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Pollutants in soil, particularly chromium (Cr), pose high environmental and health risks due to their persistence, bioavailability, and potential for causing toxicity. Cr impairment in plants act as a deleterious environmental pollutant that enters the food chain and eventually disturbs human health. Current study demonstrated the potential of integrative foliar application of magnesium-iron (Mg + Fe) nanocomposite with Staphylococcus aureus strains to alleviate Cr toxicity in rice (Oryza sativa) crops by improving yield and defense system. Growth and yield traits such as shoot length (15%), root length (17%), shoot fresh weight (14%), shoot dry weight (9%), root fresh weight (23%), root dry weight (7%), number of tillers (33%), number of grains (10%) and spike length (13%) improved by combined application of Mg + Fe (20 mg L -1 ) nanocomposite and S. aureus strains with Cr (110 mg kg -1 ), compared to when applied alone. Mutual Mg + Fe and S. aureus strains application augmented the SPAD value (9%), total chlorophyll (11%), a (12%), b (17%), and carotenoids (32%), with Cr (110 mg kg -1 ), compared to alone. Malondialdehyde (13%), hydrogen peroxide (H 2 O 2 ) (11%), and electrolyte leakage (7%) were significantly regulated in shoots with combined Mg + Fe and S. aureus strains application with Cr (110 mg kg -1 ) contrasted to alone. Peroxidase (20%), superoxide dismutase (17%), ascorbate peroxidase (18%), and catalase (20%) were increased in shoots with combined Mg + Fe and S. aureus strains application with Cr (110 mg kg -1 ) in comparison to alone. The combined application of Mg + Fe (20 mgL -1 ) nanocomposite and S. aureus strains with Cr (110 mg kg -1 ) enhanced the macro-micronutrients in shoots compared to alone. Cr accumulation in roots (21%), shoots (25%), and grains (47%) were significantly reduced under Cr (110 mg kg -1 ) with combined Mg + Fe and S. aureus strains application, compared to alone. Subsequently, applying combined Mg + Fe and S. aureus strains is a sustainable solution to boost crop production under Cr toxicity., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Oral bioavailability of glibenclamide (Glb) was appreciably improved by the formation of an amorphous solid dispersion with Poloxamer-188 (P-188). Poloxamer-188 substantially enhanced the solubility and thereby the dissolution rate of the biopharmaceutics classification system (BCS) class II drug Glb and simultaneously exhibited a better stabilizing effect of the amorphous solid dispersion prepared by the solvent evaporation method. The physical state of the dispersed Glb in the polymeric matrix was characterized by differential scanning calorimetry, X-ray diffraction, scanning electron microscope and Fourier transform infrared studies. In vitro drug release in buffer (pH 7.2) revealed that the amorphous solid dispersion at a Glb-P-188 ratio of 1:6 (SDE 4 ) improved the dissolution of Glb by 90% within 3 h. A pharmacokinetic study of the solid dispersion formulation SDE 4 in Wistar rats showed that the oral bioavailability of the drug was greatly increased as compared with the market tablet formulation, Daonil®. The formulation SDE 4 resulted in an AUC 0-24h ~2-fold higher. The SDE 4 formulation was found to be stable during the study period of 6 months., (© 2024 John Wiley & Sons Ltd.)

This study aimed to investigate the dissipation pattern, risk assessment, and waiting period of myclobutanil on apple fruit (Malus domestica Borkh.) under temperate conditions in Kashmir, India. The study involved the application of myclobutanil 10 WP at a single recommended dosage (125 g a.i. ha -1 ) and double dosage (250 g a.i. ha -1 ) on Red Velox apple trees, 2 months before harvest. GC equipped with an electron capture detector was used to analyze myclobutanil residues in fruit samples. The study revealed that myclobutanil, at both recommended and double recommended doses, dissipated rapidly and became nondetectable after 55 and 60 days, respectively. The waiting period for myclobutanil application was determined to be 12.41 days for the single dose and 25.58 days for the double dose, respectively. These waiting periods were based on the maximum residue limit of 0.6 ppm as prescribed by the Codex Alimentarius Commission, Food Safety and Standards Authority of India, and European Commission. The study concludes that myclobutanil 10 WP is safe for consumers at both recommended and double recommended doses when applied 2 months before harvest. Risk assessment, considering the average daily apple consumption in India and theoretical maximum residue contributions (TMRCs), indicates negligible health hazards even at double the recommended dosage. The calculated TMRC values at Day 0 were significantly below the maximum permissible intake. For average and maximum myclobutanil residues at single and double doses, the TMRC values were found to be 0.0069 and 0.0070 mg day -1 person -1 and 0.0105 and 0.0106 mg day -1 person -1 , respectively. These results indicate that myclobutanil, when used according to recommended dosages and waiting periods, poses minimal health risks to consumers. The study emphasizes the importance of prudent fungicide use to minimize fungicide residues on fruits, thereby ensuring their safety for consumption., (© 2024 John Wiley & Sons Ltd.)

