Search

Background: Several studies give a superficial description that HEPACAM family member 2 (HEPACAM2) seems to be a prognostic biomarker in colon adenocarcinoma (COAD). While, systematic and in-depth research about diagnostic and prognostic value of HEPACAM2 in COAD patients is lacked. Besides, relationship between HEPACAM2 gene expression levels and immune cell infiltration is unclear. Methods: Firstly, we analyzed the differential expression levels of HEPACAM2 gene and diagnostic value from different databases. Secondly, a cohort of Guangxi COAD patients was established to verify HEPACAM2 expression pattern and diagnostic value. Thirdly, univariate and multivariate survival analysis of the prognostic value of HEPACAM2 gene in patients with COAD was performed. We also utilized joint-effects analysis and comprehensive prognosis analysis to investigate the prognostic value of HEPACAM2 and related genes. Finally, we explored the relationship between HEPACAM2 gene expression levels and immune cell infiltration.Results: In several biological databases, HEPACAM2 mRNA expression level in COAD tumor tissues was significantly lower than that of adjacent normal tissues. The diagnostic ROC curve results indicated that HEPACAM2 gene had a high diagnostic value in COAD. The qPCR verification results in the Guangxi cohort showed that HEPACAM2 expression level in COAD tumor tissues was significantly lower than that of adjacent normal tissues (PHEPACAM2 gene had a poorer overall survival (OS) in COAD patients when compared with those with high expression ((P = 0.038, HR (95% CI) = 0.635(0.414-0.976)). Joint-effects analysis and comprehensive prognosis analysis showed that high expression of HEPACAM2 combined with high expression of CLCA1, high expression of REP15, and high expression of B3GNT6 were associated with a better overall survival of COAD.Conclusion: This study suggested that the HEPACAM2 may be a diagnostic and prognostic biomarker for COAD. Besides, HEPACAM2 was involved with immune response progress, Chemokine signaling pathway, Ras signaling pathway and Hematopoietic cell lineage.

Pseudomonas syringae pv. actinidiae (Psa) causes bacterial canker, a devastating disease threatening the Actinidia fruit industry. In a search for non-host resistance genes against Psa, we find that the nucleotide-binding leucine-rich repeat receptor (NLR) protein ZAR1 from both Arabidopsis and Nicotiana benthamiana (Nb) recognizes HopZ5 and triggers cell death. The recognition requires ZED1 in Arabidopsis and JIM2 in Nb plants, which are members of the ZRK pseudokinases and known components of the ZAR1 resistosome. Surprisingly, Arabidopsis ZAR1 and RPM1, another NLR known to recognize HopZ5, confer disease resistance to HopZ5 in a strain-specific manner. Thus, ZAR1, but not RPM1, is solely required for resistance to P. s. maculicola ES4326 (Psm) carrying hopZ5, whereas RPM1 is primarily required for resistance to P. s. tomato DC3000 (Pst) carrying hopZ5. Furthermore, the ZAR1-mediated resistance to Psm hopZ5 in Arabidopsis is insensitive to SOBER1, which encodes a deacetylase known to suppress the RPM1-mediated resistance to Pst hopZ5. In addition, hopZ5 enhances P. syringae virulence in the absence of ZAR1 or RPM1 and that SOBER1 abolishes such virulence function. Together the study suggests that ZAR1 may be used for improving Psa resistance in Actinidia and uncovers previously unknown complexity of effector-triggered immunity and effector-triggered virulence.

Inflammation is involved in the progression and prognosis of cancer because it can affect the physical status and prognosis of patients. Among numerous systemic inflammatory markers, the optimal prognostic indicator of older adults with cancer is still unclear. We aimed to identify an ideal inflammatory immune marker in older adults with cancer and assess the survival outcome combined with eastern cooperative oncology group performance status (ECOG PS).We included 1767 older adults with cancer (66.2% males, 70.97 ± 5.49 years old) from a prospective cohort study. Fifteen systemic inflammatory biomarkers were compared to identify the optimal biomarker using prognostic area under the curve (AUC) and concordance index (C-index) analysis. The prognostic value of the clinical parameters was elucidated by performing uni- and multivariate analyses.The AUC, C-index, and the subgroup survival analysis of ECOG PS groups showed that the lymphocyte-C reactive protein ratio (LCR) and C-reactive protein/albumin ratio (CAR) were more accurate in reflecting patient prognosis than the other 13 inflammatory markers. Compared with patients in the high LCR group, those in the low LCR group had worse survival (hazard ratio (HR) 1.64, 95% confidence interval (95%CI) 1.42-1.91, p 0.001). Compared with patients in the low CAR group, those in the high CAR group had worse survival (HR 1.65, 95% CI 1.43-1.91, p 0.001). Older adults with cancer with an ECOG PS score of 2 or 3-4 and a high inflammation (low LCR, 13.3 months and 9.2 months, respectively; or high CAR, 9.6 months and 9.6 months, respectively) had shorter median survival time compared to those with an ECOG PS score of 0/1 and a low inflammation (high LCR, 77.4 months; or low CAR, 77.0 months).LCR and CAR might be the better predictive immune inflammatory factors for OS, which improved the survival prediction of different ECOG PS groups in older adults with cancer. High ECOG PS (≥2) and high inflammation increased the risk of death in older adults with cancer.

