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Abstract Background Flavivirus is a highly prevalent and outbreak-prone disease, affecting billions of individuals annually and posing substantial public health challenges. Vaccination is critical to reducing the global impact of flavivirus infections, making the development of a safe and effective vaccine a top priority. The self-assembled pan-epitope vaccine presents key advantages for improving immunogenicity and safety without relying on external vectors or adding immunomodulatory elements, both of which are essential for successful vaccine development. Results In this study, the pan-epitope peptide TBT was combined with adjuvant CpG to form the TBT-CpG nanovaccine (TBT-CpG NaVs), which was found to be spherical, uniform in shape, and demonstrated strong serum stability. In vitro studies showed that the TBT-CpG NaVs were efficiently taken up and internalized by bone marrow-derived dendritic cells (BMDCs). Flow cytometry and transcriptomic analysis indicated that the antigens were effectively presented to antigen-presenting cells (APCs) via the MHC II pathway, which facilitated BMDCs maturation and promoted the release of pro-inflammatory cytokines IL-1β, TNF-α, and IL-6. In vivo studies confirmed that TBT-CpG NaVs enhanced antigen-specific IgG levels, significantly increased IFN-γ and IL-4 expression in spleen cells, and offered protective effects against Dengue virus (DENV) and Zika virus (ZIKV) infections. Safety evaluations revealed no hepatotoxicity and no significant organ damage in immunized mice. Conclusion The self-assembled candidate nanovaccine TBT-CpG NaVs effectively activates BMDCs and triggers a targeted immune response, providing antiviral effects against DENV and ZIKV. This vaccine demonstrates good immunogenicity and safety, establishing a promising foundation and a new strategy for the development of safe and effective vaccines. Graphical Abstract

Abstract Aiming to improve the voltage distribution and realize the proportional sharing of active and reactive power in the distribution network (DN), this article proposes a distributed optimal control strategy based on the grouping cooperation mechanism of the distributed generation (DG). The proposed strategy integrates the local information of the DG and the global information of the DN. Considering the high resistance/reactance ratio of DN, distributed optimization control strategies for node voltage control and active power management are developed with the consensus variable of active utilization rate. And distributed strategy for reactive power management is proposed with a consensus variable of reactive utilization rate. The convergence of the distributed control system for each group is proved. The validity and robustness of the proposed strategy are verified by several simulations in the IEEE 33‐bus system.

Abstract Aiming at the consumption problem caused by the increasing scale of wind power and photovoltaic (PV) grid-connected, a multi-energy co-generation system is constructed with wind power, PV, concentrated solar power (CSP), and thermal power; in addition, in order to reduce the impact of the prediction errors of wind power, PV, and loads on the system’s economic operation, the photovoltaic and thermal power plants are used to provide the system's backup capacity together, and the opportunity constraint model of the reliability of the backup capacity is established, so as to satisfy the system reliability constraints at a certain higher confidence level; finally, a sampling-based deterministic transformation method is introduced to simplify the model. The model is simplified by introducing a sampling-based deterministic transformation method of opportunity constraint; finally, a stochastic optimal dispatch model of the combined wind-photovoltaic-CSP-fire system, which accounts for the conversion of electricity and heat, is constructed with the objective of minimising the integrated operating cost of the combined system, and the effectiveness of the proposed model is analysed by simulation verification.

Abstract The overall electricity consumption of electrolytic aluminum and ferroalloy loads is significant, and some of these loads have dispatch potential that can be used to locally absorb wind power while reducing dependence on conventional thermal power. To characterize the uncertainty of wind power, a fuzzy set of wind power forecasting error probability distribution based on the Wasserstein distance was first established, and the approximate radius of the fuzzy set was corrected under extreme scenarios. By introducing joint chance constraints, the inequalities of uncertain variables were established at the lowest confidence level to improve the reliability of the model. Next, a two-stage distributed robust optimal scheduling model for source-load coordination was developed. In the first stage, wind power forecasting information was fully utilized to schedule the electrolytic aluminum load and optimize unit commitment. In the second stage, the uncertainty of wind power output was considered to schedule the ferroalloy load and optimize unit output. The model was approximately transformed into a mixed-integer linear programming problem and solved using a sequential algorithm. The IEEE 24-bus system was used for case validation. The validation results show that the model can effectively improve wind power absorption capacity, reduce overall operating costs, and achieve a balance between low carbon emissions and robustness.

Abstract Objective To elucidate the potential benefits of combining radiotherapy and epidermal growth factor receptor‐tyrosine kinase inhibitors (EGFR‐TKIs) for individuals with Stage IV lung adenocarcinoma (LUAD) harboring either exon 19 deletion (19‐Del) or exon 21 L858R mutation (21‐L858R). Methods In this real‐world retrospective study, 177 individuals with Stage IV LUAD who underwent EGFR‐TKIs and radiotherapy at Shandong Cancer Hospital from June 2012 to August 2017 were included. The main focus of this real‐world study was overall survival (OS). Results The clinical characteristics of patients with Stage IV LUAD harboring 19‐Del were similar to those harboring 21‐L858R (p > 0.05). Overall, the patients had a median OS (mOS) of 32.0 months (95% confidence interval [CI]: 28.6–35.5). Subsequently, multivariate analysis indicated that both EGFR mutations and thoracic radiotherapy were independent predictors of OS (p = 0.001 and 0.013). Furthermore, subgroup analysis highlighted a longer OS for the 19‐Del group compared to the 21‐L858R group, especially when EGFR‐TKIs were combined with bone metastasis or thoracic radiotherapy (mOS: 34.7 vs. 25.1 months and 51.0 vs. 29.6 months; p = 0.0056 and 0.0013, respectively). However, no significant differences were found in OS when considering patients who underwent brain metastasis radiotherapy (mOS: 34.7 vs. 25.1 months; p = 0.088). Conclusions Patients with Stage IV LUAD harboring 19‐Del experience a notably prolonged OS following combined therapy with EGFR‐TKIs and radiotherapy, while this OS benefit is observed despite the absence of substantial differences in the clinical characteristics between the 19‐Del and 21‐L858R groups.

