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The initial size distribution and morphological parameters of sodium aerosols are critical in evaluating the accidental suspended aerosol behaviour in Sodium-cooled Fast Reactor (SFR) containment. Mass-based measurements were more familiar in characterizing the sodium aerosols. Real-time number size distribution measurements are carried out in this study. The sensitivity analysis of sodium aerosol effective density (ρe) in deriving the actual number size distributions from the measured Aerodynamic Particle Size Distributions (APSD) and predicting suspended aerosol dynamics is presented. Tests are conducted in a 1 m3 chamber at 47 ± 3% RH for different initial mass concentrations (M0) of 0.1, 1, and 2.9 g/m3. The initial APSDs measured just after the generation completions are observed to be polydisperse with the count median aerodynamic diameter (CMAD)

A 72-year-old man presented to his general practitioner with worsening dyspnea and was diagnosed with having recurrent ROS1-positive stage IIIB NSCLC 8 years after initial diagnosis and radical treatment for early stage disease. He was subsequently started on entrectinib but required hospital admissions for recurrent acute kidney injuries on a background of chronic kidney disease. His entrectinib was withheld on day 20 since his first dose of treatment while he was being investigated. Nevertheless, he continued to experience worsening dyspnea and bilateral pedal edema and later developed acute pulmonary edema 31 days after his first dose of entrectinib, despite the drug being withheld for the past 11 days. Results of biochemical tests and cardiac imaging confirmed acute myocarditis. Initially, he was treated with standard heart failure medications without clinical improvement or decline in N-terminal pro B-type natriuretic peptide levels. Nevertheless, he noticed significant improvement after starting a short course of prednisolone, which led to complete resolution of symptoms, improved N-terminal pro B-type natriuretic peptide levels, and recovery of left ventricular ejection fraction. His treatment was subsequently changed to crizotinib, which was well tolerated. This is the third reported case of entrectinib-induced myocarditis and the first reported case which has been successfully managed with steroid therapy. This case was also associated with concurrent acute heart failure after entrectinib treatment which responded promptly to prednisolone (40 mg). Entrectinib-induced cardiotoxicity is an important adverse event to be aware of, particularly as patients may be asymptomatic for an initial period before significant deterioration.

Abstract The phenomenon of mixed/heterogenous treatment responses to cancer therapies within an individual patient presents a challenging clinical scenario. Furthermore, the molecular basis of mixed intra-patient tumor responses remains unclear. Here, we show that patients with metastatic lung adenocarcinoma harbouring co-mutations of EGFR and TP53, are more likely to have mixed intra-patient tumor responses to EGFR tyrosine kinase inhibition (TKI), compared to those with an EGFR mutation alone. The combined presence of whole genome doubling (WGD) and TP53 co-mutations leads to increased genome instability and genomic copy number aberrations in genes implicated in EGFR TKI resistance. Using mouse models and an in vitro isogenic p53-mutant model system, we provide evidence that WGD provides diverse routes to drug resistance by increasing the probability of acquiring copy-number gains or losses relative to non-WGD cells. These data provide a molecular basis for mixed tumor responses to targeted therapy, within an individual patient, with implications for therapeutic strategies.

BackgroundOnly a small group of patients with glioblastoma multiforme (GBM) survives more than 36 months, so-called long-term survivors. Recent studies have shown that chromosomal instability (CIN) plays a prognostic and predictive role among different cancer types. Here, we compared histological (chromosome missegregation) and bioinformatic metrics (CIN signatures) of CIN in tumors of GBM typical survivors (≤36 months overall survival), GBM long-term survivors and isocitrate dehydrogenase (IDH)-mutant grade 4 astrocytomas.MethodsTumor sections of all gliomas were examined for anaphases and chromosome missegregation. Further CIN signature activity analysis in the The Cancer Genome Atlas (TCGA)-GBM cohort was performed.ResultsOur data show that chromosome missegregation is pervasive in high grade gliomas and is not different between the 3 groups. We find only limited evidence of altered CIN levels in tumors of GBM long-term survivors relative to the other groups, since a significant depletion in CIN signature 11 relative to GBM typical survivors was the only alteration detected. In contrast, within IDH-mutant grade 4 astrocytomas we detected a significant enrichment of CIN signature 5 and 10 activities and a depletion of CIN signature 1 activity relative to tumors of GBM typical survivors.ConclusionsOur data suggest that CIN is pervasive in high grade gliomas, however this is unlikely to be a major contributor to the phenomenon of long-term survivorship in GBM. Nevertheless, further evaluation of specific types of CIN (signatures) could have prognostic value in patients suffering from grade 4 gliomas.

