The potent human CAR activator CITCO is a non-genotoxic hepatic tumour-promoting agent in humanised constitutive androstane receptor mice but not in wild-type animals.

A large number of drugs and compounds produced by the chemical and agrochemical industry, often referred to as 'non-genotoxic carcinogens' (NGC), score as tumour promotors in rodent models. It is unclear whether these compounds act similarly in humans. The most extensively investigated compounds have been the anti-convulsive drugs, phenobarbital (PB), and phenytoin.

Ecological and Social Pressures Influence Diel Activity Patterns in Wild Tibetan Macaques.

The nighttime behavior of diurnal species is a "black box." Although diurnal animals spend approximately half their lives in the dark, research has, for too long, relied on the simplifying assumption that what we can't observe isn't important. Advances in our ability to monitor nighttime behavior reveal that this is incorrect; essential biological and behavioral processes play out in the dark which are critical for understanding a species' ecology and evolution.

Sociodemographic and clinical profiles of individuals with opioid dependence syndrome presenting to a tertiary care center in Assam: A retrospective review.

Background: Opioid dependence is a critical public health issue in Northeast India, with limited data available on the affected population.

Aim: This study examines the sociodemographic and clinical profiles of opioid-dependent individuals in Assam.

Methods: A retrospective review was conducted of 238 patients diagnosed with opioid dependence at a tertiary care addiction treatment center in Assam, covering records from January 2022 to January 2023.

Epi-microRNA mediated metabolic reprogramming counteracts hypoxia to preserve affinity maturation.

To increase antibody affinity against pathogens, positively selected GC-B cells initiate cell division in the light zone (LZ) of germinal centers (GCs). Among these, higher-affinity clones migrate to the dark zone (DZ) and vigorously proliferate by utilizing energy provided by oxidative phosphorylation (OXPHOS). However, it remains unknown how positively selected GC-B cells adapt their metabolism for cell division in the glycolysis-dominant, cell cycle arrest-inducing, hypoxic LZ microenvironment.

Disulfiram-induced psychosis still an important clinical entity: A case series.

Disulfiram, an FDA-approved medication for treating alcohol dependence syndrome (ADS), is often used surreptitiously, resulting in severe adverse drug reactions such as disulfiram-induced psychosis (DIP). DIP presents diagnostic challenges, despite being perceived as common; however, there is limited literature available on DIP in India. We describe four cases with a history of psychosis in the background of disulfiram exposure.

Use of differential scanning calorimetry as a rapid, effective in-process check method for impurity quantitation of an early clinical batch of Giredestrant (GDC-9545).

Giredestrant (GDC-9545) is a selective estrogen receptor degrader (SERD) that was developed for treatment of ER+/HER2- metastatic breast cancer. An anhydrous crystalline tartrate salt was identified as the solid form suitable for clinical development. An early clinical batch of the active pharmaceutical ingredient (API)/drug substance failed to pass the GMP purity specifications owing to the presence of a substantial amount of high molecular weight impurities (oligomers), as determined by size exclusion chromatography.

Cancer cell - Fibroblast crosstalk via HB-EGF, EGFR, and MAPK signaling promotes the expression of macrophage chemo-attractants in squamous cell carcinoma.

Interactions between cells in the tumor microenvironment (TME) shape cancer progression and patient prognosis. To gain insights into how the TME influences cancer outcomes, we derive gene expression signatures indicative of signaling between stromal fibroblasts and cancer cells, and demonstrate their prognostic significance in multiple and independent squamous cell carcinoma cohorts. By leveraging information within the signatures, we discover that the HB-EGF/EGFR/MAPK axis represents a hub of tumor-stroma crosstalk, promoting the expression of CSF2 and LIF and favoring the recruitment of macrophages.

The sociality of sleep in animal groups.

Group-living animals sleep together, yet most research treats sleep as an individual process. Here, we argue that social interactions during the sleep period contribute in important, but largely overlooked, ways to animal groups' social dynamics, while patterns of social interaction and the structure of social connections within animal groups play important, but poorly understood, roles in shaping sleep behavior. Leveraging field-appropriate methods, such as direct and video-based observation, and increasingly common on-animal motion sensors (e.

Growth mechanisms of amorphous nanoparticles in solution and during heat drying.

The purpose of this study was twofold: to identify the growth mechanisms of amorphous nanoparticles in solution and during the drying process at high temperatures, and to guide the process condition and stabilizer selection for amorphous nanoparticle formulations. In contrast to nanocrystals that are mostly mechanically robust, amorphous nanoparticles tend to undergo deformation under stress. As a result, development of a stable formulation and evaluation of the drying process for re-dispersible amorphous nanoparticles present considerable challenges.

Investigation of the State of Hydration of a Non-Stoichiometric Hydrate in a Low Dose Formulation Using F Solid-State NMR.

A variable or non-stoichiometric hydrate of GDC-4379 was developed into a formulated capsule with a 1% drug loading. The water content of this hydrate varied from 0-0.7 moles over the relative humidity (RH) range of 0-98% (25°C).

Comparing the Knowledge, Attitude, and Practices on Oral Fluids, Electrolytes, and Energy Management in Non-diarrheal Illnesses across Different Physician Specialties in India.