The dengue virus, the primary cause of dengue fever, dengue hemorrhagic fever, and dengue shock syndrome, is the most widespread mosquito-borne virus worldwide. In recent decades, the prevalence of dengue fever has increased markedly, presenting substantial public health challenges. Consequently, the development of an efficacious vaccine against dengue remains a critical goal for mitigating its spread. Our research utilized Celcradle™, an innovative tidal bioreactor optimized for high-density cell cultures, to grow Vero cells for dengue virus production. By maintaining optimal pH levels (7.0 to 7.4) and glucose concentrations (1.5 g/L to 3.5 g/L) during the proliferation of cells and viruses, we achieved a peak Vero cell count of approximately 2.46 × 109, nearly ten times the initial count. The use of Celcradle™ substantially decreased the time required for cell yield and virus production compared to conventional Petri dish methods. Moreover, our evaluation of the immunogenicity of the Celcradle™-produced inactivated DENV4 through immunization of mice revealed that sera from these mice demonstrated cross-reactivity with DENV4 cultured in Petri dishes and showed elevated antibody titers compared to those from mice immunized with virus from Petri dishes. These results indicate that the dengue virus cultivated using the Celcradle™ system exhibited enhanced immunogenicity relative to that produced in traditional methods. In conclusion, our study highlights the potential of the Celcradle™ bioreactor for large-scale production of inactivated dengue virus vaccines, offering significant promise for reducing the global impact of dengue virus infections and accelerating the development of effective vaccination strategies.

ABSTRACTIntroduction Objective structured clinical examination (OSCE) results could be affected by low homogeneity of examiners, non-retrospectiveness of test results, and examiner-cohort effect. In China, many students participate in medical qualification examinations, and this issue is particularly significant. This study aimed to develop a video recording, video-based rating method and compare the reliability of video and on-site ratings to enhance the quality assurance of OSCEs.Methods The subjects of this study were clinical students one year after graduation participating in the clinical skills portion of the National Medical Licensing Examination. The participants were from four cities in Jiangsu province. Participants were randomly allocated to on-site and video rating groups to evaluate the rating methods consistency. We verified the reliability of recording equipment and evaluability of video recording. Moreover, we compared the consistency and equivalence of the two rating methods and analyzed the impact of video recording on scores.Results The reliability of recording equipment and evaluability of video recording were high. Evaluation consistency between experts and examiners was acceptable, and there was no difference in evaluation results (P = 0.61). There was good consistency between video and on-site rating; however, a difference between the two rating methods was detected. The scores of video-based rating group students were lower than those of all students (P

The emergence of immunotherapy, particularly programmed cell death 1 (PD-1) and programmed cell death ligand-1 (PD-L1) produced profound transformations for treating non-small cell lung cancer (NSCLC). Nevertheless, not all NSCLC patients can benefit from immunotherapy in clinical practice. In addition to limited response rates, exorbitant treatment costs, and the substantial threats involved with immune-related adverse events, the intricate interplay between long-term survival outcomes and early disease progression, including early immune hyperprogression, remains unclear. Consequently, there is an urgent imperative to identify robust predictive and prognostic biological markers, which not only possess the potential to accurately forecast the therapeutic efficacy of immunotherapy in NSCLC but also facilitate the identification of patient subgroups amenable to personalized treatment approaches. Furthermore, this advancement in patient stratification based on certain biological markers can also provide invaluable support for the management of immunotherapy in NSCLC patients. Hence, in this review, we comprehensively examine the current landscape of individual biological markers, including PD-L1 expression, tumor mutational burden, hematological biological markers, and gene mutations, while also exploring the potential of combined biological markers encompassing radiological and radiomic markers, as well as prediction models that have the potential to better predict responders to immunotherapy in NSCLC with an emphasis on some directions that warrant further investigation which can also deepen the understanding of clinicians and provide a reference for clinical practice.

The NanChang Spherical Tokamak (NCST) is a new compact tokamak with an aspect ratio of R/a = 1.67. The vacuum system is one of the most important sub-systems of the tokamak device and has been designed especially for the NCST device. It consists of three main parts: a pumping system, a gas puffing system, and a wall conditioning system. The pumping system includes two turbo-molecular pumps, a cryopump, and two rotary pumps. The gas puffing system consists of a gas supply, transfer lines, a gas reservoir, pressure gauges, and piezoelectric valves. The wall conditioning system includes baking and glow discharge cleaning functions. The vacuum system and related experimental results are described in detail in this paper. The test results indicate that the NCST vacuum system is reliable. Inside the vessel, the ultimate pressure reached 4.2 × 10−6 Pa after 307 h of pumping. The upgraded gas puffing system can accurately control the gas entering the vacuum vessel. The wall conditioning systems, such as those for baking and glow discharge cleaning, also play a very important role in plasma operation. The plasma discharge results show that the basic function of the vacuum system meets the essential requirements of the present experiments on the NCST tokamak.