Traditional rice is gaining popularity worldwide due to its high nutritional and pharmaceutical value, as well as its high resistance to abiotic and biotic stresses. This has attracted significant attention from breeders, nutritionists, and plant protection scientists in recent years. Hence, it is critical to investigate the grain metabolome to reveal germination and nutritional importance. This research aimed to explore non-targeted metabolites of five traditional rice varieties, viz., Chinnar, Chithiraikar, Karunguruvai, Kichili samba, and Thooyamalli, for their nutritional and therapeutic properties. Approximately 149 metabolites were identified using the National Institute of Standards and Technology (NIST) library and Human Metabolome Database (HMDB) and were grouped into 34 chemical classes. Major classes include fatty acids (31.1–56.3%), steroids and their derivatives (1.80–22.4%), dihydrofurans (8.98–11.6%), prenol lipids (0.66–4.44%), organooxygen compounds (0.12–6.45%), benzene and substituted derivatives (0.53–3.73%), glycerolipids (0.36–2.28%), and hydroxy acids and derivatives (0.03–2.70%). Significant variations in metabolite composition among the rice varieties were also observed through the combination of univariate and multivariate statistical analyses. Principal component analysis (PCA) reduced the dimensionality of 149 metabolites into five principle components (PCs), which explained 96% of the total variance. Two clusters were revealed by hierarchical cluster analysis, indicating the distinctiveness of the traditional varieties. Additionally, a partial least squares-discriminant analysis (PLS-DA) found 17 variables important in the projection (VIP) scores of metabolites. The findings of this study reveal the biochemical intricate and distinctive metabolomes of the traditional therapeutic rice varieties. This will serve as the foundation for future research on developing new rice varieties with traditional rice grain metabolisms to increase grain quality and production with various nutritional and therapeutic benefits.

In this study, an extensive exploration survey of wild progeny was conducted which yielded 18 candidate plus trees (CPTs) of Terminalia bellerica. Seeds of these CPTs were collected from diverse locations between 10°54′ and 28°07′ E longitude, and 76°27′ and 95°32′ N latitude, covering 18 different locations across 5 states of the Indian subcontinent. The objective of the progeny trial was to assess genetic associations and variability in growth and physio-chemical characteristics. Significant variations (p < 0.05) were observed among the growth traits, encompassing plant height, basal diameter, girth at breast height and volume, as well as physio-chemical characteristics such as leaf length, width, area and chlorophyll content, carotenoids, and protein in the progeny trial. Broad-sense heritability (h2b) estimates were consistently high, exceeding 80% for all growth and physiological related traits under investigation except for plant height, leaf length, and girth at breast height. A correlation study revealed that selecting based on plant height, leaf area, and girth at breast height effectively enhances T. bellerica volume. A moderate genetic advance in percent of the mean (GAM) was observed for most traits, except leaf length, leaf width, girth at breast height, and plant height. Across all 13 traits, phenotypic coefficient of variation (PCV) surpassed genotypic coefficient of variation (GCV). Utilizing principal component analysis (PCA) and dendrogram construction categorized the genotypes into seven distinct groups. In conclusion, the study has demonstrated that targeting girth at breast height and plant height would be a highly effective strategy for the establishment of elite seedling nurseries and clonal seed nurseries for varietal and hybridization programs in the future.

