Syn-COM: A Multi-Level Predictive Synergy Framework for Innovative Drug Combinations.

Drug prediction and treatment using bioinformatics and large-scale modeling have emerged as pivotal research areas. This study proposes a novel multi-level collaboration framework named Syn-COM for feature extraction and data integration of diseases and drugs. The framework aims to explore optimal drug combinations and interactions by integrating molecular virtuality, similarity clustering, overlap area, and network distance.

Unraveling the CDK9/PP2A/ERK Network in Transcriptional Pause Release and Complement Activation in KRAS-mutant Cancers.

Selective inhibition of the transcription elongation factor (P-TEFb) complex represents a promising approach in cancer therapy, yet CDK9 inhibitors (CDK9i) are currently limited primarily to certain hematological malignancies. Herein, while initial responses to CDK9-targeted therapies are observed in vitro across various KRAS-mutant cancer types, their efficacy is far from satisfactory in nude mouse xenograft models. Mechanistically, CDK9 inhibition leads to compensatory activation of ERK-MYC signaling, accompanied by the recovery of proto-oncogenes, upregulation of immediate early genes (IEGs), stimulation of the complement C1r-C3-C3a cascade, and induction of tumor immunosuppression.

Efficacy of FERscore in predicting sensitivity to ferroptosis inducers in breast cancer.

Recent studies have highlighted the potential of ferroptosis in treating breast cancer. However, the efficacy of ferroptosis induction in the most common subtype, estrogen receptor-positive (ER + ) breast cancer, remains inadequately explored. This study unveils that both short-term and long-term treatment with ER-targeted endocrine agents sensitizes ER+ breast cancer cells to ferroptosis inducers, particularly the GPX4 inhibitor, revealing a non-mutational sensitization mechanism.

An injectable and coagulation-independent Tetra-PEG hydrogel bioadhesive for post-extraction hemostasis and alveolar bone regeneration.

Effective control of post-extraction hemorrhage and alveolar bone resorption is critical for successful extraction socket treatment, which remains an unmet clinical challenge. Herein, an injectable Tetra-PEG hydrogel that possesses rapid gelation, firm tissue adhesion, high mechanical strength, suitable degradability, and excellent biocompatibility is developed as a sutureless and coagulation-independent bioadhesive for the management of extraction sockets. Our results demonstrate that the rapid and robust adhesive sealing of the extraction socket by the Tetra-PEG hydrogel can provide reliable protection for the underlying wound and stabilize blood clots to facilitate tissue healing.

Engineering the electronic structure of sub-nanometric Ru clusters Pt single-atom modification for highly efficient electrocatalytic hydrogen evolution.

Developing electrocatalysts with high activity toward the hydrogen evolution reaction (HER) is a prerequisite for hydrogen fuel generation and sustainable development, but current Pt-based catalysts usually suffer from high cost and unsatisfactory performance in non-acidic media. In this work, we report an environmentally friendly and pyrolysis-free synthesis strategy to prepare an efficient catalyst, CNT-NPA-PtRu, with Pt single-atom engineered sub-nanometric Ru clusters anchored at phytic acid-modified carbon nanotubes for electrochemical HER at all pH conditions. The electronic structure of active sub-nanometric Ru clusters was optimized, which further enhanced the HER activity.

Dynamic causes contribute to the increasing trend of red tides in the east China sea during 2020-2022.

Red tide is a marine phenomenon caused by the excessive growth of microscopic algae in the ocean. This study aims to analyze the development trends of red tides in the past 20 years and the dynamic external causes that induce red tides based on existing satellite remote sensing and numerical simulation data. And the changes in dominant species of red tides in different seasons are analyzed.

Enhanced Electrochemical Catalysis: Hydrogen Evolution Using Bimetallic Sulfides on Nickel Foam.

Hydrogen is considered clean energy with broad application prospects for the 21st century, and water electrolysis plays a crucial role in hydrogen production. However, economic limitations and large overpotential values hinder its development. In this study, we deposited nickel (Ni), iron (Fe), and sulfur (S) onto nickel foam (NF) using the constant potential method to form the Ni-S-Fe/NF catalyst, which exhibited an exceptionally low overpotential (31 mV) at a current density of -10 mA cm, and a Tafel slope of 75.

From sky to road: Incorporating the satellite imagery into analysis of freight truck-related crash factors.