Background: Colorectal cancer liver metastasis (CRLM) and hepatocellular carcinoma (HCC) are both high incidence tumors in China. In certain poorly differentiated cases they can exhibit comparable imaging and pathological characteristics, which impedes accurate clinical diagnosis. The use of protein-based techniques with tissue slides offers a more precise means to assess pathological changes and has the potential to assist with tumor diagnosis. Methods: A simple in situ protein digestion protocol was established for protein fingerprint analysis of paraffin-embedded tissue slide samples. Additionally, machine learning techniques were employed to construct predictive models for CRLM and HCC. The accuracy of these models was validated using tissue slides and a clinical database. Results: Analysis of differential protein expression between CRLM and HCC groups reliably identified 977 proteins. Among these, 53 were highly abundant in CRLM samples and 57 were highly abundant in HCC samples. A prediction model based on the expression of six proteins (CD9, GSTA1, KRT20, COL1A2, AKR1C3, and HIST2H2BD) had an area under curve (AUC) of 0.9667. This was further refined to three proteins (CD9, ALDH1A1, and GSTA1) with an AUC of 0.9333. Conclusions: Tissue slide proteomics can facilitate accurate differentiation between CRLM and HCC. This methodology holds great promise for improving clinical tumor diagnosis and for identifying novel markers for challenging pathological specimens.

Abstract Mesenchymal stromal/stem cells (MSCs) possess multi-lineage differentiation and self-renewal potentials. MSCs-based therapies have been widely utilized for the treatment of diverse inflammatory diseases, due to the potent immunoregulatory functions of MSCs. An increasing body of evidence indicates that MSCs exert their therapeutic effects largely through their paracrine actions. Growth factors, cytokines, chemokines, extracellular matrix components, and metabolic products were all found to be functional molecules of MSCs in various therapeutic paradigms. These secretory factors contribute to immune modulation, tissue remodeling, and cellular homeostasis during regeneration. In this review, we summarize and discuss recent advances in our understanding of the secretory behavior of MSCs and the intracellular communication that accounts for their potential in treating human diseases.

Enhancing virus multiplication could assist in the rapid production of vaccines against viral diseases. Cold atmospheric plasma (CAP), a physical approach relying on reactive oxygen species to achieve the desirable cellular outcome, was shown to be effective in enhancing virus propagation, where bovine rhinotrachieitis virus and Madin-Darby Bovine Kidney cells were used as the modeling virus and cell line, respectively. CAP was shown to create synergies with virus infection in arresting host cells at the G2/M stage, decreasing cell membrane potential, increasing intracellular calcium level, and inducing selective autophagy. In addition, CAP was demonstrated to suppress virus-triggered immunogenic signaling as evaluated by IRF7 expression. We presented evidences on CAP-triggered maximization of host resources toward virus multiplication that is advantageous for viral vaccine production, and opened a novel regime for applying CAP in the sector of medical care and health.

Background and Objectives: We aimed to investigate the role of Wnt2 expression in colorectal cancer (CRC) prognosis and evaluate its potential as a therapeutic target in BRAF-mutated CRC. Materials and Methods: Exactly 136 samples of formalin-fixed paraffin-embedded CRC tissue specimens were obtained from patients who underwent surgical resection for CRC. The gene mutation status of the samples was detected using fluorescence PCR. Wnt2 expression was detected using immunohistochemistry. Survival curves with high Wnt2 expression and BRAF mutations were compared using the Kaplan–Meier method. A nomogram was constructed to determine the estimated overall survival probability. We also predicted the 3-year and 5-year survival rates for patients with high Wnt2 expression and BRAF mutations. In total, 50 samples of BRAF-mutated CRC were collected and detected Wnt2 expression by immunohistochemistry. The Chi-squared test was used to analyze the association between Wnt2 expression and BRAF-mutated CRC. Results: High Wnt2 expression and BRAF mutations are associated with poor prognosis of CRC. Multivariate survival analyses indicated that high Wnt2 expression and BRAF mutations are significant independent predictors of CRC prognosis. Furthermore, high Wnt2 expression was significantly associated with BRAF-mutated CRC, and Wnt2 may be a potential therapeutic target for BRAF-mutated CRC. Conclusions: High Wnt2 expression confers poor prognosis in colorectal cancer and represents a novel therapeutic target in BRAF-mutated CRC.

Abstract Background Dioscorea nipponica Makino is widely used in traditional Chinese medicine to treat gouty arthritis. Methods Sixty male Wistar rats were divided into six groups: the normal group, model group, colchicine group (COL) and three total saponin groups (RDN) (high dose [160 mg/kg], middle dose [80 mg/kg] and low dose [40 mg/kg]). HE staining was used to detect the histopathologic changes of the synovial tissue of joint. Immunohistochemical method was used to detect the protein expressions of P-38, p-P38, JNK, p-JNK, ERK1/2, p-ERK1/2, MEK1/2, p-MEK1/2, MKK4, p-MKK4, ICAM1, VCAM1, and PPARγ in the synovial tissue of joint. Realtime PCR and WB methods were used to detect the mRNA and protein expressions of PPARγ and AdipoR2 in the synovial tissue of joint. The contents of CXCL1 and ADP in the blood serum were measured by Elisa method. Results Our study showed that RDN could improve the situation of the synovial tissue, reduce the protein expressions of MKK4, p-MEK1/2, p-JNK, p-ERK1/2, ICAM1. They could also decrease the content of CXCL1 and increase the content of ADP in the blood serum. Conclusion RDN has good effect of anti-inflammation. This is in part realized by influencing MAPK signalling pathway. It provides a new visual angle to reveal the mechanism of RDN to treat GA.

