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The elemental composition of the lunar surface provides insights into mechanisms of the formation and evolution of the Moon1,2. The chemical composition of lunar regolith have so far been precisely measured using the samples collected by the Apollo, Luna and Chang’e 5 missions, which are from equatorial to mid-latitude regions3,4; lunar meteorites, whose location of origin on the Moon is unknown5,6; and the in situ measurement from the Chang’e 3 and Chang’e 4 missions7–9, which are from the mid-latitude regions of the Moon. Here we report the first in situ measurements of the elemental abundances in the lunar southern high-latitude regions by the Alpha Particle X-ray Spectrometer (APXS) experiment10aboard the Pragyan rover of India’s Chandrayaan-3 mission. The 23 measurements in the vicinity of the Chandrayaan-3 landing site show that the local lunar terrain in this region is fairly uniform and primarily composed of ferroan anorthosite (FAN), a product of the lunar magma ocean (LMO) crystallization. However, observation of relatively higher magnesium abundance with respect to calcium in APXS measurements suggests the mixing of further mafic material. The compositional uniformity over a few tens of metres around the Chandrayaan-3 landing site provides an excellent ground truth for remote-sensing observations.

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Introduction: Phytase, recognized for its ability to enhance the nutritional value of phytate-rich foods, has has gained significant prominence. The production of this enzyme has been significantly boosted while preserving economic efficiency by utilizing natural substrates and optimizing essential factors. This study focuses on optimizing phytase production through solid-state fermentation and evaluating its effectiveness in enhancing nutrient utilization in chicken diets. Objective: The objective is to optimize phytase production via solid-state fermentation, characterize purified phytase properties, and assess its impact on nutrient utilization in chicken diets. Through these objectives, we aim to deepen understanding of phytase's role in poultry nutrition and contribute to more efficient feed formulations for improved agricultural outcomes. Methodology: We utilized solid-state fermentation with Pichia kudriavzeviiFSMP-Y17 yeast on orange peel substrate, optimizing variables like temperature, pH, incubation time, and supplementing with glucose and ammonium sulfate. Following fermentation, we purified the phytase enzyme using standard techniques, characterizing its properties, including molecular weight, optimal temperature and pH, substrate affinity, and kinetic parameters. Results: The optimized conditions yielded a remarkable phytase yield of 7.0 U/gds. Following purification, the enzyme exhibited a molecular weight of 64 kDa and displayed optimal activity at 55 °C and pH 5.5, with kinetic parameters (Km = 3.39 × 10–3M and a Vmaxof 7.092 mM/min) indicating efficient substrate affinity. Conclusion: The addition of purified phytase to chicken diets resulted in significant improvements in nutrient utilization and overall performance, including increased feed intake, improved feed conversion ratio, enhanced bird growth, better phosphorus retention, and improved egg production and quality. By addressing challenges associated with phytate-rich diets, such as reduced nutrient availability and environmental pollution, phytase utilization promotes animal welfare and sustainability in poultry production.

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In the current study, the phytochemical composition and biological activity (antimicrobial, antioxidant, antigenotoxic, and antimutagenic) of different leaf extracts of green tea (Camellia Sinensis) were investigated. Maximum total polyphenol content (17.12 ± 0.02), total flavonoid content (16.18 ± 0.03), antioxidant activity (DPPH) to scavenge free radicals (95.9%) and highest antimicrobial activity against Escherichia coliand Staphylococcus aureuswith a minimum inhibitory concentration value of 3.12 mg/ml and a 26 mm zone of inhibition were recorded for the methanolic extract. The antigenotoxic potential of various extracts of C. sinensisat a concentration of 1000 µg/ml reduced DNA damaged by 37% against Cd-induced genotoxicity as indicated by tail moment (7.9 ± 0.4) during comet assay. Antimutagenic potential of methanolic extracts showed a mutagenic inhibition of 52% against sodium azide mutagen in TA98 strain (+ S9) during the ames test. Gas chromatography–mass spectrometry analysis of methanolic extract showed the presence of a number of compounds The above findings suggest the potential application of C. sinensismethanol extract in food and the health business, and to meet expanding human requirements.

AbstractThe current study was performed to analyse the phytochemical composition, in vitroantioxidant and α-amylase inhibitory activities of the essential oil separated from Curcuma caesiaRoxb. (black turmeric) rhizomes. The essential oil of Curcuma caesia(C. caesia) rhizomes was separated by hydrodistillation technique. Further, essential oil was subjected to GC-MS and FTIR analysis for chemical analysis. Additionally, rhizome powder was investigated for nutritional content using standard reported methods. Subsequently, antioxidant potential of essential oil was analysed using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay followed by α-amylase inhibitory assay. Results of the study suggested the presence of various important compound viz. curzerenone (29.78%), α-Bulnesene (14.43%), eucalyptol (13.32%), curzerene (4.88%), and camphor (4.71%), respectively. Similarly, potent antioxidant and α-amylase inhibitory activities were observed in oil. It was concluded from the present work that essential oil of C. caesiarhizomes contains many therapeutic useful aromatic bioactive and nutritional components. Additionally, essential oil of C. caesiarhizomes exhibits profound antioxidant and α-amylase inhibitory activities.

