Regulatory role of lnc-MAP3K13-3:1 on miR-6894-3p and SHROOM2 in modulating cellular dynamics in hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is a prevalent primary liver malignancy and a leading cause of cancer-related mortality worldwide. Despite advancements in therapeutic strategies, the 5-year survival rate for individuals undergoing curative resection remains between 10% and 15%. Consequently, identifying molecular targets that specifically inhibit the proliferation and metastasis of HCC cells is critical for improving treatment outcomes.

Targeting the tumor immune microenvironment: GPCRs as key regulators in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) poses a significant clinical challenge due to its aggressive nature and limited therapeutic options. Recent research underscores the pivotal role of G protein-coupled receptors (GPCRs) in shaping the tumor immune microenvironment (TIME) within TNBC. This review focuses on four principal GPCRs-chemokine receptors, sphingosine-1-phosphate receptors, prostaglandin E2 receptors, and lactate receptors-that have garnered substantial attention in TNBC studies.

Atomic-Scale Tailoring C-N Coupling Sites for Efficient Acetamide Electrosynthesis over Cu-Anchored Boron Nitride Nanosheets.

Electrochemical conversion of carbon and nitrogen sources into valuable chemicals provides a promising strategy for mitigating CO emissions and tackling pollutants. However, efficiently scaling up C-N products beyond basic compounds like urea remains a significant challenge. Herein, we upgrade the C-N coupling for acetamide synthesis through coreducing CO and nitrate (NO) on atomic-scale Cu dispersed on boron nitride (Cu/BN) nanosheets.

Suitability evaluation of rural domestic sewage treatment processes in cold areas of Northeast China: Regional differences analysis and engineering application.

Rural domestic sewage (RDS) has been identified as one of the major factors hindering rural revitalization. The results of field research show that the cold areas of Northeast China have the characteristics such as scattered rural distribution and long duration of low temperature in winter, which makes it difficult to choose the most effective domestic sewage treatment processes. As a multi-objective decision-making issue based on specific scenarios, this study combines Analytic Hierarchy Process (AHP) with Fuzzy Comprehensive Evaluation (FCE) to establish a new suitability evaluation model for RDS in those areas.

Re-Evaluating PIN1 as a Therapeutic Target in Oncology Using Neutral Inhibitors and PROTACs.

Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) has emerged as a promising therapeutic target for cancer treatment. However, the current PIN1 inhibitors have shown limited efficacy in animal models, leaving the question of whether PIN1 is a proper oncologic target still unanswered. By screening a 1 trillion DNA-encoded library (DEL), we identified novel nonacidic compounds.

Small molecule tyrosine kinase inhibitors approved for systemic therapy of advanced hepatocellular carcinoma: recent advances and future perspectives.

Liver cancer is the sixth most commonly diagnosed cancer and the third leading cause of cancer death in the world, and hepatocellular carcinoma (HCC) is the most common form of liver cancer. More than half of the HCC patients are diagnosed at an advanced stage and often require systemic therapy. Dysregulation of the activity of receptor tyrosine kinases (RTKs) is involved in the development and progress of HCC, RTKs are therefore the potential targets for systemic therapy of advanced HCC (aHCC).

Promotion and Mechanism of Acupotomy on Chondrocyte Autophagy in Knee Osteoarthritis Rabbits.

Objective: To explore the effect of acupotomy intervention on autophagy of chondrocytes in rabbits with knee osteoarthritis (KOA), and to determine the possible mechanisms of acupotomy to alleviate cartilage degeneration.

Methods: The modified Videman method was used to construct a KOA rabbit model. After modeling, 40 rabbits were randomly divided into 4 groups by a random number table: control; KOA (model); KOA + acupotomy (acupotomy), and KOA + sham acupotomy (sham), 10 in each group.

Recent advances in dynamic reconstruction of electrocatalysts for carbon dioxide reduction.

Electrocatalysts undergo structural evolution under operating electrochemical CO reduction reaction (CORR) conditions. This dynamic reconstruction correlates with variations in CORR activity, selectivity, and stability, posing challenges in catalyst design for electrochemical CORR. Despite increased research on the reconstruction behavior of CORR electrocatalysts, a comprehensive understanding of their dynamic structural evolution under reaction conditions is lacking.

Structure-based design of pan-coronavirus inhibitors targeting host cathepsin L and calpain-1.

Respiratory disease caused by coronavirus infection remains a global health crisis. Although several SARS-CoV-2-specific vaccines and direct-acting antivirals are available, their efficacy on emerging coronaviruses in the future, including SARS-CoV-2 variants, might be compromised. Host-targeting antivirals provide preventive and therapeutic strategies to overcome resistance and manage future outbreak of emerging coronaviruses.

A study of clinical and serological correlation of early myocardial injury in elderly patients infected with the Omicron variant.

Introduction: Myocardial injury in elderly Omicron variant patients is a leading cause of severe disease and death. This study focuses on elucidating the clinical characteristics and potential risk factors associated with myocardial injury in elderly patients infected with the Omicron variant.

Methods: Myocardial injury was defined based on elevated cardiac troponin concentrations exceeding the 99th percentile upper reference limit.

Dynamic Reconstruction of Two-Dimensional Defective Bi Nanosheets for Efficient Electrocatalytic Urea Synthesis.

Catalyst surface dynamics drive the generation of active species for electrocatalytic reactions. Yet, the understanding of dominant site formation and reaction mechanisms is limited. In this study, we thoroughly investigate the dynamic reconstruction of two-dimensional defective Bi nanosheets from exfoliated BiSe nanosheets under electrochemical CO and nitrate (NO ) reduction conditions.