Abstract Background We aimed to develop a clinical applicable nomogram to predict overall survival (OS) for patients with curatively resected nonmetastatic colorectal cancer. Methods Records from a retrospective cohort of 846 patients with complete information were used to construct the nomogram. The nomogram was validated in a prospective cohort of 379 patients. The performance of the nomogram was evaluated with concordance index (c‐index), time‐dependent receiver operating characteristic (ROC) curves, calibration plots, and decision curve analyses for discrimination, accuracy, calibration ability, and clinical net benefits respectively, and further compared with AJCC 8th TNM staging and the MSKCC nomogram. Risk stratification based on nomogram scores was performed with recursive partitioning analysis. Results The nomogram incorporated age, Glasgow prognostic score, pretreatment carcinoembryonic antigen levels, T staging, N staging, number of harvested lymph nodes, and histological grade. Compared with the 8th AJCC staging and MSKCC model, the nomogram had a statistically higher c‐index (0.77, 95% CI: 0.73‐0.80), bigger areas under the time‐dependent ROC curves (AUC at 3 years: 79; at 5 years: 79), and improved clinical net benefits. Calibration plots revealed no deviations from reference lines. All results were reproducible in the validation cohort. Nomogram‐based risk stratification successfully discriminated patients within each AJCC stage (all log‐rank P

Recurrence is the main reason of treatment failure of redical resected colorectal cancer (CRC). Although some factors including staging and differentiation have been proven to useful for recurrence evaluation, prognosis of certain patients does not conform to this evaluation approach. Circulating tumor cells (CTC) have been found to have prognostic value in CRC, and previous studies on CTC have primarily focused on their numbers. CTC are functionally heterogeneous cell populations, and different CTC subgroups may have different functions and clinical values. In our previous study, we discovered that elevated expression of the transient receptor potential channel TRPC5 was associated with a significantly poor prognosis in CRC. In this study, we collected peripheral blood from CTC-positive CRC patients, identified the TRPC5 protein expression on CTC (CTC-TRPC5), and analyzed the relationship between CTC-TRPC5 expression levels and the prognosis. The results showed that CTC-TRPC5 level is significantly related to the T stage and differentiation of tumors. High level of CTC-TRPC5 is more common in a high T stage as well as poorly differentiated tumors and is significantly associated with shorter disease free survival (DFS). The median DFS of CRC patients with high and low CTC-TRPC5 level was 17.1 and 22.0 months, respectively (p < 0.05). This study revealed a clinically significant CTC subgroup of CRC, providing a new indicator for clinical evaluation of CRC prognosis.

In recent years, immunotherapies have emerged as effective therapeutic strategies for treating human cancers. However, accumulating evidence has revealed an inconsistency between the response to immune checkpoint inhibitors and programmed death ligand 1 (PD-L1) expression status detected by immunohistochemistry staining. Recent research has revealed that the removal of N-Linked glycosylation significantly enhanced PD-L1 detection, resulting in both more accurate PD-L1 quantification and clinical outcome prediction. In the present study, we evaluated natural and deglycosylated PD-L1 expression in colon cancer using the PD-L1 28–8 antibody. The results of the present study validated the hypothesis that PD-L1 had a higher expression in colon cancer tissues compared with normal tissues. Additionally, colon tumors with defective mismatch repair tended to express higher PD-L1 than those without. Most importantly, the results of the present study indicated that the removal of N-linked glycosylation remarkably enhanced PD-L1 detection. Moreover, the PD-L1 signal intensity of samples with a low natural PD-L1 signal was enhanced more remarkably than that of samples with high signal intensity. Overall, our research provides an improved strategy for patient stratification for anti-PD-1/PD-L1 therapy, which deepens the clinical significance of this established strategy for treatment of colon cancer.

Dengue virus, the causative agent of dengue fever, life-threatening hemorrhagic fever, and shock syndrome, is mainly transmitted to humans through mosquito vectors. It can also be transmitted through atypical routes, including needle stick injury, vertical transmission, blood transfusion, and organ transplantation. In addition, sporadic cases which have no clear infectious causes have raised the respiratory exposure concerns, and the risks remain unclear. Here, we analyze the respiratory infectivity of the dengue virus in BALB/c suckling and adult immunodeficient mice by the intranasal inoculation of dengue virus serotype 2. The infected mice presented with clinical symptoms, including excitement, emaciation, malaise, and death. Viremia was detected for 3 days post inoculation. Histopathological changes were observed in the brain, liver, and spleen. The virus showed evident brain tropism post inoculation and viral loads peaked at 7 days post inoculation. Furthermore, the virus was isolated from the infected mice; the sequence homology between the origin and isolates was 99.99%. Similar results were observed in adult IFN-α/β receptor-deficient mice. Overall, dengue virus can infect suckling mice and adult immune-deficient mice via the nasal route. This study broadens our perception of atypical dengue transmission routes and provides evidence of nasal transmission of dengue virus in the absence of mosquito vectors.