Background Systemic inflammation and insulin resistance (IR) are often associated with poor prognosis in cancer. This study aimed to investigate the prognostic value of surrogate systemic inflammation and IR indices in patients with cancer. Methods This multicenter prospective study included 5,221 patients with cancer, with a mean age of 59.41±11.15 years, of whom 3,061 (58.6%) were male. The surrogate IR indices included low-density lipoprotein cholesterol to high-density lipoprotein cholesterol (LHR) ratio, total cholesterol to high-density lipoprotein cholesterol (TC/ HDL-c) ratio, triglyceride to high-density lipoprotein cholesterol (TG/HDL-c) ratio, and fasting triglyceride glucose (TyG). Prognostic receiver operator characteristic (ROC) curves and C-indices were used to select a better surrogate IR index in patients with cancer. The prognostic value of the indicators was evaluated using univariate and multivariate survival analyses. Results In this study, the median survival time of patients was 44.5 (40.5–51.4) months, and the overall mortality in the 12-month period was 1,115 (53.7%), with 196 mortality events per 1,000 patient-years of patients’ follow-up. The prognostic ROC curve and C-index suggested that the prognostic value of LHR was better than that of the other IR indices. The multivariate-adjusted hazard ratios (HRs) for overall survival (OS) were higher in patients with high C-reactive protein (CRP) (HR, 1.51; 95% confidence interval [CI]: 1.38–1.65) and high LHR (HR, 1.20; 95% CI: 1.06–1.37), respectively. The mortality rate of patients with both high CRP and LHR was 1.75-fold higher than that of patients with both low CRP and LHR. Conclusion Both CRP and LHR showed good survival predictions in patients with cancer. CRP combined with LHR can improve the predictive power of patients with cancer.

BackgroundElderly patients with cancer face the challenge of systemic inflammation, which can lead to a poor prognosis. Existing inflammatory indices cannot fully reflect the immune-inflammatory status of patients. This study aimed to develop a new scoring system to predict the survival of elderly patients with cancer using inflammatory indices, namely, the systemic inflammation prognostic score (SIPS).Materials and MethodsThis prospective multicenter study included a total of 1,767 patients with cancer, with a mean age of 70.97 ± 5.49 years, of whom 1,170 (66.2%) were men. We performed the least absolute shrinkage and selection operator (LASSO) regression to screen inflammatory indicators to include in constructing SIPS. Prognostic analysis of SIPS was performed using univariate and multivariate survival analyzes. The prognostic value of SIPS and its components were compared using the prognostic receiver operating characteristic curve and concordance index. The population was divided into the training cohort and the validation cohort in a 7:3 ratio and a SIPS prognostic analysis was performed.ResultsThe LASSO regression selected C-reactive protein (CRP) (≤ 9.81, “0”; > 9.81, “1”), geriatric nutritional risk index (GNRI) (≤ 93.85, “1”; 93.85, “0”), advanced lung cancer inflammation index (ALI) (≤ 23.49, “1”; > 23.49, “0”), and lymphocyte to C-reactive protein ratio (LCR) (≤ 2523.81, “1”; > 2523.81, “0”) to develop SIPS. Patients were divided into the three groups based on the total SIPS: low-risk (0), moderate-risk (1–2), and high-risk (3–4). On the multivariate survival analysis, patients in the moderate-risk [P < 0.001, hazard ratio (HR) = 1.79, 95% CI: 1.47–2.17] and high-risk groups (P < 0.001, HR = 2.40, 95% CI: 1.98–2.92) showed a worse prognosis than those in the low-risk group. The total cohort, training cohort, and validation cohort all showed that SIPS had better survival prediction than CRP, GNRI, ALI, and LCR. The HRs were 2.81 times higher in patients in the high-risk group with malnutrition than in patients in the low-risk group without malnutrition.ConclusionSIPS was an independent prognostic indicator in elderly patients with cancer. Malnutrition in the high-risk group increased the mortality risk.

The uptake of modified low-density lipoprotein (LDL) and the accumulation of lipid droplets induce the formation of vascular smooth muscle cells (VSMCs)-derived foam cells, thereby promoting the development and maturation of plaques and accelerating the progression of atherosclerosis. Celastrol is a quinine methide triterpenoid isolated from the root bark of traditional Chinese herb Tripterygium wilfordii. It possesses various biological properties, including anti-obesity, cardiovascular protection, anti-inflammation, etc. In the present study, we found that celastrol significantly reduced lipid accumulation induced by oxidized LDL (ox-LDL) in VSMCs. Mechanistically, celastrol up-regulated adenosine triphosphate-binding cassette transporter A1 (ABCA1) expression through activating liver X receptor α (LXRα) expression, which contributed to inhibit lipid accumulation in VSMCs. Meanwhile, celastrol decreased lipid accumulation by triggering autophagy in VSMCs. Therefore, these findings supported celastrol as a potentially effective agent for the prevention and therapy of atherosclerosis.