In this article, we present a physics-based model for drain current calculation in delta ( $\delta $ )-doped $\beta $ -(AlxGa1−x)2O3/Ga2O3 heterostructure field-effect transistor (HFET). The presented model also takes into account the effect of parallel conduction in the $\beta $ -(AlxGa1−x)2O3 layer at higher gate voltages ( ${V}_{\text {g}}$ ). At gate voltage below parallel pinch-off voltage ( ${V}_{\text {gop}}$ ), drain current ( ${I}_{\text {2deg}}$ ), primarily due to the two dimensional electron gas (2DEG) charge density, is modeled. At gate voltages beyond ${V}_{\text {gop}}$ , the model for V-shaped charge density ( ${n}_{\text {par}}$ ) in $\beta $ -(AlxGa1−x)2O3 layer is first developed, which is further used to model the secondary current ( ${I}_{\text {par}}$ ) in this layer. Then, the net drain current ( ${I}_{\text {d}}$ ) is the summation of both current at different gate voltages. The obtained model for ${I}_{\text {d}}$ demonstrates a good accuracy with different experimental data, thus validating the model. Hence, the proposed models will be very useful for predicting device current characteristics for various applications.

Maintaining body temperature is calorically expensive for endothermic animals1. Mammals eat more in the cold to compensate for energy expenditure2, but the neural mechanism underlying this coupling is not well understood. Through behavioural and metabolic analyses, we found that mice dynamically switch between energy-conservation and food-seeking states in the cold, the latter of which are primarily driven by energy expenditure rather than the sensation of cold. To identify the neural mechanisms underlying cold-induced food seeking, we used whole-brain c-Fos mapping and found that the xiphoid (Xi), a small nucleus in the midline thalamus, was selectively activated by prolonged cold associated with elevated energy expenditure but not with acute cold exposure. In vivo calcium imaging showed that Xi activity correlates with food-seeking episodes under cold conditions. Using activity-dependent viral strategies, we found that optogenetic and chemogenetic stimulation of cold-activated Xi neurons selectively recapitulated food seeking under cold conditions whereas their inhibition suppressed it. Mechanistically, Xi encodes a context-dependent valence switch that promotes food-seeking behaviours under cold but not warm conditions. Furthermore, these behaviours are mediated by a Xi-to-nucleus accumbens projection. Our results establish Xi as a key region in the control of cold-induced feeding, which is an important mechanism in the maintenance of energy homeostasis in endothermic animals.

AbstractProtein function is encoded in its sequence, manifested in its three-dimensional structure, and facilitated by its dynamics. Studies have suggested that protein structures with higher sequence similarity could have more similar patterns of dynamics. However, such studies of protein dynamics within and across protein families typically rely on coarse-grained models, or approximate metrics like crystallographic B-factors. This study uses µs scale molecular dynamics (MD) simulations to explore the conservation of dynamics among homologs of ∼50 kDa N-terminal module of Spt16 (Spt16N). Spt16N from Saccharomyces cerevisiae(Sc-Spt16N) and three of its homologs with 30–40% sequence identities were available in the PDB. To make our data-set more comprehensive, the crystal structure of an additional homolog (62% sequence identity with Sc-Spt16N) was solved at 1.7 Å resolution. Cumulative MD simulations of 6 µs were carried out on these Spt16N structures and on two additional protein structures with varying degrees of similarity to it. The simulations revealed that correlation in patterns of backbone fluctuations vary linearly with sequence identity. This trend could not be inferred using crystallographic B-factors. Further, normal mode analysis suggested a similar pattern of inter-domain (inter-lobe) motions not only among Spt16N homologs, but also in the M24 peptidase structure. On the other hand, MD simulation results highlighted conserved motions that were found unique for Spt16N protein, this along with electrostatics trends shed light on functional aspects of Spt16N.Communicated by Ramaswamy H. Sarma.

This work demonstrates the influence of alternative edge passivation via H/F on the electronic and magnetic characteristics of gallium nitride nanoribbons (GaNNRs). For this study, the first-principles density functional theory (DFT) and non-equilibrium green function (NEGF) frameworks are deployed. Our study demonstrates that the selective edge passivation with F/H zigzag GaN nanoribbon (NR) is a strong contender for spintronics due to its half-metallic property under specific conditions. Various nano-configurations for the H/F ZGaNNRs passivation are investigated here. Thermodynamically, most stable configuration is alternate fluorinated F-GaN-F NR. Further, the negative differential resistance (NDR) behavior is also reported along with the perfect spin-filtering properties. This study paves the way to employ these 2-D nanostructures-based devices for spin filters, spin logic switches, and steep switching nanoelectronic devices.

Given the environmental pollution caused by petroleum-based plastics, finding alternative substitutes for sustainability has become critical. Polyhydroxybutyrate (PHB), a storage food material that is accumulated by several bacteria, is biodegradable, safe, environment friendly and comparable to conventional plastics. However, scale-up is an issue due to high production cost. Substrate replacement using renewable, plentiful, sustainable and low-cost carbon sources derived from industrial waste facilitates waste reduction, while also enabling the synthesis of value-added products. In this context, inexpensive pulp and paper industrial waste as carbon source was exploited for production of PHB by using previously isolated (Source: hot springs of Manikarn, Himachal Pradesh, India) thermophilic bacteria Bacillus sonorensisNAM5 under optimized conditions in a fermenter. Production was done in a fermenter under optimized conditions (72 h of incubation at 50 °C temperature and 7 pH) to enhance the accumulation of PHB. The bacterial strain was able to produce 5.28 ± 0.11 g L−1after 72 h of growth without any carbon and nitrogen source supplementation to the industrial effluent. The culture accumulated 66% PHB of cell dry weight (CDW). The produced polymer was characterized through FTIR, NMR and TGA. Additionally, bacteria-treated industrial wastewater was used for phytotoxicity assay on agriculturally important crops such as wheat, maize and mung, which exhibited considerable difference in growth parameters.

