LeScore: a scoring function incorporating hydrogen bonding penalty for protein-ligand docking.

Context: Molecular docking is vital for structure-based virtual screening and heavily depends on accurate and robust scoring functions. Scoring functions often inadequately account for the breakage of solvent hydrogen bonds, hindering the accuracy of predicting binding energy. Here, we introduce LeScore, a novel scoring function that specifically incorporates the hydrogen bonding penalty (HBP) in an aqueous environment, aiming to penalize unfavorable polar interactions when hydrogen bonds with water are broken but the energy loss is not fully compensated by newly formed protein-ligand interactions.

Preparation, in vitro and in vivo evaluation of phloretin-loaded TPGS/Pluronic F68 modified mixed micelles with enhanced bioavailability and anti-aging activity.

Phloretin exhibits strong antioxidant and anti-aging properties by inhibiting mitochondrial oxidation of glutamate, succinic acid, and ascorbic acid. However, its clinical application is limited by poor aqueous solubility and low oral bioavailability. To enhance its bioavailability and efficacy, we incorporated phloretin into nano-micelles (phloretin-MM) using the thin film dispersion method.

Preparation, in vitro and in vivo evaluation and anti-renal injury effects of Niazimicin-loaded mixed polymeric micelles.

Background: Chronic Kidney Disease (CKD) has become one of the major life-threatening conditions. Moringa seeds have been reported to exhibit renoprotective effects, with Niazimicin as its characteristic component.

Objective: To investigate the anti-renal injury effects of Niazimicin and its mixed micelles (N-M) that composed of monomethyl ether poly (ethylene glycol)-polycaprolactone (mPEG-PCL) and polyethylene glycolated chitosan (PEG-CS) on adenine-induced CKD mice.

A Druglike Ferrostatin-1 Analogue as a Ferroptosis Inhibitor and Photoluminescent Indicator.

Redox-based diagnostic and therapeutic applications have long suffered from a shortage of suitable drugs and probes of high specificity. In the context of anti-ferroptosis research for neurological diseases, the inaccessibility of a blood-brain barrier (BBB) permeable small molecular ferroptosis inhibitor, and the lack of specific ferroptosis probes, seriously impeded a deeper understanding of the mechanism of ferroptosis and the development of clinically applicable drugs. We report herein a novel 1,3,4-thiadiazole-functionalized druglike ferrostatin analogue entitled Ferfluor-1 with superior anti-ferroptosis potency, favorable BBB permeability and in vivo activity against stroke and Parkinson's disease.

Increase Docking Score Screening Power by Simple Fusion With CNNscore.

Scoring functions (SFs) of molecular docking is a vital component of structure-based virtual screening (SBVS). Traditional SFs yield their inherent shortage for idealized approximations and simplifications predicting the binding affinity. Complementarily, SFs based on deep learning (DL) have emerged as powerful tools for capturing intricate features within protein-ligand (PL) interactions.

Metal-organic framework nanoparticles activate cGAS-STING pathway to improve radiotherapy sensitivity.

Tumor immunotherapy aims to harness the immune system to identify and eliminate cancer cells. However, its full potential is hindered by the immunosuppressive nature of tumors. Radiotherapy remains a key treatment modality for local tumor control and immunomodulation within the tumor microenvironment.

Recent advances of physiochemical cues on surfaces for directing cell fates.

Surface modification plays an essential role in dictating cell behavior and fate, as it creates a microenvironment that profoundly influences cell attachment, migration, proliferation, and differentiation. This review aims to the intricate interplay of culture surface properties, including topography, stiffness, charge, and chemical modifications, demonstrating their profound impact on cell destiny. We explore the nuanced responses of cells to varying surface topographies, from nano- to microscale features, elucidating the influence of geometric patterns and roughness.

Improving the thermostability of ulvan lyase from polysaccharide lyase family 25 based on multiple computational rational design strategies.

A rational design strategy to improve the thermal stability of enzymes is essential for advancing industrial applications. This study proposes a computer-aided rational design strategy combining deep learning and multiple energy function methods to enhance the thermal stability of ulvan lyase. ColabFold was employed for structure prediction.

Comprehensive analysis of mitochondrial solute carrier family 25 (SLC25) identifies member 19 (SLC25A19) as a regulatory factor in hepatocellular carcinoma.

Background: The mitochondrial solute carrier family 25 (SLC25) is known to play a pivotal role in oncogenesis, yet its specific involvement in hepatocellular carcinoma (HCC) remains poorly elucidated.

Methods: In this study, we performed a clustering analysis of HCC patients in the Cancer Genome Atlas database based on the expression levels of SLC25 members, and conducted clinical feature analysis for each patient within the clusters. Subsequently, we developed a prognostic model using a Lasso regression approach with SLC25A19, SLC25A49, and SLC25A51 as features, and generated a risk score for each HCC patient.

Novel inhibitors of the (VIBVN) NAT protein identified through pharmacophore modeling.

Arylamine N-acetyltransferases (NATs, E.C. 2.

A phase II trial of anlotinib plus EGFR-TKIs in advanced non-small cell lung cancer with gradual, oligo, or potential progression after EGFR-TKIs treatment (CTONG-1803/ALTER-L001).

Background: The study is to evaluate the efficacy and safety of combined anlotinib and EGFR-tyrosine kinase inhibitors (TKIs) in patients with advanced non-small cell lung cancer (NSCLC) who had gradual, oligo, or potential progression after previous EGFR-TKIs treatment.