ObjectiveThis study aimed to investigate the clinical and prognostic relevance of B7-H3 expression and indicators of glucose metabolism in patients with colorectal cancer (CRC).MethodsUsing immunohistochemistry, the expression of B7-H3 was detected in a total of 213 formalin-fixed paraffin-embedded CRC tissue specimens. Furthermore, levels of fasting blood glucose (FBG), lactic dehydrogenase (LDH), and fructosamine (FMN) as indicators of glucose metabolism were analyzed in CRC patients and stratified into high or low expression sub-groups based on Youden Index. The relationship between B7-H3, FBG, LDH, FMN expression, and clinicopathological characteristics were also evaluated to establish their prognostic significance in patients with CRC.ResultsB7-H3 was highly expressed in CRC tissue. The positive rates of B7-H3 expression was 63.8% (136/213). We found a linear correlation between B7-H3 and FBG in depth of tumor invasion (T3/4) (p = 0.037, r = 0.259), lymph node metastasis (N0) (p = 0.004, r = 0.259), and TNM stage (I/II) (p = 0.009, r = 0.242). High expression of FBG, LDH, FMN [hazard ratio (HR) = 1.916, 95% CI: 1.223–3.00, p = 0.005; HR = 1.801, 95% CI: 1.153–2.813, p = 0.010; HR = 2.154, 95% CI: 1.336–3.472, p = 0.002], respectively, was identified as a significant independent predictor of poor overall survival (OS). Although B7-H3 expression did not affect OS, CRC patients expressing both high B7-H3 and high FMN contributed to a significant decrease in OS (HR = 1.881, 95%CI: 1.059–3.339, p = 0.031). Moreover, with low expression of B7-H3, high expression of FBG, LDH and FMN were also recognized as predictors of inferior OS (HR = 3.393, 95% CI: 1.493-7.709, p = 0.004; HR = 7.107, 95% CI: 2.785–18.138, p = 0.000; HR = 2.800, 95% CI: 1.184–6.625, p = 0.019).ConclusionB7-H3 combined with FBG, LDH, or FMN, could reflect the clinical outcomes of patients with CRC.

Wnt2 mRNA is widely expressed in various tumor tissues. Wnt2 overexpression promotes tumor growth, migration, invasion, and metastasis. However, its underlying molecular action mechanisms and clinical implications in colon adenocarcinoma (COAD) remain unclear. mRNA expression data, obtained from tissue samples, and pathophysiological data of 368 COAD patients were obtained from the Cancer Genome Atlas (TCGA) database. Further, Pearson's correlation analysis was performed to explore the correlation between the expression levels of Wnt2 and other genes in the human genome. Subsequently, a protein-protein interaction (PPI) network was constructed for hub gene identification. Overall survival and significance were determined by Kaplan-Meier analysis, and the log-rank test was used to further identify genes with prognostic significance in COAD from GEO datasets (GSE17538 and GSE39582). Subsequently, 158 tissue samples from Affiliated Hospital of Jiangnan University were used for expression verification. Gene set enrichment analysis (GSEA) was performed on high and low Wnt2 expression datasets to identify potential signaling pathways activated in COAD. In all, 10 hub genes associated with Wnt2 were screened by Pearson's correlation analysis and PPI network, with Wnt2 and COL8A1 having significantly poor prognosis by Kaplan-Meier analysis and log-rank test. Furthermore, high expressions of COL8A1 and Wnt2 were associated with poor survival both in TCGA and GEO cohorts. We further found a correlation between the expressions of Wnt2 and COL8A1 in COAD as per immunohistochemical analysis. To further elucidate the underlying molecular mechanisms of Wnt2 in COAD, we searched for pathways enriched in Wnt2 overexpressing datasets by GSEA. Our findings revealed that high Wnt2 levels were significantly associated with extracellular matrix receptor and focal adhesion pathways. Wnt2 expression correlated with COL8A1 expression in COAD; patients with high Wnt2 and COL8A1 expressions had worse survival outcomes. Pathways identified in this study prompt the molecular role of Wnt2 in COAD and provide directions to further elucidate the involved molecular mechanisms in COAD.

Objective We aimed to investigate the relationship of Helicobacter pylori infection with alcohol and smoking. Methods We conducted a cross-sectional study among participants who underwent health check-ups for H. pylori infection between January 2013 and March 2017. We subsequently investigated the relationship of H. pylori infection with alcohol and smoking. Results A total of 7169 participants were enrolled in this study. The overall prevalence of H. pylori infection was 55.2%. Participants with H. pylori infection were more likely to be older than those without H. pylori infection. For male participants with H. pylori infection, multivariable logistic regression analysis indicated that both smoking (odds ratio (OR): 1.61; 95% confidence interval (CI): 1.41–1.83) and alcohol consumption (OR: 1.30; 95% CI: 1.10–1.52) were independently positively associated with H. pylori infection. For female participants, multivariable logistic regression analysis indicated that both smoking (OR: 0.03; 95% CI: 0.02–0.07) and alcohol consumption (OR: 0.20; 95% CI: 0.12–0.33) were inversely significantly associated with H. pylori infection after adjustment for age. Conclusions Smoking and alcohol consumption were risk factors for male participants but these were protective factors for female individuals with H. pylori infection.