Freight truck-related crashes in urban contexts have caused significant economic losses and casualties, making it increasingly essential to understand the spatial patterns of such crashes. Limitations regarding data availability have greatly undermined the generalizability and applicability of certain prior research findings. This study explores the potential of emerging geospatial data to delve deeply into the determinants of these incidents with a more generalizable research design.

Effect of injectable calcium alginate-amelogenin hydrogel on macrophage polarization and promotion of jawbone osteogenesis.

Due to persistent inflammation and limited osteogenesis, jawbone defects present a considerable challenge in regenerative medicine. Amelogenin, a major protein constituent of the developing enamel matrix, demonstrates promising capabilities in inducing regeneration of periodontal supporting tissues and exerting immunomodulatory effects. These properties render it a potential therapeutic agent for enhancing jawbone osteogenesis.

Targeting ST8SIA6-AS1 counteracts KRAS inhibitor resistance through abolishing the reciprocal activation of PLK1/c-Myc signaling.

Background: KRAS inhibitors (KRASi) AMG510 and MRTX849 have shown promising efficacy in clinical trials and been approved for the treatment of KRAS-mutant cancers. However, the emergence of therapy-related drug resistance limits their long-term potential. This study aimed to identify the critical mediators and develop overcoming strategies.

Thermally Activated Delayed Fluorescence Emitters Based on a Special Tetrahedral Silane Core.

Based on the tetraphenylsilane skeleton, a new class of thermally activated delayed fluorescence (TADF) molecules have been designed and synthesized. Benefiting from the unique tetrahedron architecture of tetraphenylsilane, the intermolecular distance between TADF units can be enlarged and thus weakened the aggregation-induced quenching of triplet excitons. By adjusting the numbers of TADF subunits, the spin-orbit coupling processes can be controlled, leading to efficient up-conversion processes.

Hospitalization costs of COPD cases and its associated factors: an observational study at two large public tertiary hospitals in Henan Province, China.

Background: The increasing prevalence of Chronic Obstructive Pulmonary Disease (COPD) has imposed a considerable economic burden. However, there remains a paucity of relevant evidence regarding the hospitalization costs of COPD cases. Therefore, in this study, we aimed to assess the hospitalization costs among COPD cases and investigate the factors that contribute to their costs in Henan Province, China.

Discovery, structural optimization, and anti-tumor bioactivity evaluations of betulinic acid derivatives as a new type of RORγ antagonists.

Betulinic acid (BA) is a natural pentacyclic triterpenoid that has a wide range of biological and pharmacological effects. Here, computational methods such as pharmacophore screening and reverse docking were used to predict the potential target for BA. Retinoic acid receptor-related orphan receptor gamma (RORγ) was confirmed as its target by several molecular assays as well as crystal complex structure determination.

Construct of an Electrodeposited Cobalt-Molybdenum Film and Evaluation of Its Efficiency in Hydrogen Evolution.

Hydrogen is a valuable clean energy source, and electrolysis to produce hydrogen from water is a crucial component. However, a major problem of hydrogen generation by electrolysis is its large overpotential and poor economics. To reduce the overpotential, we mainly use nickel foam and Co-Mo ions as feedstock and create an efficient catalytic material by electrodeposition.

Self-perception and COVID-19 vaccination self-efficacy among Chinese adults: A moderated mediation model of mental health and trust.

Background: Optimal Corona Virus Disease 2019 (COVID-19) vaccination coverage is necessary to achieve community protection, and self-efficacy independently predict vaccination behavior. The current study examined the effect of self-perception on COVID-19 vaccination self-efficacy as well as potential mechanisms among Chinese adults.

Methods: A cross-sectional survey was conducted from four cities in China (n = 6781).

Design and Synthesis of Triazole-Containing HDAC Inhibitors That Induce Antitumor Effects and Immune Response.

Histone deacetylase (HDAC) is an epigenetic antitumor drug target, but most existing HDAC inhibitors show limited antitumor activity and their use is often accompanied by serious adverse effects. To overcome these problems, we designed and synthesized a series of triazole-containing compounds as novel HDAC inhibitors. Among them, compound exhibited potent and selective inhibition of HDAC1, with good antiproliferative activity in vitro and an excellent pharmacokinetic profile.

Prominin 1 Significantly Correlated with Bone Metastasis of Breast Cancer and Influenced the Patient's Prognosis.