Post-replicative DNA methylation is essential for diverse biological processes in both eukaryotes and prokaryotes. Mycobacterium tuberculosis (M. tuberculosis), the causative agent of tuberculosis,...

Background Curcumol was presented to unleash antitumor effects in a variety of cancers, including gastric cancer. However, the relevance between curcumol and cisplatin resistance in gastric cancer still remains unclear. Therefore, the current research was performed to survey the role of curcumol in cisplatin sensitivity in gastric cancer. Methods First, BGC-823 and BGC-823/DDP cells were incubated with cisplatin for 48 hr and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) analysis was applied to determine the inhibition rate of cell proliferation and the half-maximal inhibitory concentration (IC50 ) of cisplatin. In addition, BGC-823 and BGC-823/DDP cells were treated with curcumol for 48 hr followed with detection of cell viability and apoptosis using MTT and flow cytometry assay, respectively. Moreover, MTT analysis was applied to test the effects of curcumol on cisplatin sensitivity in gastric cancer cells. Lastly, Western blot assay and qRT-PCR analysis were utilized to check the functions of curcumol on PI3K/AKT pathway-related markers. Results We found that BGC-823/DDP cells exhibited stronger resistance to cisplatin compared with BGC-823 cells. Furthermore, curcumol evidently reduced cell proliferation and facilitated cell apoptosis in BGC-823/DDP and BGC-823 cells. Moreover, results from MTT assay demonstrated that curcumol notably promoted the suppression effect of cisplatin and decreased the IC50 of cisplatin in BGC-823/DDP and BGC-823 cells. It was also presented that curcumol suppressed the PI3K/AKT pathway dose-dependently in BGC-823/DDP and BGC-823 cells. Conclusion The findings in the current research demonstrated that curcumol could promote the sensitivity of gastric cancer cells to cisplatin-based chemotherapies via inhibiting the phosphatidylinositol 3-kinase (PI3K)/Protein Kinase B (AKT) pathway.

In this paper, by use of test combined with numerical simulation, the out-of-plane loading-bearing failure process of CFRP and C/C joints were studied, while Hashin failure criterion was selected t...

Folic acid attenuates high-fat diet-induced steatohepatitis via deacetylase SIRT1-dependent restoration of PPARα

Purpose: From a motor control perspective, the balance and propulsion are needed to proceed smoothly, and using high heeled shoes based on two conditions led to more difficult and complex gait. High heeled alter the natural form of body and present a chain reaction of disadvantageous affected that throughout the entire body from the toe to spine. Therefore, the purpose of this review provides a comprehensive guide of understanding HH gait. Methods: Electronic database which includes PubMed, Embase, Medline, Amed, and Cinahl were searched for controlled trials comparing high heeled shoes with barefoot or flat shoes, which include changes of the lower limb and upper limb. The kinematic change of body was the primary outcome measure. The comparison was conducted with mean differences and 95% confidence intervals. Result: Major findings were focused on the joint of the ankle, knee, hip, pelvis, and spine. The results of collecting articles show that a significant difference in ankle and knee joint during the gait when high heels and barefoot are compared. There are still conflicting results in terms of lumbar lordosis, and few studies indicate that the pelvic anteversion increased significantly. Conclusion: On direction for future research should establish an effective method to estimate the result of the HH effect on body posture.

In the present study, the significance of GABAA genes in colon adenocarcinoma (COAD) were investigated from the view of diagnosis and prognosis. All data were achieved from The Cancer Genome Atlas. Overall survival was analyzed by the Kaplan-Meier analyses and Cox regression model and the hazard ratios and 95% confidence interval were calculated for computation. The Database for Annotation, Visualization and Integrated Discovery, and the Biological Networks Gene Ontology (BiNGO) softwares were applied to assess the biological processes and Kyoto Encyclopedia of Genes and Genomes (KEGG) was used for pathway analysis to predict the biological function of GABAA genes. The associated Gene Ontology and KEGG pathways were conducted by Gene Set Enrichment Analysis (GSEA). From receiver operating characteristics curves analysis, it was found that the expression of GABR, γ-aminobutyric acid type A receptor GABRA2, GABRA3, GABRB2, GABRB3, GABRG2, GABRG3, GABRD, GABRE were correlated with COAD occurrence [P0.7]. The low expression of the GABRB1, GABRD, GABRP and GABRQ in genes after tumor staging adjustment were positively correlated with the overall survival rate [P=0.049, hazard ratio (HR)=1.517, 95% confidence interval (CI)=1.001–2.297; P=0.006, HR=1.807, 95% CI=1.180–2.765; P=0.005, HR=1.833, 95% CI=1.196–2.810; P=0.034, HR=1.578, 95% CI=1.036–2.405). GSEA showed enrichment of cell matrix adhesion, integrin binding, angiogenesis, endothelial growth factor and endothelial migration regulation in patients with COAD with GABRD overexpression. GABRB1, GABRD, GABRP and GABRQ were associated with the prognostic factors of COAD. The expression levels of GABRA2, GABRA3, GABRB2, GABRB3, GABRG2, GABRD and GABRE may allow differentiation between tumor tissues and adjacent normal tissues.

