Molecular determinants of Ras-mTORC2 signaling.

Recent research has identified the mechanistic Target of Rapamycin Complex 2 (mTORC2) as a conserved direct effector of Ras proteins. While previous studies suggested the involvement of the Switch I (SWI) effector domain of Ras in binding mTORC2 components, the regulation of the Ras-mTORC2 pathway is not entirely understood. In Dictyostelium, mTORC2 is selectively activated by the Ras protein RasC, and the RasC-mTORC2 pathway then mediates chemotaxis to cAMP and cellular aggregation by regulating the actin cytoskeleton and promoting cAMP signal relay. Here, we investigated the role of specific residues in RasC's SWI, C-terminal allosteric domain, and hypervariable region (HVR) related to mTORC2 activation. Interestingly, our results suggest that RasC SWI residue A31, which was previously implicated in RasC-mediated aggregation, regulates RasC's specific activation by the Aimless RasGEF. On the other hand, our investigation identified a crucial role for RasC SWI residue T36, with secondary contributions from E38 and allosteric domain residues. Finally, we found that conserved basic residues and the adjacent prenylation site in the HVR, which are crucial for RasC's membrane localization, are essential for RasC-mTORC2 pathway activation by allowing for both RasC's own cAMP-induced activation and its subsequent activation of mTORC2. Therefore, our findings revealed new determinants of RasC-mTORC2 pathway specificity in Dictyostelium, contributing to a deeper understanding of Ras signaling regulation in eukaryotic cells.

Role of Annealing with Electric Field Toward Improvement of Ferroelectric and Electroactive Properties of PVDF Copolymer and Terpolymer Thin Films.

The present study elucidates the role of annealing with electric field on lamellar crystalline structure and molecular orientation of polymer chains in ferroelectric copolymer (P(VDF-TrFE)) and ferroelectric terpolymer (P(VDF-TrFE-CFE)) spin-coated thin films. The ferroelectric polymer thin films annealed under an electric field support the growth of nanostructure with an "edge-on" lamellar crystalline structure having in-plane molecular chain orientation. The poled P(VDF-TrFE) thin films have higher remnant polarization (Pr) ≈6.2 µC cm-2 and saturation polarization (Ps) ≈8.2 µC cm-2 at an applied electric field of 250 MV/m compared to unpoled thin films having Pr ≈4.7 and Ps ≈6.2 µC cm-2. Also, poled P(VDF-TrFE) thin films show lower coercive field (Ec) ≈94 MV/m compared to an unpoled thin film having Ec ≈105 MV/m. Similarly, poled PVDF-TrFE-CFE thin film shows better ferroelectric properties having Pr ≈0.4 and Ps ≈5.7 µC cm-2 at an applied electric field of 200 MV m-1 compared to unpoled thin films having Pr ≈0.4 and Ps ≈4.1 µC cm-2. The storage energy efficiency of unpoled and poled P(VDF-TrFE-CFE) thin films is measured to be ≈75% and 80%. Annealing of ferroelectric P(VDF-TrFE) polymer thin films under an electric field demonstrates improved ferroelectric and electroactive properties.

Genome-wide association studies of salinity tolerance in local aman rice.

The present study aimed to identify and characterize new sources of salt tolerance among 94 rice varieties from varied geographic origins. The genotypes were divided into five groups based on their morphological characteristics at both vegetative and reproductive stages using salinity scores from the Standard Evaluation System (SES). The experiment was designed as per CRD (Completely Randomized Design) with 2 sets of salinity treatments for 8 dS/meter and 12 dS/meter, respectively compared with one non-salinized control set. Using a Soil Plant Analysis Development (SPAD) meter, assessments of the apparent chlorophyll content (greenness) of the genotypes were done to comprehend the mechanism underlying their salt tolerance.  To evaluate molecular genetic diversity, a panel of 1 K RiCA SNP markers was employed. Utilizing TASSEL 5.0 software, 598 filtered SNPs were used for molecular analysis. Whole-genome association studies (GWAS) were also used to investigate panicle number per plant (pn, tiller number per plant (till), SPAD value (spad), sterility (percent) (str), plant height (ph) and panicle length (pl. It is noteworthy that these characteristics oversee conveying the visible signs of salt damage in rice. Based on genotype data, diversity analysis divided the germplasm groups into four distinct clusters (I, II, III and IV). For the traits studied, thirteen significant marker-trait associations were discovered. According to the phenotypic screening, seven germplasm genotypes namely Koijuri, Asha, Kajal, Kaliboro, Hanumanjata, Akundi and Dular, are highly tolerant to salinity stress. The greenness of these genotypes was found to be more stable over time, indicating that these genotypes are more resistant to stress. Regarding their tolerance levels, the GWAS analysis produced comparable results, supporting that salinity-tolerant genotypes having minor alleles in significant SNP positions showed more greenness during the stress period. The Manhattan plot demonstrated that at the designated significant SNP position, the highly tolerant genotypes shared common alleles. These genotypes could therefore be seen as important genomic resources for accelerating the development and release of rice varieties that are tolerant to salinity.

