Ligand-based cheminformatics and free energy-inspired molecular simulations for prioritizing and optimizing G-protein coupled receptor kinase-6 (GRK6) inhibitors in multiple myeloma treatment.

Multiple myeloma (MM) is the second most frequently diagnosed hematological malignancy, presenting limited treatment options with no curative potential and significant drug resistance. Recent studies involving genetic knockdown established the crucial role of GRK6 in upholding the viability of MM cells, emphasizing the need to identify potential inhibitors. Computational exploration of GRK6 inhibitors has not been attempted previously.

In Light of the LANDI-SEP Trial: New Evidence or Double Jeopardy?

Datta PK, Sathe P, Bhattacharjee A, Kundu R. In Light of the LANDI-SEP Trial: New Evidence or Double Jeopardy? Indian J Crit Care Med 2025;29(1):84-85.

From Antipsychotic to Neuroprotective: Computational Repurposing of Fluspirilene as a Potential PDE5 Inhibitor for Alzheimer's Disease.

Phosphodiesterase 5 (PDE5) inhibitors have shown great potential in treating Alzheimer's disease by improving memory and cognitive function. In this study, we evaluated fluspirilene, a drug commonly used to treat schizophrenia, as a potential PDE5 inhibitor using computational methods. Molecular docking revealed that fluspirilene binds strongly to PDE5, supported by hydrophobic and aromatic interactions.

The Clinical Utility of Targeted Heart Rate Control in Septic Shock: A Systematic Review and Meta-analysis of Randomized Controlled Trials with Trial Sequential Analysis.

Objectives: Heart rate control using beta-blockers in sepsis has traditionally been avoided because of concerns with worsening cardiac index and organ perfusion. Recent studies has explored the possible beneficial effects of targeted heart rate control in patients with septic shock who have tachycardia despite initial resuscitation. We performed a systematic review and meta-analysis to explore the effects of heart rate control in septic shock patients.

Green synthesis of gold nano-particles using Madhuca indica flower extract and their anticancer activity on head and neck cancer: Characterization and mechanistic study.

Complete eradication of aggressive head and neck squamous cell carcinoma (HNSCC) still remains a major challenging problem due to numerous resistance properties of cancer stem cells (CSC) which is crucially responsible for tumor recurrence and metastasis. This challenge causes a high demand for the emergence of novel targeted treatment modalities for improved therapeutic efficacies. Phytochemicals derived from plants proves to be a wide reservoir of important drug candidates which have the potential to impede multiple aspects of malignant growth and progression.

Proposed biosensor for the detection of Bovine Serum Albumin using 7CB liquid crystals: A preliminary study.

Liquid crystal (LC) based biosensors offer a sensitive platform for detecting biomolecules due to their ability to respond to molecular interactions through changes in LC orientations. In this paper, we introduce a novel LC biosensor using 4-heptyl-4-biphenyl carbonitrile (7CB) to detect Bovine Serum Albumin (BSA). The interaction between BSA and 7CB was investigated using polarising optical microscopy (POM), molecular docking (MD), and Raman spectroscopy.

An influenza mRNA vaccine protects ferrets from lethal infection with highly pathogenic avian influenza A(H5N1) virus.

The global spread of the highly pathogenic avian influenza (HPAI) A(H5N1) virus poses a serious pandemic threat, necessitating the swift development of effective vaccines. The success of messenger RNA (mRNA) vaccine technology in the COVID-19 pandemic, marked by its rapid development and scalability, demonstrates its potential for addressing other infectious threats, such as HPAI A(H5N1). We therefore evaluated mRNA vaccine candidates targeting panzootic influenza A(H5) clade 2.

A staphylococcal capsule-producing enzyme that unfolds via multiple intermediates predominantly exists as the trimers at low concentrations.

CapG, an enzyme expressed by , catalyzes an epimerization reaction to synthesize -acetyl-L-fucosamine, a constituent of capsule involved in pathogenesis. This protein has two domains, exists as the homohexamers in the solution, and usually produces products at hundred-nanomolar concentrations. To determine the folding-unfolding mechanism and the oligomeric form of CapG, particularly at low concentrations, we have investigated a recombinant CapG (rCapG) using different probes.

Bacteriophages carry auxiliary metabolic genes related to energy, sulfur and phosphorus metabolism during a harmful algal bloom in a freshwater lake.

Cyanophages play an important role in nutrient cycling in lakes since they can modulate the metabolism of cyanobacteria. A proper understanding of the impact of cyanophage infection on the metabolism and ecology of cyanobacteria is critical during a complete cycle of harmful algal bloom (HAB). The ecology of cyanophages in marine environments has been well-delineated, but cyanophages in freshwater lakes remain less studied.

Sulfatide deficiency-induced astrogliosis and myelin lipid dyshomeostasis are independent of Trem2-mediated microglial activation.

Disrupted lipid homeostasis and neuroinflammation often co-exist in neurodegenerative disorders including Alzheimer's disease (AD). However, the intrinsic connection and causal relationship between these deficits remain elusive. Our previous studies show that the loss of sulfatide (ST), a class of myelin-enriched lipids, causes AD-like neuroinflammatory responses, cognitive impairment, bladder enlargement, as well as lipid dyshomeostasis.

Developing a biosensing prototype utilising a 7CB liquid crystal for human insulin detection.

This paper presents a novel prototype for human insulin detection using a 4-heptyl-4-biphenylcarbonitrile liquid crystal (7CB-LC). Human insulin is essential for regulating blood glucose levels and facilitating the metabolism of carbohydrates, lipids, and proteins. Insufficient insulin can lead to hyperglycemia, where cells cannot utilise glucose effectively for energy production.