Taking NREL 5 MW large offshore wind turbine as a research object, a theoretical model considering geometrical nonlinearity is established, and the dynamic response analysis is carried out. Besides...

Rock mass fraction is one of the main indexes to evaluate the blasting effect of mining. We take some rock blocks after blasting as the research objects and use 3D laser scanner to obtain the point cloud data of rock blocks. Then we use statistical filtering method to process the original point cloud data, and then calculate the point cloud data after pre-processing. We obtain the supervoxel clustering point cloud. On the supervoxel clustering algorithm, the concave convex criterion is used to fuse the clustering results. The regional growth algorithm is used to complete the segmentation of rock point cloud, so as to achieve the purpose of automatic recognition of blasting rock block contour. Based on the segmentation results of the rock block point cloud, the rock block point cloud with obvious characteristics is extracted, and the length of the long axis of the rock block is obtained according to the feature information of the rock block. The results show that the method can solve the defects of traditional measurement methods. The proposed recognition algorithm will meet the requirement of the intelligent of blasting fragmentation analysis. Additionally, it will satisfy the requirements of blasting quality analysis and evaluation.

Despite the considerable contributions of remittances to households and economic advancements, their environmental implications have received little attention in empirical research. This study was, therefore, conducted to help fill that gap, using Ghana as an evidence. In achieving the above goal, robust econometric methods that control for endogeneity, heteroscedasticity and serial correlation among others, were engaged for the analysis. From the results, the studied variables were first-differenced stationary and cointegrated in the long run. The elasticities of the predictors were explored via the FMOLS, DOLS and CCR estimators, and from the results, remittance inflows worsened the ecological quality in Ghana through high CO

With the worldwide spread of acupuncture as a therapeutic modality and the rapid development of acupuncture clinical research, the number of acupuncture randomized controlled trial (RCT) studies is steadily increasing in China and around the world. However, the results of these studies seem to come from two different worlds indeed. Chinese RCT studies overwhelmingly demonstrate positive outcomes from acupuncture, whereas Western-based studies generally conclude that there is no discernible difference between acupuncture and a placebo. Why should there be such different outcomes when the same scientific method is being used? This paper analyzes factors that may be contributing to the different outcomes between China-based and Western-based RCT studies by considering and comparing starting points, purpose, study design, investigators, acupuncture treatment regimen, methodological quality, results, conclusions, and deficiencies in acupuncture RCT. Based on these comparisons, this paper examines the value of acupuncture RCT in general, and the methodological confusion which seems to have propagated from study to study. We propose the following suggestions to remediate the acupuncture clinical research paradigm: First, acupuncture clinical researches should be carried out step-by-step according to universal, agreed-upon research protocols. Second, norms for reporting outcome metrics need to be standardized for each stage of a study.随着针灸的国际传播及针灸临床研究的迅速发展，中西方针刺随机对照试验（RCT）研究数量持续增长。然而，西方针刺RCT研究得出针刺效应相当于安慰剂的结果，与中国针刺RCT研究几乎全部是阳性结果形成鲜明对比。为什么同一种方法产生如此不同的结果？本文从针刺RCT研究的缘起与国内外针刺RCT研究现状出发，系统比较中西方针刺RCT在需求与起点、研究目的、研究设计、研究者、针刺治疗方案、研究的方法学质量、研究结果、研究结论及研究不足等方面的差异。在此基础上重新思考针刺RCT的价值及针刺临床研究中的方法学困惑，对针刺临床研究范式提出以下建议：根据研究方案成熟度，开展阶梯递进的临床研究；在不同研究阶段设置明确的实施指导和报告规范。.