Experimental observation of Bethe strings.

Almost a century ago, string states-complex bound states of magnetic excitations-were predicted to exist in one-dimensional quantum magnets. However, despite many theoretical studies, the experimental realization and identification of string states in a condensed-matter system have yet to be achieved. Here we use high-resolution terahertz spectroscopy to resolve string states in the antiferromagnetic Heisenberg-Ising chain SrCo2V2O8 in strong longitudinal magnetic fields. In the field-induced quantum-critical regime, we identify strings and fractional magnetic excitations that are accurately described by the Bethe ansatz. Close to quantum criticality, the string excitations govern the quantum spin dynamics, whereas the fractional excitations, which are dominant at low energies, reflect the antiferromagnetic quantum fluctuations. Today, Bethe's result is important not only in the field of quantum magnetism but also more broadly, including in the study of cold atoms and in string theory; hence, we anticipate that our work will shed light on the study of complex many-body systems in general.

Analyzing the morphology and avian ß-defensins genes (AvßD) expression in the small intestine of Cobb500 broiler chicks fed with sodium butyrate.

BACKGROUND: Sodium butyrate is a potential antibiotic growth promoter and has had advantageous effects on the poultry industry. METHODS: Evaluating the effect of sodium butyrate on the intestinal villi and the humoral part of innate immunity of the male Cobb 500 broiler using scanning electron microscopy and quantitative real-time PCR analysis, the control group and treated group of Cobb 500 with SB supplemented received water containing 0.98 mg sodium butyrate. RESULTS: The administration of sodium butyrate changed the villi characters, as the shape changed from tongue to long tongue. They were mainly parallel to each other and long finger-like at the duodenum. The tips of the villi in the control group appeared thin-slight curved with a prominent center in the duodenum, thin rectangular in the jejunum, and ileum in the control group. In contrast, in the treatment group, they changed to thick rectangular in the duodenum and ileum zigzag shape in the jejunum. The epithelium lining of the duodenal villi showed a dome shape, the jejunal villi showed a polygonal shape, and the ileal villi appeared scales-like. The epithelium lining showed irregular microfolds and many different-sized pores, and the treatment group showed islands of long microvilli in the duodenum and solitary long microvilli in the ileum. Real-time PCR of AvBD 1, 2, 10, and 12 significantly (P < 0.01). The better expression of AvBD 1, 2, and 12 was determined in the duodenum, while AvBD 10 was in the jejunum. CONCLUSION: Sodium butyrate enhanced the chicks' growth and small intestine parameters, modified the morphology of the intestinal villi, and improved the humoral part of innate immunity.

Co-impacts of cation type and humic acid on migration of polystyrene microplastics in saturated porous media.

