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The clinical burden of mental illness, in particular schizophrenia and bipolar disorder, are driven by frequent chronic courses and increased mortality, as well as the risk for comorbid conditions such as cardiovascular disease and type 2 diabetes. Evidence suggests an overlap of molecular pathways between psychotic disorders and somatic comorbidities. In this study, we developed a computational framework to perform comorbidity modeling via an improved integrative unsupervised machine learning approach based on multi-rank non-negative matrix factorization (mrNMF). Using this procedure, we extracted molecular signatures potentially explaining shared comorbidity mechanisms. For this, 27 case–control microarray transcriptomic datasets across multiple tissues were collected, covering three main categories of conditions including psychotic disorders, cardiovascular diseases and type II diabetes. We addressed the limitation of normal NMF for parameter selection by introducing multi-rank ensembled NMF to identify signatures under various hierarchical levels simultaneously. Analysis of comorbidity signature pairs was performed to identify several potential mechanisms involving activation of inflammatory response auxiliarily interconnecting angiogenesis, oxidative response and GABAergic neuro-action. Overall, we proposed a general cross-cohorts computing workflow for investigating the comorbid pattern across multiple symptoms, applied it to the real-data comorbidity study on schizophrenia, and further discussed the potential for future application of the approach. [ABSTRACT FROM AUTHOR]

Motivation In multi-cohort machine learning studies, it is critical to differentiate between effects that are reproducible across cohorts and those that are cohort-specific. Multi-task learning (MTL) is a machine learning approach that facilitates this differentiation through the simultaneous learning of prediction tasks across cohorts. Since multi-cohort data can often not be combined into a single storage solution, there would be the substantial utility of an MTL application for geographically distributed data sources. Results Here, we describe the development of 'dsMTL', a computational framework for privacy-preserving, distributed multi-task machine learning that includes three supervised and one unsupervised algorithms. First, we derive the theoretical properties of these methods and the relevant machine learning workflows to ensure the validity of the software implementation. Second, we implement dsMTL as a library for the R programming language, building on the DataSHIELD platform that supports the federated analysis of sensitive individual-level data. Third, we demonstrate the applicability of dsMTL for comorbidity modeling in distributed data. We show that comorbidity modeling using dsMTL outperformed conventional, federated machine learning, as well as the aggregation of multiple models built on the distributed datasets individually. The application of dsMTL was computationally efficient and highly scalable when applied to moderate-size (n  < 500), real expression data given the actual network latency. Availability and implementation dsMTL is freely available at https://github.com/transbioZI/dsMTLBase (server-side package) and https://github.com/transbioZI/dsMTLClient (client-side package). Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

In order to take into account the physical health of athletes and the quality of sports training, an optimization modeling and simulation method for the relationship between high-intensity training and sports injuries of athletes is proposed. The research of the specific content of the method is based on the two-dimensional and three-dimensional registration principles. In the research process, the program is written strictly according to the registration principle, and the correctness of the method is effectively tested by means of experimental methods. Digital image reconstruction measures based on 3D models may be based on ray tracing methods. The experimental results show that the number of accurate cases of this method is 77, and the accuracy rate is 96.3%. The proposed method can formulate a scientific and effective injury prevention strategy for athletes during high-intensity training. [ABSTRACT FROM AUTHOR]

Cu/Al composites have the excellent properties of both Cu and Al, and have the properties of light weight and high conductivity, so they have been widely concerned. In this paper, 5-mm-thick Cu/Al composites prepared by the cast-rolling process are used as experimental materials. To reveal the strengthening and toughening mechanisms of the Cu/Al composites, the interfacial structure, micro-morphology, stress-strain condition, and GND distribution of Cu/Al composites before and after deformation were characterized utilizing TEM, TKD, and EBSD. The results show that the submicron intermetallic compounds Al 2 Cu and Al 4 Cu 9 are formed from the casting-rolling Cu/Al composites. After 15% tensile deformation, many gaps occurred in the interface layer, but at the gaps, there was no crack spreading to the Cu and Al layers. Meanwhile, the deformation in different directions occurs in the Cu grains near the interface, forming a dislocation wall, and the entanglement of the dislocation occurs in the Cu layer near the interface, which contributes to the improvement of tensile strength. The Al layer near the interface layer produces kink bands, which helps to improve the ductility of the composites. Besides, due to the action of the hard intermetallic compound layer, with the increase in tensile deformation, a large number of GND are gradually accumulated in the Cu and Al layers near the interface, resulting in remote back stress, which makes the softer Cu and Al layers obtain higher strength. At the same time, the back stress caused by GND will induce strain hardening, which helps to maintain ductility, so that Cu/Al composites have higher plastic deformation ability while improving mechanical properties. • The effect of the interfacial layer on the strengthening and toughening of Cu/Al composites during deformation was studied. • The Cu/Al composites could induce dislocation pile-up in the Cu side, after tensile deformation. • The deformation in different directions is generated in the Cu layer grain and the dislocation wall is formed. • GND accumulates gradually at the interface, with the progress of tensile deformation. [ABSTRACT FROM AUTHOR]

A low-loss, polarization-insensitive and tunable electromagnetically induced transparency (EIT) at terahertz frequency has been demonstrated in this paper. It is obtained by the excitation of the two resonators at the same time, which could be excited by the incident electric and magnetic fields separately. The metamaterial electromagnetically induced transparency (EIT) structure is composed of silver cross strip and silver cross block. The transmission spectrum's peak could reach as high as 0.97 and the frequency band that the transmission peak above 0.95 could reach 0.32 THz. In addition, through exciting different region of solid-state plasmas, the transmission window could be tuned in a narrow frequency band, which offers an effective approach to produce low-loss and tunable EIT metamaterials. [ABSTRACT FROM AUTHOR]

