Generation of frameshift-mutated TGFβR2-specific T cells in healthy subjects following administration with cancer vaccine candidate FMPV-1/GM-CSF in a phase 1 study.

FMPV-1 is a component of FMPV-3, an investigational cancer-specific vaccine and being developed to activate anti-cancer T cell responses targeting frameshift mutations of MSI-H cancers. FMPV-1 is designed to activate T cell responses against transforming growth factor β receptor 2 (TGFβR2) frameshift mutation. Microsatellite instability high (MSI-H) gastrointestinal cancers frequently harbour TGFβR2 frameshift mutations.

First-in-human safety, tolerability, pharmacokinetics and pilot food-effect study of the candidate antimalarial compound MMV367.

Aim: To evaluate the safety, tolerability and pharmacokinetics in healthy participants of orally administered MMV367 (GSK3772701), a novel antimalarial interfering with Plasmodium falciparum acyl coenzyme A synthetase 10/11 function.

Methods: This first-in-human study enrolled 47 healthy male and female participants. Part 1 was a randomised, double-blind, placebo-controlled study in which four sequential fasted cohorts received MMV367 single ascending doses (100, 300, 750 and 1500 mg) or placebo (six active, two placebo per cohort).

Mass Balance Recovery, Absorption, Metabolism, and Excretion of Elinzanetant in Healthy Human Volunteers and in vitro Biotransformation.

Background: Elinzanetant is a dual neurokinin-1,3 receptor antagonist in development for the treatment of menopausal vasomotor symptoms. The objectives of these studies were to characterize the mass balance and biotransformation of elinzanetant.

Methods: In the clinical evaluation, whole blood, plasma, urine, and feces were collected from healthy fasted male volunteers (n = 6) following a single dose of 120 mg [C]-elinzanetant oral suspension for analysis of total radioactivity and metabolite profiling.

Human exposure to uranium through drinking water and its detrimental impact on the human body organs.

Human exposure to high concentrations of uranium is a major concern due to the risk of developing numerous internal organ malignancies over time. In addition to the numerous attributes of uranium in the nuclear power industry, the radiological characteristics and chemical toxicity of uranium present a substantial risk to human health. This study aims to evaluate potential negative health impacts associated with the ingestion of uranium through drinking water in the Noida and Greater Noida region within the Gautam Buddha districts of Uttar Pradesh (India), due to extreme industrial revolution in this geological location.

Two-Part Phase 1 Study to Evaluate the Taste Profile of Novel Belumosudil Oral Suspensions and Assess the Relative Bioavailability and Food Effect of the Selected Belumosudil Oral Suspension Compared With Oral Tablet Reference in Healthy Male Participants.

Belumosudil is a selective rho-associated coiled-coil-containing protein kinase 2 inhibitor in clinical use for the treatment of chronic graft-versus-host disease. The current tablet formulation may be inappropriate for children or adults with dysphagia and/or upper gastrointestinal manifestations of chronic graft-versus-host disease. This study (NCT04735822) assessed the taste and palatability of oral suspensions of belumosudil, evaluated the relative bioavailability of an oral suspension versus the tablet formulation, and characterized the effect of food on the pharmacokinetics of an oral suspension.

Evaluation of the drug disposition of RO7049389 with in vitro data and human mass balance supported by physiologically based pharmacokinetic modelling.

Aims: RO7049389 (linvencorvir) is a developmental oral treatment for chronic hepatitis B virus infection. The aim of this work was to conduct mass balance (MB) and absolute bioavailability (BA) analyses in healthy volunteers, alongside in vitro evaluations of the metabolism of RO7049389 and a major circulating active metabolite M5 in human hepatocytes, and physiologically based pharmacokinetic (PBPK) modelling to refine the underlying drug disposition paradigm.

Methods: Participants in the clinical study (MB: Caucasian, male, n = 6; BA: Caucasian and Asian, male and female, n = 16, 8 in each ethnic groups) received oral [ C] or unlabelled RO7049389 (600/1000 mg) followed by 100 μg intravenous [ C]RO7049389.

Agronomic Investigation of Spray Dispersion of Metal-Based Nanoparticles on Sunflowers in Real-World Environments.