The aging process of microplastics (MPs) could significantly change their physical and chemical characteristics and impact their migration behavior in soil. However, the complex effects of different cations and humic acids (HA) on the migration of aged MPs through saturated media are not clear. In this research, the migration and retention of pristine/aged PSMPs (polystyrene microplastics) under combined effects of cations (Na+, Ca2+) (ionic strength = 10 mM) and HA (0, 5, 15 mg/L) were investigated and analyzed in conjunction with the two-site kinetic retention model and DLVO theory. The findings showed that the aging process accelerated PSMPs migration under all tested conditions. Aged PSMPs were less susceptible to Ca2+ than pristine PSMPs. Under Ca2+ conditions, pristine/aged PSMPs showed higher retention than under Na+ conditions in the absence of HA. Furthermore, under Na+ conditions, the migration of aged PSMPs significantly increased at higher concentrations of HA. However, under Ca2+ conditions, the migration of aged PSMPs decreased significantly at higher concentrations of HA. In higher HA conditions, HA, Ca2+, and PSMPs interact to cause larger aggregations, resulting in the sedimentation of aged PSMPs. The DLVO calculations and two-site kinetic retention models' results showed the detention of PSMPs was irreversible under higher HA conditions (15 mg/L) with Ca2+, and aged PSMPs were more susceptible to clogging. These findings may help to understand the potential risk of migration behavior of PSMPs in the soil-groundwater environment.

Biodegradation and antimicrobial capability-induced heavy metal resistance of the marine-derived actinomycetes Nocardia harenae JJB5 and Amycolatopsis marina JJB11.

Currently, heavy metal-resistant (HMR) marine actinomycetes have attracted much attention worldwide due to their unique capabilities. In this study, 27 marine-derived actinomycetes were isolated from coastal beaches in the Arabian Gulf of Al-Jubail in Saudi Arabia and screened for resistance to 100 mg/L of the heavy metals Cd2+, Cr6+, Cu2+, Fe2+, Pb2+, and Ni2+ using different assay techniques. Six isolates were selected as HMRs, of which two isolates, JJB5 and JJB11, exhibited the highest maximum tolerance concentrations (200- > 300 mg/L). Both isolates were the highest among six-HMR screened for their biodegradation potential of plastics low-density polyethylene, polystyrene, and polyvinyl chloride, recording the highest weight loss (15 ± 1.22 - 65 ± 1.2%) in their thin films. They also showed the highest biodegradability of the pesticides acetamiprid, chlordane, hexachlorocyclohexane, indoxacarb and lindane, indicating promising removal capacities (95.70-100%) for acetamiprid and indoxacarb using HPLC analysis. Additionally, the cell-free filtrate (CFF) of both isolates displayed the highest antimicrobial activity among the six-HMR screened against a variety of microbial test strains, recording the highest inhibition zone diameters (13.76 ± 0.66 - 26.0 ± 1.13 mm). GC‒MS analyses of the ethyl acetate extract of their CFFs revealed the presence of diverse chemical compounds with a multitude of remarkable biological activities. Based on their spore morphology and wall-chemotype, they were assigned to the nocardioform-actinomycetes. Furthermore, their phenotypic characteristics, together with 16S rRNA gene sequencing (OR121525-OR121526), revealed them as Nocardia harenae JJB5 and Amycolatopsis marina JJB11. Our results suggest that marine HMR actinomycetes are promising candidates for various biotechnological applications.

Spinon Heat Transport in the Three-Dimensional Quantum Magnet PbCuTe_{2}O_{6}.

Quantum spin liquids (QSLs) are novel phases of matter which remain quantum disordered even at the lowest temperature. They are characterized by emergent gauge fields and fractionalized quasiparticles. Here we show that the sub-kelvin thermal transport of the three-dimensional S=1/2 hyperhyperkagome quantum magnet PbCuTe_{2}O_{6} is governed by a sizeable charge-neutral fermionic contribution which is compatible with the itinerant fractionalized excitations of a spinon Fermi surface. We demonstrate that this hallmark feature of the QSL state is remarkably robust against sample crystallinity, large magnetic field, and field-induced magnetic order, ruling out the imitation of QSL features by extrinsic effects. Our findings thus reveal the characteristic low-energy features of PbCuTe_{2}O_{6} which qualify this compound as a true QSL material.

Association of recent respiratory illness and influenza with acute myocardial infarction among the Bangladeshi population: A case-control study.

