New insights into protein-protein interaction modulators in drug discovery and therapeutic advance.

Protein-protein interactions (PPIs) are fundamental to cellular signaling and transduction which marks them as attractive therapeutic drug development targets. What were once considered to be undruggable targets have become increasingly feasible due to the progress that has been made over the last two decades and the rapid technological advances. This work explores the influence of technological innovations on PPI research and development.

Strong exciton-photon coupling in self-hybridized organic-inorganic lead halide perovskite microcavities.

Controlling coherent light-matter interactions in semiconductor microcavities is at the heart of the next-generation solid-state polaritonic devices. Organic-inorganic hybrid perovskites are potential materials for room-temperature polaritonics owing to their high exciton oscillator strengths and large exciton binding energies. Herein, we report on strong exciton-photon coupling in the micro-platelet and micro-ribbon shaped methylammonium lead bromide single crystals.

Effects of platelet-rich plasma combined with exercise therapy for one year on knee osteoarthritis: retrospective cohort study.

Background: Platelet-rich plasma (PRP) is a promising treatment for knee osteoarthritis (OA). However, exercise therapy and activities of daily living (ADL) guidance are recommended as core treatments in the Osteoarthritis Research Society International (OARSI) guidelines. However, the effects of PRP combined with exercise therapy are not fully understood.

From pixels to druggable leads: A CADD strategy for the design and synthesis of potent DDR1 inhibitors.

Background And Objective: While numerous in silico tools exist for target-based drug discovery, the inconsistent integration of in vitro data with predictive models hinders research and development productivity. This is particularly apparent during the Hit-to-Lead stage, where unreliable in-silico tools often lead to suboptimal lead selection. Herein, we address this challenge by presenting a CADD-guided pipeline that successfully integrates rational drug design with in-silico hits to identify a promising DDR1 lead.

Fully Additively Manufactured Counter Electrodes for Dye-Sensitized Solar Cells.

In dye-sensitized solar cells (DSSCs), the counter electrode (CE) plays a crucial role as an electron transfer agent and regenerator of the redox couple. Unlike conventional CEs that are generally made of glass-based substrates (e.g.

PT-Finder: A multi-modal neural network approach to target identification.

Efficient target identification for bioactive compounds, including novel synthetic analogs, is crucial for accelerating the drug discovery pipeline. However, the process of target identification presents significant challenges and is often expensive, which in turn can hinder the drug discovery efforts. To address these challenges machine learning applications have arisen as a promising approach for predicting the targets for novel chemical compounds.

Machine Learning-Based Approach to Developing Potent EGFR Inhibitors for Breast Cancer-Design, Synthesis, and In Vitro Evaluation.

The epidermal growth factor receptor (EGFR) is vital for regulating cellular functions, including cell division, migration, survival, apoptosis, angiogenesis, and cancer. EGFR overexpression is an ideal target for anticancer drug development as it is absent from normal tissues, marking it as tumor-specific. Unfortunately, the development of medication resistance limits the therapeutic efficacy of the currently approved EGFR inhibitors, indicating the need for further development.

An Efficient Green Approach to Constructing Adenine Sulfate-Derived Multicolor Sulfur- and Nitrogen-Codoped Carbon Dots and Their Bioimaging Applications.

A cost-effective and environmentally friendly approach is proposed for producing N- and S-codoped multicolor-emission carbon dots (N- and S-codoped MCDs) at a mild reaction temperature (150 °C) and relatively short time (3 h). In this process, adenine sulfate acts as a novel precursor and doping agent, effectively reacting with other reagents such as citric acid, -aminosalicylic acid, and -phenylenediamine, even during solvent-free pyrolysis. The distinctive structures of reagents lead to the increased amount of graphitic nitrogen and sulfur doping in the N- and S-codoped MCDs.

Identification of Potent hDHODH Inhibitors for Lung Cancer via Virtual Screening of a Rationally Designed Small Combinatorial Library.

Cancer is characterized by altered cellular metabolism, and metabolic enzymes are considered as a promising target for anticancer therapy. Pyrimidine metabolism dysregulation is associated with various types of cancer, particularly lung cancer, which is one of the leading causes of cancer-related mortality worldwide. Recent studies have shown that small-cell lung cancer cells are particularly reliant on the pyrimidine biosynthesis pathway and are sensitive to its disruption.

Perspective for Discovery of Small Molecule IL-6 Inhibitors through Study of Structure-Activity Relationships and Molecular Docking.

Interleukin-6 (IL-6) is a proinflammatory cytokine that plays a key role in the pathogenesis and physiology of inflammatory and autoimmune diseases, such as coronary heart disease, cancer, Alzheimer's disease, asthma, rheumatoid arthritis, and most recently COVID-19. IL-6 and its signaling pathway are promising targets in the treatment of inflammatory and autoimmune diseases. Although, anti-IL-6 monoclonal antibodies are currently being used in clinics, huge unmet medical needs remain because of the high cost, administration-related toxicity, lack of opportunity for oral dosing, and potential immunogenicity of monoclonal antibody therapy.

Discovery and optimization of natural-based nanomolar c-Kit inhibitors via in silico and in vitro studies.

c-Kit is a receptor tyrosine kinase which is involved in intracellular signaling and mutations of c-Kit have been associated with various types of cancers. Investigations have shown that inhibition of c-Kit, using tyrosine kinase inhibitors, yielded promising results in cancer treatment marking it as a promising target for cancer therapy. However, the emerging resistance for the current therapy necessitates the development of more potent inhibitors which are not affected by these mutations.

