Hydrochemical facies distribution, controlling mechanisms and natural background concentrations of major pollutants in Ganga-Yamuna interfluve aquifer, India.

Evolution of groundwater genesis in Central Ganga Plain (CGP) is scrutinized with due consideration of hydrochemical and hydrodynamic environment within Quaternary alluviums. Wide variation in hydrochemical facies in CGP indicates a dynamic hydro-geochemical environment influenced from the seasonal rainfall, return flows, canal seepages, and anthropogenic activities. The Ca-HCO facies retaining meteoric nature is characterized by shallow water levels, high recharge rate, high hydraulic conductivity, low salinity and trace elemental load.

Prospective Utilization of Nanocarriers Loaded with Drug Combination for Treating Alzheimer's Disease.

Alzheimer's disease (AD) is a debilitating condition that significantly affects the elderly. Early diagnosis is not only critical for improving patient outcomes but also directly influences the success of emerging therapeutic interventions. A therapeutic strategy targeting only one pathogenic mechanism is unlikely to be very effective, as there is increasing evidence that AD does not have a single pathogenic cause.

Performance, isotherm, kinetics and mechanism of simultaneous removal of Cr(VI), Cu(II) and F ions by CeO-MgO binary oxide nanomaterials.

This study focuses on the synthesis of a novel Cerium-Magnesium (CeO-MgO) binary oxide nanomaterials by a simple co-precipitation process and used to remove harmful pollutants such as Cr(VI), Cu(II), and F. The morphology, phase, crystallite size, thermal stability, functional groups, surface area, and porosity of the synthesized nanomaterial were determined by using XRD, SEM, FTIR, TGA/DTA, and BET studies. The prepared nanomaterials showed adsorption selectivity of Cu(II) ≈ F> Cr(VI) with a high adsorption capacity of 84.

Molecular mechanisms of inverse agonism via κ-opioid receptor-G protein complexes.

Opioid receptors, a subfamily of G protein-coupled receptors (GPCRs), are key therapeutic targets. In the canonical GPCR activation model, agonist binding is required for receptor-G protein complex formation, while antagonists prevent G protein coupling. However, many GPCRs exhibit basal activity, allowing G protein association without an agonist.

Targeting Refractory Triple-Negative Breast Cancer with Sacituzumab Govitecan: A New Era in Precision Medicine.

Advanced triple-negative breast cancer (TNBC) has poorer outcomes due to its aggressive behavior and restricted therapeutic options. While therapies like checkpoint inhibitors and PARP inhibitors offer some benefits, chemotherapy remains ineffective beyond the first line of treatment. Antibody-drug conjugates (ADCs) like sacituzumab govitecan-hziy (SG) represent a significant advancement.

Inhibition of the polyol pathway by extract: plausible implications for diabetic retinopathy treatment.

Introduction: Diabetic retinopathy is a significant microvascular disorder and the leading cause of vision impairment in working-age individuals. Hyperglycemia triggers retinal damage through mechanisms such as the polyol pathway and the accumulation of advanced glycation end products (AGEs). Inhibiting key enzymes in this pathway, aldose reductase (AR) and sorbitol dehydrogenase (SD), alongside preventing AGE formation, may offer therapeutic strategies for diabetic retinopathy and other vascular complications.

An opioid efficacy switch for reversible optical control of peripheral analgesia.

The mu-opioid receptor (MOR) is a major target for the treatment of pain. However, opioids are prone to side effects which limit their effectiveness as analgesics and can lead to opioid use disorders or, even, lethal overdose. The systemic administration of opioid agonists makes it both very difficult to decipher their underlying circuit mechanisms of action and to limit drug action to specific receptor subpopulations to isolate therapeutic effects from adverse side effects.

Drugs and drug targets for the treatment of HPV-positive cervical cancer.

Cervical cancer is primarily driven by persistent infection with high-risk human papillomavirus (HPV) strains and remains a significant global health challenge, particularly in low- and middle-income countries where late-stage diagnoses is common. While vaccination and screening programs have reduced incidence rates, the need for novel and more effacacious and cost-effective therapeutic options is therefore critical especially for advanced cervical cancer. This review highlights several key advances in the understanding of HPV-induced carcinogenesis and the development of therapeutic strategies over the past five years.

