The KRAS signaling pathway's impact on the characteristics of pancreatic cancer cells.

Pancreatic ductal adenocarcinoma (PDAC) is classified as a cancer with high metastasis so that its mortality rate is high and most of the patients could not survive longer than 5 years. RAS signaling participate in cellular processes, so it has a key role in PDAC.RAS activation is associated via three different signaling pathway including somatic oncogenic point mutations in KRAS, upstream signaling like EGFR, oncogenic activation of the downstream B-RAF molecule. Several targeted therapies have been developed against kinase effectors particularly those in the MAPK and PI3K (phosphoinositide 3-kinase)/mTOR signaling pathways and several inhibitors are undergoing clinical studies at the moment. However, because it is highly metastatic and frequently diagnosed at advanced disease stages, pancreatic cancer continues to be a challenging cancer to treat. This article will explore therapeutic approaches that focus on oncogenic KRAS signaling in pancreatic cancer and provide an updated synopsis of our knowledge of how mutant KRAS function in the illness.

2D Transition Metal Dichalcogenides for Photocatalysis.

Two-dimensional (2D) transition metal dichalcogenides (TMDs), a rising star in the post-graphene era, are fundamentally and technologically intriguing for photocatalysis. Their extraordinary electronic, optical, and chemical properties endow them as promising materials for effectively harvesting light and catalyzing the redox reaction in photocatalysis. Here, we present a tutorial-style review of the field of 2D TMDs for photocatalysis to educate researchers (especially the new-comers), which begins with a brief introduction of the fundamentals of 2D TMDs and photocatalysis along with the synthesis of this type of material, then look deeply into the merits of 2D TMDs as co-catalysts and active photocatalysts, followed by an overview of the challenges and corresponding strategies of 2D TMDs for photocatalysis, and finally look ahead this topic.

Numerical Modeling of Fracture Height Propagation in Multilayer Formations Considering the Plastic Zone and Induced Stress.

Hydraulic fracturing and acid fracturing are very effective stimulation technologies and are widely used in unconventional reservoir development. Fracture height, as an essential parameter to describe the geometric size of a fracture, is not only the input parameter of two-dimensional fracturing models but also the output parameter of three-dimensional fracturing models. Accurate prediction of fracture height growth can effectively avoid some risks. For example, petroleum reservoirs produce a large amount of formation water because wrong fracture height prediction leads to the connection between the oil or gas reservoir and the water layer. Although some fracture height prediction models were developed, few models considered the effects of the plastic zone, induced stress, and heterogeneous multilayer formation and its interaction. Therefore, considering the influence of many factors, an improved fracture-equilibrium-height model was developed in this study. The successive over-relaxation iteration method and the displacement discontinuity method were used to solve the model. We investigated the effects of the geological and engineering factors on fracture height growth by using the model, and some important conclusions were obtained. The higher the fracture height, the larger the plastic zone size, and the more obvious its influence on fracture height propagation. High overlying or underlying in situ stress and fracture toughness and low fluid density played a positive role in limiting the growth of the fracture height. Induced stress caused by fracture 1 could not only inhibit the height growth of fracture 2 but also promote its growth. The model established in this paper could be coupled to a fracturing simulator to provide a more reliable fracture height prediction.

CdS-based artificial leaf for photocatalytic hydrogen evolution and simultaneous degradation of biological wastewater.

Rational design of all-solid-state Z-scheme heterojunction with advanced structure is essential for boosting photocatalytic efficiency. Herein, we design and fabricate a novel Z-scheme photocatalyst with leaf architecture (named artificial leaf) via a simple dipping-calcination (DC) process followed by a successive ionic layer adsorption and reaction (SILAR) strategy. The prepared artificial leaf, composing of CdS, InVO4, and BiVO4, holds advanced leaf-like structure and Z-scheme electron transfer pathway. As a result, this novel artificial leaf exhibits outstanding capability for the harvesting of visible light and superior efficiency for the separation of photogenerated electron-hole pairs, as well as remarkably enhanced photocatalytic performance and stability for H2 evolution (with the rate of 5033 µm g-1∙h-1) and pollution degradation (46% pollution can be degraded within 3 h).

