Resistance of osteosarcoma cells to the proapoptotic effects of carfilzomib involves activation of mitogen activated protein kinase pathways.

New Findings: What is the central question of this study? Carfilzomib, a second-generation proteasome inhibitor approved for the treatment of multiple myeloma, shows efficacy against osteosarcoma. However, drug resistance remains a major challenge. What is the role of carfilzomib-induced changes in mitogen-activated protein kinase (MAPK) pathways in the sensitivity of osteosarcoma cells to the proapoptotic effects of the drug? What is the main finding and its importance? The dose-dependent antiapoptotic effects in osteosarcoma are associated with activation of MAPK signalling.

An 8-layer residual U-Net with deep supervision for segmentation of the left ventricle in cardiac CT angiography.

Background And Objectives: Accurate segmentation of left ventricle (LV) is a fundamental step in evaluation of cardiac function. Cardiac CT angiography (CCTA) has become an important clinical diagnostic method for cardio-vascular disease (CVD) due to its non-invasive, short exam time, and low cost. To obtain the segmentation of the LV in CCTA scans, we present a deep learning method based on an 8-layer residual U-Net with deep supervision.

Nanocomposite adhesive hydrogels: from design to application.

With the rapid development of hydrogels, hydrogel adhesion has attracted increasing attention in the last decade, but strong adhesion remains a challenge due to the large amount of water in hydrogels. The factors that affect hydrogel adhesion mainly include chemistries of bonds, topologies of connection, and mechanisms of energy dissipation. Strategies such as surface modification, surface initiation, bulk modification, bridging polymers, topological adhesion, and the use of nanocomposites have been developed to achieve strong hydrogel adhesion.

ER stress arm XBP1s plays a pivotal role in proteasome inhibition-induced bone formation.

Background: Bone destruction is a hallmark of multiple myeloma (MM). It has been reported that proteasome inhibitors (PIs) can reduce bone resorption and increase bone formation in MM patients, but the underlying mechanisms remain unclear.

Methods: Mesenchymal stem cells (MSCs) were treated with various doses of PIs, and the effects of bortezomib or carfilzomib on endoplasmic reticulum (ER) stress signaling pathways were analyzed by western blotting and real-time PCR.

[Prognostic analysis of drug-eluting stent implantation and coronary artery bypass grafting in patients with unprotected left main coronary artery disease complicated with chronic renal failure].

Objective: To analyze the long-term prognosis of undergoing drug-eluting stent implantation (DES) or coronary artery bypass grafting (CABG) in patients with unprotected left main (ULM) coronary artery disease complicated with chronic renal failure (CRF).

Methods: Patients with UML coronary artery disease complicated with CRF admitted to the department of cardiology intensive care unit (ICU) and cardiac surgery ICU of Beijing Anzhen Hospital Affiliated to Capital Medical University were enrolled. According to the estimated glomerular filtration rate (eGFR), the patients were divided into two layers, and the clinical characteristics of DES patients and CABG patients were analyzed.

Utilization of an Electronic Medical Record-integrated Dashboard Improves Identification and Treatment of Anemia and Iron Deficiency in Pediatric Inflammatory Bowel Disease.

Background: Iron deficiency (ID) and anemia are one of the most common extraintestinal manifestations of inflammatory bowel disease (IBD), usually complicating the course both in ulcerative colitis and Crohn's disease. Despite their high prevalence and significant impact on patients, this particular aspect is still underestimated by clinicians. Although guidelines have been recently published to address this problem, these recommendations do not address pediatric specific concerns and do not provide guidance as to how implement these guidelines in clinical practice.

Histone Loaders CAF1 and HIRA Restrict Epstein-Barr Virus B-Cell Lytic Reactivation.

Epstein-Barr virus (EBV) infects 95% of adults worldwide and causes infectious mononucleosis. EBV is associated with endemic Burkitt lymphoma, Hodgkin lymphoma, posttransplant lymphomas, nasopharyngeal and gastric carcinomas. In these cancers and in most infected B-cells, EBV maintains a state of latency, where nearly 80 lytic cycle antigens are epigenetically suppressed.

Regio- and Enantioselective (3+3) Cycloaddition of Nitrones with 2-Indolylmethanols Enabled by Cooperative Organocatalysis.

The regio- and enantioselective (3+3) cycloaddition of nitrones with 2-indolylmethanols was accomplished by the cooperative catalysis of hexafluoroisopropanol (HFIP) and chiral phosphoric acid (CPA). Using this approach, a series of indole-fused six-membered heterocycles were synthesized in high yields (up to 98 %), with excellent enantioselectivities (up to 96 % ee) and exclusive regiospecificity. This approach enabled not only the first organocatalytic asymmetric (3+3) cycloaddition of nitrones but also the first C3-nucleophilic asymmetric (3+3) cycloaddition of 2-indolylmethanols.