Designed and synthesized novel tripeptides targeting diabetes and its related pathologies.

In diabetes and its associated pathologies, glycation, α-amylase, and α-glucosidase play crucial roles. This study introduces a novel tripeptide, RWW, designed to target glycation and key enzymes in diabetes management. Using in silico methods, RWW was optimized to interact with the glycation-prone Human serum albumin (HSA) sites, as well as inhibit α-amylase and α-glucosidase.

A High-Throughput Drug Repurposing Strategy to Treat TBX2 and/or TBX3 Dependent Cancers.

Background: The highly homologous T-box transcription factors TBX2 and TBX3 are critical for embryonic development, and their overexpression in postnatal tissues contributes to a wide range of malignancies, including melanoma and rhabdomyosarcoma. Importantly, when TBX2 and TBX3 are depleted in cancers where they are overexpressed, the malignant phenotype is inhibited, and they have therefore been regarded as druggable targets. However, the time and costs associated with de novo drug development are challenging and result in drugs that are costly, especially for patients in low- and middle-income countries.

Exploring aldose reductase inhibitors as promising therapeutic targets for diabetes-linked disabilities.

Diabetes mellitus significantly increases mortality and morbidity rates due to complications like neuropathy and nephropathy. It also leads to retinopathy and cataract formation, which is a leading cause of vision disability. The polyol pathway emerges as a promising therapeutic target among the various pathways associated with diabetic complications.

Barriers and Strategies to Effective Serious Illness Communication for Patients with End-Stage Liver Disease in the Intensive Care Setting.

Patients with end-stage liver disease (ESLD) often require Intensive Care Unit (ICU) admission during the disease trajectory, but aggressive medical treatment has not resulted in increased quality of life for patients or caregivers. This narrative review synthesizes relevant data thematically exploring the current state of serious illness communication in the ICU with identification of barriers and potential strategies to improve performance. We provide a conceptual model underscoring the importance of providing comprehensible disease and prognosis knowledge, eliciting patient values and aligning these values with available goals of care options through a series of discussions.

Aldose reductase inhibitory and antiglycation properties of phytoconstituents of Cichorium intybus: Potential therapeutic role in diabetic retinopathy.

Diabetic vascular complication including diabetic retinopathy is a major morbidity in Saudia Arabia. The polyol pathway aka aldose reductase (AR) pathway has gained significant association with diabetic retinopathy with regard to chronically enhanced glucose metabolism. Considerable research has been put forth to develop more effective therapeutic strategies to overcome the overwhelming challenges of vascular complications associated with diabetes.

Artificial intelligence derived categorizations significantly improve HOMA IR/β indicators: Combating diabetes through cross-interacting drugs.

Improvements in the homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of beta-cell function (HOMA-β) significantly reduce the risk of disabling diabetic pathies. Nanoparticle (AuNP-AgNP)-metformin are concentration dependent cross-interacting drugs as they may have a synergistic as well as antagonistic effect(s) on HOMA indicators when administered concurrently. We have employed a blend of machine learning: Artificial Neural Network (ANN), and evolutionary optimization: multiobjective Genetic Algorithms (GA) to discover the optimum regime of the nanoparticle-metformin combination.

Multivariable prognostic modelling to improve prediction of colorectal cancer recurrence: the PROSPeCT trial.

Objective: Improving prognostication to direct personalised therapy remains an unmet need. This study prospectively investigated promising CT, genetic, and immunohistochemical markers to improve the prediction of colorectal cancer recurrence.

Material And Methods: This multicentre trial (ISRCTN 95037515) recruited patients with primary colorectal cancer undergoing CT staging from 13 hospitals.

Short-term, nonsurgical periodontal therapy boosts interleukin-12 levels and reduces oral cancer risk.