Aim: Only seven cases of liver transplantation (OLT) with positive serum hepatitis B surface antigen (HBsAg) grafts have been reported in the world till now. Here we report the 4-year follow-up results and clinical pathologic characteristics of two recipients of chronic hepatitis B transplanted with HBsAg-positive cadaveric liver grafts from asymptomatic carriers. Methods: Lamivudine combined with hepatitis B immune globulin were used for the control of hepatitis B virus (HBV) infection in both of the recipients post-OLT. The liver functions, virus status and pathologic characteristics of two recipients were followed up according to the rounte protocol of Liver Transplantation Center of West China Hospital. Results: The serum HBV deoxyribonucleic acid (DNA) turned negative within 30 days post-OLT, but HBsAg remained positive for both of the recipients during follow up. HBV breakthrough occurred in one recipient at the month 12 post-OLT, with detectable serum HBV-DNA (740 copies/mL) and tyrosine-methionine-aspartate-aspartate motif mutation (rtM204I and rtM204V). After the replacement of lamivudine by adefovir dipivoxil 10 mg daily for 2 months, serum HBV-DNA of this recipient became undetectable again and maintained undetectable during follow up. Both of the recipients have survived for more than 4 years post-OLT, with stable liver function and mild hepatitis. Conclusion: Due to extreme scarcity of liver graft, we think that HBsAg-positive liver graft without active HBV-DNA replication and severe pathological manifestation from asymptomatic carriers may deserve consideration when no other graft is available in a bearable waiting time. [ABSTRACT FROM AUTHOR]

Lupeol (Lup-20(29)-en-3H-ol), a novel dietary triterpene, was found in fruits, vegetables, and several medicinal plants. Here, we investigated its growth-inhibitory effect and associated mechanisms in hepatocellular carcinoma SMMC7721 cells. Lupeol treatment resulted in significant inhibition of cell viability in a dose-dependent manner and caused apoptotic death of this cell line with activation of caspase3 expression. Caspase8 inhibitor pretreatment was found to partially block the apoptosis induced by Lupeol. Moreover, Lupeol specifically caused a significant decrease in the expression of Death receptor 3 (DR3) mRNA and protein and a significant elevated expression of FADD mRNA whereas Fas mRNA and protein expression was not detectable. Further more, knockdown of DR3 by small interfering RNA inhibited the growth and induced apoptosis of hepatocellular carcinoma cell. These results suggested that Lupeol treatment induced growth inhibition and apoptosis in SMMC7721 cells, the mechanism is due to down-regulation of DR3 expression. We demonstrated that Lupeol appears to be a promising chemopreventive agent for treating hepatocellular carcinoma, and DR3 may be an important target for liver cancer therapy. [ABSTRACT FROM AUTHOR]

Abstract: The expression of alpha-fetoprotein (AFP), a tumor-associated antigen, is silenced in normal adult hepatocyte but reactivated in human hepatocellular carcinoma (HCC). To investigate the roles of AFP in the regulation of cell growth, we silenced AFP expression in the HCC cell line Huh7 by transfection of specific Stealth™ RNAi. After the transfection for 48h, the expression of AFP gene was almost abolished, the cell proliferation was inhibited by 46.15%, and the number of cells undergoing early apoptosis was significantly increased to 63.93%. Inhibition of AFP expression also resulted in an increased in Bax/Bcl-2 ratio, the release of cytochrome c from mitochondria and activation of caspase-3. The results suggest that AFP may positively regulate cell proliferation by enhancing the apoptosis resistance via dysfunction of the p53/Bax/cytochrome c/caspase-3 signaling pathway in AFP-producing HCC cell line. As such, the knockdown of AFP gene should be further investigated in vivo as a novel approach to HCC treatment. [Copyright &y& Elsevier]

Aim: Insulin-like growth factors (IGFs) and their receptors play a critical role in the growth and regulation of many type of malignant cells. The purpose of this study was to clarify the expression of Insulin-like growth factor I receptor (IGF-IR) in a human colorectal cancer cell line HT-29 and investigate the effects of 2 IGF-IR monoclonal antibodies (Mab) on the biological behavior of HT-29 cell line. Methods: Immunohistochemistry was used to test the expression of IGF-IR in HT-29 cell line, MTT assay was used to determine the antiproliferation effects of 2 kinds of IGF-IR monoclonal antibody on HT-29 cells. The effects of apoptosis rate and cell cycle of HT-29 cells were estimated by flow cytometry (FCM). Results: IGF-IR was expressed in the membranes of HT-29 cell line; MTT results show that each IGF-IR (α-Subunit)Ab-3 Mab group has remarkable difference (p < 0.01) as compared with control group, each IGF-IRα(1H7)L Mab group has no remarkable difference (p > 0.05) as compared with control group, each IGF-IRα(1H7)L Mab group has light antiproliferation effect on the HT-29 cells. IGF-IR(α-Subunit)Ab-3 has stronger antiproliferation effect on the HT-29 cells and dose-depended growth inhibition effects were observed when concentration is less than 1.5 ug/ml;The 2 kinds of IGF-IR monoclonal antibody can arrest the cell cycle at any phase of HT-29 cells and induce apoptosis. Under the incubating conditions of containing 5 percent fetal bovine serum (FCS) and no FCS, the apoptosis percentage of IGF-IR(α-Subunit)Ab-3 group and IGF-IRα(1H7)L group have obviously increased (p < 0.01). After the number of cells was increased 30 times, the apoptosis percentage of IGF-IR(α-Subunit)Ab-3 group and IGF-IRα(1H7)L group have no remarkable differences as compared with control group (p > 0.05). Conclusions: Blockade of the IGF-IR with IGF-IR Mab inhibiting proliferation, arresting cell cycle and inducing apoptosis of HT-29 cells may represent a valid approach to inhibit tumor growth. [ABSTRACT FROM AUTHOR]

