles in eukaryotes that evolved from aerobic bacteria. In recent years, many studies have shown that mitochondria play important roles in tumorigenesis and may act as chemotherapeutic targets in PC. In addition, according to recent studies, mitochondria may play important roles in the chemoresistance of PC by affecting apoptosis, metabolism, mtDNA metabolism, and mitochondrial dynamics. Interfering with some of these factors in mitochondria may improve the sensitivity of PC cells to chemotherapeutic agents, such as gemcitabine, making mitochondria promising targets for overcoming chemoresistance in PC.

To identify shield grouting quality based on impact echo method, an impact echo test of segment-grouting (SG) test piece was carried out to explore effect of acoustic impedance of grouting layers and grouting defects on impact echo law. A finite element numerical simulation on the impact echo process was implemented. Test results and simulation results were compared. Results demonstrated that, under some working conditions, finite element simulation results and test results both agree with theoretical values. The acoustic impedance ratio of SG material influenced the echo characteristics significantly. But thickness frequency could not be detected under some working conditions because the reflected energy is weak. Frequency feature under grouting defects was more complicated than that under no grouting defects.

IgG4-related disease (IgG4-RD) is a chronic systemic disease involved in many organs and tissues. As only limited autoantigens have been found since the beginning of this century, the aim of this study was to reveal new candidate autoantigens of IgG4-RD.Multiple cell lines including HT-29, EA.hy926, HEK 293 and HepG2 were used to test the binding ability of circulating autoantibodies from IgG4-RD sera. The amino-acid sequence was then analyzed by matrix-assisted laser desorption/ionization time-of-flight tandem (MALDI-TOF/TOF) mass spectrometry. After the cloning and expression of recombinant putative autoantigen in a bacterial expression system, the corresponding immuno assay was set up and utilized to observe the prevalence of serum autoantibodies in a large set of confirmed clinical samples.One positive autoantigen was identified as prohibitin. ELISA analysis showed that a majority of patients with IgG4-RD have antibodies against prohibitin. Anti-prohibitin antibodies were present in the sera of patients with definite autoimmune pancreatitis (25/34; 73.5%), Mikulicz's disease (8/15; 53.3%), retroperitoneal fibrosis (6/11; 54.5%), other probable IgG4-RD (26/29; 89.7%) and Sjögren's syndrome (4/30; 13.3%) but not in apparently healthy donors (1/70; 1.4%).An association between prohibitin and patients with some IgG4-RD was observed, although the results were quite heterogeneous among different individuals within autoimmune pancreatitis, Mikulicz's disease and retroperitoneal fibrosis.

Behçet's disease (BD) is a chronic inflammatory disease with multisystem involvement, and it is listed as a rare disease in the United States but is common in the Middle East, China, and Japan. The aim of this study was to identify novel autoantigens in Chinese patients with BD. First, the candidate autoantigens were screened by Western blotting, and the sequences of putative antigens were identified by LC-MALDI-TOF/TOF mass spectrometry. Next, the screened protein was cloned, expressed and purified. Then, an optimized ELISA was developed, and the serological criteria were evaluated using a large number of confirmed patients. One antigen with a molecular weight of approximately 28 kDa was identified as electron transfer flavoprotein subunit beta (ETFB). Positive reactivity was detected in recombinant human ETFB sera from 38 of 92 BD patients (41 %) and 1 of 90 healthy controls (1 %).

An improved differential evolution (DE) method based on the dynamic search strategy (IDEBDSS) is proposed to solve dynamic economic dispatch problem with valve-point effects in this paper. The proposed method combines the DE algorithm with the dynamic search strategy, which improves the performance of the algorithm. DE is the main optimizer in the method proposed. While chaotic sequences are applied to obtain the dynamic parameter settings in DE, dynamic search strategy which consists of two steps, global search strategy and local search strategy, is used to improve algorithm efficiency. To accelerate convergence, a new infeasible solution handing method is adopted in the local search strategy; meanwhile, an orthogonal crossover (OX) operator is added to the global search strategy to enhance the optimization search ability. Finally, the feasibility and effectiveness of the proposed methods are demonstrated by three test systems, and the simulation results reveal that the IDEBDSS method can obtain better solutions with higher efficiency than the standard DE and other methods reported in the recent literature.

The zinc finger protein A20 is an important negative regulator of inflammation; polymorphisms in the corresponding gene, TNFAIP3, have been reported to be associated with several inflammation diseases. However, only a few studies have focused on the relationship between TNFAIP3 polymorphisms and acute pancreatitis (AP).We enrolled 201 healthy controls and 190 acute pancreatitis patients (including 47 systemic inflammatory response syndrome patients) for this study and used DNA sequencing to investigate polymorphisms in the TNFAIP3 promoter. The functional effects of these variants on transcriptional activity, A20 expression, NF-κB activity, and TNF-α and IL-1β levels, after in vitro lipopolysaccharide stimulation, were assessed.Two SNPs (rs59693083 and rs5029924) in the TNFAIP3 promoter were selected based on bioinformatic analysis. Neither of these SNPs was associated with susceptibility to AP; however, acute pancreatitis patients who possessed the T allele of rs5029924 were more likely to experience systemic inflammatory response syndrome. Moreover, rs5029924 was found to affect TNFAIP3 promoter activity. After lipopolysaccharide stimulation, the expression of A20 protein significantly decreased, while the activity of NF-κB and the production of TNF-α and IL-1β significantly increased in whole blood leukocytes from subjects with the T allele.The rs5029924 polymorphism in the TNFAIP3 promoter may alter the risk of systemic inflammatory response syndrome in acute pancreatitis patients by influencing the expression of A20 protein.