Thermoplastic Molding of Silk-Curcumin Sustainable Composite Materials with Antibacterial Properties.

Silk fibroin (SF) is a natural protein generated from the silkworm cocoons. It is useful for many different material applications. Versatile aqueous process engineering options can be used to support the morphological and structural modifications of silk materials related to tailored physical, chemical, and biological properties.

Accessing Fungal Contributions to the Birch Effect: Real-Time Respiration from Pore-Scale Microfluidics.

Drying and rewetting of soil stimulates soil carbon emission. The Birch effect, driven by these cycles, leads to CO efflux, which can be monitored using real-time mass spectrometry (RTMS). Although soil fungi retain water during droughts, their contribution to CO release during drying-rewetting cycles remains unclear.

Extended-spectrum β - lactamase inhibitory potential of : an and computational studies.

Extended-spectrum β-lactamases (ESBL) producing enterobacteriales are a major global health concern since they often result in the ineffectiveness of empirical antibiotic therapy with β-lactams. This study aims to identify potential medicinal plants that can inhibit β-lactamase and subsequently enhance the activity of the β-lactams against resistant bacterial strains. A synergistic study of extract exhibited good synergistic activity against a CTX-M-producing organism, which was confirmed using an agar-based diffusion bioassay method.

Relaxation of weakly collisional plasma: Continuous spectra, discrete eigenmodes, and the decay of echoes.

The relaxation of a weakly collisional plasma, which is of fundamental interest to laboratory astrophysical plasmas, can be described by the self-consistent Boltzmann-Poisson equations with the Lenard-Bernstein collision operator. We perform a perturbative (linear and second-order) analysis of the Boltzmann-Poisson equations and obtain exact analytic solutions which resolve some longstanding controversies regarding the impact of weak collisions on the continuous spectra, the discrete Landau eigenmodes, and the decay of plasma echoes. We retain both damping and diffusion terms in the collision operator throughout our treatment.

Imipenem exposure influences the expression of quorum-sensing receptor sdiA in Escherichia coli.

The increasing trend of carbapenem resistance amongst Escherichia coli poses a major public health crisis and requires active surveillance of resistance mechanisms to control the threat. Quorum-sensing system plays a role in bacterial resistance to antibiotics. Quorum sensing is a cell-cell communication system where bacteria alter their gene expression in response to specific stimuli.

Bioprospecting amylase from Samiti Lake, situated in the eastern Himalayas.

Enzymes, especially amylases, have been an economic boon to the industrial sector, their bioprospective and biotechnological use is an added advantage. Our primary focus of the study was to isolate the most potent amylase producer and to optimize its production parameters through One Factor At A Time (OFAT), Central Composite Rotatable Design Response Surface Methodology (CCRD RSM) and Artificial Neural Network (ANN). Based on the qualitative and quantitative analysis, SLAB1 was selected as the most potent amylase producer out of the potential isolates.

Quantifying tumor specificity using Bayesian probabilistic modeling for drug and immunotherapeutic target discovery.

In diseases such as cancer, the design of new therapeutic strategies requires extensive, costly, and unfortunately sometimes deadly testing to reveal life threatening off-target effects. We hypothesized that the disease specificity of targets can be systematically learned for all genes by jointly evaluating complementary molecular measurements of healthy tissues using a hierarchical Bayesian modeling approach. Our method, BayesTS, integrates protein and gene expression evidence and includes tunable parameters to moderate tissue essentiality.

Pharmacologically enabling the degradation of NaV1.8 channels to reduce neuropathic pain.

In phase II clinical trials, NaV1.8 channels were identified as viable targets to treat acute pain. Results were modest, however, and NaV1.

Neuroimaging-based drug discovery for amyloid clearance therapy in Alzheimer's disease using validated causation analysis.

Aging-induced hepatic dysfunction can impair cholesterol metabolism, reducing the availability of cholic acid (CA, bile-acid) in brain. CA is reported to have neuroprotective characteristics in preclinical investigations of Alzheimer's disease (AD). Our aim is to probe the causal-connectivity between the players: amyloid, cholic acid and cerebral-blood-flow, and thereby explore therapeutic applicability in AD.

Correlative X-ray micro-nanotomography with scanning electron microscopy at the Advanced Light Source.

Geological samples are inherently multi-scale. Understanding their bulk physical and chemical properties requires characterization down to the nano-scale. A powerful technique to study the three-dimensional microstructure is X-ray tomography, but it lacks information about the chemistry of samples.

Improved Dissolution Time and Oral Bioavailability of Pioglitazone Using Liquisolid Tablets: Formulation, Characterization, and Pharmacokinetics in Rabbits.

In the current study, it was intended to prepare liquisolid tablets of pioglitazone HCl to improve the bioavailability and dissolution time of the drug, as it has low solubility in water. Mathematical formulas were adopted, and the quantities of the carrier (MCC), coating material (colloidal silicon dioxides), and nonvolatile liquid vehicle (Tween 80) were taken. Various ratios of the drug to liquid and carrier to coating had been used in the formulation of liquisolid compacts.

Mouse innate resistance to infection is driven by early production of IFNγ by NK cells in response to parasite ligands.

Unlabelled: is capable of being transmitted by nearly all warm-blooded animals, and rodents are a major source of parasite dissemination, yet mechanisms driving its broad host range are poorly understood. Although a phylogenetically close relative of , differs from in that it does not infect mice and only infects a small number of ruminant and canine species. We recently showed that and grow similarly in mice during the first 24 h post-infection, but only induces an IFNγ-driven response within hours that controls the infection.