Ternary chalcogenides have emerged as potential candidates for ultrathin photovoltaics, and NaBiS2 nanocrystals (NCs) have gained appeal because of their months‐long phase‐stability in air, high absorption coefficients >105 cm−1, and a pseudo‐direct bandgap of 1.4 eV. However, previous investigations into NaBiS2 NCs used long‐chain organic ligands separating individual NCs during synthesis, which severely limits macroscopic charge‐carrier transport. In this work, these long‐chain ligands are exchanged for short iodide‐based ligands, allowing to understand the macroscopic charge‐carrier transport properties of NaBiS2 and evaluate its photovoltaic potential in more depth. It is found that ligand exchange results in simultaneous improvements in intra‐NC (microscopic) and inter‐NC (macroscopic) mobilities, while charge‐carrier localization still takes place, which places a fundamental limit on the transport lengths achievable. Despite this limitation, the high absorption coefficients enable ultrathin (55 nm thick) solar absorbers to be used in photovoltaic devices, which have peak external quantum efficiencies > 50%. In addition, temperature‐dependent transient current measurements uncover a small activation energy barrier of 88 meV for ion migration, which accounts for the strongly hysteretic behavior of NaBiS2 photovoltaic devices. This work not only reveals how the charge‐carrier transport properties of NaBiS2 NCs over several length and time scales are influenced by ligand engineering, but also unveils the facile ionic transport in this material, which limits the potential of NaBiS2 in photovoltaics. On the other hand, the discovery shows that there are opportunities to use this material in memristors, electrolytes, and other applications requiring ionic conduction. [ABSTRACT FROM AUTHOR]

Background: Previous studies have observed a close association between hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC) as well as extrahepatic cancers. However, research concerning the effect of HBV infection on the risk of colorectal cancer (CRC) is rare and inconsistent. This study aims to determine the relationship between HBV infection and new-onset CRC.Methods: We prospectively examined the relationship between HBV infection and new-onset CRC among 93,390 participants from Kailuan Cohort study. Cox proportional hazards regression models, subgroup analyses and competing risk analyses were used to evaluate the association between HBV infection and the risk of new-onset CRC.Results: During a median follow-up of 11.28 years, 448 incident CRC cases were identified. The adjusted HR (95%confidence interval (CI)) for the association of HBsAg Seropositive with CRC was 1.85(1.15 ~ 2.96) in the Cox regression. Subgroup analyses showed that the HBsAg seropositive group was associated with increased risk of new-onset CRC among male, middle-aged, normal weight, smokers and non-drinker participants, respectively. A positive association of HBV infection with the risk of CRC was observed in the adjusted sub-distribution proportional hazards (SD) models (HRSD = 1.77, 95% CI:1.11-2.84) and cause-specific hazards (CS) models (HRCS = 1.79, 95% CI: 1.13-2.91).Conclusions: Our results have found a significant association between HBV infection and the risk of incident CRC among Chinese participants.Trial Registration: Kailuan study, ChiCTR-TNRC-11001489. Registered 24 August 2011 - Retrospectively registered, http:// http://www.chictr.org.cn/showprojen.aspx?proj=8050. [ABSTRACT FROM AUTHOR]

Organic semiconductors are a family of pi‐conjugated compounds used in many applications, such as displays, bioelectronics, and thermoelectrics. However, their susceptibility to processing‐induced contamination is not well understood. Here, it is shown that many organic electronic devices reported so far may have been unintentionally contaminated, thus affecting their performance, water uptake, and thin film properties. Nuclear magnetic resonance spectroscopy is used to detect and quantify contaminants originating from the glovebox atmosphere and common laboratory consumables used during device fabrication. Importantly, this in‐depth understanding of the sources of contamination allows the establishment of clean fabrication protocols, and the fabrication of organic field effect transistors (OFETs) with improved performance and stability. This study highlights the role of unintentional contaminants in organic electronic devices, and demonstrates that certain stringent processing conditions need to be met to avoid scientific misinterpretation, ensure device reproducibility, and facilitate performance stability. The experimental procedures and conditions used herein are typical of those used by many groups in the field of solution‐processed organic semiconductors. Therefore, the insights gained into the effects of contamination are likely to be broadly applicable to studies, not just of OFETs, but also of other devices based on these materials. [ABSTRACT FROM AUTHOR]

Background: Laparoscopy has been widely used in treatment of pediatric intussusception. However, controversy still exists on the best surgical approach for children with multiple recurrences. This cohort study is aimed to compare the efficacy and safety of laparoscopic ileopexy versus laparoscopic simple reduction for treatment of ileocolic intussusception with three or more episodes of recurrence in pediatric patients. Patients and Methods: This study enrolled 74 children with three or more recurrences of ileocolic intussusception treated at our department between January 2016 and June 2018. Of these children, 37 cases undergoing laparoscopic ileopexy were matched with 37 cases undergoing laparoscopic simple reduction according to age. Data on patient characteristics, duration of follow-up, operative parameters, and recurrence rate after laparoscopic operation were reviewed and analyzed. Results: Patient characteristics, including age, gender, weight, number of recurrences at surgery, clinical manifestations, and duration of follow-up, were well comparable between the two groups (each P > .05). During follow-up, recurrence occurred in 16 (43.24%) children undergoing laparoscopic simple reduction, whereas recurrence occurred in 1 (2.70%) case undergoing laparoscopic ileopexy. In comparison, laparoscopic ileopexy significantly decreased the risk of recurrence (P < .001). No statistical difference was observed between the two groups in terms of operative time, length of postoperative stay, and intra- and postoperative complications (each P > .05). No morbidity was documented in both groups. Conclusions: Laparoscopic ileopexy is effective and safe as a surgical approach for multiple recurrences of ileocolic intussusception in pediatric patients. The underlying mechanisms are yet to be fully clarified. [ABSTRACT FROM AUTHOR]