The keto-enol tautomerism of avobenzone (AVO) is pivotal to its photostability, influenced by microenvironmental factors, such as, the type of solvent and complexation with macrocyclic compounds. This study explores the effect of host-guest complexation on AVO photostabilization, employing cucurbit[7]uril (CB[7]) and β-cyclodextrin (β-CD) to form inclusion complexes. CB[7] exhibits a higher affinity to the keto form of AVO, a UVC radiation absorber. The complexed keto form facilitates the regeneration of the enol form, reducing skin permeation. Spectroscopic and thermal analyses confirm 1 : 1 AVO-CB[7] and AVO-β-CD complex formation. Computational and MD simulations show that host-guest complex is favored over isolated AVO and β-CD or CB[7] molecules by 95-125 kJ mol -1 , depending on the presence of implicit solvent. Both macrocycles enhance AVO photostabilization in aqueous environments, with CB[7] displaying greater selectivity for the keto form, while β-CD shows ethanol concentration-dependent binding., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

This study details the synthesis and characterization of surfactant-modified sodium alginate hydrogel beads crosslinked with Ba 2+ ions through ionotropic gelation. Cationic surfactants such as, dodecyltrimethylammonium bromide (DTAB), didodecyldimethylammonium bromide (DDAB), and butanediyl-α,ω-bis-(dimethyldodecylammonium bromide) (GEM), were employed in the modification process. The surfactant-modified ALG-DTAB, ALG-DDAB, and ALG-GEM beads were investigated for the removal of cationic dye Malachite Green (MG) to elucidate the impact of hydrophobicity of amphiphiles on the adsorption process. The characterizations were carried out using Rheometry, Field Emission Scanning Electron Microscopy (FESEM), Infrared Spectroscopy (IR), and Energy Dispersive X-ray Spectroscopy (EDX). Under optimized conditions, ALG-GEM and ALG-DDAB demonstrated highest maximum adsorption capacity (Q max  > 700 mgg -1 ). The adsorption data fitted well to pseudo-second order kinetic and Langmuir adsorption models, suggesting the involvement of chemisorption phenomena with notable contributions from pore diffusion. The effects of pH, initial dye concentration, adsorbent dose, temperature, and competing ions on the removal of MG were investigated. Interestingly, ALG-GEM beads exhibited an increase in adsorption capacity with rising pH and a subsequent decrease with increasing temperature, showcasing optimal adsorption at pH 7.0 and 25 °C. The study proposes that ALG beads modified with cationic surfactants with higher hydrophobicity could offer a promising avenue in wastewater treatment processes., Competing Interests: Declaration of competing interest The authors declare no conflict of interests and any competing financial interest., (Copyright © 2024. Published by Elsevier B.V.)