Background: The extent of natural salt-laden groundwaters used for irrigation is increasing worldwide, which is a fast-emerging threat to agroecosystems and global food security. The salt buildup in the soil is linked to deteriorated soil chemical, physical, and biological health and decreased land productivity. Alkali waters with high residual sodium carbonate (RSC) is one of the severe poor-quality waters that deteriorate soil. We evaluated soil microbial dynamics and soil health at critical growth stages of rice crop receiving two-decade-long irrigation with three levels of alkali water and two reclamation strategies. These included good-quality water (GQW), alkali water (ALKW) with an RSC concentration of 5 me L⁻1(ALKW1), ALKW with an RSC concentration of 10 me L⁻1(ALKW2), ALKW2 treated to neutralize RSC to 5 me L⁻1using gypsum (CaSO4·2H2O; ALKW2 + GYP), and ALKW2 treated with sulfuric acid (H2SO4; ALKW2 + SA). Eleven microbial parameters were used to develop a soil microbial activity index (SMAI), and eight soil health indicators were correlated with changes in SMAI and crop productivity. Results: The SMAI peaked under good-quality water (GQW) conditions (0.84–0.89), while the lowest values were recorded under ALKW2 (0.06–0.18). Neutralized alkali waters, ALKW2+ SA and ALKW2+ GYP, significantly improved SMAI with corresponding values of 0.25–0.35 and 0.13–0.32, respectively. SMAI across all stages correlated positively (R2= 0.91–0.98) with rice yield. Microbial activity varied with the crop growth stage, peaking at tillering. Gypsum application alone, aimed at neutralizing alkalinity from an RSC of 10 to 5 me L⁻1, proved insufficient in bringing the SMAI up to the ALKW1 (RSC level of 5 me L⁻1). Conclusions: The application of dilute sulfuric acid demonstrated better results in restoring the soil microbial activity index than gypsum amendment; however, sulfuric acid treatment depends on native calcium carbonate (CaCO3) dissolution for its effectiveness. It may not suffice for soil stability improvement in the long term, especially when native CaCO3is low. Therefore, integrating gypsum and dilute sulfuric acid for RSC neutralization is worthwhile; however, further assessment is needed to confirm their combined impact on soil biochemical and physical properties.

Coordination polymers and their subgroup metal–organic frameworks are renowned as the esteemed categories of materials with multifarious properties and possess extensive advantageous applications in the domain of sensing and energy-mimetic applications on account of their expanded surface area, higher charge transfer ability, tunable porous framework, and flexible functionality. This review ruminates on a comprehensive analysis of contemporary outcomes regarding optimized synthetic protocols and structural modulations for various classes of coordination polymers, highlighting their deliberate implications as photoluminescent sensor materials and as energy-mimetic and organoconversion catalysts, along with outlining the significant applicative shortcomings. The additional coordination polymer–assisted exclusive applications have also been discussed, such as the development of ratiometric fluorescent-based probes for specific biological sensing, metal–organic complexes for efficient energy catalysis, and incorporation of bio-inspired photoactive linkers for maximum light harvesting, where the premeditatedly executed frameworks demonstrated augmented results in specialized scientific fields. Finally, a brief overview has been addressed on the effectually applied strategies for assessing electronic mobility, product scalability, and light stability–derived challenges in practical implementations, alongside reviewing the green approaches that expedite sustainable and industrially scalable synthetic pathways consisting potentialities for large-scale outcomes.

The translocation t(14;18) activates BCL2 and is considered the initiating genetic lesion in most follicular lymphomas (FL). Surprisingly, FL patients fail to respond to the BCL2 inhibitor, Venetoclax. We show that mutations and deletions affecting the histone lysine methyltransferase SETD1B (KMT2G) occur in 7% of FLs and 16% of diffuse large B cell lymphomas (DLBCL). Deficiency in SETD1B confers striking resistance to Venetoclax and an experimental MCL-1 inhibitor. SETD1B also acts as a tumor suppressor and cooperates with the loss of KMT2D in lymphoma development in vivo. Consistently, loss of SETD1B in human lymphomas typically coincides with loss of KMT2D. Mechanistically, SETD1B is required for the expression of several proapoptotic BCL2 family proteins. Conversely, inhibitors of the KDM5 histone H3K4 demethylases restore BIM and BIK expression and synergize with Venetoclax in SETD1B-deficient lymphomas. These results establish SETD1B as an epigenetic regulator of cell death and reveal a pharmacological strategy to augment Venetoclax sensitivity in lymphoma.