Background: Leakage of the alveolar epithelial barrier can lead to pulmonary oedema, leading to organ dysfunction. Objectives: Combination anthraquinone (CA) and free anthraquinone (FA) were extracted from Rhubarb, and the prevention and therapeutic effects of Rhubarb anthraquinones (RA) on lipopolysaccharide (LPS)-induced lung injury were investigated. Materials and Methods: The CA and FA were extracted from Rhubarb by water solvent extraction and ethanol solvent extraction. The extracted RA content was determined using spectrophotometry and high-performance liquid chromatography (HPLC). A mouse model of inflammatory lung injury was established by LPS induction to study the mechanism of RA activity. Inflammatory factors were measured using an enzyme-linked immunosorbent assay. Changes in alveolar epithelial leakage were assessed using a permeability assay. Changes in lung injury were evaluated by histopathological and ultrastructural observations. Tight junction (TJ) markers and Ras homolog gene family member A (RhoA)/Rho-associated protein kinase 1 (ROCK1) pathway-related proteins were measured using immunohistochemistry and Western blotting. As an agonist of RhoA/Rock signalling, U46619 was used to further verify whether RA acts through this pathway. Results: RA could inhibit pulmonary inflammation by decreasing the level of inflammatory factors. The alveolar epithelial permeability was reduced, and the pathological injury of the lung tissue was alleviated after administration with RA. Furthermore, the expression of TJ proteins was up regulated and RhoA/ROCK1 signalling was inhibited in the presence of RA. The effects of RA on TJ proteins were partially reversed by U46619. Conclusion: RA effectively protects mice against inflammatory lung injury by enhancing alveolar epithelial TJ via RhoA/ROCK1 signalling. [ABSTRACT FROM AUTHOR]

Programmed death ligand 1 (PD-L1) is expressed in hepatocellular carcinoma (HCC) cells. PD-L1 function and structure are regulated through glycosylation and various signaling pathways. However, the relationship between Pseudomonas aeruginosa mannose sensitive hemagglutinin (PA-MSHA), glycosylation and PD-L1 warrants further study. In this study, we investigated the effects of PA-MSHA on the regulation of mannosyl and N-glycosylation to identify the mechanisms underlying its function. PD-L1, β-catenin, c-Myc, mannosyl, MGAT1 and mannosidase II in HCC were identified by postoperative specimens from the HCC cohort with immunohistochemistry and immunofluorescence. PA-MSHA was used to suppress tumor progression. Alterations to the expression of PD-L1, β-catenin, c-Myc, MGAT1, and mannosidase II at the gene and protein levels were detected by qRT-PCR and Western blot analysis. Soluble PD-L1 (sPD-L1) were detected using enzyme-linked immunosorbent assay. Mannosyl and mannosidase II expression levels increased, whereas those of MGAT1 decreased in the HCC cells. The glycosylation-related pathway proteins, namely, β-catenin, c-Myc and PD-L1, had increased expression levels. Moreover, proliferation in the HCC cells was inhibited after PA-MSHA treatment, PD-L1 function was significantly inhibited. Transmission electron microscopy showed that PA-MSHA penetrated into the HCC cytoplasm through the cytomembrane, resulting in apoptosis. Here, PA-MSHA significantly reduced sPD-L1 expression levels in the tumor cells. PA-MSHA plays the role of a lectin, affecting receptors on the cytomembrane. This strain inhibits mannosyl by suppressing β-catenin signaling. We hypothesized that PA-MSHA suppresses PD-L1 by: 1. Inhibiting the glycosylation process; and 2. Suppressing β-catenin and c-Myc, thereby reducing the transcription of this protein. [ABSTRACT FROM AUTHOR]

Simple Summary: Lymphatic vessels are low-pressure, blind-ended tubular structures essential in maintaining tissue fluid homeostasis, immune cell transport, and lipid transport. More and more evidence showed that lymphangiogenesis might be closely related to the development of many diseases, and the intervention of lymphangiogenesis may be a new direction of disease treatment. This review aims to discuss the molecular mechanisms of lymphangiogenesis, the effect of lymphangiogenesis on tumor immune tolerance, the emerging role of meningeal lymphatics and cardiac lymphatics, and the promising applications of lymphangiogenesis in immunotherapy and bioengineering materials. The lymphatic system is a channel for fluid transport and cell migration, but it has always been controversial in promoting and suppressing cancer. VEGFC/VEGFR3 signaling has long been recognized as a major molecular driver of lymphangiogenesis. However, many studies have shown that the neural network of lymphatic signaling is complex. Lymphatic vessels have been found to play an essential role in the immune regulation of tumor metastasis and cardiac repair. This review describes the effects of lipid metabolism, extracellular vesicles, and flow shear forces on lymphangiogenesis. Moreover, the pro-tumor immune tolerance function of lymphatic vessels is discussed, and the tasks of meningeal lymphatic vessels and cardiac lymphatic vessels in diseases are further discussed. Finally, the value of conversion therapy targeting the lymphatic system is introduced from the perspective of immunotherapy and pro-lymphatic biomaterials for lymphangiogenesis. [ABSTRACT FROM AUTHOR]