While unmanned aerial vehicles (UAVs) facilitate transmission line inspection to some extent, they also generate numerous raw images rather than defect analysis results. Because analyzing the UAV-taken images by a human approach is an arduous work, an automatic method is needed to improve the analysis efficiency. In this paper, a framework is proposed to perform the image semantic segmentation of transmission lines and their accessories to generate the final defect detection results. A segment connection algorithm based on matrix operations is proposed to rapidly connect the segment features of objects. In line accessory detection, a background filter and an artificial contour segment feature generator are constructed to improve the detection performance. In addition, a distance threshold parameter automatic tuning mechanism is presented. Images provided by China Southern Power Grid Company taken by the UAVs are employed to validate the effectiveness of the proposed image semantic segmentation framework.

Abstract Background Systemic inflammation has been implicated in cancer development and progression. This study examined the best cutoff value of erythrocyte sedimentation rate (ESR) in diffuse large B-cell lymphoma (DLBCL) patients. Methods The relationship between ESR and clinical characteristics was analyzed in 182 DLBCL patients from 2006 to 2017. The log-rank test, univariate analysis, and Cox regression analysis were applied to evaluate the relationship between ESR and survival. An ESR of more than 37.5 mm/hour was found to be the optimal threshold value for predicting prognosis. Results ESR was associated with more frequent advanced Ann Arbor stage, poorer performance status, elevated lactate dehydrogenase level, the presence of B symptoms, high-risk International Prognostic Index (IPI 3–5), more extranodal involvement (ENI ≥2), non-germinal-center B-cell (non-GCB) subtypes, and more frequent Myc protein positivity. Shorter overall survival (OS) and progression-free survival (PFS) were found for patients with higher ESRs. Multivariate analysis demonstrated that ESR level is an independent prognostic factor of both OS and PFS. In addition, dynamic changes in ESR are valuable in assessing curative effect and predicting disease recurrence. Conclusion High ESR in DLBCL patients indicated unfavorable prognosis that may require alternative treatment regimens.

Objective Two experiments were conducted to determine the effects of feeding level on nutrient digestibility and enteric methane (CH4) emissions in growing goats and Sika deer. Methods Three growing male goats (initial body weight [BW] of 22.4±0.9 kg) and three growing male deer (initial BW of 20.2±4.8 kg) were each allotted to a respiration-metabolism chamber for an adaptation period of 7 d and a data collection period of 3 d. An experimental diet was offered to each animal at one of three feeding levels (1.5%, 2.0%, and 2.5% of BW) in a 3×3 Latin square design. The chambers were used for measuring enteric CH4 emission. Results Nutrient digestibility decreased linearly in goats as feeding level increased, whereas Sika deer digestibility was not affected by feeding level. The enteric production of CH4 expressed as g/kg dry matter intake (DMI), g/kg organic matter intake, and % of gross energy intake decreased linearly with increased feeding level in goats; however, that of Sika deer was not affected by feeding level. Six equations were estimated for predicting the enteric CH4 emission from goats and Sika deer. For goat, equation 1 was found to be of the highest accuracy: CH4 (g/d) = 6.2 (±14.1)+10.2 (±7.01)×DMI (kg/d)+0.0048 (±0.0275)×dry matter digestibility (DMD, g/kg)–0.0070 (±0.0187)×neutral detergent fiber digestibility (NDFD; g/kg). For Sika deer, equation 4 was found to be of the highest accuracy: CH4 (g/d) = −13.0 (±30.8)+29.4 (±3.93)×DMI (kg/d)+0.046 (0.094)×DMD (g/kg)–0.0363 (±0.0636)×NDFD (g/kg). Conclusion Increasing the feeding level increased CH4 production in both goats and Sika deer, and predictive models of enteric CH4 production by goats and Sika deer were estimated.

Abstract Background Elevated intracellular Ca2+ ([Ca2+] i ) level could lead to [Ca2+] i overload and promote apoptosis via different pathways. In our previously study, up-regulated expression of transient receptor potential canonical channel (TRPC5) was proven to increase [Ca2+] i level, and resulted in chemoresistance whereas not apoptosis in human colorectal cancer (CRC) cells. The ATP-dependent homeostatic maintenance of resting [Ca2+] i should be important in this process. Increased glycolysis was found to be an important adenosine triphosphate (ATP) source in cancer. This study aimed to explore the potential mechanism of aerobic glycolysis in transient receptor potential channel TRPC5 induced chemoresistance. Methods In this study, we examined glucose transporter 1 (GLUT1) expression, glucose consumption and celluar ATP production to determine glycolytic activity. Real-time PCR and western blot were analyzed to determine TRPC5 expression at the mRNA and protein levels in human CRC cells (HCT-8, LoVo), and fluorouracil (5-Fu) resistant CRC cells (HCT-8/5-Fu, LoVo/5-Fu). 3-bromopyruvate (3-BP) and 2-Deoxy-D-glucose (2DG) were used to inhibit glycolysis. Glycolytic activity, intracellular Ca2+ ([Ca2+] i ) and the half maximal inhibitory concentration of 5-Fu (5-Fu IC50) were measured. Western blot was analyzed to determine cleaved Caspase-3 protein level. Flow cytometry was performed to detect the apoptosis rates. Immunohistochemistry staining was performed to determine TRPC5 and GLUT1 expression level in human CRC tissues. Results Overproduced of TRPC5 and increased glycolysis were found in HCT-8/5-Fu and LoVo/5-Fu than in HCT-8 and LoVo cells. Compared to HCT-8 cells, the HCT-8/5-Fu cells showed higher [Ca2+] i levels which decreased after treated with TRPC5-specific shRNA. Furthemore, inhibition of glycolysis resulted in decreased ATP production, elevation of [Ca2+] i level and cleaved caspase-3, increased apoptotic cells rate, and a remarkable reversal of 5-Fu resistance in HCT-8/5-Fu cells, while showed no effect in HCT-8 cells. BAPTA-AM, a [Ca2+] i chelator, could reduce the elevation of cleaved caspase-3 and increased apoptotic cells rate due to glycolysis inhibition. Advanced CRC patients with high expression of TRPC5/GLUT1 displayed poorer chemotherapy outcome, and notably, the significant association between high TRPC5 expression and chemoresistance is GLUT1 expression level dependent. Conclusions We demonstrated the essential role of glycolysis in TRPC5 induced chemoresistance in human CRC cells via maintaining [Ca2+] i homeostasis.