Background: This study is aimed at identifying the important biomarkers associated with bone metastasis (BM) in breast cancer (BRCA).

Methods: The GSE175692 dataset was used to detect significant differential expressed genes (DEGs) between BRCA samples with or without BM, and DEG-related pathways were then explored. Further, we constructed the protein-protein interaction (PPI) network on GEGs and filtered 5 vital nodes.

Remotely Temporal Scheduled Macrophage Phenotypic Transition Enables Optimized Immunomodulatory Bone Regeneration.

Precise timing of macrophage polarization plays a pivotal role in immunomodulation of tissue regeneration, yet most studies mainly focus on M2 macrophages for their anti-inflammatory and regenerative effects while the essential proinflammatory role of the M1 phenotype on the early inflammation stage is largely underestimated. Herein, a superparamagnetic hydrogel capable of timely controlling macrophage polarization is constructed by grafting superparamagnetic nanoparticles on collagen nanofibers. The magnetic responsive hydrogel network enables efficient polarization of encapsulated macrophage to the M2 phenotype through the podosome/Rho/ROCK mechanical pathway in response to static magnetic field (MF) as needed.

Neoadjuvant Endocrine Therapy: A Potential Way to Make Cold Hormone Receptor-Rich Breast Cancer Hot.

Background: Turning the "cold" tumor immune microenvironment into "hot" is a critical issue in cancer treatment today. Hormone receptor-rich breast cancer (HR+ BC) was previously considered immunologically quiescent.

Objective: This study aims to explore the immunomodulatory effects of endocrine therapy on HR+ BCs.

Study of the Osteoimmunomodulatory Properties of Curcumin-Modified Copper-Bearing Titanium.

Peri-implantitis can lead to implant failure. In this study, curcumin (CUR) was modified onto the copper-bearing titanium alloy (Cu-Ti) with the assistance of polydopamine (PDA) in order to study the bone immune response and subsequent osteogenesis. FE-SEM, XPS and water contact angle were utilized to characterize the coating surface.

Tribological and Antibacterial Properties of Polyetheretherketone Composites with Black Phosphorus Nanosheets.

Over the past few decades, polyetheretherketone (PEEK) artificial bone joint materials faced problems of poor wear resistance and easy infection, which are not suitable for the growing demand of bone joints. The tribological behavior and wear mechanism of polyetheretherketone (PEEK)/polytetrafluoroethylene (PTFE) with black phosphorus (BP) nanosheets have been investigated under dry sliding friction. Compared with pure PEEK, the COF of PEEK/10 wt% PTFE/0.

Astragalus polysaccharide alleviates alveolar bone destruction by regulating local osteoclastogenesis during periodontitis.

Inflammatory imbalance of bone formation/resorption leads to alveolar bone destruction. Astragalus polysaccharide has been confirmed to have anti-inflammatory effects. We sought to disclose the protective effect and its potential mechanisms of astragalus polysaccharide in the periodontitis model.

Preparation of Triple-Functionalized Montmorillonite Layers Promoting Thermal Stability of Polystyrene.

The objective of this study was to investigate the effect of three different treatments on the morphology, microstructure, and the thermal characteristics of a montmorillonite (Mt) sample, by using hydrochloric acid (HCl), tributyl tetradecyl phosphonium chloride (TTPC) surfactant, and γ-methacryloxypropyltrimethoxysilane (γ-MPS). The resultant nanofillers were characterized by Fourier transform infrared (FTIR), X-ray diffraction (XRD), transmission electron microscopy (TEM), nitrogen adsorption-desorption analysis, X-ray fluorescence spectrometry (XRF), and thermogravimetric analysis (TGA). The results showed that the amount of chemical grafting of the γ-MPS was increased after the acid treatment, whereas the amount of intercalation of the TTPC surfactant was decreased.

Comparative Effectiveness and Functional Outcome of C2 Dome-like Expansive Versus C2 Expansive Open-door Laminoplasty for Upper Cervical Ossification of the Posterior Longitudinal Ligament: A Retrospective Cohort Study.

Study Design: Retrospective Cohort Study.

Objectives: This study compared the function and radiographical outcomes of the patients who underwent C2 dome-like expansive laminoplasty to those C2 expansive open-door laminoplasty for the treatment of OPLL with C2 involved.

Summary Of Background Data: There are few comparative studies of these two surgical methods.