Simple Summary: Enhancer of zeste homolog 2 (EZH2) modifies the trimethylation of Lys-27 of histone 3, affecting downstream target genes' expression. It was reported that EZH2 is highly expressed in gastric cancer and may be a potential prognostic molecule and promising therapeutic target. We aim to present the value of EZH2 research in gastric cancer by focusing on the crucial events of EZH2 involvement in gastric cancer progression. Therefore, in this review, we present the two main functions of EZH2: histone methylation modification and DNA methylation by EZH2; the molecular mechanism of the action of EZH2 in regulating target genes; a detailed description of the mechanism of EZH2 in gastric cancer-related events. Finally, progress in the development of EZH2 inhibitors is summarized. This review article provides researchers studying the epigenetics of gastric cancer with research ideas to find new targets for studying gastric cancer pathogenesis. Gastric cancer is the fifth most common cancer and the third leading cause of cancer deaths worldwide. Understanding the factors influencing the therapeutic effects in gastric cancer patients and the molecular mechanism behind gastric cancer is still facing challenges. In addition to genetic alterations and environmental factors, it has been demonstrated that epigenetic mechanisms can also induce the occurrence and progression of gastric cancer. Enhancer of zeste homolog 2 (EZH2) is the catalytic subunit of the polycomb repressor complex 2 (PRC2), which trimethylates histone 3 at Lys-27 and regulates the expression of downstream target genes through epigenetic mechanisms. It has been found that EZH2 is overexpressed in the stomach, which promotes the progression of gastric cancer through multiple pathways. In addition, targeted inhibition of EZH2 expression can effectively delay the progression of gastric cancer and improve its resistance to chemotherapeutic agents. Given the many effects of EZH2 in gastric cancer, there are no studies to comprehensively describe this mechanism. Therefore, in this review, we first introduce EZH2 and clarify the mechanisms of abnormal expression of EZH2 in cancer. Secondly, we summarize the role of EZH2 in gastric cancer, which includes the association of the EZH2 gene with genetic susceptibility to GC, the correlation of the EZH2 gene with gastric carcinogenesis and invasive metastasis, the resistance to chemotherapeutic drugs of gastric cancer mediated by EZH2 and the high expression of EZH2 leading to poor prognosis of gastric cancer patients. Finally, we also clarify some of the current statuses of drug development regarding targeted inhibition of EZH2/PRC2 activity. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) cell-intrinsic programmed death 1 (PD-1) promotes tumor progression. However, the mechanisms that regulate its expression are unclear. This study investigated the impact of alpha-fetoprotein (AFP) on HCC cell-intrinsic PD-1 expression. The expression of PD-1 and AFP at the gene and protein levels was detected using real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and western blotting (WB). Proteins interacting with AFP were examined by co-immunoprecipitation (CO-IP). Chromatin immunoprecipitation (ChIP) and dual luciferase reporter assays were used to identify transcription-enhanced association domain 1 (TEAD1) binding to the promoter of PD-1. The expression of HCC cell-intrinsic PD-1 was positively correlated with AFP. Mechanistically, AFP inhibited the phosphorylation of large tumor suppressor 2 (LATS2) and yes-associated protein (YAP). As a result, YAP is transferred to the nucleus and forms a transcriptional complex with TEAD1, promoting PD-1 transcription by binding to its promoter. AFP is an upstream regulator of the HCC cell-intrinsic PD-1 and increases PD-1 expression via the LATS2/YAP/TEAD1 axis. Our findings provide insight into the mechanisms of HCC development and offer new ideas for further in-depth studies of HCC. • Hepatocellular carcinoma (HCC) cells express programmed death protein 1 (PD-1). • HCC cell-intrinsic PD-1 expression is associated with alpha-fetoprotein (AFP). • The YAP/TEAD1 complex promotes HCC cell-intrinsic PD-1 transcription. • AFP enhances the transcriptional function of the YAP/TEAD1 complex via LATS2/YAP. • AFP upregulates HCC cell-intrinsic PD-1 transcription via the LATS2/YAP/TEAD1 axis. [ABSTRACT FROM AUTHOR]

Background and Aim: Long non‐coding RNA (lncRNA) TNK2 AS1 is a noncoding RNA with the capability of affecting microRNAs (miRNAs) levels and gene expression. The study was designed to investigate the mechanism of TNK2 AS1 in gastric cancer. Methods: The loss and gain of function of TNK2 AS1 were investigated by analyzing the malignant behavior of AGS cells including the abilities of migration, invasion, and epithelial‐mesenchymal transition (EMT) process via wound healing and transwell assay, as well as western blot. The targeting relationship of LncRNA TNK2 AS1 was analyzed through searching bioinformatics database, luciferase reporter assay, and RNA immunoprecipitation (RIP) assay. Tumor‐bearing experiment in nude mice was performed to further confirm the regulatory role of TNK2 AS1 in vivo. Immunofluorescence assay for Ki67 expression was carried out in tumor tissues of mice model. Results: The results showed that TNK2 AS1 overexpression promoted the malignant behaviors of AGS cells, which could be weakened by miR‐125a‐5p mimic addition. In addition, Jumonji, At‐rich interaction domain (JARID2), and phosphatidylinositol 3 kinase (PI3K)/AKT pathway were regulated by TNK2‐AS1/miR‐125a‐5p axis. In vivo, TNK2 AS1/miR‐125a‐5p axis promoted tumor growth and led to increases in green fluorescence intensity and vimentin expression and a decrease in E‐cadherin level, which could be mediated by JARID2 and PI3K/AKT pathway. Conclusion: Therefore, a conclusion was drawn that TNK2‐AS1/miR‐125a‐5p promoted the progression of gastric cancer. [ABSTRACT FROM AUTHOR]