Nanostructured Metal Borides for Energy-Related Electrocatalysis: Recent Progress, Challenges, and Perspectives.

The discovery of durable, active, and affordable electrocatalysts for energy-related catalytic applications plays a crucial role in the advancement of energy conversion and storage technologies to achieve a sustainable energy future. Transition metal borides (TMBs), with variable compositions and structures, present a number of interesting features including coordinated electronic structures, high conductivity, abundant natural reserves, and configurable physicochemical properties. Therefore, TMBs provide a wide range of opportunities for the development of multifunctional catalysts with high performance and long durability. This review first summarizes the typical structural and electronic features of TMBs. Subsequently, the various synthetic methods used thus far to prepare nanostructured TMBs are listed. Furthermore, advances in emerging TMB-catalyzed reactions (both theoretical and experimental) are highlighted, including the hydrogen evolution reaction, the oxygen evolution reaction, the oxygen reduction reaction, the carbon dioxide reduction reaction, the nitrogen reduction reaction, the methanol oxidation reaction, and the formic acid oxidation reaction. Finally, challenges facing the development of TMB electrocatalysts are discussed, with focus on synthesis and energy-related catalytic applications, and some potential strategies/perspectives are suggested as well, which will profit the design of more efficient TMB materials for application in future energy conversion and storage devices.

Comprehensive Analysis of Gene Expression Profiles Identifies a P4HA1-Related Gene Panel as a Prognostic Model in Colorectal Cancer Patients.

Objective: Colorectal cancer (CRC) is the leading cause of mortality worldwide. Growing evidence suggests that the current pathological staging system is inadequate for efficient and accurate prognosis. In this study, we aim to build a prognosis model to predict the survival outcome of CRC patients by using gene expression profiles from The Cancer Genome Atlas (TCGA). Materials and Methods: Univariate and multivariate Cox regression analysis were used to assess the relationship between clinical factors and P4HA1 expression regarding the prognosis of patients with colon adenocarcinoma (COAD). The least absolute shrinkage and selection operator (LASSO) Cox regression model was used to select prognostic differential expression genes (DEGs) for the construction of prognostic risk score model. Kaplan-Meier and receiver operating characteristic (ROC) survival analysis were used to assess the performance of the model on both TCGA cohort and an independent dataset GSE39582. Results: Overexpression of P4HA1 was confirmed to be associated with poor clinical outcome of colon cancer patients in both TCGA and GSE39582 cohorts. Using the TCGA cohort, we identified 1528 DEGs related to elevated P4HA1 expression, and we established a 11-gene panel to construct the prognostic risk score model by LASSO Cox regression analysis based on their expression profiles. The 11-gene signature was further validated in the independent dataset GSE39582. Time-dependent ROC curves indicated good performance of our model in predicting 1, 2, and 3-years overall survival in COAD patients. Additionally, gene set enrichment analysis indicated that the 11-gene signature was related to pathways involved in tumor progression. Conclusions: Together, we have established a 11-gene signature significantly associated with prognosis in COAD patients, which could serve as a promising tool for clinical application in the future.

Electrocatalytic Oxygen Evolution Reaction in Acidic Conditions: Recent Progress and Perspectives.