Naive CD4+ T cells differentiate into effector (Th1, Th2, Th17) cells and immunosuppressive (Treg) cells upon antigenic stimulation in the presence of a specific cytokine milieu. The T cell in vitro culture system provides a very efficient model to study compounds’ therapeutic activity and mechanism of action. Tinospora cordifolia (Willd.) Hook.f. & Thomson (Family. Menispermaceae) is one of the widely used drugs in Ayurveda (ancient Indian system of medicine) for various ailments such as inflammatory conditions, autoimmune disorders, and cancer as well as for promoting general health. In vitro and in vivo studies on immune cells comprising dendritic cells, macrophages, and B cells suggest its immune-modulating abilities. However, to date, the effect of T. cordifolia on individual purified and polarized T cell subsets has not been studied. Studying drug effects on T cell subsets is needed to understand their immunomodulatory mechanism and to develop treatments for diseases linked with T cell abnormalities. In this study, we examined the immunomodulatory activity of T. cordifolia on primary CD4+ T cells, i.e., Th1, Th17, and iTreg cells. An aqueous extract of T. cordifolia was non-cytotoxic at concentrations below 1500 µg/ml and moderately inhibited the proliferation of naive CD4+ T cells stimulated with anti-CD3ε and anti-CD28 for 96 h. T. cordifolia treatment of naive CD4+ T cells differentiated under Th17-polarizing conditions exhibited reduced frequency of IL-17 producing cells with inhibition of differentiation and proliferation. For the first time, in-depth genome-wide expression profiling of T. cordifolia treated naive CD4+ T cells, polarized to Th17 cells, suggests the broad-spectrum activity of T. cordifolia. It shows inhibition of the cytokine-receptor signaling pathway, majorly via the JAK-STAT signaling pathway, subsequently causing inhibition of Th17 cell differentiation, proliferation, and effector function. Additionally, the molecular docking studies of the 69 metabolites of T. cordifolia further substantiate the inhibitory activity of T. cordifolia via the cytokine-receptor signaling pathway. Furthermore, in vitro polarized Th1 and iTreg cells treated with T. cordifolia extract also showed reduced IFN-γ production and FoxP3 expression, respectively. This study provides insight into the plausible mechanism/s of anti-inflammatory activity of T. cordifolia involving T cells, mainly effective in Th17-associated autoimmune and inflammatory diseases.

Standard unit operations/equipment have not evolved for the traditional rice varieties of the Cauvery Deltaic region of Tamil Nadu. The fame of traditional rice is increasing nowadays owing to its health benefits. Non-standard unit operations may cause rice grains to crack during milling, accumulating more broken rice and yields in products of inferior quality. As a result, research into the physical properties of rice is crucial for the development of rice processing equipment that minimizes post-harvest losses during milling. Hence, an assessment was made to evaluate 30 traditional rice cultivars on their Physical (grain length, width, thickness, shape, and size), gravimetric (bulk, true, tapped density, porosity, Carr’s index, and Hausner ratio), and engineering characteristics (equivalent, arithmetic, square mean, and geometric mean diameter) using standard protocols, with the goal of reviving and preserving older varieties. The results from the analysis showed significant variations (p < 0.05) between all properties that were evaluated. According to length, a substantial amount of traditional rice varieties were long grain (76.7%), whereas (16.7%) belonged to the medium type and (3.3%) were short-grain types, respectively. There were variations among the three different categories of local rice grains when it comes to size, ranging from 3.26 to 4.69 mm for arithmetic mean diameter, 2.84 to 4.00 mm for geometric mean diameter, and 3.02 to 4.28 mm for square mean diameter, respectively. Sphericity, aspect ratio, and surface area measurements of the samples varied from 37.7% to 81.2%, 0.26 to 1.00, and 25.4 to 50.1 mm2, respectively. Of the 30 varieties, 28 were under the high amylose category, and 2 belonged to the intermediate type. The Pearson correlation was established to study the interrelationships between the dimensions and engineering properties. Principal component analysis (PCA) reduced the dimensionality of 540 data into five principal components (PC), which explained 95.7% of the total variance. These findings suggest that it is possible to revive old landraces through careful selection and analysis of these properties. The superior characteristics of these traditional varieties can be further evaluated for breeding programs in order to improve the cultivation of these cherished rice landraces to enhance nutritional security.