Current evidence suggests that recent acute respiratory infections and seasonal influenza may precipitate acute myocardial infarction (AMI). This study examined the potential link between recent clinical respiratory illness (CRI) and influenza, and AMI in Bangladesh. Conducted during the 2018 influenza season at a Dhaka tertiary-level cardiovascular (CV) hospital, it included 150 AMI cases and two control groups: 44 hospitalized cardiac patients without AMI and 90 healthy individuals. Participants were matched by gender and age groups. The study focused on self-reported CRI and laboratory-confirmed influenza ascertained via quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) within the preceding week, analyzed using multivariable logistic regression. Results showed that cases reported CRI, significantly more frequently than healthy controls (27.3% vs. 13.3%, adjusted odds ratio (aOR): 2.21; 95% confidence interval (CI): 1.05-4.06), although this was not significantly different from all controls (27.3% vs. 22.4%; aOR: 1.19; 95% CI: 0.65-2.18). Influenza rates were insignificantly higher among cases than controls. The study suggests that recent respiratory illnesses may precede AMI onset among Bangladeshi patients. Infection prevention and control practices, as well as the uptake of the influenza vaccine, may be advocated for patients at high risk of acute CV events.

Hepatic ß-arrestins: potential roles in liver health and disease.

Β-arrestins are intracellular scaffolding proteins that have multifaceted roles in different types of disorders. In this review article, we gave a summary about the discovery, characterization and classification of these proteins and their intracellular functions. Moreover, this review article focused on the hepatic expression of ß-arrestins and their hepatocellular distribution and function in each liver cell type. Also, we showed that ß-arrestins are key regulators of distinct types of hepatic disorders. On the other hand, we addressed some important points that have never been studied before regarding the role of ß-arrestins in certain types of hepatic disorders which needs more research efforts to cover.

Lateral Route Endoscopic Thyroidectomy with gas Insufflation: Proposed Critical View of Safety.

BACKGROUND: The extra-cervical lateral route endoscopic thyroidectomy (LRET) approaches such as the trans-axillary, breast and axillo-breast approaches are proved to be safe, feasible, esthetic, highly effective. The inherent difficulty and long learning curve of these techniques prevents its widespread application. METHODS: Benefiting from the experience of more than 5 years in LRET approaches with CO2 insufflation, the authors developed ten surgical key steps and a critical view of safety (CVS) for performing thyroid lobectomy via LRET approaches. A detailed description and a video of the surgical technique is provided. RESULTS: Application of these structured key steps and CVS was feasible and effective in achieving thyroid lobectomy in all selected cases with unilateral goiter up to 8 cm, even in cases with thyroiditis or controlled toxic adenoma, without any adverse events and with shorter operative time than the non-structured surgical technique. CONCLUSION: The described ten key steps and CVS are conclusive, applicable, easy to learn. Our video could act as a guide for promoting the standardized, safe, and wide application of LRET techniques.

Localization and characterization of human papillomavirus-16 in oral squamous cell carcinoma.

OBJECTIVES: The role of Human papillomavirus (HPV) in the oral squamous cell carcinoma (OSCC) has not been completely elucidated. The purpose of the present study was to investigate the prevalence and localization of HPV-16 virus in OSCC and to correlate HPV-16 positivity and p16INK4A expression with the clinical and pathological features of OSCC. METHODS: The archives of Oral Pathology at the University of Florida, College of Dentistry were accessed for demographic, clinical, histopathological data, and slides of 114 OSCC patients. HPV-16 positivity of OSCC was evaluated by p16INK4A immunohistochemistry (IHC) and HPV-16 E6/E7mRNA by in situ hybridization (ISH). RESULTS: Out of 114 consecutive pathological slides of OSCC, 16 samples (14%) showed positivity for p16INK4A by IHC and 14 samples (12%) were positive for HPV-16 E6/E7mRNA ISH and the Positivity showed a significant correlation with the patients' age, alcohol consumption, and the degree of OSSC differentiation. The hard palate showed the highest positivity of p16INK4A IHC and HPV-16 mRNA ISH (38%, 36% respectively). CONCLUSION: HPV-16 is a significant factor in oral carcinogenesis. We recommend using p16INK4A as a surrogate marker for HPV detection in OSCC, which can be complemented by RNA ISH for the identification of HPV subtypes.

Water level changes, subsidence, and sea level rise in the Ganges-Brahmaputra-Meghna delta.