Background: Cytokines, including interleukin-12 (IL-12), are proteins that regulate cell survival, proliferation, differentiation, and function. IL-12 is a heterodimeric proinflammatory cytokine. It possesses tumoricidal properties and promotes M1 macrophage polarization and IFN-γ production by T helper (Th1) cells, which in turn stimulates the antitumor cytotoxic cluster of eight positive (CD8+) and natural killer cells, therefore activating an effector immune response against tumor cells.

Trinuclear ruthenium(II) polypyridyl complexes: Evaluation as photosensitizers for enhanced cervical cancer treatment.

Trinuclear ruthenium(II) polypyridyl complexes anchored to benzimidazole-triazine / trisamine scaffolds were investigated as photosensitizers for photodynamic therapy. The trinuclear complexes were noted to produce a significant amount of singlet oxygen in both DMF and aqueous media, are photostable and show appreciable emission quantum yields (ɸ). In our experimental setting, despite the moderate phototoxic activity in the HeLa cervical cancer cell line, the phototoxic indices (PI) of the trinuclear complexes are superior relative to the PIs of a clinically approved photosensitizer, Photofrin®, and the pro-drug 5-aminolevulinic acid (PI: >7 relative to PI: >1 and PI: 4.

[F]FDG PET/CT Signal Correlates with Neoangiogenesis Markers in Patients with Fibrotic Interstitial Lung Disease Who Underwent Lung Biopsy: Implication for the Use of PET/CT in Diffuse Lung Diseases.

The use of [F]FDG PET/CT as a biomarker in diffuse lung diseases is increasingly recognized. We investigated the correlation between [F]FDG uptake with histologic markers on lung biopsy of patients with fibrotic interstitial lung disease (fILD). We recruited 18 patients with fILD awaiting lung biopsy for [F]FDG PET/CT.

Taking cues from machine learning, compartmental and time series models for SARS-CoV-2 omicron infection in Indian provinces.

SARS-CoV-2, the virus responsible for COVID-19, posed a significant threat to the world. We analyzed COVID-19 dissemination data in the top ten Indian provinces by infection incidences using the Susceptible-Infectious-Removed (SIR) model, an Autoregressive Integrated Moving Average (ARIMA) time series model, a machine learning model based on the Random Forest, and distribution fitting. Outbreaks are expected to continue if the Basic Reproduction Number (R) > 1, and infection waves are anticipated to end if the R < 1, as determined by the SIR model.

Path-dependent morphology of CH hydrates and their dissociation studied with high-pressure microfluidics.

Methane hydrates (MHs) have been considered a promising future energy source due to their vast resource volume and high energy density. Understanding the behavior of MH formation and dissociation at the pore-scale and the effect of MH distribution on the gas-liquid two phase flow is of critical importance for designing effective production strategies from natural gas hydrate (NGH) reservoirs. In this study, we devised a novel high-pressure microfluidic chip apparatus that is capable of direct observation of MH formation and dissociation behavior at the pore-scale.

Campesterol and dithymoquinone as a potent inhibitors of SARS cov-2 main proteases-promising drug candidates for targeting its novel variants.

The sudden outbreak of the COVID-19 pandemic has currently taken approximately 2.4 million lives, with no specific medication and fast-tracked tested vaccines for prevention. These vaccines have their own adverse effects, which have severely affected the global healthcare system.

Aminoquinoline-based Re(I) tricarbonyl complexes: Insights into their antiproliferative activity and mechanisms of action.

In an effort to develop new potent anticancer agents, two Schiff base rhenium(I) tricarbonyl complexes, containing the ubiquitous aminoquinoline scaffold, were synthesized. Both aminoquinoline ligands and Re(I) complexes showed adequate stability over a 48-h incubation period. Furthermore, the cytotoxic activity of the precursor ligands and rhenium(I) complexes were evaluated against the hormone-dependent MCF-7 and hormone-independent triple negative MDA-MB-231 breast cancer cell lines.

Whole-genome sequence of CR112, isolated from the gut of a healthy .

Bacteria of the genus are gram-negative bacilli. CR112 was isolated from fish gut based on its antibacterial activity against fish pathogens. The genome sequence of CR112 provided valuable information about its secondary metabolite gene clusters.