The regeneration of critical-sized bone defects with biomimetic scaffolds remains clinically challenging due to avascular necrosis, chronic inflammation, and altered osteogenic activity. Two confounding mechanisms, efficacy manipulation, and temporal regulation dictate the scaffold’s bone regenerative ability. Equally critical is the priming of the mesenchymal stromal cells (MSCs) toward lineage-specific differentiation into bone-forming osteoblast, which particularly depends on varied mechanochemical and biological cues during bone tissue regeneration. This study sought to design and develop an optimized osteogenic scaffold, adenosine/epigallocatechin gallate-N,O-carboxymethyl chitosan/collagen type I (AD/EGCG-g-NOCC@clgn I), having osteoinductive components toward swift bone regeneration in a calvarial defect BALB/c mice model. The ex vivofindings distinctly establish the pro-osteogenic potential of adenosine and EGCG, stimulating MSCs toward osteoblast differentiation with significantly increased expression of alkaline phosphatase, calcium deposits, and enhanced osteocalcin expression. Moreover, the 3D matrix recapitulates extracellular matrix (ECM) properties, provides a favorable microenvironment, structural support against mechanical stress, and acts as a reservoir for sustained release of osteoinductive molecules for cell differentiation, proliferation, and migration during matrix osteointegration observed. Evidence from in vivoexperiments, micro-CT analyses, histology, and histomorphometry signify accelerated osteogenesis both qualitatively and quantitatively: effectual bone union with enhanced bone formation and new ossified tissue in 4 mm sized defects. Our results suggest that the optimized scaffold serves as an adjuvant to guide bone tissue regeneration in critical-sized calvarial defects with promising therapeutic efficacy.

OBJECTIVE--To determine altered gene expression profiles in subcutaneous adipose and skeletal muscle from nondiabetic, insulin-resistant individuals compared with insulin-sensitive individuals matched for BMI. RESEARCH DESIGN AND METHODS--A total of 62 non-diabetic individuals were chosen for extremes of insulin sensitivity (31 insulin-resistant and 31 insulin-sensitive subjects; 40 were European American and 22 were African American) and matched for age and obesity measures. Global gene expression profiles were determined and compared between ethnic groups and between insulin-resistant and insulin-sensitive participants individually and using gene-set enrichment analysis. RESULTS--African American and European American subjects differed in 58 muscle and 140 adipose genes, including many inflammatory and metabolically important genes. Peroxisome proliferator-activated receptor [gamma] cofactor 1A (PPARGC1A) was 1.75-fold reduced with insulin resistance in muscle, and fatty acid and lipid metabolism and oxidoreductase activity also were down-regulated. Unexpected categories included ubiquitination, citrullination, and protein degradation. In adipose, highly represented categories included lipid and fatty acid metabolism, insulin action, and cell-cycle regulation. Inflammatory genes were increased in European American subjects and were among the top Kyoto Encyclopedia of Genes and Genomes pathways on gene-set enrichment analysis. FADS1, VEGFA, PTPN3, KLF15, PER3, STEAP4, and AGTR1 were among genes expressed differentially in both adipose and muscle. CONCLUSIONS--Adipose tissue gene expression showed more differences between insulin-resistant versus insulin-sensitive groups than the expression of genes in muscle. We confirm the role of PPARGC1A in muscle and show some support for inflammation in adipose from European American subjects but find prominent roles for lipid metabolism in insulin sensitivity independent of obesity in both tissues., The international obesity epidemic has been accompanied by a rapidly increasing prevalence of type 2 diabetes across ethnic groups (1). The connection between obesity and impaired glucose homeostasis is indisputable. [...]

Background The impact of cancer on health-related quality of life (HRQOL) is poorly understood because of the lack of baseline HRQOL status before cancer diagnosis. To our knowledge, this is the first population-based study to quantify the nature and extent of HRQOL changes from before to after cancer diagnosis for nine types of cancer patients and to compare their health with individuals without cancer. Methods The Surveillance, Epidemiology, and End Results cancer registry data were linked with the Medicare Health Outcomes Survey (MHOS) data; data were collected from Medicare beneficiaries who were aged 65 years and older from 1998 through 2003. Cancer patients (n = 1432; with prostate, breast, colorectal, lung, bladder, endometrial, or kidney cancers; melanoma; or non-Hodgkin lymphoma [NHL]) were selected whose first cancer diagnosis occurred between their baseline and follow-up MHOS assessments. Control subjects without cancer (n = 7160) were matched to cancer patients by use of propensity scores that were estimated from demographics and comorbid medical conditions. Analysis of covariance models were used to estimate changes in HRQOL as assessed with the Medical Outcomes Study Short Form-36 survey (mean score = 50, SD = 10). All statistical tests were two-sided. Results Patients with all cancer types (except melanoma and endometrial cancer) reported statistically significant declines in physical health (mean scores: prostate cancer = -3.4, 95% confidence interval [Cl] = -2.5 to -4.2; breast cancer = 3.5, 95% CI = 2.5 to -4.5; bladder cancer = 4.3, 95% CI = 2.5 to -6.1; colorectal cancer = -4.4, 95% Cl = -3.3 to -5.5; kidney cancer = -5.7, 95% Cl = -3.2 to -8.2; NHL = -6.7, 95% Cl = -4.4 to -9.1; and lung cancer = -7.5, 95% CI = 5.9 to -9.2) compared with the control subjects (mean score = -1.8, 95% Cl = -1.6 to -2.0) (all P< .05). However, only lung (mean score = -5.4, 95% Cl = -3.5 to -7.2), colorectal (mean score = -3.5, 95% Cl = -2.2 to -4.7), and prostate (mean score = -2.8, 95% Cl = -1.8 to -3.7) cancer patients showed statistically significant decreases in mental health relative to the mean change of the control subjects (mean score = -1.2, 95% Cl = -0.9 to -1.4) (all P< .05). Conclusion These findings provide validation of the specific deleterious effects of cancer on HRQOL and an evidence base for future research and clinical interventions aimed at understanding and remediating these effects.