Glycoproteins can be used as biomarkers to detect many diseases. Reliable and efficient sample materials are essential to separate and enrich glycopeptides before detection and analysis. In this report, glutathione (GSH)-modified magnetic covalent organic framework (TpBD) composite Fe

Cold seeps and hydrothermal vents are deep-sea reducing environments that are characterized by a lack of oxygen, photosynthesis-derived nutrients and a high concentration of reducing chemicals. Apodida is an order of deep-sea echinoderms lacking tube feet and complex respiratory trees, which are commonly found in holothurians. Chiridota heheva Pawson & Vance, 2004 (Apodida: Chiridotidae) is one of the few echinoderms that resides in deep-sea reducing environments. Unlike most cold seep and hydrothermal vent-dwelling animals, C. heheva does not survive by maintaining an epi- or endosymbiotic relationship with chemosynthetic microorganisms. The species acquires nutrients by extracting organic components from sediment detritus and suspended material. Here, we report a high-quality genome of C. heheva as a genomic reference for echinoderm adaptation to reducing environments. Chiridota heheva likely colonized its current habitats in the early Miocene. The expansion of the aerolysin-like protein family in C. heheva compared with other echinoderms might be involved in the disintegration of microbes during digestion, which in turn facilitates the species’ adaptation to cold seep environments. Moreover, several hypoxia-related genes were subject to positive selection in the genome of C. heheva, which contributes to their adaptation to hypoxic environments.

Background: Colon adenocarcinoma (COAD) is still the main cause of cancer deaths worldwide. Although immunotherapy has made progress in recent years, there is still a need to improve diagnosis, prognosis, and treatment tools. UL-16 binding protein 1 (ULBP1) is a ligand that activates the receptor natural killer cell group 2 receptor D (NKG2D) and plays an important immunomodulatory role. We aimed to investigate the clinical significance of ULBP1 in COAD.Methods: We obtained the relevant data from The Cancer Genome Atlas (TCGA). A total of 438 patients with COAD were included in this study, with a mean age of 67.1 ± 13.03 years old, of which 234 (53.42%) were male. The diagnostic value of COAD tumor tissues and adjacent tissues was analyzed by ROC curve. Univariate and multivariate survival analysis investigated the prognostic value of ULBP1 gene, and Gene Set Enrichment Analysis (GSEA) curve was performed to analyze the biological process and enriched enrichment pathway of ULBP1 in COAD. Combination survival analysis investigated the combined prognostic effect of prognostic genes.Results:ULBP1 gene had a high diagnostic value in COAD [AUC (TCGA) = 0.959; AUC (Guangxi) = 0.898]. Up-regulated ULBP1 gene of patients with COAD predicted a worse prognosis compared to those patients with down-regulated ULBP1 gene (Adjusted HR = 1.544, 95% CI = 1.020–2.337, p = 0.040). The GSEA showed that ULBP1 was involved in the apoptotic pathway and biological process of T cell mediated cytotoxicity, regulation of natural killer cell activation, and T cell mediated immunity of COAD. The combination survival analysis showed that the combination of high expression of ULBP1, AARS1, and DDIT3 would increase the 2.2-fold death risk of COAD when compared with those of low expression genes.Conclusion: The immune-related ULBP1 gene had diagnostic and prognostic value in COAD. The combination of ULBP1, AARS1, and DDIT3 genes could improve the prognostic prediction performance in COAD.

Background & Aims: Gut microbiota and microbial factors regulate the pathogenesis of nonalcoholic fatty liver disease (NAFLD) in patients with obesity and metabolic abnormalities, but little is known about their roles in nonobese NAFLD. Expansion of Escherichia is associated with NAFLD pathogenesis. We aimed to investigate the pathogenic role of Escherichia fergusonii and its products in the development of nonobese NAFLD. Methods: We characterized the intestinal microbiome signature in a cohort of NAFLD patients and healthy controls by 16S ribosomal RNA sequencing. The role of E fergusonii was estimated in rats after 16 weeks of administration, and features of NAFLD were assessed. E fergusonii–derived microRNA-sized, small RNAs (msRNAs) were analyzed by deep sequencing. Results: We detected an expansion of Escherichia_Shigella in NAFLD patients compared with healthy controls, and its increase was associated with disease severity independent of obesity. E fergusonii, a member of the genus Escherichia, induced the development of nonobese NAFLD characterized by hepatic steatosis and hepatocyte ballooning in rats without obesity. It disturbed host lipid metabolism by inhibiting hepatic lipid β-oxidation and promoting de novo lipogenesis. We also showed that E fergusonii caused the development of hepatic inflammation and fibrosis in a sizable fraction of animals at an advanced stage of NAFLD. Mechanistically, E fergusonii–derived msRNA 23487 down-regulated host hepatic peroxisome proliferator-activated receptor α expression, which could contribute to lipid accumulation in the liver. Conclusions: These results suggest that E fergusonii promotes the pathogenesis of steatohepatitis and fibrosis in nonobese rats by secreting msRNA 23487, and it might be a potential biomarker for predicting steatohepatitis in nonobese NAFLD.