Halide double perovskites have gained significant attention, owing to their composition of low‐toxicity elements, stability in air, and recent demonstrations of long charge‐carrier lifetimes that can exceed 1 µs. In particular, Cs2AgBiBr6 is the subject of many investigations in photovoltaic devices. However, the efficiencies of solar cells based on this double perovskite are still far from the theoretical efficiency limit of the material. Here, the role of grain size on the optoelectronic properties of Cs2AgBiBr6 thin films is investigated. It is shown through cathodoluminescence measurements that grain boundaries are the dominant nonradiative recombination sites. It also demonstrates through field‐effect transistor and temperature‐dependent transient current measurements that grain boundaries act as the main channels for ion transport. Interestingly, a positive correlation between carrier mobility and temperature is found, which resembles the hopping mechanism often seen in organic semiconductors. These findings explain the discrepancy between the long diffusion lengths >1 µm found in Cs2AgBiBr6 single crystals versus the limited performance achieved in their thin film counterparts. This work shows that mitigating the impact of grain boundaries will be critical for these double perovskite thin films to reach the performance achievable based on their intrinsic single‐crystal properties. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is one of common malignant tumors in the digestive system. There is still no effective means for the early diagnosis of pancreatic cancer. As a mixture of oral gland secretion and oral mucosal transudate, saliva contains abundant biological information including microorganisms, proteins, and nucleic acids, which wiil change when the disease occurs. So saliva can be used for the early diagnosis of pancreatic cancer. Trough summarizing and analyzing the current studies and advantages of its application for early diagnosis, this article suggests that saliva bioinformatics holds promise for the application in the early diagnosis of pancreatic cancer. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is the third-most prevalent malignant tumor. Taurine upregulated gene 1 (TUG1), a long non-coding RNA (lncRNA), is reportedly involved in the physiological and pathological processes of CRC. However, the role of TUG1 in the progression of CRC and its underlying mechanisms are largely unknown. Here, we measured the expression of TUG1 in clinical samples from CRC patients and found that the expression level of TUG1 was higher in CRC tissues compared with the normal adjacent tissues. We then performed knockdown of TUG1 with siRNAs in two CRC cell lines and found that TUG1 knockdown inhibited the viability, proliferation, and migration of CRC cells, and reduced the ability of CRC cells to form subcutaneous tumors. Furthermore, we discovered that TUG1 affects the cellular processes in CRC cells by sponging miR-145-5p. We further found that miR-145-5p inhibits the expression of the protein-encoding gene Transient Receptor Potential Cation Channel Subfamily C Member 6 (TRPC6), and that overexpression of TRPC6 restored the inhibitory role of miR-145-5p in CRC cells. In conclusion, we have demonstrated that TUG1 exerts its role by modulating the TUG1–miR-145-5p–TRPC6 regulatory axis, thus revealing a novel molecular mechanism for the effects of TUG1 in the progression of CRC. Our data indicate that the TUG1–miR-145-5p–TRPC6 signaling pathway could serve as a target for the diagnosis and treatment of CRC. [ABSTRACT FROM AUTHOR]

Background: Apatinib showed promising efficacy in the treatment of advanced or metastatic gastric cancer (mGC) in previous clinical studies. However, the real-world data are limited, and this study aimed to assess the effectiveness and safety of apatinib for the treatment of advanced or mGC in this setting. Methods: In this prospective observational study, progression-free survival (PFS), overall survival (OS), overall response rate (ORR), disease control rate (DCR) and treatment-related adverse events (AEs) were recorded and evaluated. Univariate and multivariate analyses were conducted to explore potential biomarkers which might be related to the effectiveness. Results: A total of 321 mGC patients from 47 centers in China were enrolled between July 1, 2015, and March 1, 2018. Thirty-two patients achieved partial response, 155 patients achieved stable disease, and 115 patients had progressive disease, and no CR was achieved, illustrating an ORR of 10.60% and a DCR of 61.92%. The median PFS and OS were 4.0 and 8.2 months, respectively. Multivariate Cox analysis showed that the potential biomarkers associated with longer PFS were combination regimens plus taxel/docetaxel, and apatinib initial dosage ≥ 500mg, occurrence of AEs of leukopenia, and hand-foot syndrome. Main AEs were proteinuria (17.1%), hypertension (15.9%), and handfoot syndrome (8.7%). Conclusion: The present prospective observational study showed favorable effectiveness and safety of apatinib in real-world patients with advanced or metastatic GC in China. (A prospective, multi-center, non-intervention study of apatinib in the treatment of advanced gastric cancer-Trial Registry Number: ChiCTR-OPN-15006601). [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is the third leading cause of cancer-associated mortality worldwide. Ginsenoside Rh1 (Rh1) is a traditional medicine monomer with antitumor activity; however, the effects of Rh1 in CRC remain to be determined. In the present study, SW620 cells were treated with different concentrations of Rh1. Cell Counting Kit-8, wound healing and Transwell assays were performed to measure cell viability and proliferation, migration and invasion, respectively. Subsequently, the mRNA expression levels of matrix metallopeptidase (MMP)1, MMP3 and tissue inhibitor of metalloproteinases 3 (TIMP3) were detected by reverse transcription-quantitative PCR analysis. In addition, the protein expression levels of MMP1, MMP3, TIMP3, and total or phosphorylated (p-)ERK1/2, P38, JNK were detected by western blotting. Furthermore, tumor growth was examined in a nude mouse xenograft model. The results of the present study indicated that Rh1 was not toxic to CRC cells at various concentrations (0, 50 or 100 µM) and treatment durations (24 or 48 h). However, cell proliferation was suppressed by Rh1 in a dose-dependent manner. Rh1 (100 µM) significantly inhibited cell migration and invasion in vitro. Additionally, Rh1 suppressed the mRNA and protein expression of MMP1 and MMP3, and promoted TIMP3 expression. Rh1 decreased the ratios of p-P38/P38, p-ERK1/2/ERK1-2 and p-JNK/JNK in vitro and in vivo, which suggested that Rh1 inactivated the mitogen-activated protein kinase (MAPK) signaling pathway. Notably, Rh1 markedly decreased tumor volume and weight in vivo. In conclusion, the present study demonstrated that Rh1 inhibited the proliferation, migration and invasion of CRC cells in vitro and tumor growth in vivo. This inhibition was at least partially due to the inhibition of MMP1 and MMP3 expression, the increase in TIMP3 expression level and the MAPK signaling pathway inactivation. Therefore, Rh1 may effectively inhibit the development of CRC as an anticancer drug, and may have a supporting effect during CRC treatment. [ABSTRACT FROM AUTHOR]