The electrochemical oxygen evolution reaction (OER) is an important half-cell reaction in many renewable energy conversion and storage technologies, including electrolyzers, nitrogen fixation, CO2 reduction, metal-air batteries, and regenerative fuel cells. Among them, proton exchange membrane (PEM)-based devices exhibit a series of advantages, such as excellent proton conductivity, high durability, and good mechanical strength, and have attracted global interest as a green energy device for transport and stationary sectors. Nevertheless, with a view to rapid commercialization, it is urgent to develop highly active and acid-stable OER catalysts for PEM-based devices. In this Review, based on the recent advances in theoretical calculation and in situ/operando characterization, the OER mechanism in acidic conditions is first discussed in detail. Subsequently, recent advances in the development of several types of acid-stable OER catalysts, including noble metals, non-noble metals, and even metal-free OER materials, are systematically summarized. Finally, the current key issues and future challenges for materials used as acidic OER catalysis are identified and potential future directions are proposed.

A Combined Experimental and Computational Analysis of Failure Mechanisms in Open-Hole Cross-ply Laminates under Flexural Loading.

In this study, integrated experimental tests and computational modeling are proposed to investigate the failure mechanisms of open-hole cross-ply carbon fiber reinforced polymer (CFRP) laminated composites. In particular, we propose two effective methods, which include width-tapered double cantilever beam (WTDCB) and fixed-ratio mixed-mode end load split (FRMMELS) tests, to obtain the experimental data more reliably. We then calibrate the traction-separation laws of cohesive zone model (CZM) used among laminas of the composites by leveraging these two methods. The experimental results of fracture energy, i.e. G Ic and G Tc , obtained from WTDCB and FRMMELS tests are generally insensitive to the crack length thus requiring no effort to accurately measure the crack tip. Moreover, FRMMELS sample contains a fixed mixed-mode ratio of G IIc /G Tc depending on the width taper ratio. Examining comparisons between experimental results of FRMMELS tests and failure surface of B-K failure criterion predicted from a curve fitting, good agreement between the predictions and experimental data has been found, indicating that FRMMELS tests are an effective method to determine mixed-mode fracture criterion. In addition, a coupled experimental-computational modeling of WTDCB, edge notched flexure, and FRMMELS tests are adopted to calibrate and validate the interfacial strengths. Finally, failure mechanisms of open-hole cross-ply CFRP laminates under flexural loading have been studied systematically using experimental and multi-scale computational analyses based on the developed CZM model. The initiation and propagation of delamination, the failure of laminated layers as well as load-displacement curves predicted from computational analyses are in good agreement with what we have observed experimentally.

Meso-scale Modeling and Damage Analysis of Carbon/Epoxy Woven Fabric Composite under In-plane Tension and Compression Loadings.

The mechanical properties and damage behaviors of carbon/epoxy woven fabric composite under in-plane tension and compression are studied at the meso-scale level through experiment and simulation. An efficient representative volume element (RVE) modeling method with consistent mesh, high yarn volume fraction and realistic geometry is proposed. The material constitutive laws with plasticity, tension-compression asymmetry and damage evolution are established for the three components - yarn, matrix and interface, respectively. Significantly different mechanical properties and damage evolutions are observed depending on loading conditions and initial geometry characteristics. It shows a non-linear stress-strain curve with clear transition region and intensive damage in tension, while a quasi-linear behavior up to facture is observed in compression with little damage prior to final fracture. Moreover, compared to the constant Poisson's ratio with straining in compression, a dramatic increase in Poisson's ratio appears in tension. Simulation shows damage mechanisms including transverse damage, matrix damage and delamination, which all play critical roles in the property evolution. In particular, the rapid damage accumulation after elastic deformation destroys the strong bonds and causes the easy deformation of transverse yarns which results in the transition region and large Poisson's ratio in tension. All the mechanical behaviors and damage evolutions are well captured and explained with the current RVE model.

Giant Solitary Fibrous Tumor of Esophagus Resected by Endoscopic Submucosal Dissection.

Solitary fibrous tumor is one of the most common soft tissue benign tumors that occur in adults, but it rarely occurs in the gastrointestinal tract and even more infrequently occurs in the esophagus. Only 4 cases of esophageal solitary fibrous tumors have been reported in PubMed using the search terms "solitary fibrous tumor" and "esophagus". These cases were all treated using surgical methods. Thus, we report a case of primary solitary fibrous tumor of the esophagus treated by endoscopic submucosal dissection. Endoscopic submucosal dissection was well tolerated in this patient, suggesting that it may be a therapeutic option for primary giant esophageal neoplasms.