In environmental and agronomic settings, even minor imbalances can trigger a range of unpredicted responses. Despite the widespread use of metal-based nanoparticles (NPs) and new bio-nanofertilizers, their impact on crop production is absent in the literature. Therefore, our research is focused on the agronomic effect of spray application of gold nanoparticles anchored to SiO mesoporous silica (AuSi-NPs), zinc oxide nanoparticles (ZnO-NPs), and iron oxide nanoparticles (FeO-NPs) on sunflowers under real-world environments.

Clinicomycological Profile and Risk Factors for Dermatophytosis at a Teaching Tertiary Care Centre in North India: A Cross-sectional Study.

Background: Dermatophytosis has gained significant importance in recent years owing to increased incidence, more atypical lesions, changing mycological profile and growing antifungal resistance. Therefore, this study was planned to know the clinicomycological profile of dermatophytic infections in patients attending our tertiary care centre.

Materials And Methods: A total of 700 patients with superficial fungal infections belonging to all age groups and both sexes were taken up for this cross-sectional study.

Screening for Multifarious Plant Growth Promoting and Biocontrol Attributes in Strains Isolated from Indo Gangetic Soil for Enhancing Growth of Rice Crops.

Multifarious plant growth-promoting strains recovered from rhizospheric soils of the Indo Gangetic plains (IGPs) were identified as MNNITSR2 and MNNITSR18 based on their biochemical characteristics and 16S rDNA gene analysis. Both strains exhibited the ability to produce IAA, siderophores, ammonia, lytic enzymes, HCN production, and phosphate solubilization capability and strongly inhibited the growth of phytopathogens such as and in vitro. In addition, these strains are also able to grow at a high temperature of 50 °C and tolerate up to 10-15% NaCl and 25% PEG 6000.

Molecular Weight Controls Interactions between Plastic Deformation and Fracture in Cold Spray of Glassy Polymers.

Polymer cold spray has gained considerable attention as a novel manufacturing process. A promising aspect of this technology involves the ability to deposit uniform polymer coatings without the requirements of solvent and/or high-temperature conditions. The present study investigates the interplay between shear instability, often considered to be the primary mechanism for bond formation, and fracture, as a secondary energy dissipation mechanism, collectively governing the deposition of glassy thermoplastics on similar and dissimilar substrates.

Improving biofortification success rates and productivity through zinc nanocomposites in rice (Oryza sativa L.).

Rice (Oryza sativa L.) is a staple food crop; most of it is consumed in nations where malnutrition is a serious problem, and its enrichment through biofortification can be used to efficiently combat hidden hunger. Here, we studied the effect of two zinc forms, i.

Effect of zinc and iron oxide nanoparticles on plant physiology, seed quality and microbial community structure in a rice-soil-microbial ecosystem.

In this study, we assessed the impact of zinc oxide (ZnO) and iron oxide (FeO) (<36 nm) nanoparticles (NPs) as well as their sulphate salt (bulk) counterpart (0, 25, 100 mg/kg) on rice growth and seed quality as well as the microbial community in the rhizosphere environment of rice. During the rice growing season 2021-22, all experiments were conducted in a greenhouse (temperature: day 30 °C; night 20 °C; relative humidity: 70%; light period: 16 h/8 h, day/night) in rice field soil. Results showed that low concentrations of FeO and ZnO NPs (25 mg/kg) promoted rice growth (height (29%, 16%), pigment content (2%, 3%)) and grain quality parameters such as grains per spike (8%, 9%), dry weight of grains (12%, 14%) respectively.

Sustainable approaches towards green synthesis of TiO nanomaterials and their applications in photocatalysis-mediated sensing to monitor environmental pollution.

Nanomaterials are gaining enormous interests due to their novel applications that have been explored nearly in every field of our contemporary society. In this scenario, preparations of nanomaterials following green routes have attracted widespread attention in terms of sustainable, reliable, and environmentally friendly practices to produce diverse nanostructures. In this review, we summarize the fundamental processes and mechanisms of green synthesis approaches of TiO nanoparticles (NPs).

Absorption, metabolism and excretion of opicapone in human healthy volunteers.