Being one of the most vulnerable regions in the world, the Ganges-Brahmaputra-Meghna delta presents a major challenge for climate change adaptation of nearly 200 million inhabitants. It is often considered as a delta mostly exposed to sea-level rise and exacerbated by land subsidence, even if the local vertical land movement rates remain uncertain. Here, we reconstruct the water-level (WL) changes over 1968 to 2012, using an unprecedented set of 101 water-level gauges across the delta. Over the last 45 y, WL in the delta increased slightly faster (∼3 mm/y), than global mean sea level (∼2 mm/y). However, from 2005 onward, we observe an acceleration in the WL rise in the west of the delta. The interannual WL fluctuations are strongly modulated by El Niño Southern Oscillation (ENSO) and Indian Ocean Dipole (IOD) variability, with WL lower than average by 30 to 60 cm during co-occurrent El Niño and positive IOD events and higher-than-average WL, by 16 to 35 cm, during La Niña years. Using satellite altimetry and WL reconstructions, we estimate that the maximum expected rates of delta subsidence during 1993 to 2012 range from 1 to 7 mm/y. By 2100, even under a greenhouse gas emission mitigation scenario (Representative Concentration Pathway [RCP] 4.5), the subsidence could double the projected sea-level rise, making it reach 85 to 140 cm across the delta. This study provides a robust regional estimate of contemporary relative WL changes in the delta induced by continental freshwater dynamics, vertical land motion, and sea-level rise, giving a basis for developing climate mitigation strategies.

"Anosmia" the mysterious collateral damage of COVID-19.

COVID-19 pandemic spreads worldwide, with more than 100 million positive cases and more than 2 million deaths. From the beginning of the COVID-19 pandemic, several otolaryngologists described many cases of a sudden loss of smell (anosmia) associated with the disease with or without additional symptoms. Anosmia is often the first and sometimes the only sign in the asymptomatic carriers of COVID-19. Still, this disorder is underestimated, and it is not life-threatening. However, it significantly decreases the quality of life. This olfactory dysfunction continues in several cases even after the nasopharyngeal swab was negative. The occurrence of anosmia can be used as a screening tool for COVID-19 patients and can be used to identify these patients to accomplish the isolation and tracking procedures. In this review, we highlighted the possible mechanisms of anosmia in COVID-19 patients, major pathologies and features of anosmia, implications of anosmia in early diagnosis of COVID-19, evaluation of the smell function during COVID-19, and management and treatment options of COVID-19 anosmia.

Integrative profiling of Epstein-Barr virus transcriptome using a multiplatform approach.

BACKGROUND: Epstein-Barr virus (EBV) is an important human pathogenic gammaherpesvirus with carcinogenic potential. The EBV transcriptome has previously been analyzed using both Illumina-based short read-sequencing and Pacific Biosciences RS II-based long-read sequencing technologies. Since the various sequencing methods have distinct strengths and limitations, the use of multiplatform approaches have proven to be valuable. The aim of this study is to provide a more complete picture on the transcriptomic architecture of EBV. METHODS: In this work, we apply the Oxford Nanopore Technologies MinION (long-read sequencing) platform for the generation of novel transcriptomic data, and integrate these with other's data generated by another LRS approach, Pacific BioSciences RSII sequencing and Illumina CAGE-Seq and Poly(A)-Seq approaches. Both amplified and non-amplified cDNA sequencings were applied for the generation of sequencing reads, including both oligo-d(T) and random oligonucleotide-primed reverse transcription. EBV transcripts are identified and annotated using the LoRTIA software suite developed in our laboratory. RESULTS: This study detected novel genes embedded into longer host genes containing 5'-truncated in-frame open reading frames, which potentially encode N-terminally truncated proteins. We also detected a number of novel non-coding RNAs and transcript length isoforms encoded by the same genes but differing in their start and/or end sites. This study also reports the discovery of novel splice isoforms, many of which may represent altered coding potential, and of novel replication-origin-associated transcripts. Additionally, novel mono- and multigenic transcripts were identified. An intricate meshwork of transcriptional overlaps was revealed. CONCLUSIONS: An integrative approach applying multi-technique sequencing technologies is suitable for reliable identification of complex transcriptomes because each techniques has different advantages and limitations, and the they can be used for the validation of the results obtained by a particular approach.