The interfacial structure is critical in the practical application of layered materials. To comprehend the interfacial bonding of Cu/Al layered composites more deeply, the interface binding properties at the Al 2 Cu(110)/Cu(111) interface were investigated using first-principles calculations. In this work, four different interface models are considered. Among them, the Al A terminal, one of the four terminals on the surface of Al 2 Cu(110), exhibited the best stability among the Al 2 Cu/Cu interfaces, with the maximum adhesion work (3.094 J/m2) and the lowest interfacial energy. The Cu-3d and Al-3p states at its interface exhibit hybridization. Electronic analysis has shown that the covalent and metallic bonds between the Al and Cu atoms at the interface are the main sources of the interfacial bonding. The results discussed above offer critical recommendations for enhancing the interfacial stability and strength of Cu/Al layered composites. • The convergence of Al2Cu(110) surface was studied. • Al2Cu(110)/Cu(111) interface was studied. • AlA-terminated interface is the most stable. • AlA-terminated interface has more charge accumulation and stronger interaction. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a common and fatal malignancy of the liver. Sorafenib is a small molecule multikinase inhibitor that acts against different cancer cell lines and is used for the treatment of HCC. However, some advanced HCC patients fail to respond to sorafenib, and those who do lack a meaningful clinical benefit. Interferon-lambda 3 (IFN-λ3) is a type III interferon with antiviral, antiproliferative, and immunomodulatory functions. Here, we evaluated the use of IFN-λ3 as an adjuvant treatment with sorafenib in HCC. In the present study, CCK-8 and colony formation assay results showed that treatment with a combination of IFN-λ3 and sorafenib suppresses the viability of HepG2 and SMMC7721 liver cancer cell lines more than treatment with either alone. In addition, flow cytometry results confirmed that treatment with a combination of IFN-λ3 and sorafenib promotes the loss of mitochondrial membrane potential and induces the production of ROS more than treatment with either alone. Furthermore, using a subcutaneous SMMC7721 tumor model, treatment with a combination of IFN-λ3 and sorafenib significantly reduced the tumor growth/volume and induced apoptosis compared to treatment with sorafenib alone. These results show that combined treatment with IFN-λ3 and sorafenib facilitates a synergistic effect on suppressing HCC cancer growth and promoting cell apoptosis in vitro and in vivo . Thus, IFN-λ3 in combination with sorafenib might prove to be a useful adjunctive strategy for the clinical treatment of HCC. [ABSTRACT FROM AUTHOR]

Euphorbia helioscopia L. is a traditional Chinese medicine; recently research found that its ethyl acetate extract (EAE) plays an important role on tumor cell proliferation, apoptosis, invasion, and metastasis in vitro. But the effect of EAE for tumor cells in vivo has not been reported. To explore the inhibitory effect of EAE and molecular mechanism on hepatocellular carcinoma (HCC) SMMC-7721 cells in vivo, we utilized the nude mouse xenograft model of HCC. Treated with EAE (50, 100, and 200 μg/mL), the volume of xenograft was measured during the entire process of EAE treatment. In EAE treatment group, the volume of xenograft was significantly reduced compared with the control group (P<0.05) and the protein expressions of CyclinD1, bcl-2, and MMP-9 were reduced, while those of bax, caspase-3, and nm23-H1 were increased. A significant change trend with increasing EAE concentrations has presented, compared with controls. Moreover, the ultrastructural morphology of xenografts showed significant changes, including nuclear pyknosis and chromatin condensation, We found that EAE could effectively inhibit tumor growth, induce apoptosis, and inhibit tumor invasion and metastasis in vivo; it is suggested that EAE is a potential candidate for as a new anticancer agent. [ABSTRACT FROM AUTHOR]

Aim. To compare the effectiveness of surgical procedures (selective or nonselective shunt, devascularization, and combined shunt and devascularization) in preventing recurrent variceal bleeding and other complications in patients with portal hypertension. Methods. A systematic literature search of the Medline and Cochrane Library databases was carried out, and a meta-analysis was conducted according to the guidelines of the Quality of Reporting Meta-Analyses (QUOROM) statement. Results. There were a significantly higher reduction in rebleeding, yet a significantly more common encephalopathy (P = 0.05) in patients who underwent the shunt procedure compared with patients who had only a devascularization procedure. Further, there were no significant differences in rebleeding, late mortality, and encephalopathy between selective versus non-selective shunt. Next, the decrease of portal vein pressure, portal vein diameter, and free portal pressure in patients who underwent combined treatment with shunt and devascularization was more pronounced compared with patients who were treated with devascularization alone (P < 0.05). Conclusions. This meta-analysis shows clinical advantages of combined shunt and devascularization over devascularization in the prevention of recurrent variceal bleeding and other complications in patients with portal hypertension. [ABSTRACT FROM AUTHOR]

DNA mismatch repair is required for correcting any mismatches that are created during replication and recombination, and a defective mismatch repair system contributes to DNA damage-induced growth arrest. The colorectal cancer cell line HCT116 is known to have a mutation in the hMLH1 mismatch repair gene resulting in microsatellite instability and defective mismatch repair. Honokiol is a biphenolic compound that has been used in traditional Chinese medicine for treating various ailments including cancer. This study was designed to test the hypothesis that honokiol enhances the radiosensitivity of cancer cells with mismatch repair defect (HCT116) compared with those that are mismatch repair proficient (HCT116-CH3). We first determined that the combination of honokiol and γ-irradiation treatment resulted in dose-dependent inhibition of proliferation and colony formation in both cell lines. However, the effects were more pronounced in HCT116 cells. Similarly, the combination induced higher levels of apoptosis (caspase 3 activation, Bax to Bcl2 ratio) in the HCT116 cells compared with HCT116-CH3 cells. Cell cycle analyses revealed higher levels of dead cells in HCT116 cells. The combination treatment reduced expression of cyclin A1 and D1 and increased phosphorylated p53 in both cell lines, although there were significantly lower amounts of phosphorylated p53 in the HCT116-CH3 cells, suggesting that high levels of hMLH1 reduce radiosensitivity. These data demonstrate that honokiol is highly effective in radiosensitizing colorectal cancer cells, especially those with a mismatch repair defect. [ABSTRACT FROM AUTHOR]