Multiple sclerosis, and its murine model experimental autoimmune encephalomyelitis (EAE), is a neurodegenerative autoimmune disease of the CNS characterized by T cell influx and demyelination. Similar to other autoimmune diseases, therapies can alleviate symptoms but often come with side effects, necessitating the exploration of new treatments. We recently demonstrated that the Cullin-RING E3 ubiquitin ligase 4b (CRL4b) aided in maintaining genome stability in proliferating T cells. In this study, we examined whether CRL4b was required for T cells to expand and drive EAE. Mice lacking Cul4b (Cullin 4b) in T cells had reduced EAE symptoms and decreased inflammation during the peak of the disease. Significantly fewer CD4+ and CD8+ T cells were found in the CNS, particularly among the CD4+ T cell population producing IL-17A, IFN-γ, GM-CSF, and TNF-α. Additionally, Cul4b-deficient CD4+ T cells cultured in vitro with their wild-type counterparts were less likely to expand and differentiate into IL-17A- or IFN-γ-producing effector cells. When wild-type CD4+ T cells were activated in vitro in the presence of the recently developed CRL4 inhibitor KH-4-43, they exhibited increased apoptosis and DNA damage. Treatment of mice with KH-4-43 following EAE induction resulted in stabilized clinical scores and significantly reduced numbers of T cells and innate immune cells in the CNS compared with control mice. Furthermore, KH-4-43 treatment resulted in elevated expression of p21 and cyclin E2 in T cells. These studies support that therapeutic inhibition of CRL4 and/or CRL4-related pathways could be used to treat autoimmune disease., (Copyright © 2024 by The American Association of Immunologists, Inc.)

The balance between a protective and a destructive immune response can be precarious, as exemplified by inborn errors in nucleotide metabolism. This class of inherited disorders, which mimics infection, can result in systemic injury and severe neurologic outcomes. The most common of these disorders is Aicardi Goutières syndrome (AGS). AGS results in a phenotype similar to "TORCH" infections (Toxoplasma gondii, Other [Zika virus (ZIKV), human immunodeficiency virus (HIV)], Rubella virus, human Cytomegalovirus [HCMV], and Herpesviruses), but with sustained inflammation and ongoing potential for complications. AGS was first described in the early 1980s as familial clusters of "TORCH" infections, with severe neurology impairment, microcephaly, and basal ganglia calcifications (Aicardi & Goutières, Ann Neurol, 1984;15:49-54) and was associated with chronic cerebrospinal fluid (CSF) lymphocytosis and elevated type I interferon levels (Goutières et al., Ann Neurol, 1998;44:900-907). Since its first description, the clinical spectrum of AGS has dramatically expanded from the initial cohorts of children with severe impairment to including individuals with average intelligence and mild spastic paraparesis. This broad spectrum of potential clinical manifestations can result in a delayed diagnosis, which families cite as a major stressor. Additionally, a timely diagnosis is increasingly critical with emerging therapies targeting the interferon signaling pathway. Despite the many gains in understanding about AGS, there are still many gaps in our understanding of the cell-type drivers of pathology and characterization of modifying variables that influence clinical outcomes and achievement of timely diagnosis., (© 2024 SSIEM.)