Heat Shock Protein-90 Inhibition Alters Activation of Pancreatic Stellate Cells and Enhances the Efficacy of PD-1 Blockade in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) has a prominent fibrotic stroma, which is a result of interactions between tumor, immune and pancreatic stellate cells (PSC), or cancer-associated fibroblasts (CAF). Targeting inflammatory pathways present within the stroma may improve access of effector immune cells to PDAC and response to immunotherapy. Heat shock protein-90 (Hsp90) is a chaperone protein and a versatile target in pancreatic cancer.

Enhanced antitumor effect via amplified oxidative stress by near-infrared light-responsive and folate-targeted nanoplatform.

The efficiency of producing hydroxyl radicals (·OH) from hydrogen peroxide (HO) catalyzed by different iron compounds have been explored extensively. Exclusively, ferrocenecarboxylic acid (FCA) showed the best catalyzed activity for ·OH generation. Then, we designed and prepared near-infrared (NIR) light-responsive and folate-targeted nanoplatform, which co-delivered FCA, cisplatin and indocyanine green (ICG) for improving antitumor therapy through amplified oxidative stress.

A Cell-Free Platform Based on Nisin Biosynthesis for Discovering Novel Lanthipeptides and Guiding their Overproduction In Vivo.

Lanthipeptides have extensive therapeutic and industrial applications. However, because many are bactericidal, traditional in vivo platforms are limited in their capacity to discover and mass produce novel lanthipeptides as bacterial organisms are often critical components in these systems. Herein, the development of a cell-free protein synthesis (CFPS) platform that enables rapid genome mining, screening, and guided overproduction of lanthipeptides in vivo is described.

Curcumin suppresses doxorubicin-induced cardiomyocyte pyroptosis via a PI3K/Akt/mTOR-dependent manner.

Background: Doxorubicin (DOX) is one of the most effective anti-neoplastic drugs although its clinical use is limited by the severe cardiotoxicity. Apoptosis and defective autophagy are believed to contribute to DOX-induced cardiotoxicity. Here we explored the effect of curcumin (Cur) on DOX-induced cardiac injury and the mechanism involved with a focus on oxidative stress, autophagy and pyroptosis.

Solid-State Effect Induced Thermally Activated Delayed Fluorescence with Tunable Emission: A Multiscale Study.

Thermally activated delayed fluorescence (TADF) molecules with tunable solid-state luminescence have shown great application potential in organic light-emitting diodes. However, theoretical studies on luminescence properties of organic emitters with consideration of solid-state effect are limited. In this work, the photophysical properties of a difluoroboron β-diketonate-based molecule (M1) in liquid, crystal, and amorphous states are studied using multiscale methods combined with the thermal vibration correlation function theory.

The value of spleen-preserving lymphadenectomy in total gastrectomy for gastric and esophagogastric junctional adenocarcinomas: A long-term retrospective propensity score match study from a high-volume institution in China.

Background: The benefit of removing the splenic lymph nodes in patients with proximal gastric cancer has been controversial. The purpose of our study was to investigate the importance of performing a splenic hilar lymph node dissection without splenectomy in patients undergoing total gastrectomy for gastric cancer.

Methods: From January 2006 to December 2015, we retrospectively reviewed patients who underwent a curative total gastrectomy for gastric cancer.

Streptococcus thermophilus Inhibits Colorectal Tumorigenesis Through Secreting β-Galactosidase.

Background & Aims: Streptococcus thermophilus was identified to be depleted in patients with colorectal cancer (CRC) by shotgun metagenomic sequencing of 526 multicohort fecal samples. Here, we aim to investigate whether this bacterium could act as a prophylactic for CRC prevention.

Methods: The antitumor effects of S thermophilus were assessed in cultured colonic epithelial cells and in 2 murine models of intestinal tumorigenesis.

Atroposelective Access to Oxindole-Based Axially Chiral Styrenes via the Strategy of Catalytic Kinetic Resolution.

Atroposelective synthesis of axially chiral molecules has attracted substantial attention from chemists because of the importance of such molecules. However, catalytic asymmetric synthesis of axially chiral styrenes or vinyl arenes is underdeveloped and challenging due to the low rotational barrier and weak configurational stability of such molecules. Therefore, the development of powerful strategies for the catalytic atroposelective synthesis of axially chiral styrenes or vinyl arenes is of great importance.

Tunable lifetimes and efficiencies of room temperature phosphorescent liquids by modulating the length and number of alkyl chains.

Organic room temperature phosphorescence (RTP) liquid composites exhibit the potential to make innovative changes in large area flexible lighting applications, and it is extremely challenging to achieve high-efficiency RTP in pure organic solvent-free liquid systems. The excited state properties and inner lighting mechanisms of these composites are unclear; therefore, a theoretical perspective to design high efficiency RTP liquids with tunable lifetime is highly desired. Herein, we systematically investigate the photophysical properties of a series of long swallow-tailed bromonaphthalimide (BT unit) molecules by the newly proposed optimally tuned range-separated (RS) functional method, and a state-of-the-art RTP molecule with an absolute quantum yield (ΦRTP) of 57.

Long-term chemical fertilization-driving changes in soil autotrophic microbial community depresses soil CO fixation in a Mollisol.