We investigated whether X-ray radiation induced apoptosis of the proliferative ependymal cells (ECs) in adult rats with spinal cord injury (SCI) and the effect of X-ray radiation on the proliferative activities of ECs. A rat model with SCI was developed and used to determine the proliferation and apoptosis of ECs in the spinal cords after X-ray exposure. TUNEL assay and BrdU incorporation were used to detect apoptosis and proliferation respectively. We found that there were few TUNEL-positive cells in proliferative ependymal zone (EZ) after SCI except at the epicenter, and approximately half of the irradiated ECs became TUNEL-positive. However, these radiated ECs did not lose their proliferative activity until 1 week later and started to decrease rapidly after 1 week. The observation suggested that only part of ECs were sensitive to radiation and the nonsensitive cells continued their mitosis process. These findings indicated that X-ray exposure of the rats with SCI in early stage induced apoptosis of the proliferative ECs and partially inhibited their proliferative activities. [ABSTRACT FROM AUTHOR]

Graphene has been widely used as an electrode material for supercapacitors. However, parallelly-stacked graphene layers often result in inefficient ion diffusion and electron transfers that usually reduce the rate capability of a supercapacitor. In this study, reduced graphene oxide (rGO) and poly (3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) composite films were prepared by a solvent evaporation method using PEDOT:PSS as the binder to fix aligned graphene for its good conductivity and strong π-π stacking interactions with the graphene sheets. Analyses using scanning electron microscopy (SEM), nitrogen adsorption-desorption, and small-angle X-ray scattering show that the graphene sheets were well aligned when a magnetic field was applied, though they were oriented randomly without the magnetic field. As a capacitor electrode material, the aligned rGO shows a specific capacitance of 169 F g−1 with a capacitance retention of about 70% at a current density of 50 A g−1 and its cyclic voltammetry (CV) loops maintained a rectangular shape at a voltage scan rate of 2 V s−1. The aligned rGO electrode can help break through the limitations of traditional supercapacitors and increase significantly their charge/discharge rate and power density. Image 1 • Electrode is developed with graphene aligned vertically in 12T magnetic field. • The electrode has a capacitance retention of 70% at current density of 50 A g−1. • The stability of the vertically aligned structure is outstanding. [ABSTRACT FROM AUTHOR]

• MiR-150 was down-regulated in colorectal cancer. • Overexpression of miR-150 repressed colorectal cancer in vitro and in vivo. • β-catenin was the target of miR-150. Colorectal cancer remains as a serious global cause of morbidity and mortality. The current therapies for colorectal cancer treatment are still unsatisfactory and thus, identification of novel targets is an urgent requisite. Recent evidence has reported miRNAs are closely correlated with colorectal cancer development. miR-150 has been identified in tumor progression in various cancers. Nevertheless, its roles in colorectal cancer remain poorly known. In our study, a decreased miR-150 expression in colorectal cancer tissues and cells was observed. Meanwhile, we reported a negative correlation between miR-150 and β-catenin in colorectal cancer. β-catenin can participate in the physiological mechanism of many types of cancers. Then, miR-150 was overexpression in SW480 and HT-29 cells and it was show that miR-150 repressed SW480 and HT-29 cell viability, proliferation and colony formation capacity. Moreover, colorectal cancer cell progression was triggered by the inhibition of miR-150 via negatively regulating β-catenin. Subsequently, the direct binding correlation between miR-150 and β-catenin was demonstrated. β-catenin, c-myc and CyclinD1 level was significantly restrained by the up-regulation of miR-150 in SW480 and HT-29 cells. Finally, it was proved that miR-150 depressed colorectal cancer growth through modulating β-catenin in vivo. Overall, it was implied that miR-150 could inhibit colorectal cancer progression and serve as a tumor suppressor via inactivating β-catenin pathway. [ABSTRACT FROM AUTHOR]

Objective. To assess the effects of bariatric surgery versus medical therapy for type 2 diabetes mellitus. Methods. The Cochrane library, PubMed, Embase, Chinese biomedical literature database, and Wanfang database up to February 2012 were searched. The literature searches strategies contained terms ("diabetes*", "surg*", and "medic*" were used), combined with the medical subject headings. Randomized controlled trails (RCTs) of frequently used bariatric surgery for obese patients with type 2 diabetes were included. Study selection, data extraction, quality assessment, and data analyses were performed according to the Cochrane standards. Results. Three randomized controlled trials (RCTs) involving 170 patients in the bariatric surgery groups and 100 patients in the medical therapy group were selected. Compared with medical therapy, bariatric surgery for type 2 diabetes can significantly decrease the levels of HbA1c, FBG, weight, triglycerides, and the dose of hypoglycemic, antihypertensive, and lipid-lowering medicine, while increasing the rate of diabetes remission (RR = 9.74,95%CI, (1.36,69.66)) and the levels of high-density lipoprotein. However, there are no statistical differences in serious adverse events between the surgical and medical groups (RR = 1.23, 95%CI, (0.80,1.87)). Conclusions. Surgical procedures were more likely to help patients achieve benefits than medical therapy alone. Further intensive RCTs of high-quality, multiple centers and long-term followup should be carried out to provide more reliable evidence. [ABSTRACT FROM AUTHOR]