Expression of enoyl coenzyme A hydratase, short chain, 1, in colorectal cancer and its association with clinicopathological characteristics.

This study aimed to investigate the expression and clinical significance of enoyl coenzyme A hydratase, short chain, 1 (ECHS1), in patients with colorectal cancer (CRC). The ECHS1 protein expression as detected by immunohistochemistry in 148 CRC specimens was evaluated and compared by clinical pathology and prognosis; 38 specimens from proximal non-cancerous colorectal tissues were included as controls. The ECHS1 protein expression was also measured by western blot analysis in 46 fresh CRC tissue specimens and 22 normal colorectal tissue specimens. The rate of positive ECHS1 expression differed significantly between the CRC tissues (56.76%, 84/148) and the proximal non-cancerous colorectal tissues (5.26%, 2/38) (P<0.001). The ECHS1 protein expression was confirmed not to be associated with gender or age. However, the positive expression of ECHS1 tended to be positively associated with clinical TNM stage (P=0.015), lymph node metastasis (P=0.011) and histological differentiation (P=0.028). The expression of the ECHS1 protein on western blot analysis was significantly increased in CRC vs. normal tissues. In addition, the overall survival curves estimated with the Kaplan-Meier method demonstrated that CRC patients exhibiting low ECHS1 expression survived significantly longer compared to patients with high ECHS1 levels (P=0.039). Our data suggested that ECHS1 protein expression may contribute to the occurrence, progression and metastasis of CRC, is closely associated with prognosis and may provide useful information for CRC molecular-targeted therapy.

Drug resistance reversed by silencing LIM domain-containing protein 1 expression in colorectal carcinoma.

The role of LIM domain-containing protein 1 (LIMD1) in the multidrug resistance of colorectal carcinoma (CRC) has not yet been established. The aim of the current study was to investigate the chemosensitivity of CRC multidrug-resistant (MDR) cells following the silencing of LIMD1. The MDR phenotypic Colo205 and HCT-8 cell lines were examined, which were established by exposure to increasing doses of 5-fluorouracil (5-FU) over a period of one year. LIMD1 siRNA constructs were transfected into CRC MDR cells and the phenotypic effects were determined comprehensively. The Colo205 and HCT-8 cell lines were more resistant to 5-FU compared with their respective parental cell lines. In addition, the two MDR cell types expressed significantly more LIMD1 compared with their parental lines. The stably transfected cells showed various degrees of reversal of the MDR phenotype, and 5-FU-induced apoptosis was increased in the transfected cells compared with the controls. In conclusion, RNA interference targeting LIMD1 may present a novel therapeutic option for CRC.

Knockdown of ECHS1 protein expression inhibits hepatocellular carcinoma cell proliferation via suppression of Akt activity.

Overexpression of ECHS1 occurs in different cancers, including hepatocellular carcinoma (HCC). ECHS1 is also reported to have an oncogenic activity in various human cancers. This study investigated the effect of ECHS1 knockdown on the regulation of HCC growth. ECHS1 shRNA suppressed the expression of ECHS1 protein in HepG2 cells compared to the negative control vector-transfected HCC cells. ECHS1 knockdown also reduced HCC cell viability and enhanced cisplatin-induced apoptosis in HCC cells. Akt activation and the expression of various cell cycle-related genes were inhibited following ECHS1 knockdown. ECHS1 shRNA suppressed hepatocellular carcinoma growth in tumor xenograft mice. These data demonstrate that ECHS1 may play a role in HCC progression, suggesting that inhibition of ECHS1 expression using ECHS1 shRNA should be further evaluated as a novel target for the control of HCC.