We have developed a graph-based Variational Autoencoder with Gaussian Mixture hidden space (GraphGMVAE), a deep learning approach for controllable magnitude of scaffold hopping in generative chemistry. It can effectively and accurately generate molecules from a given reference compound, with excellent scaffold novelty against known molecules in the literature or patents (97.9% are novel scaffolds). Moreover, a pipeline for prioritizing the generated compounds was also proposed to narrow down our validation focus. In this work, GraphGMVAE was validated by rapidly hopping the scaffold from FDA-approved upadacitinib, which is an inhibitor of human Janus kinase 1 (JAK1), to generate more potent molecules with novel chemical scaffolds. Seven compounds were synthesized and tested to be active in biochemical assays. The most potent molecule has 5.0 nM activity against JAK1 kinase, which shows that the GraphGMVAE model can design molecules like how a human expert does but with high efficiency and accuracy.

In this paper, the PWM plus phase-shift control with certain voltage balanced condition is applied to a hybrid dual bridge series resonant converter (HDBSRC). The control strategy is unified for the whole variation range of load, input/output voltage and with simple calculation. By using this voltage balanced strategy, the effective unity-gain operation condition can be obtained. A decoupled control can be derived then, in which the converter gain can be controlled by the PWM in the hybrid primary bridge and and load level is regulated by the phase-shift modulation. The equivalent unity-gain operation naturally extend the ZVS range and reduce the resonant current. A design example based on the analysis results is presented and then verified through experiment.

To enhance the efficiency of a semi dual-bridge resonant converter(SDBRC), a control strategy to minimize the root mean square(RMS) current and eliminate the backflow power is proposed. An optimal operating point is precisely selected to reduce the conduction loss due to backflow power and high rms current. The converter is enabled to work with the optimal operating point in the whole load range by adjusting the switch-controlled capacitor (SCC) based tunable resonant tank continuously. Soft-switching of all switches can be maintained along the control route as well. A lab prototype converter designed at 300 W is tested to validate the SCC-based topology and proposed modulation scheme. The experimental result has demonstrated that the proposed topology and modulation scheme can improve the converter efficiency over the whole load range, especially in the light load condition.

BACKGROUND: This paper aimed to evaluate the effectiveness of ovarian transposition (OT) and the dose constraint for preserving ovarian function in young cervical cancer patients who underwent postoperative volumetric modulated arc therapy (VMAT). METHODS: A retrospective analysis was conducted of young cervical cancer patients who accepted postoperative VMAT in the Affiliated Cancer Hospital of Nanjing Medical University from September 2015 to September 2018. VMAT plans for OT and non-OT patients were compared, and the patients’ ovarian function was followed up. The transposed position of the ovaries and the radiation dose constraint were further explored using a receiver operator characteristic (ROC) curve. RESULTS: A total of 51 young patients (age ≤40 years) were included in the study, 32 of whom underwent OT and 19 of whom did not. For these OT and non-OT patients, the homogeneity index (HI), conformity index (CI), organs at risk (OARs), average number of monitor units (MUs), and mean treatment time were similar and showed no statistically significant difference (P≥0.05). Through follow-up studies, the number of patients with preserved ovarian function was found to be 22 (out of 32) and 0 (out of 19) in the OT and non-OT patients, respectively. The minimal distance for preserving ovarian function was determined as 2.1 cm between the center of a transposed ovary and the planning target volume (PTV) margin. The optimal limited radiation doses were estimated as maximum dose (D(max)) 9.8 Gy and mean dose (D(mean)) 4.6 Gy, respectively. CONCLUSIONS: OT shows no negative effects on dose distribution, target region conformity, protection of OARs, or treatment efficacy and is therefore a reliable method in the preservation of ovarian function for young cervical cancer patients undergoing postoperative radiotherapy using the VMAT technique. Specifically, when the distance between the center of a transposed ovary and the PTV margin is more than 2.1 cm, and the radiation dose is limited to a D(max) of less than 9.8 Gy and a D(mean) of less than 4.6 Gy, the function of transposed ovaries may be preserved.

The selectivity of gas sensing materials is increasingly important for their applications. The oxygen-regulated SnO2 films with (110) and (101) preferred orientation were obtained through magnetron sputtering, followed by annealing treatment. Their micro-structure, surface morphology and gas response were investigated by advanced structural characterization and property measurement. The results showed that the as-prepared (110)-oriented SnO2 film was oxygen-rich and had more adsorption sites while the as-prepared (101)-oriented SnO2 film was oxygen-poor and more sensitive to de-oxidation. H2 gas sensitivity, response speed, selectivity between H2 and CO of the (110)-orientated SnO2 film was superior to that of the (101)-orientated SnO2 film. After treated at high temperature and high vacuum, the reduction of gas-sensing properties of the annealed (110) SnO2 film was much more than that of the annealed (101) SnO2 film. The lattice oxygen was responsible for the difference in gas-sensing response between (110) and (101)-oriented SnO2 films under oxygen regulation. This work indicated the gas-sensing selectivity of the different crystal planes in SnO2 film, providing a significant reference for design and extension of the related materials.