The reactive power optimisation (RPO) is generally used to design an optimal profile of the voltage and reactive power of power systems in the steady state for deterministic sets of demand loads and generation values, and it is a significant procedure in voltage control. However, the input data of a power system is actually uncertain in practise, which makes RPO an uncertain non‐linear programme. To address this problem, the input data were considered as intervals, and the RPO incorporating interval uncertainties model was proposed. To solve this model, the genetic algorithm was employed as the solution algorithm, where the reliable power flow calculation was used to judge the constraints of the model. The Pareto front was established as the solution of the proposed model since it has two objective functions, i.e. the midpoint and radius of real power losses. The application of this technique to the uncertain RPO was explained in detail. Two numerical results were analysed to demonstrate the effectiveness of the proposed method, especially in comparison with the previously proposed chance‐constrained programming method.

Abstract To investigate the association of microRNA (miRNA) binding-site polymorphisms in the drug transporter genes with the efficacy of 5-Fluorouracil (5-FU)/capecitabine-based chemotherapy in colorectal cancer (CRC), 6 polymorphisms were determined in 432 CRC patients by using DNA sequencing method. The impacts of the polymorphisms on the miRNA-mediated regulation of gene expression were evaluated by using the methods including quantitative real-time PCR, western blotting, and luciferase reporter assays. The effects of miRNA on the intracellular concentration and cytotoxicity of 5-FU in CRC cells were measured by high performance liquid chromatography conjected tandem mass spectrometry (HPLC-MS/MS) and MTT methods, respectively. Statistical analysis showed that a polymorphism rs3742106 in the 3′-UTR of ATP-binding cassette subfamily C member 4 (ABCC4) gene was significantly associated with the efficacy of 5-FU/capecitabine-based chemotherapy in CRC. The patients with T/T genotype had significantly higher response rate than those with G/G and G/T genotypes. The expression of ABCC4 was inhibited by miR-3190-5p through binding to the 3′-UTR of the ABCC4 gene. This regulatory role of miR-3190-5p was disrupted by rs3742106. Furthermore, we found that the intracellular concentration of 5-FU was elevated by miR-3190-5p, and consequently the sensitivity of CRC cells to 5-FU was also enhanced. Rs3742106 might be regarded as a genetic biomarker for individualized use of 5-FU and capecitabine in CRC.

Abstract Epidermal growth factor receptor tyrosine-kinase inhibitors (EGFR-TKIs) are standard treatment for advanced non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation. However, EGFR mutation testing is not attainable in approximately 20% of patients. The current study examined intercalating and maintaining gefitinib treatment in stage IIIB/IV non-squamous NSCLC, never or former light smoking patients with unknown EGFR mutation status. Briefly, 219 patients who achieved stable disease (SD) with gemcitabine (1250 mg/m2) plus carboplatin (5 AUC) were randomized at 1:1 ratio to continue chemotherapy (n = 110) or intercalating gefitinib (250 mg/day on days 15–25 of each cycle until disease progress (n = 109). Progression-free survival (PFS) was 9.7 vs. 4.2 month in the gefitinib vs. control arm (HR: 0.41, 95% CI: 0.31–0.56; P

Objective Two experiments were conducted to determine the effects of forage-to-concentrate (F:C) ratio on the nutrient digestibility and enteric methane (CH4) emission in growing goats and Sika deer. Methods Three male growing goats (body weight [BW] = 19.0±0.7 kg) and three male growing deer (BW = 19.3±1.2 kg) were respectively allotted to a 3×3 Latin square design with an adaptation period of 7 d and a data collection period of 3 d. Respiration-metabolism chambers were used for measuring the enteric CH4 emission. Treatments of low (25:75), moderate (50:50), and high (73:27) F:C ratios were given to both goats and Sika deer. Results Dry matter (DM) and organic matter (OM) digestibility decreased linearly with increasing F:C ratio in both goats and Sika deer. In both goats and Sika deer, the CH4 emissions expressed as g/d, g/kg BW0.75, % of gross energy intake, g/kg DM intake (DMI), and g/kg OM intake (OMI) decreased linearly as the F:C ratio increased, however, the CH4 emissions expressed as g/kg digested DMI and OMI were not affected by the F:C ratio. Eight equations were derived for predicting the enteric CH4 emission from goats and Sika deer. For goat, equation 1 was found to be of the highest accuracy: CH4 (g/d) = 3.36+4.71×DMI (kg/d)−0.0036×neutral detergent fiber concentrate (NDFC, g/kg)+0.01563×dry matter digestibility (DMD, g/kg)−0.0108×neutral detergent fiber digestibility (NDFD, g/kg). For Sika deer, equation 5 was found to be of the highest accuracy: CH4 (g/d) = 66.3+27.7×DMI (kg/d)−5.91×NDFC (g/kg)−7.11× DMD (g/kg)+0.0809×NDFD (g/kg). Conclusion Digested nutrient intake could be considered when determining the CH4 generation factor in goats and Sika deer. Finally, the enteric CH4 prediction model for goats and Sika deer were estimated.