Clinical development of antivirals against SARS-CoV-2 and its variants.

The unceasing global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) calls for the development of novel therapeutics. Although many newly developed antivirals and repurposed antivirals have been applied to the treatment of coronavirus disease 2019 (COVID-19), antivirals showing satisfactory clinical efficacy are few in number. In addition, the loss of sensitivity to variants of concern (VOCs) and lack of oral bioavailability have also limited the clinical application of some antivirals.

Design of MERS-CoV entry inhibitory short peptides based on helix-stabilizing strategies.

Interaction between Middle East respiratory syndrome coronavirus (MERS-CoV) spike (S) protein heptad repeat-1 domain (HR1) and heptad repeat-2 domain (HR2) is critical for the MERS-CoV fusion process. This interaction is mediated by the α-helical region from HR2 and the hydrophobic groove in a central HR1 trimeric coiled coil. We sought to develop a short peptidomimetic to act as a MERS-CoV fusion inhibitor by reproducing the key recognition features of HR2 helix.

Repurposing Navitoclax to block SARS-CoV-2 fusion and entry by targeting heptapeptide repeat sequence 1 in S2 protein.

Along with the long pandemic of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has come the dilemma of emerging viral variants of concern (VOC), particularly Omicron and its subvariants, able to deftly escape immune surveillance and the otherwise protective effect of current vaccines and antibody drugs. We previously identified a peptide-based pan-CoV fusion inhibitor, termed as EK1, able to bind the HR1 region in viral spike (S) protein S2 subunit. This effectively blocked formation of the six-helix bundle (6-HB) fusion core and, thus, showed efficacy against all human coronaviruses (HCoVs).

Recompensation in treatment-naïve HBV-related decompensated cirrhosis: a 5-year multi-center observational study comparing patients with ascites and bleeding.

Background And Aims: Recompensation between patients with ascites and bleeding was unknown in treatment-naïve HBV-related decompensated cirrhosis.

Methods: In this retrospective multi-center study, treatment-naïve HBV-related decompensated patients were enrolled at first decompensating event of ascites and/or variceal bleeding. Further complications and clinical characteristics were collected using standard case report form every 6 months to year-5 of antiviral treatment.

IgG Fc-Binding Peptide-Conjugated Pan-CoV Fusion Inhibitor Exhibits Extended In Vivo Half-Life and Synergistic Antiviral Effect When Combined with Neutralizing Antibodies.

The peptide-based pan-coronavirus fusion inhibitor EK1 is in phase III clinical trials, and it has, thus far, shown good clinical application prospects against SARS-CoV-2 and its variants. To further improve its in vivo long-acting property, we herein developed an Fc-binding strategy by conjugating EK1 with human immunoglobulin G Fc-binding peptide (IBP), which can exploit the long half-life advantage of IgG in vivo. The newly engineered peptide IBP-EK1 showed potent and broad-spectrum inhibitory activity against SARS-CoV-2 and its variants, including various Omicron sublineages and other human coronaviruses (HCoVs) with low cytotoxicity.

[Effect of acupotomy on mitophagy mediated by PINK1/Parkin pathway in cartilage of rabbits with knee osteoarthritis].

Objective: To observe the effect of acupotomy on mitophagy mediated by PINK1/Parkin pathway in cartilage of rabbits with knee osteoarthritis (KOA), so as to explore its mechanism in inhibiting cartilage damage.

Methods: Twenty-one New Zealand rabbits were randomly divided into normal, model, and acupotomy groups, with 7 rabbits in each group. The KOA rabbit model was established by using the Videman method.

Pressure-driven membrane filtration technology for terminal control of organic DBPs: A review.

Disinfection by-products (DBPs), a series of undesired secondary contaminants formed during the disinfection processes, deteriorate water quality, threaten human health and endanger ecological safety. Membrane-filtration technologies are commonly used in the advanced water treatment and have shown a promising performance for removing trace contaminants. In order to gain a clearer understanding of the behavior of DBPs in membrane-filtration processes, this work dedicated to: (1) comprehensively reviewed the retention efficiency of microfiltration (MF), ultrafiltration (UF), nanofiltration (NF) and reverse osmosis (RO) for DBPs.

An engineered recombinant protein containing three structural domains in SARS-CoV-2 S2 protein has potential to act as a pan-human coronavirus entry inhibitor or vaccine antigen.

The threat to global health caused by three highly pathogenic human coronaviruses (HCoV), SARS-CoV-2, MERS-CoV and SARS-CoV, calls for the development of pan-HCoV therapeutics and vaccines. This study reports the design and engineering of a recombinant protein designated HR1LS. It contains three linked molecules, each consisting of three structural domains, including a heptad repeat 1 (HR1), a central helix (CH), and a stem helix (SH) region, in the S2 subunit of SARS-CoV-2 spike (S) protein.

Flexible Modulation of Cellular Activities with Cationic Photosensitizers: Insights of Alkyl Chain Length on Reactive Oxygen Species Antimicrobial Mechanisms.

Cationic photosensitizers have good binding ability with negatively charged bacteria and fungi, exhibiting broad applications potential in antimicrobial photodynamic therapy (aPDT). However, cationic photosensitizers often display unsatisfactory transkingdom selectivity between mammalian cells and pathogens, especially for eukaryotic fungi. It is unclear which biomolecular sites are more efficient for photodynamic damage, owing to the lack of systematic research with the same photosensitizer system.