In cancer observational studies, differences between groups on confounding variables may have a significant effect on results when examining health outcomes. This study demonstrates the utility of propensity score matching to balance a non-cancer and cancer cohort of older adults on multiple relevant covariates. This approach matches cases to controls on a single indicator, the propensity score, rather than multiple variables. Results indicated that propensity score matching is an efficient and useful way to create a matched case-control study out of a large cohort study, and allows confidence in the strength of the observed outcomes of the study., INTRODUCTION Observational research is often used to understand the burden of cancer on patients and survivors, and allows scientists to examine relevant factors that may provide the framework for future [...]

Health plan member survey and cancer registry data were analyzed to understand differences in health-related quality of life (HRQOL) among cancer survivors and those without a cancer diagnosis enrolled in Medicare managed care. HRQOL was measured by the physical component summary score (PCS) and mental component summary score (MCS) of the Medical Outcomes Study SF-36®, version 1.0. Cancer survivors enrolled in Medicare managed care have lower PCS and MCS scores than those enrollees who have never been diagnosed with cancer. PCS scores are worse than the MCS scores, and lowest for cancer survivors who are Hispanic, Medicaid enrollees, and those who have low income or education. HRQOL disparities are greatest among cancer survivors diagnosed with lung cancer and those with multiple primary cancer diagnoses. The influence of these variables persists when controlling for multiple variables including comorbidity status. Health plans should focus on addressing these disparities., INTRODUCTION Advances in cancer screening and treatment enable many elderly cancer patients to survive their diagnosis and live much longer than their peers 10-20 years ago. However, increased survival brings [...]

Background: Despite extensive literature, the diagnostic role of D-dimer for deep venous thrombosis (DVT) of pulmonary embolism (PE) remains unclear, reflecting multiple D-dimer assays and concerns about differing sensitivities and variability. Purpose: To systematically review trials that assessed sensitivity, specificity, likelihood ratios, and variability among D-dimer assays. Data Sources: Studies in all languages were identified by searching PubMed from 1983 to January 2003 and EMBASE from 1988 to January 2003. Study Selection: The researchers selected prospective studies that compared D-dimer with a reference standard. Studies of high methodologic quality were included in the primary analyses; sensitivity analysis included additional weaker studies. Data Extraction: Two authors collected data on study-level factors: D-dimer assay used, cutoff value, and whether patients had suspected DVT or PE. Data Synthesis: For DVT, the enzyme-linked immunosorbent assay (ELISA) and quantitative rapid ELISA dominate the rank order for these values: sensitivity, 0.96 (95% confidence limit [CL], 0.91 to 1.00), and negative likelihood ratio, 0.12 (CL, 0.04 to 0.33); and sensitivity, 0.96 (CL, 0.90 to 1.00), and negative likelihood ratio, 0.09 (CL, 0.02 to 0.41), respectively. For PE, the ELISA and quantitative rapid ELISA also dominate the rank order for these values: sensitivity, 0.95 (CL, 0.85 to 1.00), and negative likelihood ratio, 0.13 (CL, 0.03 to 0.58); and sensitivity, 0.95 (CL, 0.83 to 1.00), and negative likelihood ratio, 0.13 (CL, 0.02 to 0.84), respectively. The ELISA and quantitative rapid ELISA have negative likelihood ratios that yield a high certainty for excluding DVT or PE. The positive likelihood values, which are in the general range of 1.5 to 2.5, do not greatly increase the certainty of diagnosis. Sensitivity analyses do not affect these findings. Limitations: Although many studies evaluated multiple D-dimer assays, findings are based largely on indirect comparisons of test performance characteristics across studies. Conclusion: The ELISAs in general dominate the comparative ranking among the D-dimer assays for sensitivity and negative likelihood ratio. For excluding PE of DVT, a negative result on quantitative rapid ELISA is as diagnostically useful as a normal lung scan or negative duplex ultrasonography finding.

Purpose: This study attempts to determine the incidence of established acute pulmonary embolism (PE) in a community/teaching general hospital. Background: The reported incidence of objectively diagnosed acute PE among hospitalized [...]

The recent development of solvent- and polymer-based brain-clearing techniques has advanced our ability to visualize the mammalian nervous system in three dimensions. However, it remains challenging to image the mammalian body en bloc. Here we developed HYBRiD (hydrogel-based reinforcement of three-dimensional imaging solvent-cleared organs (DISCO)), by recombining components of organic- and polymer-based clearing pipelines. We achieved high transparency and protein retention, as well as compatibility with direct fluorescent imaging and immunostaining in cleared mammalian bodies. Using parvalbumin- and somatostatin-Cre models, we demonstrated the utility of HYBRiD for whole-body imaging of genetically encoded fluorescent reporters without antibody enhancement of signals in newborn and juvenile mice. Using K18-hACE2 transgenic mice, HYBRiD enabled perfusion-free clearing and visualization of SARS-CoV-2 infection in a whole mouse chest, revealing macroscopic and microscopic features of viral pathology in the same sample. HYBRiD offers a simple and universal solution to visualize large heterogeneous body parts or entire animals for basic and translational research.