Methods: We conducted an open-label, single-arm, multicenter, phase II trial in China. Eligible patients were 18-75 years old with histologically or cytologically confirmed NSCLC who were EGFR mutation positive and showed gradual, oligo, or potential progression after EGFR-TKIs.

Adverse drug events associated with capecitabine: a real-world pharmacovigilance study based on the FAERS database.

Background: Capecitabine, a prodrug of 5-fluorouracil, is extensively utilized for the treatment of metastatic breast cancer, colorectal cancer, and gastric cancer. Nevertheless, there exist limitations in comprehending adverse reactions (AEs) in clinical practice. In this study, we investigated the distribution of AEs associated with capecitabine and explored potential rare adverse reactions by mining the Food and Drug Administration Adverse Event Reporting System (FAERS).

Hypertension and 28-day mortality in sepsis patients: An observational and mendelian randomization study.

Background: Predicting and reducing the 28-day mortality in sepsis remains a challenge in this research field.

Objective: This study aimed to explore the association between hypertension and 28-day mortality in sepsis.

Methods: This study is a cross-sectional approach with Mendelian Randomization (MR).

Improved Function After Anterior Controllable Antedisplacement and Fusion for Cervical Ossification of Posterior Longitudinal Ligament: A Long-Term Follow-Up.

Background: Anterior controllable antedisplacement and fusion (ACAF) is an emerging surgical approach for treating cervical ossification of the posterior longitudinal ligament (C-OPLL), yet there is limited data on its long-term efficacy and safety. The present study aimed to analyze the short- and long-term postoperative clinical and radiological outcomes and perioperative complications of ACAF for patients with C-OPLL.

Methods: This was a single-center, retrospective, cohort study, with the mean duration of follow-up of at least 24 months.

Impact of different nephrectomy types on M0 renal cell carcinoma outcomes in a propensity score matching and deep learning study.

There are few analyses comparing complete nephrectomy with resection of the renal parenchyma only (CN) or radical nephrectomy that includes simultaneous resection of the parenchyma, affected perirenal fascia, perirenal fat, and ureter (RN) relative to partial nephrectomy (PN) for patients with nonmetastatic (M0) renal cell carcinoma (RCC) in terms of overall survival (OS). This study aimed to evaluate the effect of different nephrectomy on the OS of M0 RCC and to identify the main beneficiaries of different nephrectomy. The data was collected from the Surveillance, Epidemiology and End Results (SEER) database.

Lycium barbarum oligosaccharide-derived carbon quantum dots inhibit glial scar formation while promoting neuronal differentiation of neural stem cells.

Overexpression of glial fibrillary acidic protein (GFAP) in activated astrocytes following spinal cord injury is closely associated with glial scar formation, which harms axonal regrowth. In this study, we prepared ultrasmall cationic carbon quantum dots (CQDs) via one-step hydrothermal carbonization. Lycium barbarum oligosaccharides were used as the carbon source for the first time, and polyetherimide (PEI) and ethylenediamine (ED) were used as cationic reagents.

Formononetin-Loaded Self-Microemulsion Drug Delivery Systems for Improved Solubility and Oral Bioavailability: Fabrication, Characterization, In Vitro and In Vivo Evaluation.

This study aimed to construct a self-microemulsion drug delivery system (SMEDDS) for Formononetin (FMN) to improve its solubility and bioavailability while combining the nanocrystals (NCs) technology. The SMEDDS prescription composition was optimized with a pseudo-three-phase diagram, followed by a series of in vitro and in vivo evaluations of the selected optimal prescriptions. FMN-NCs loaded SMEDDS showed a homogeneous spherical shape in the Transmission electron microscope and the particle size was measured as (20.

Anti-inflammatory oligosaccharide licensed mesenchymal stem cells allow prolonged survival of septic rats via the promotion of glutathione synthesis.

Background: Mesenchymal stem cells (MSCs) possess the capability to mitigate multiorgan failure (MOF) and reduce mortality rates in sepsis. However, their survival is significantly limited due to oxidative stress responses triggered by excessive sepsis inflammation. Previous studies have demonstrated that the paracrine effect of MSCs can be enhanced by cytokine stimuli such as IL-1β, TNF-α, and IFN-γ, a process known as inflammatory licensing.

IGFALS suppresses hepatocellular carcinoma progression by stabilizing PPAR-γ.

IGFALS forms stable ternary complexes with insulin-like growth factors (IGF1 and IGF2) and IGF-binding proteins (IGFBP3 and IGFBP5), which prolong the half-lives of IGFs. Through immunohistochemical analysis of 90 pairs of clinical samples and bioinformatics analysis, we observed downregulation of IGFALS in hepatocellular carcinoma tissues, which was associated with poor patient prognosis. This prompted us to explore the specific molecular mechanism of action of IGFALS in the inhibition of hepatocellular carcinoma (HCC), which could be a potential new target for the treatment of HCC.

Matrix stiffness-related extracellular matrix signatures and the DYNLL1 protein promote hepatocellular carcinoma progression through the Wnt/β-catenin pathway.

Background: In hepatocellular carcinoma (HCC) treatment, first-line targeted therapy in combination with immune checkpoint inhibitors (ICIs) has improved patient prognosis, but the 5-year survival rate is far from satisfactory. Studies have shown that the extracellular matrix (ECM) is an essential part of the tumour microenvironment (TME) and participates in the progression of malignant tumours. ECM remodelling can enhance matrix stiffness in cirrhosis patients, induce an immunosuppressive microenvironment network, and affect the efficacy of targeted therapies and ICIs for treating HCC.