Tamil Nadu in particular is a key rice-producing region in peninsular India. Hydrochemistry, viz., redox potential (Rh), soil temperature and dissolved oxygen (DO), of rice soils can determine the production of greenhouse gas methane (CH4). In recent decades, the cultivation of crops organically became a viable option for mitigating climate change. Hence, this study aimed to investigate the effects of different organic amendments on CH4 emission, Rh, DO, and soil and water temperature (T) in relation to the yield of paddy. The treatments composed of viz., control, blue-green algae (BGA), Azolla, farm yard manure (FYM), green leaf manure (GLM), blue-green algae + Azolla, FYM + GLM, BGA + Azolla + FYM + GLM, vermicompost and decomposed livestock manure. With the addition of BGA + Azolla, the highest reduction in CH4 emission was 37.9% over the control followed by BGA. However, the same treatment had a 50% and 43% increase in Rh and DO, respectively, over the control. Established Pearson correlation analyses showed that the CH4 emission had a positive correlation with soil (r = 0.880 **) and water T (r = 0.888 **) and negative correlations with Rh (r = −0.987 **) and DO (r = −0.963 **). The higher grain yield of 26.5% was associated with BGA + Azolla + FYM + GLM application. Our findings showed that there are significant differences in CH4 emissions between different organic amendments and that hydro-parameters may be a more important controlling factor for methane emissions than temperature. The conclusion has been drawn based on valid research findings that bio-fertilization using BGA and Azolla is an efficient and feasible approach to combat climate change, as it assists in reducing methane emissions while simultaneously boosting crop yield by fixing nitrogen into the soil in the studied agro-climatic zone.

The realm of atomic catalysts has witnessed notable advancements; yet, the predominant focus remains on single atomic catalysts (SACs). The exploration and successful implementation of dual atomic catalysts (DACs) pose intricate challenges, primarily concerning thermodynamic stability and optimal metallic composition. To address these issues, we present a comprehensive theoretical investigation of α-2 graphyne (GPY)-based DACs, synthesized in-house with a keen focus on formation stability. Density functional theory (DFT) simulations were leveraged to ascertain each DAC structure's stability, considering numerous transition metal permutations totalling about 823 DACs. Furthermore, we developed a machine learning (ML) model that predicts stability based solely on the physical characteristics of the constituent elements in the DACs, thus eliminating the need for extensive DFT calculations. Our findings not only offer detailed insights into atomic interactions but also highlight promising candidates for DACs, pushing beyond traditional trial-and-error synthesis approaches. This study fosters a deeper understanding of DACs and paves new pathways for exploring atomic catalysts for practical applications. [ABSTRACT FROM AUTHOR]

Our recent study revealed that APOBEC3B is upregulated during the preinvasive stages of non-small cell lung cancer and breast cancer. In addition to its role in mediating single nucleotide variants, we propose that APOBEC3 promotes copy number intratumor heterogeneity prior to invasion, providing a substrate for cancer evolution.

To understand the spread of SARS-CoV2, in August and September 2020, the Council of Scientific and Industrial Research (India) conducted a serosurvey across its constituent laboratories and centers across India. Of 10,427 volunteers, 1058 (10.14%) tested positive for SARS-CoV2 anti-nucleocapsid (anti-NC) antibodies, 95% of which had surrogate neutralization activity. Three-fourth of these recalled no symptoms. Repeat serology tests at 3 (n = 607) and 6 (n = 175) months showed stable anti-NC antibodies but declining neutralization activity. Local seropositivity was higher in densely populated cities and was inversely correlated with a 30-day change in regional test positivity rates (TPRs). Regional seropositivity above 10% was associated with declining TPR. Personal factors associated with higher odds of seropositivity were high-exposure work (odds ratio, 95% confidence interval, p value: 2.23, 1.92–2.59,