The shared buffer (SB) window policy achieves the maximum throughput among all the four window sizes, considering that in this method, one input can send one or more packets within the given time slot provided that the concerned output ports have not been appointed to any other inputs. In the other three window policies, namely dedicated buffer, dedicated buffer with pointers and dedicated split buffers, an input can transmit at most one packet in a given time slot, despite a free output and an assigned cell for that output in the input queue.

The Indian economy is growing at one of the fastest rates in the world. Energy demands in India have consequently risen enormously and the government is promoting power station projects [...]

Reliable, fast, and affordable diagnosis for tuberculosis (TB) remains a challenge to reduce disease incidence in resource-poor countries. Tests based on nucleotide sequences that are signature to Mycobacterium tuberculosishave the potential to make a positive impact on case detection rates, which can eventually help control TB. Using extensive comparative bioinformatics approach, we mined the genome for M. tuberculosis–specific genes and identified four genes so-called signature sequence (SS). With <25% homology with other known genes/proteins of mycobacterial/nonmycobacterial origin in various databases, these SS genes are ideal targets for species-specific identification. Sputum from suspected patients was liquefied using novel complete liquefying reagent, and DNA was isolated. Samples from patients (n = 417), reporting to TB clinics at two different hospitals, which met our inclusion criteria, were collected for this study. A small number (n = 143) was used for initial standardization, and the remaining patient samples (n = 274) were evaluated by SS and compared with smear microscopy, GeneXpert, culture, and clinical outcome. An overwhelming sensitivity of 97.0%, significantly higher than GeneXpert (95.0%), was seen. SS could pick all smear-negative, but culture-positive samples, along with other culture-negative samples; some of the latter were declared clinically positive. Our results yielded superior sensitivity and specificity through conventional PCR.

The current decade witnesses the regenerative potential of Stem Cells (SCs) based lifesaving therapies for the treatment of various disease conditions. Human teeth act as a reservoir for SCs that exist in high abundance in baby, wisdom, and permanent teeth. The collection of Stem cells from Human Exfoliated Deciduous teeth (SHED) is considered a simple process as it offers the convenience of little or no pain. In comparison to the SCs from dental or bone marrow or other tissues, the SHED offers the benefit of higher cellular differentiation and proliferation. Massive in vitro and in vivo studies reveal the regenerative potential of SHED in the engineering of the dental pulp tissue, neuronal tissue, root, bio root, cardiovascular tissues, lymphatic tissues, renal tissues, dermal tissues, hepatic tissues, and bone tissues. The current review describes the methods of collection/ isolation/storage, various biomarkers, and types of SHED. This review highlights the regenerative potential of SHED in the engineering of different tissues of the human body. As per the available research evidence, the present study supports that SHED may differentiate into the endothelial cells, neurons, odontoblasts, pancreatic β-cells, hepatocytes, renal cells, fibroblasts, osteoblasts, and many other types of cells. The present study recommends that further clinical trials are required before the clinical application of SHED-based therapies.

A technology for systemic and repeated administration of osteogenic factors for orthopedic use is an unmet medical need. Lactoferrin (∼80 kDa), present in milk, is known to support bone growth. We discovered a lactoferrin-mimetic peptide, LP2 (an 18-residue fragment from the N-terminus of the N-lobe of human lactoferrin), which self-assembles into a nano-globular assembly with a β-sheet structure in an aqueous environment. LP2 is non-hemolytic and non-cytotoxic against human red blood cells and 3T3 fibroblasts, respectively, and appreciably stable in the human serum. LP2 through the bone morphogenetic protein-dependent mechanism stimulates osteoblast differentiation more potently than the full-length protein as well as the osteoblastic production of osteoprotegerin (an anti-osteoclastogenic factor). Consequently, daily subcutaneous administration of LP2 to rats and rabbits with osteotomy resulted in faster bone healing and stimulated bone formation in rats with a low bone mass more potently than that with teriparatide, the standard-of-care osteogenic peptide for osteoporosis. LP2 has skeletal bioavailability and is safe at the 15× osteogenic dose. Thus, LP2 is a novel peptide that can be administered systemically for the medical management of hard-to-heal fractures.

Purpose: To determine the prevalence of proximal deep venous thrombosis (DVT) in a general hospital. Background: In spite of the importance of proximal DVT, its prevalence in hospitalized patients has [...]

Background: Darolutamide is recently approved for the treatment of non-metastatic castrate resistance prostate cancer. Hitherto, no stereoselective pharmacokinetic data have been published pertaining to darolutamide and its diastereomers in animals or humans. The key aims of the experiment were to examine darolutamide, S,S-darolutamide and S,R-darolutamide with respect to (a) assessment of in vitro metabolic stability and protein binding and (b) characterization of in vivo oral and intravenous pharmacokinetics in mice. Methods: In vitro (liver microsomes stability and protein binding) and in vivo experiments (oral/intravenous dosing to mice) were carried out using darolutamide, S,S-darolutamide and S,Rdarolutamide. Besides, tissue levels of darolutamide, S,S-darolutamide and S,R-darolutamide were measured following oral and intravenous dosing. Appropriate plasma/tissue samples served to determine the pharmacokinetics of various analytes in mice. Liquid chromatography in tandem with mass spectrometry procedures enabled the delineation of the plasma pharmacokinetics, in vitro and tissue uptake data of the various analytes. Results: Chiral inversion was absent in the metabolic stability study. However, darolutamide showed profound stereoselectivity (S,S-darolutamide greater than S,R-darolutamide) after either intravenous or oral dosing. S,R-darolutamide but not S,S-darolutamide showed conversion to its antipode post oral and intravenous dosing to mice. Regardless of oral or intravenous dosing, active keto darolutamide formation was evident after administration of darolutamide, S,S-darolutamide or S,R- darolutamide. Tissue data supported the observations in plasma; however, tissue exposure of darolutamide, S,Sdarolutamide and S,R-darolutamide was much lower as compared to plasma. Conclusion: In lieu of the human pharmacokinetic data, although the administration of diastereomeric darolutamide was justified, it is proposed to delineate the clinical pharmacokinetics of S,Rdarolutamide and S,S-darolutamide relative to darolutamide in future clinical pharmacology studies.