Lower Silurian sandstone of the Xiaoheba formation in Southeastern Sichuan has a good reservoir seal combination, and an oil and gas geological condition, but the hypothesis that the sedimentary environment belongs to continental or marine sedimentary deltas remains a matter of debate. In order to solve this problem, 74 samples were collected from 9 typical sections. The elemental composition was determined by the trace element ratio method. Combined with the tectonic background and source characteristics, the sedimentary and paleoclimatic environment were discussed. X-ray Fluorescence Spectrometry (XRF) was used to analyze Ba, Mn, Sr, Cu and other trace elements, which are useful in discriminating between the sea and land facies sedimentary environment. The results show that the average Sr/Ba value is 0.2790 with the maximum of 2.31, the Mn/Fe value is 0.0093 to 0.0778, and the Sr/Ca value is 0.0005 to 0.0414, typical of freshwater delta sedimentary characteristics. The average Sr/Ba is less than 1, the average Sr/Cu is 4.8758, and more than 8.1% samples have Sr/Cu values greater than 10, reflecting the warm, moist, ancient climate environment.

Objective The study objective was to enhance clinical skills among undergraduate students majoring in clinical medicine in performing physical examination by establishing a novel platform for peer assessment of clinical skills. Methods A total 126 Year 2012 students majoring in medicine and receiving traditional training were assigned to the control group, and 126 Year 2013 students receiving instruction via the peer assessment platform of clinical skills were allocated to the study group. Scores of the physical examination, paper exam, and peer assessment were compared using a t -test, and we performed linear correlation analysis of the data. Results Scores of the physical examination and peer assessment among Year 2013 students (the study group) were significantly higher than those in the control group. Paper exam scores in the study group were also significantly higher than those in the controls. The three assessment scores did not differ significantly according to sex. Conclusions The peer assessment platform can not only improve medical students’ skills and capabilities in physical examination, it can also enhance their theoretical knowledge of basic clinical principles. We determined that sex was not related to the assessment scores obtained by medical students.

Identification of effective biomarkers is crucial for monitoring the treatment and remission of colorectal cancer (CRC) and improving survival. It is particularly important to diagnose CRC before the tumor metastasizes (stage I–II disease) where possible, to provide the greatest opportunity for patient recovery. Here, we evaluated the clinical value of serum chemokine (C-X-C) ligand 7 (CXCL7) concentration as a biomarker for CRC diagnosis. An enzyme-linked immunosorbent assay was used to measure CXCL7 concentration in 560 serum samples from patients with CRC and controls. Logistic regression and receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic efficacy and build mathematical diagnostic models. The concentration of CXCL7 in the CRC group was significantly higher than that in the control group (P < 0.001), with an area under the ROC curve (AUC) value of 0.862 [95% confidence interval (CI): 0.831–0.890]. Further, the AUC of a regression model including the markers carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and carbohydrate antigen 125 (CA125), along with CXCL7, was 0.933 (95% CI: 0.909–0.952). For stage I–II tumors, CXCL7 had the highest AUC (0.823, 95% CI: 0.783–0.858) among the four individual biomarkers. The AUC value for combination model analysis of samples from patients with stage I–II tumors was 0.904 (95% CI: 0.872–0.930), with a sensitivity of 82.76% and a specificity of 87.14%, and an optimal cut-off value of 2.66. AUC values for application of the regression model in subgroup analysis were 0.947 (0.917–0.968) and 0.919 (0.874–0.951) for males and females, respectively. These results suggest that CXCL7 has potential as a serum diagnostic biomarker for detection of CRC. Importantly, the combination of CXCL7, CEA, CA125, and CA19-9 may facilitate diagnosis of CRC with relatively high sensitivity and specificity.Clinical Trial Registration Number: LS2017001.

Colorectal cancer (CRC) is one of the most prevalent digestive tumors in China. Recent studies indicate that long intergenic non-coding RNAs (lincRNAs) play a crucial role in predicting survival for CRC patients. However, the novel lincRNA, LINC00957, is largely unclear in CRC. The purpose of the current study was to determine LINC00957 expression, assess its the clinical significance and explore the potential mechanism in CRC. The qRT-PCR was used to quantify the expression levels of LINC00957 in tissues and cell lines. Our research revealed that LINC00957 was significantly higher expression in CRC. In addition, the LINC00957 expression was associated with TNM stage and chemotherapy outcome, but age, gender, tumor size, histological grade, primary tumor location. CRC patients with high LINC00957 expression level showed poor overall survival (P = 0.002). Multivariate survival analysis indicated that LINC00957 was a prognostic factor for CRC patients (P = 0.010). Mechanically, inhibition of LINC00957 expression reversed 5-FU resistance by down-regulating P-gP. In summary, our study indicated that this novel lncRNA expression signature might be a useful biomarker of the prognosis and therapeutic target for CRC patients.