: The management of non-diarrheal illnesses requires careful attention to maintaining the proper balance of fluids, electrolytes, and energy (FEE). Nevertheless, there is a limited amount of information accessible regarding the utilization of oral FEE formulations in the treatment of these conditions. : The objective of this study was to assess and contrast the levels of knowledge, attitude, and practices (KAP) among various medical specialties in India when it comes to addressing FEE imbalances in non-diarrheal illnesses through the use of oral FEE formulations, as well as to examine how these approaches influence perceived patient outcomes.

Vitamin D regulates microbiome-dependent cancer immunity.

A role for vitamin D in immune modulation and in cancer has been suggested. In this work, we report that mice with increased availability of vitamin D display greater immune-dependent resistance to transplantable cancers and augmented responses to checkpoint blockade immunotherapies. Similarly, in humans, vitamin D-induced genes correlate with improved responses to immune checkpoint inhibitor treatment as well as with immunity to cancer and increased overall survival.

Blimp-1 and c-Maf regulate immune gene networks to protect against distinct pathways of pathobiont-induced colitis.

Intestinal immune responses to microbes are controlled by the cytokine IL-10 to avoid immune pathology. Here, we use single-cell RNA sequencing of colon lamina propria leukocytes (LPLs) along with RNA-seq and ATAC-seq of purified CD4 T cells to show that the transcription factors Blimp-1 (encoded by Prdm1) and c-Maf co-dominantly regulate Il10 while negatively regulating proinflammatory cytokines in effector T cells. Double-deficient Prdm1MafCd4 mice infected with Helicobacter hepaticus developed severe colitis with an increase in T1/NK/ILC1 effector genes in LPLs, while Prdm1Cd4 and MafCd4 mice exhibited moderate pathology and a less-marked type 1 effector response.

Green titanium dioxide (TiO) nanoparticles assisted biodegradation of anthracene employing Serratia quinivorans HP5.

The anthracene biodegradation potential of Serratia quinivorans HP5 was studied under a controlled laboratory environment. The green TiO nanoparticles (NPs) synthesized from Paenibacillus sp. HD1PAH was used to accelerate the biodegradation process.

Distinct ontogenetic lineages dictate cDC2 heterogeneity.

Conventional dendritic cells (cDCs) include functionally and phenotypically diverse populations, such as cDC1s and cDC2s. The latter population has been variously subdivided into Notch-dependent cDC2s, KLF4-dependent cDC2s, T-bet cDC2As and T-bet cDC2Bs, but it is unclear how all these subtypes are interrelated and to what degree they represent cell states or cell subsets. All cDCs are derived from bone marrow progenitors called pre-cDCs, which circulate through the blood to colonize peripheral tissues.

SOX9-positive pituitary stem cells differ according to their position in the gland and maintenance of their progeny depends on context.

Stem cell (SC) differentiation and maintenance of resultant progeny underlie cell turnover in many organs, but it is difficult to pinpoint the contribution of either process. In the pituitary, a central regulator of endocrine axes, adult SCs undergo activation after target organ ablation, providing a well-characterized paradigm to study an adaptative response in a multi-organ system. Here, we used single-cell technologies to characterize SC heterogeneity and mobilization together with lineage tracing.

Investigation of Recrystallization Kinetics in 1050 Al Alloy by Experimental Evidence and Modeling Approach.

The recrystallization (RX) kinetics of commercially pure Al alloy is studied under the scope of annealing temperature, time, and degree of deformation. To examine the distribution of recrystallization, Johnson-Mehl-Avrami-Kolmogorov (JMAK) theory is employed, where the path of microstructural transformation from the deformed state to the fully recovered one is studied as a function of the volume fraction of recrystallized grains (XV) and annealing time. The drop in hardness is recorded for the samples at various stages of annealing with a corresponding decrease in stored energy as the annealing time increases.

Epi-microRNA mediated metabolic reprogramming ensures affinity maturation.

To increase antibody affinity against pathogens, positively selected GC-B cells initiate cell division in the light zone (LZ) of germinal centres (GCs). Among those, higher-affinity clones migrate to the dark zone (DZ) and vigorously proliferate by relying on oxidative phosphorylation (OXPHOS). However, it remains unknown how positively selected GC-B cells adapt their metabolism for cell division in the glycolysis-dominant, cell cycle arrest-inducing, hypoxic LZ microenvironment.

Review of the Requirements for a Wearable, Low-Cost External Cardiac Loop Recorder with WBAN in Resource-Constrained Settings.

Cardiovascular disease (CVD) has become the most serious health concern in India and globally. The cost of treatment for CVD is very high and in a country like India, where most of the population belongs to rural area, affording treatment is not possible. Diagnosis and treatment are further hampered due to shortage of medical expertise as well as the unavailability of the wearable device.

Endothelial AHR activity prevents lung barrier disruption in viral infection.

Disruption of the lung endothelial-epithelial cell barrier following respiratory virus infection causes cell and fluid accumulation in the air spaces and compromises vital gas exchange function. Endothelial dysfunction can exacerbate tissue damage, yet it is unclear whether the lung endothelium promotes host resistance against viral pathogens. Here we show that the environmental sensor aryl hydrocarbon receptor (AHR) is highly active in lung endothelial cells and protects against influenza-induced lung vascular leakage.