Selective Deposition of Candle Soot on a Cellulose Membrane for Efficient Solar Evaporation.

Owing to their natural abundance, seawater together with sunlight has a potential to meet the global challenges in terms of water scarcity and energy crisis. Herein, we demonstrate a solar vapor generator composed of an inner flame candle soot (IFCS) deposited on a cellulose filter paper (FP) prepared by a simple two-step process. The resultant IFCS/FP device exhibits a high photothermal conversion ability owing to the broadband solar absorption of the IFCS layer along with the multiple scattering of the incoming sunlight in the porous microstructure of the cellulose FP.

Highly Efficient Solar Vapor Generation via a Simple Morphological Alteration of TiO Films Grown on a Glassy Carbon Foam.

Effectively utilizing eco-friendly solar energy for desalination and wastewater purification has immense potential to overcome the global water crisis. Herein, we demonstrate a highly efficient solar vapor generator (SVG) developed via a simple morphological alteration, from a two-dimensional (2D) TiO film (TF) to one-dimensional (1D) TiO nanorods (TNRs) grown on a glassy carbon foam (CF). Given that evaporation is primarily a surface physical phenomenon, the 1D morphology of TNRs provides a higher evaporation surface area compared to their 2D counterpart.

Nitrogen-Plasma-Treated Continuous Monolayer MoS for Improving Hydrogen Evolution Reaction.

Theoretically, the edges of a MoS flake and S-vacancy within the lattice have nearly zero Gibbs free energy for hydrogen adsorption, which is essentially correlated to the exchange currents in hydrogen evolution reaction (HER). However, MoS possesses insufficient active sites (edges and S-vacancies) in pristine form. Interestingly, active sites can be effectively engineered within the continuous MoS sheets by treating it with plasma in a controlled manner.

Renoprotective effect of Tanshinone IIA, an active component of Salvia miltiorrhiza, on rats with chronic kidney disease.

Chronic kidney disease (CKD) is a common cause of end-stage renal disease. Antihypertensive agents are used clinically to inhibit the progression of CKD, but cannot prevent eventual renal failure. This study investigated the effect of Tanshinone IIA, an active component of Salvia miltiorrhiza, in rats suffering from CKD induced by 5/6 nephrectomy.

Clinical and histologic response to methylprednisolone pulse therapy in glomerulonephritis.

We retrospectively analyzed the data of the first and second renal biopsies to investigate the adverse effects as well as the clinical and histologic responses of methylprednisolone pulse therapy in patients with chronic glomerulonephritis. At the time of the second renal biopsy, the activity index had decreased significantly and the chronicity index was well preserved. The activity index and interstitial fibrosis were improved in the complete and partial remission groups, but not in the nonresponse group.

Linkage and association study of discoidin domain receptor 1 as a novel susceptibility gene for childhood IgA nephropathy.

In several experimental studies, it has been suggested that discoidin domain receptor 1 (DDR1) plays an important role in the regulation of mesangial proliferation, glomerular basement membrane thickening, renal fibrosis, and in the development of inflammation in several tissue types, including renal tissues. The present study was conducted to investigate the association between single nucleotide polymorphisms (SNPs) of the DDR1 gene and childhood IgA nephropathy (IgAN). The genotyping data of 180 childhood IgAN patients and 336 controls showed significant differences in the frequency of rs1264319 (dominant model, P=0.

Polymorphisms of signal transducers and activators of transcription 1 and 4 (STAT1 and STAT4) contribute to progression of childhood IgA nephropathy.

Background: Several experimental studies have suggested that signal transducers and activators of transcription 1 and 4 (STAT1 and STAT4) play important roles in the regulation of mesangial proliferation and renal fibrosis, and in the development of inflammation in several types of glomerulonephritis.

Methods: The present study was conducted to investigate the association between single nucleotide polymorphisms (SNPs) of the STAT1 and STAT4 genes and childhood IgA nephropathy (IgAN).

Results: Genotyping of 170 childhood IgAN patients and 442 controls showed no significant differences in allele frequency.

The enabled homolog gene polymorphisms are associated with susceptibility and progression of childhood IgA nephropathy.

The enabled homolog gene (ENAH, hMena) is abundantly expressed in mesangial tissue, and might play an important role in inflammatory processes of IgA nephropathy (IgAN). The present study was conducted to investigate the association between single nucleotide polymorphisms (SNPs) of the ENAH and childhood IgAN. We analyzed 12 SNPs of ENAH in 176 patients with childhood IgAN and 397 healthy controls.

Effects of Bupleurum falcatum and its combination with an angiotensin II receptor blocker on cytokine and chemokine expression in human mesangial cells.

This study aimed to investigate the inhibitory effect of Bupleurum falcatum and its combination with angiotensin II receptor blocker (ARB) on cytokine and chemokine production in cultured human mesangial cells. Human mesangial cells were isolated and cultured in Dulbecco's modified Eagle's medium culture medium. Bupleurum falcatum, ARB, and the combination of the two were added to human mesangial cells.

Remission of refractory minimal change nephrotic syndrome after basiliximab therapy.

Minimal change nephrotic syndrome has been proposed to be a disorder of T cell dysfunction. It is hypothesized that a circulating factor(s) from activated T cells might alter glomerular permeability to protein. Some studies have provided evidence that up-regulation of interleukin-2 may be involved, not only in the pathophysiology of minimal change nephrotic syndrome, but also in steroid resistance.