Aims: The absorption, metabolism and excretion of opicapone (2,5-dichloro-3-(5-[3,4-dihydroxy-5-nitrophenyl]-1,2,4-oxadiazol-3-yl)-4,6-dimethylpyridine 1-oxide), a selective catechol-O-methyltransferase inhibitor, were investigated.

Methods: Plasma, urine and faeces were collected from healthy male subjects following a single oral dose of 100 mg [ C]-opicapone. The mass balance of [ C]-opicapone and metabolic profile were evaluated.

A Phase 1 Pharmacokinetic Drug Interaction Study of Belumosudil Coadministered With CYP3A4 Inhibitors and Inducers and Proton Pump Inhibitors.

Belumosudil is a selective Rho-associated protein kinase 2 inhibitor. Inhibition of Rho-associated protein kinase 2 has emerged as a promising treatment for chronic graft-versus-host disease by restoring immune homeostasis and reducing fibrosis. In vitro assessments have suggested that metabolism of belumosudil is primarily dependent on cytochrome P450 (CYP) 3A4 activity and that the solubility of belumosudil is pH dependent.

Structural analysis of extrafloral nectaries of Senna occidentalis L.: insights on diversity and evolution.

The extrafloral nectaries of S. occidentalis were studied structurally and anatomically (at secretory and post-secretory developmental stages). Role of extrafloral nectaries as a common plant-adoptive characteristic in context to diversity and phylogenetic pattern was also speculated while exploring other collaborative evolutionary implications of this plant.

Synergistic action of silicon nanoparticles and indole acetic acid in alleviation of chromium (Cr) toxicity in Oryza sativa seedlings.

The present study investigates ameliorative effect of silicon nanoparticles (SiNPs) and indole acetic acid (IAA) alone and in combination against hexavalent chromium (Cr) toxicity in rice seedlings. The results of the study revealed protective effects of SiNPs and IAA against Cr toxicity. The 100 μM of Cr imposed toxic effects in rice seedlings at morphological, physiological and biochemical levels which coincided with increased level of intracellular Cr and declined level of endogenous nitric oxide (NO).

Nanopriming with phytosynthesized zinc oxide nanoparticles for promoting germination and starch metabolism in rice seeds.

The application of zinc oxide nanoparticles (ZnO NPs) in agricultural field is emerging and relatively new. In this work, a simple, cost-efficient, non-toxic and eco-friendly method for the green synthesis of ZnO NPs by Senna occidentalis leaf extract has been described. Techniques used to characterize nanoparticles (NPs) were X-ray diffractometer (XRD), UV visible spectroscopy, Particle size analyzer (PSA), Fourier transform infrared spectroscopy (FTIR) and Scanning electron microscopy (SEM).

Transcriptomic landscape of early age onset of colorectal cancer identifies novel genes and pathways in Indian CRC patients.

Past decades of the current millennium have witnessed an unprecedented rise in Early age Onset of Colo Rectal Cancer (EOCRC) cases in India as well as across the globe. Unfortunately, EOCRCs are diagnosed at a more advanced stage of cancer. Moreover, the aetiology of EOCRC is not fully explored and still remains obscure.

Eco-friendly synthesis of phytochemical-capped iron oxide nanoparticles as nano-priming agent for boosting seed germination in rice (Oryza sativa L.).

Recently the applications of engineered nanoparticles in the agricultural sector is increased as nano-pesticides, nano-fertilizers, nanocarrier for macro- or micronutrients, nano-sensors, etc. In this study, biocompatible iron oxide nanoparticles (FeO NPs) have been synthesized through an environment-friendly route using Cassia occidentalis L. flower extract to act as nano-priming agent for promoting germination of Pusa basmati rice seeds.

A review of CRISPR associated genome engineering: application, advances and future prospects of genome targeting tool for crop improvement.

The Cas9 nuclease initiates double-stranded breaks at the target position in DNA, which are repaired by the intracellular restoration pathways to eliminate or insert pieces of DNA. CRISPR-Cas9 is proficient and cost-effective since cutting is guided by a piece of RNA instead of protein. Emphasis on this technology, in contrast with two recognized genome editing platforms (i.