Background & Objective: Networks on chip are being developed as a communication infrastructure in the design of multiprocessor SOCs. With the reduction in feature size, transient faults on the links are becoming a major issue on the performance of NOCs. Methods: In this paper, two fault-tolerant algorithms are proposed. In the first algorithm, a faulty link tolerant algorithm is designed which by measuring network loads on the links will reduce transient faults and balances the load. To address the effect of hardware faults, fault and congestion controlled algorithm is designed that not only control the congestion, but also the faults on both links and the nodes. Results: The packet size is taken as 8 flits and data width of 32 bits are considered for all switches. Input buffers are having 8 slots for storing data. The simulations are carried over two synthetic traffic scenarios that are, hotspot and transpose. Conclusion: The proposed strategies are evaluated on two different synthetic traffic patterns and the results so obtained shows better network and hardware performance of both the routing in comparison with non-fault-tolerant routing.

Activation of invariant natural killer T (iNKT) cells by α-galactosylceramides (α-GalCers) stimulates strong immune responses and potent anti-tumor immunity. Numerous modifications of the glycolipid structure have been assessed to derive activating ligands for these T cells with altered and potentially advantageous properties in the induction of immune responses. Here, we synthesized variants of the prototypical α-GalCer, KRN7000, with amide-linked phenyl alkane substitutions on the C4″-position of the galactose ring. We show that these variants have weak iNKT cell stimulating activity in mouse models but substantially greater activity for human iNKT cells. The most active of the C4″-amides in our study showed strong anti-tumor effects in a partially humanized mouse model for iNKT cell responses. In silicoanalysis suggested that the tether length and degree of flexibility of the amide substituent affected the recognition by iNKT cell antigen receptors of the C4″-amide substituted glycolipids in complex with their antigen presenting molecule CD1d. Our findings establish the use of stable C4″-amide linked additions to the sugar moiety for further exploration of the immunological effects of structural modifications of iNKT cell activating glycolipids and highlight the critical need for more accurate animal models to assess these compounds for immunotherapeutic potential in humans.

ABSTRACTThe Boxing Day tsunami of 26 December 2004 wreaked substantial havoc along the east coast of India. Repetition of an event with similar or greater magnitude will undoubtedly affect the coastal regions of India with much more severity. Precise estimation of tsunami wave heights along the coastal belts would be very important for a Risk Based Decision Making (RBDM) system. Kalpakkam located in the east coast of India, a region of strategic national interest is chosen for this study. In this study, the relevant earthquake data was extracted from NOAA-NCEI for the geographical region bounded between 92.96° E, 14.14° N to 105.75° E, 5.89°N covering regions such as Sumatra Fault, Java Trench, and Spreading Ridge in the Andaman Sea. This study examined 89 earthquake events from 1770 to 2013. The preliminary data on significant earthquake parameters viz; moderate damage, death toll exceeding a total of 10, earthquake magnitude of 7.5 or greater, modified Mercalli intensity of 10 or greater, earthquakes that generated a tsunami were subjected to Peak-over-Threshold (POT) analysis using Generalized Pareto Distribution (GPD) for varying thresholds. Thereafter, the study performed computations of five different earthquake magnitudes corresponding to return periods of 10, 102, 103, 104and 105 years. Using Mansinha deformation model and SWAN code, tsunami simulations were carried out for all the five different scenarios. In addition five different locations were identified to estimate the tsunami heights considering Kalpakkam as the nodal point. With availability of accurate near-shore bathymetry, a more detailed study can be attempted for coastal inundation characteristics arising from future tsunamigenic events.