Soil is the largest C pool in the terrestrial ecosystem. Numerous studies have been devoted to the decomposition of soil organic C as influenced by agricultural management. However, little is known about the effect of fertilization on the microbial CO fixation potential.

Spectroscopic and computational characterization of lanthanide-mediated N-H and C-H bond activation of methylamine.

Ln (Ln = La and Ce) atom reactions with methylamine are carried out in a pulsed-laser vaporization supersonic molecular beam source. A series of dehydrogenation species are observed with time-of-flight mass spectrometry, and the dehydrogenated Ln-containing species in the formula Ln(NCH) are characterized by mass-analyzed threshold ionization (MATI) spectroscopy and density functional theory and multiconfiguration spin-orbit coupling computations. The MATI spectrum of La(NCH) consists of two vibronic band systems that are assigned to the ionization of the A ground state of the C isomer La(N-CH) and the A' ground state of the C isomer La(NH-CH).

Enhancing light emission of Si nanocrystals by means of high-pressure hydrogenation.

High-density Si nanocrystal thin film composed of Si nanocrystals and SiO, or Si-NCs:SiO, was prepared by annealing hydrogen silsesquioxane (HSQ) in a hydrogen and nitrogen (H:N=5%:95%) atmosphere at 1100°C. Conventional normal-pressure (1-bar) hydrogenation failed to enhance the light emission of the Si-NCs:SiO sample made from HSQ. High-pressure hydrogenation was then applied to the sample in a 30-bar hydrogen atmosphere for this purpose.

An Integrative Analysis of Transcriptome, Proteome and Hormones Reveals Key Differentially Expressed Genes and Metabolic Pathways Involved in Flower Development in Loquat.

Flower development is a vital developmental process in the life cycle of woody perennials, especially fruit trees. Herein, we used transcriptomic, proteomic, and hormone analyses to investigate the key candidate genes/proteins in loquat () at the stages of flower bud differentiation (FBD), floral bud elongation (FBE), and floral anthesis (FA). Comparative transcriptome analysis showed that differentially expressed genes (DEGs) were mainly enriched in metabolic pathways of hormone signal transduction and starch and sucrose metabolism.

Catalytic Asymmetric Synthesis of 3,3'-Bisindoles Bearing Single Axial Chirality.

A catalytic asymmetric synthesis of 3,3'-bisindoles bearing single axial chirality has been established via chiral phosphoric acid (CPA)-catalyzed enantioselective addition reaction of 3,3'-bisindoles with ninhydrin-derived 3-indolylmethanols. The selection of ninhydrin-derived 3-indolylmethanols as suitable electrophiles is based on the consideration that the symmetric and bulky moiety of ninhydrin would increase the steric congestion around the axis to generate stable axial chirality and avoid the generation of central chirality. By this approach, a series of 3,3'-bisindoles bearing single axial chirality were synthesized via the dynamic kinetic resolution (DKR) process in generally acceptable yields and considerable enantioselectivities.

Dual Network Hydrogels Incorporated with Bone Morphogenic Protein-7-Loaded Hyaluronic Acid Complex Nanoparticles for Inducing Chondrogenic Differentiation of Synovium-Derived Mesenchymal Stem Cells.

Alginate-poloxamer (ALG-POL) copolymer with optimal POL content was synthesized, and it was combined with silk fibroin (SF) for building ALG-POL/SF dual network hydrogels. Hyaluronic acid(HA)/chitosan-poly(dioxanone)(CH-PDO) complex nanoparticles (NPs) with optimized composition and high encapsulation efficiency were employed as a vehicle for loading bone morphogenic protein-7 (BMP-7). BMP-7-loaded HA/CH-PDO NPs were incorporated into ALG-POL/SF hydrogel for constructing composite gels to achieve controlled release of BMP-7.

Construction of chiral chroman scaffolds via catalytic asymmetric (4 + 2) cyclizations of para-quinone methide derivatives with 3-vinylindoles.

A catalytic asymmetric (4 + 2) cyclization of ortho-hydroxyphenyl-substituted para-quinone methide derivatives with 3-vinylindoles has been established in the presence of chiral phosphoric acid, which provides a series of chiral chroman derivatives bearing an indole moiety in generally high yields (up to 97%), and with good enantioselectivities (up to 90% ee) and moderate to good diastereoselectivities (up to 95 : 5 dr). This reaction has not only fulfilled the need of developing catalytic asymmetric (4 + 2) cyclizations of para-quinone methide derivatives with electron-rich alkenes, but also provided a useful method for constructing chiral chroman scaffolds.

Solid-state effect on luminescent properties of thermally activated delayed fluorescence molecule with aggregation induced emission: A theoretical perspective.

Solid-state effect plays an important role in defining the nature of excited states for thermally activated delayed fluorescence (TADF) molecules and further affects their luminescence properties. Theoretical investigation of photophysical properties with explicit consideration of intermolecular interactions in solid phase, is highly desired. In this work, the luminescent properties of new TADF molecule SBF-BP-DMAC with aggregation induced emission (AIE) feature are theoretically studied both in solution and solid phase.