For four-stroke turbocharged gasoline direct injection engines, the improvement of pre-mixture homogeneity and the reduction of wall wetting are beneficial to improve combustion performance and emission characteristics, and specifically effective to suppress super-knock because of the decrease of oil dilution and soot formation. This paper investigated the effect of injection strategy and intake valve lift (IVL) on super-knock frequency and engine performance through experimental study. The validated numerical models revealed the mechanisms behind experimental results. The results showed that using late second injection under high-IVL condition and early single-injection under low-IVL condition reduced wall wetting and improved mixture homogeneity. This restrained the formation of pre-ignition origins (oil dilution and soot formation were decreased). The tendency of hot-spot self-ignition (local high-temperature region was narrowed) and end-gas detonation combustion (end-gas reactivity was reduced) was suppressed as well. These factors contributed to the reduction of the actual super-knock frequency in experiment. Further, late second injection under high-IVL condition and early single-injection under low-IVL condition also accelerated the flame propagation and promoted the complete combustion of fuel. Thus the dynamic and economic performance improved. CO and soot emissions also reduced, only NOx emission increased. Two-stage injection played the opposite role in engine performance respectively under high-IVL and low-IVL condition. In general, the combination of low-IVL and early single-injection showed the lowest super-knock frequency and best engine performance.

Obesity is considered a chronic inflammatory disease, the inflammatory factors, such as interleukin 6 (IL‐6), monocyte chemoattractant protein 1 (MCP‐1) and small inducible cytokine A5 (RANTES), are elevated in obese individuals. Pituitary adenylate cyclase‐activating polypeptide (PACAP) suppresses anti‐inflammatory cytokines and ameliorates glucose and lipid metabolism. Our previous study showed that Fas apoptosis inhibitory molecule (FAIM) is a new mediator of Akt2 signalling, increases the insulin signalling pathway and lipid metabolism. In this study, we found that PACAP promoted the expression of FAIM protein in a human hepatocyte cell line (L02). Overexpression of FAIM with lentivirus suppressed the expression of the inflammatory factor interleukin 6 (IL‐6), monocyte chemoattractant protein 1 (MCP‐1) and tumour necrosis factor alpha (TNF‐α). Following treatment of obese mice with FAIM or PACAP for 2 weeks, inflammation was alleviated and the bodyweight and blood glucose levels were decreased. Overexpression of FAIM down‐regulated the expression of adipogenesis proteins, including SREBP1, SCD1, FAS, SREBP2 and HMGCR, and up‐regulated glycogen synthesis proteins, including Akt2 (Ser474) phosphorylation, GLUT2 and GSK‐3β, in the liver of obese mice. However, down‐regulation of FAIM with shRNA promotes obesity. Altogether, our data identified that FAIM mediates the function of PACAP in anti‐inflammation, glucose regulation and lipid metabolism in obese liver.

Objective: The aim was to investigate the lncRNA KB-1471A8.2 function in ovarian cancer progression and paclitaxel resistance. Methods: The expression and distribution of KB-1471A8.2 was detected by qRT-PCR. The cell proliferation, apoptosis, invasion, migration and chemoresistance were analyzed by CCK8 assay, flow cytometry and transwell assay. The expression of DEPTOR, whose sequence is reverse overlapped with KB-1471A8.2 was analyzed by qRT-PCR, western blot and immunofluorescence. The cell cycle and the cell cycle related gene expression were analyzed by flow cytometry and qRT-PCR, respectively. Results: KB-1471A8.2 was significantly downregulated in both ovarian cancer tissues and chemoresistant ovarian cancer cells. Overexpression of KB-1471A8.2 significantly inhibited the proliferation, invasion, migration, and paclitaxel resistance, and increased the apoptosis of ovarian cancer cells. KB-1471A8.2 was mainly distributed in the nucleus of ovarian cancer cells. KB-1471A8.2 overexpression significantly decreased the S phase cell ratio, increased the G0/G1 phase cell ratio, but not affected the expression and distribution of DEPTOR. However, cyclin-dependent kinase 4 (CDK4), which is an important regulator of G1/S transition, was significantly decreased in KB-1471A8.2-overexpressed ovarian cancer cells. Conclusion: KB-1471A8.2 could significantly inhibit the development and paclitaxel resistance of ovarian cancer cells, at least partly, by suppressing CDK4 expression.

The emergence of multidrug resistant (MDR) Mycobacterium tuberculosis strains and increased incidence of HIV coinfection fueled the difficulty in controlling tuberculosis (TB). MarR (multiple antibiotic resistance regulator) family transcription factors can regulate marRAB operon and are involved in resistance to multiple environmental stresses. We have summarized the structure, function, distribution, and regulation of the MarR family proteins, as well as their implications for novel targets for antibiotics, especially for tuberculosis.