Physical particles can serve as critical abiotic factors that structure the ecology of microbial communities. For non-human vertebrate gut microbiomes, fecal particle size (FPS) has been known to be shaped by chewing efficiency and diet. However, little is known about what drives FPS in the human gut. Here, we analyzed FPS by laser diffraction across a total of 76 individuals and found FPS to be strongly individualized. Contrary to our initial hypothesis, a behavioral intervention with 41 volunteers designed to increase chewing efficiency did not impact FPS. Dietary patterns could also not be associated with FPS. Instead, we found evidence that human and mouse gut microbiomes shaped FPS. Fecal samples from germ-free and antibiotic-treated mice exhibited increased FPS relative to colonized mice. In humans, markers of longer transit time were correlated with smaller FPS. Gut microbiota diversity and composition were also associated with FPS. Finally, ex vivoculture experiments using human fecal microbiota from distinct donors showed that differences in microbiota community composition can drive variation in particle size. Together, our results support an ecological model in which the human gut microbiome plays a key role in reducing the size of food particles during digestion. This finding has important implications for our understanding of energy extraction and subsequent uptake in gastrointestinal tract. FPS may therefore be viewed as an informative functional readout, providing new insights into the metabolic state of the gut microbiome.Graphical AbstractAnalysis of fecal particle size (FPS) in humans and mice shows relationships with short-chain fatty acids, fecal moisture content, and microbiome composition and diversity. Our study included two cohorts of healthy adults (total n= 76), with one cohort undergoing an intervention designed to increase chewing (n= 41). Stool samples were used in follow-up ex vivoculture experiments. We also analyzed fecal samples from specific pathogen-free, germ-free, and antibiotic-treated mice. We quantified FPS in human and mouse samples by laser diffraction. Microscopy images show examples of low-FPS and high-FPS samples, with 100 μm scale bar. Across individuals, higher FPS was associated with greater total short-chain fatty acids, which was driven by increases in acetate and propionate, whereas low-FPS samples tended to have higher isobutyrate, isovalerate, and valerate. Fecal moisture content, a proxy for gastrointestinal transit time, was greater in high-FPS samples, suggesting a shorter transit time in these samples. Fecal microbiome α-diversity was lower in high-FPS samples, and composition of specific microbiome taxa differed by FPS as well. By contrast, our study found no evidence for a relationship between FPS and diet or chewing in humans.

Dimeric and multimeric aggregates of a model metalloporphyrin, zinc tetraphenylporphyrin (ZnTPP), have been produced in a controlled manner by incrementally increasing the water content of dilute aqueous ethanol solutions. Steady state absorption, fluorescence emission, and fluorescence excitation spectra have been measured to identify the aggregates present as a function of solvent composition. The dynamics of the excited states of the aggregates produced initially by excitation in the Soret region have been measured by ultrafast fluorescence upconversion techniques. Only the monomer produces measurable emission from S2with a picosecond lifetime; all Soret-excited aggregates, including the dimer, decay radiationlessly on a femtosecond time scale. The S1state is the only significant product of the radiationless decay of the S2state of the excited monomer, and the aggregates also produce substantial quantum yields of S1fluorescence when initially excited in the Soret region. The resulting fluorescent aggregates all decay on a subnanosecond time scale, likely by a mechanism that involves dissociation of the excited monomer from the excitonic multimer. The ZnTPP dimers excited at their ground state geometries in the Soret region exhibit a dynamic behavior that is quite different from those produced following noncoherent triplet–triplet annihilation under the same conditions. The important implications of these observations in determining the aggregation conditions promoting efficient photon upconversion by excitonic annihilation in a variety of media are thoroughly discussed.

Table of Contents Abstract Introduction Case Report & Management Discussion References Abstract Malignant fibrous histiocytoma as a primary renal tumor is rare. It is clinically and radiologically indistinguishable from a [...]

Studies over the last decade have transformed our previously simplistic view ofmicrobes, having only a pathogenic role in disease to a more robust understandingthat they are critical for maintaining human health. Indeed, our microbiota—thecollection of commensal organisms that live in and on each of us—contributes tonearly every facet of host physiology, from ontogeny of the immune system toneurological function to metabolism. Although the specific details of thesehost–microbe interactions are still being elucidated for most diseases, the couplingof clinical samples with animal models of disease have provided key insights. Thisreview provides some general background on the microbiota, highlights a few examplesof how the microbiota influences diseases of the central nervous system, and providesa perspective for how these findings may be clinically translatable.

Shankhpushpiis an Ayurvedic drug, widely used for its actions on the central nervous system, especially to improve intellect and boost memory. Four botanicals viz. Canscora decussataSchult. (CD), Clitorea ternateaLinn. (CT), Convolvulus pluricaulisChoisy. (CP) and Evolvulus alsinoidesLinn. (EA) are considered as sources of Shankhpushpiby Indian practitioners on the basis of their morphological descriptions given in ancient texts.

Parthenium hysterophorous, a widespread weed in India, contributes a substantial amount of lignocellulosic biomass. The key objective of this study is to evaluate the feasibility of producing xylanase enzyme from P. hysterophorusweed biomass using the fungus Aspergillus niger. The impact of various physiological factors was confirmed through a two-step approach: first, a one-factor-at-a-time (OFAT) investigation, and subsequently, employing the RSM-based CCD method in statistical design. This research revealed that the RSM-based model led to the optimization of enzyme activity, resulting in a value of 2098.08 IU/gds for xylanase. This was achieved with an incubation time of 4.5 days, a medium pH of 6, and a cultivation temperature of 32.5 °C. Additionally, a pretreatment involving 1% NaOH and a 30-min autoclave treatment was found to alter the chemical composition of lignocellulose substrates (cellulose 43.87% and xylan 28.7%), thereby enhancing the efficiency of enzymatic hydrolysis. Moreover, fermentable sugars were produced by autoclave-assisted alkali pretreatment (NaOH-1.0% w/v) at rates of 219.6 ± 2.05 mg/gds−1by utilizing the crude xylanase from A. nigerand 291.3 ± 1.2 mg/gds−1from commercial xylanase enzyme. Our study revealed that P. hysterophorusserved as a viable and affordable substrate for fermentable sugar liberation, and xylanase is a rate-limiting enzyme in enzymatic saccharification.