Exploration of the physical properties of the newly synthesized kagome superconductor LaIr3Ga2 using different exchange-correlation functionals.

LaIr3Ga2 is a kagome superconductor with a superconducting temperature (Tc) of 5.16 K. Here, we present the physical properties of the LaIr3Ga2 kagome superconductor computed via the DFT method wherein six different exchange-correlation functionals were used. The lattice parameters obtained using different functionals are reasonable, with a slight variation compared to experimental values. The bonding nature was explored. The elastic constants (Cij), moduli (B, G, Y), and Vickers hardness (Hv) were computed to disclose the mechanical behavior. The Hv values were estimated to be 2.56-3.16 GPa using various exchange-correlation functionals, indicating the softness of the kagome material. The Pugh ratio, Poisson's ratio, and Cauchy pressure revealed the ductile nature. In addition, mechanical stability was ensured based on the estimated elastic constants. The anisotropic mechanical behavior was confirmed via different anisotropic indices. The Debye temperature (ΘD), melting temperature (Tm), and minimum thermal conductivity (kmin) were calculated to characterize the thermal properties and predict the potential of LaIr3Ga2 as a thermal barrier coating material. The electronic density of states was investigated in detail. The McMillan equation was used to estimate Tc, and the electron-phonon coupling constant (λ) was calculated to explore the superconducting nature. The important optical constants were also calculated to explore its possible optoelectronic applications. The values of reflectivity in the IR-visible region are about 62% to 80%, indicating that the compound under study is suitable as a coating to reduce solar heating. The obtained parameters were compared with previously reported parameters, where available.

Implications of inappropriate prescription of oral nutritional supplements on the quality of life of cancer outpatients: a cross-sectional comparative study.

BACKGROUND AND AIMS: Oral nutritional supplements (ONS) are considered a cornerstone in the treatment plan of malnutrition in cancer patients. However, the prevalence of inappropriate prescription of ONS is high. In this study, we aim to investigate the effect of inappropriate oral nutritional supplementation (consisting of prescription of ONS without evident clinical indication, or the absence of ONS when at risk of malnutrition) on the quality of life of cancer outpatients. METHODS: A cross-sectional comparative study was conducted in 104 cancer outpatients, receiving ONS without prior malnutrition risk screening (n = 51), and patients not receiving ONS (n = 53). Nutritional risk screening was performed using the abridged patient-generated subjective global assessment (ab-PG-SGA). The quality of life was assessed using EORTC QLQ-C30 version 3.0 questionnaire. Multivariate analysis was conducted to determine the predictors of quality-of-life scales. Age (years), malnutrition (ab-PG-SGA scores), BMI (kg/m2), TSF (mm), MUAC (cm), ONS (yes, no) were entered into the linear regression analysis as predictors (backward stepwise linear regression analysis). RESULTS: The prevalence of malnutrition risk (ab-PG-SGA ≥ 6) was 74%. The median score of the ab-PG-SGA for ONS receiving group was significantly higher (p = 0.045). Furthermore, univariate analysis showed that the scores of the global health status (QoL) and the role functioning (RF) scales were significantly lower for the ONS receiving group (p = 0.020 and p = 0.016, respectively). Multivariately, malnutrition, inappropriate ONS prescription, and triceps skin fold were found to be predictors of the RF scale, while malnutrition was the only predictor for the QoL. CONCLUSION: The inappropriate ONS prescription does not improve nutritional status or quality of life of cancer outpatients.

Green approaches in synthesising nanomaterials for environmental nanobioremediation: Technological advancements, applications, benefits and challenges.