In the process of studying the curing deformation behavior of fiber metal laminates (FMLs) subjected to thermal stress, there are some discrepancies between analytical models and experimental results for the room-temperature stable configuration. The main reason is the uncertainty of the parameters in the analytical calculation. In present paper, a parametric sensitivity analysis of the influence of Young’s modulus, Poisson’s ratio, thermal expansion coefficients, ply thickness, ply angle and temperature difference on the cured stable configuration is carried out to identify the most sensitive properties. Accurate characterization of these sensitive properties and precise control of manufacture process can reduce the discrepancies and obtain a more accurate prediction model. It is believed that the present study can be helpful of guiding the design and manufacture of the FMLs in the engineer application.

For the 5MW offshore wind turbine blade, the control and discrete equations of the fluid domain and structural domain were established respectively, and the calculation formulas of blade loads and damping coefficient were given. Furthermore, the blade entity modeling was completed by using UG and ANSYS Workbench. Based on it, the numerical calculation of blade vibration characteristics under different wind and rotating speeds was carried out, and the reliability verification was conducted by the wind tunnel test. The results of calculation indicate that the numerical results of the first principal stresses at the blade surface along the span-wise direction are consistent with the results of wind tunnel test, which verifies the reliability of the theory and numerical models. Both the influences of the bidirectional fluid-structure interaction (BFSI) and the rotation effect on the characteristics of blade vibration should be underlined. The increase of wind or rotating speed results in the nonlinear increase of the maximum span-wise displacement of the blade and of the Mises-stresses. Under different wind or rotating speed, the blade’s maximum displacement occurs at its tip, its maximum Mises-stresses appear at the relative wingspan of 0.55, and the contribution of rotating speed and average wind speed to the displacement or Mises-stress along the span-wise direction is similar.

The scavenging process is helpful to suppress the super-knock in a 4-stroke turbocharged gasoline direct injection (GDI) engine because it can strengthen in-cylinder cooling and clear suspending residual particles from previous cycles. This paper investigates the effects of combustion system parameters on scavenging process. The simulation results showed that the piston pit with a shallow depth adjacent to the center of cylinder could intensify the scavenging motion and increase the velocity inside the pit, more residual gas and carbon particles could be therefore cleared. The intake and exhaust valve chamfer angle of 45° was beneficial to the scavenging process because more high-velocity scavenging motion occurred in piston pit and less fresh charge flowed into exhaust port directly. The injector location and ground electrode orientation has little influence on scavenging process because of its tiny volume. Finally, an optimum structural shape of combustion chamber was developed and proposed based on the research results.

Exosomes, the nano-vesicles released from living cells, were the important mediator for cell-to-cell communication. In order to clarify whether the exosomes derived from obesity adipose tissue mediate insulin resistance of hepatocytes, we extract the exosomes from the adipose tissue of different mice models. Exosomes derived from ob/ob mice (Ob-exosomes), B6 mice fed with a high-fat diet (HFD-exosomes) and normal B6 mice (WT-exosomes) displayed similar size and molecular makers, but their effect on the insulin sensitivity of hepatocytes were obviously different or opposite. Abundant exosomal miRNAs in Ob-, HFD- and WT-exosomes were detected by the Next Generation Sequencing. The levels of miR-141-3p in Ob- and HFD-exosomes were significantly lower than WT-exosomes. MiR-141-3p can be effectively delivered into AML12 cells accompanied by the absorption of exosomes, but the absorption of miR-141-3p into AML12 cells could be blocked by GW4869, an inhibitor of exosome biogenesis and release. Importantly, the Ob-exosomes or miR-141-3p knockdown in WT--exosomes obviously inhibited the insulin response and glucose uptake of AML12 cells, however, the inhibitory effects on insulin function disappeared after the overexpression of miR-141-3p in Ob-exosomes or AML12 cells. The effects of miR-141-3p on insulin function could be achieved by improving the level of phosphorylation of AKT and enhancing insulin signal transduction. Therefore, the absorption of hepatocytes for exosomes released from obesity adipose tissue containing less miR-141-3p than healthy adipose tissue can significantly inhibit the insulin sensitivity and glucose uptake. Our study may certify a novel mechanism that the secretion of “harmful” exosomes from obesity adipose tissues cause insulin resistance.

Ovarian cancer remains the most fatal gynecologic malignancy worldwide due to delayed diagnosis as well as recurrence and drug resistance. Thus, the development of new tumor-related molecules with high sensitivity and specificity to replace or supplement existing tools is urgently needed. Cancer-testis antigens (CTAs) are exclusively expressed in normal testis tissues but abundantly found in several types of cancers, including ovarian cancer. Numerous novel CTAs have been identified by high-throughput sequencing techniques, and some aberrantly expressed CTAs are associated with ovarian cancer initiation, clinical outcomes and chemotherapy resistance. More importantly, CTAs are immunogenic and may be novel targets for antigen-specific immunotherapy in ovarian cancer. In this review, we attempt to characterize the expression of candidate CTAs in ovarian cancer and their clinical significance as biomarkers, activation mechanisms, function in malignant phenotypes and applications in immunotherapy.