Green synthesis approaches of nanomaterials (NMs) have received considerable attention in recent years as it addresses the sustainability issues posed by conventional synthesis methods. However, recent works of literature do not present the complete picture of biogenic NMs. This paper addresses the previous gaps by providing insights into the stability and toxicity of NMs, critically reviewing the various biological agents and solvents required for synthesis, sheds light on the factors that affect biosynthesis, and outlines the applications of NMs across various sectors. Despite the advantages of green synthesis, current methods face challenges with safe and appropriate solvent selection, process parameters that affect the synthesis process, nanomaterial cytotoxicity, bulk production and NM morphology control, tedious maintenance, and knowledge deficiencies. Consequently, the green synthesis of NMs is largely trapped in the laboratory phase. Nevertheless, the environmental friendliness, biocompatibility, and sensitivities of the resulting NMs have wider applications in biomedical science, environmental remediation, and consumer industries. To the scale-up application of biogenic NMs, future research should be focused on understanding the mechanisms of the synthesis processes, identifying more biological and chemical agents that can be used in synthesis, and developing the practicality of green synthesis at the industrial scale, and optimizing the factors affecting the synthesis process.

Reconciling the geogenic and non-crustal origins of elements in an Indo-Bangla transboundary river, Atrai: Pollution status, sediment quality, and preliminary risk assessment.

This study has been conducted on an anthropogenically less influenced transboundary river (Atrai: Indo-Bangladesh) to comprehend the inherent geochemistry and identify potential elemental sources. In doing so, across the Bangladeshi portion, 30 river-bed samples were culled and studied by neutron activation analysis to quantify the abundances of 15 geochemically and toxicologically significant elementals (Na, Al, K, Ti, Cr, Mn, Co, Zn, As, Rb, Sb, Cs, Ba, Th, and U). The results revealed that the mean concentrations (µg/g) of Rb (154.6), Cs (7.53), Th (20.90), and U (4.88) were 1.5-2.0 times higher than crustal values. Besides, geo-environmental indices revealed 'uncontaminated to moderately contaminated' pollution status with minor enrichment or contamination for Rb, Th, Sb, U, and Cs, relatively concentrated in the mid-to-downstream zone possessed geogenic and non-crustal origins. The positive matrix factorization and other statistical approaches revealed predominant geogenic enrichment of Na, K, Al, Ti, Zn, Cs, Rb, As, Th, and U from differential mineralogical compositions via weathering, elemental fractionations, and biogeochemical mobilization. Contrariwise, several anthropogenic sources (for Cr, Sb, Co, Mn, Th) were also ascertained in the vicinity of Atari River. However, sediment characterization based on SQG threshold values manifested that Cr and Mn possess rare biological effects on local aquatic organisms. Nevertheless, SQGs-based and ecological risk indices invoked minor to no potential ecotoxicological intimidations for the considered metal(oid)s (Cr, Mn, Co, Zn, As, and Sb). Hence, this study manifested the usefulness of a less anthropogenically affected river to reckon geogenic and non-crustal elemental origins in the compounded riverine sediment.

Acute and chronic metabolic effects of carvedilol in high-fructose, high-fat diet-fed mice: implication of ß-arrestin2 pathway.

We aimed to investigate the acute and chronic effects of carvedilol on insulin resistance in high-fructose, high-fat diet (HFrHFD) - fed mice and the implication of the ß-arrestin2 pathway. The acute effect of carvedilol (10 mg/kg, i.p.) on glucose tolerance and hepatic lipid signaling in normal and insulin resistant mice was investigated. Then, the chronic effect of carvedilol on insulin resistance and dyslipidemia in HFrHFD-fed mice was examined. Changes in ß-arrestin2 and its downstream signals in liver, skeletal muscle, and adipose tissue were measured. This involved measuring phosphatidylinositol 4,5-bisphosphate (PIP2) and diacylglycerol (DAG) levels and protein kinase B (AKT) activity. Carvedilol acutely reduced fasting blood glucose levels in both normal and insulin resistant mice without significantly affecting the glucose tolerance. These acute effects were associated with increased hepatic PIP2 but decreased hepatic DAG levels. Chronic administration of carvedilol significantly ameliorated insulin resistance and dyslipidemia in HFrHFD-fed mice. These chronic effects were associated with increased ß-arrestin2, PIP2, and AKT activity levels but decreased DAG levels in the classical insulin target tissues. In conclusion, carvedilol acutely maintains glucose homeostasis and chronically ameliorates insulin resistance and dyslipidemia in HFrHFD-fed mice. The insulin sensitizing effects of carvedilol are highly correlated with the upregulation of ß-arrestin2 pathway.