Assessing the impact of greenhouse gas (GHG) emissions on agricultural soils is crucial for ensuring food production sustainability in the global effort to combat climate change. The present study delves to comprehensively assess GHG emissions in Cuba's agricultural soil and analyze its implications for rice production and climate change because of its rich agriculture cultivation tradition and diverse agro-ecological zones from the period of 1990-2022. In this research, based on Autoregressive Distributed Lag (ARDL) approach the empirical findings depicts that in short run, a positive and significant impact of 1.60 percent % in Cuba's rice production. The higher amount of atmospheric carbon dioxide (CO 2 ) levels improves photosynthesis, and stimulates the growth of rice plants, resulting in greater grain yields. On the other hand, rice production index raising GHG emissions from agriculture by 0.35 % in the short run. Furthermore, a significant and positive impact on rice production is found in relation to the farm machinery i.e., 3.1 %. Conversely, an adverse and significant impact of land quality was observed on rice production i.e., -5.5 %. The reliability of models was confirmed by CUSUM and CUSUM square plot. Diagnostic tests ensure the absence of serial correlation and heteroscedasticity in the models. Additionally, the forecasting results are obtained from the three machine learning models i.e. feed forward neural network (FFNN), support vector machines (SVM) and adaptive boosting technique (Adaboost). Through the % MAPE criterion, it is evident that FFNN has achieved high precision (91 %). Based on the empirical findings, the study proposed the adoption of sustainable agricultural practices and incentives should be given to the farmers so that future generations inherit a world that is sustainable, and healthy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The study aimed to evaluate the role of vitamin D on redox balance, insulin resistance and its predicting value for subclinical pregnancy toxemia (SPT) in pregnant ewes. At four weeks pre-lambing, fifteen healthy pregnant ewes were divided into two groups, ewes with sufficient vitamin D (25-hydroxy-vitamin D (25VitD) (SVD, n = 9) and ewes with insufficient 25VitD (ISVD, n = 6). Blood samples were collected at 4 weeks pre-lambing using modified frequently sampled intravenous glucose tolerance test for the estimation of various metabolites. The baseline glucose, insulin, non-esterified fatty acid (NEFA), fructosamine, beta-hydroxy butyric acid (β-BHA), calcium, phosphorus concentration and total oxidant status (TOS) did not differ significantly between the two groups, however, total antioxidant capacity (TAC) was significantly (p = 0.031) low in ISVD ewes. Area under the curve for glucose, insulin, elimination rate of glucose and peak insulin also did not differ significantly between the two groups. Correlation analysis revealed, positive association of 25VitD with fructosamine, calcium and TAC, and negative correlation with NEFA and TOS. Subsequent blood sampling at 2 weeks pre-lambing and at lambing showed significant difference in NEFA (p = 0.001), β-HBA (p = 0.001), and fructosamine(p = 0.012) between the two groups. A significant time x group interaction was observed in NEFA (p = 0.019), β-HBA (p = 0.031), and fructosamine (p = 0.026) concentration. The NEFA concentrations were increased and fructosamine decreased at 2 weeks pre-lambing and at lambing along with significantly increased β-HBA at 2 weeks pre-lambing in ISVD compared to SVD. Taking 0.8 mmol/L β-HBA as the cut off limit for SPT, ISVD ewes had higher odds of developing SPT two weeks prior to lambing (OD 16.00; p = 0.042) and at lambing (OD 10; p = 0.077). This study concludes that 25VitD significantly influence redox balance and energy profile and serves as a valuable predictor for SPT in pregnant sheep., Competing Interests: Declaration of Competing Interest The authors declare there is conflicting interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Bovine babesiosis, a global disease, has not been studied so far in Kashmir valley, which is having temperate type of climate as compared to rest of India having tropical to sub-tropical climate, so we felt the need to investigate it., Methods: To diagnose the babesiosis in clinically suspected cattle (n=450), peripheral blood film examination and PCR tests using generic and species-specific primers targeting Babesia / Theleria genera and B. bigemina , B. bovis as well as B. divergens , respectively were conducted. Four PCR products were sequenced and subjected to BLASTn analysis. Ticks were collected from the clinically suspected animals and identified as per the standard morphological keys., Results: The prevalence of babesiosis among suspected cattle in central Kashmir by peripheral blood film examination and PCR technique was 11.11% and 33.62%, respectively. The 18S rRNA gene of Isolate B1 of Babesia spp. showed 99.0 to 100% nucleotide sequence homology with 18S rRNA gene of different isolates of B. bigemina registered in the GenBank, while as 18S rRNA gene of Isolate Z showed 98.5 to 99.2% and 93.1 to 93.9% nucleotide sequence homology with 18S rRNA gene of different isolates of Babesia spp. and B. bigemina , respectively , registered in the GenBank. Rhipicephalus spp. and Haemaphysalis spp. were the two major tick genera identified in the present study., Conclusion: Bovine Babesiosis in Kashmir is attributed to B. bovis , B. bigemina and some other Babesia spp. or strains which needs further investigation. To our knowledge, this is the first report of Babesia bovis from northern India in cattle., Competing Interests: Conflict of Interest The authors have declared that no competing interest exists., (Copyright© 2024 Ahmad Najar et al. Published by Tehran University of Medical Sciences.)

In this study, an analytical method was developed and validated for the assessment of pesticide residues in commonly consumed vegetables and fruits. Fresh samples of apple, green peas, tomatoes, and cucumbers were processed and subjected to analysis using a modified QuEChERS (quick, easy, cheap, effective, rugged, safe) extraction technique. Subsequently, quantification of pesticide residues was conducted utilizing gas chromatography (GC)-electron capture detector. Extraction and cleanup parameters were meticulously optimized, resulting in a modification of the original QuEChERS method. This modification aimed to reduce solvent consumption, making the study more environmentally friendly. The developed method was validated in terms of selectivity, specificity, linearity, precision, and accuracy by following the SANTE guidelines. Calibration curves showed good linearity (r > 0.99) within the test range. Precision was evaluated by intra- and inter-day experiments with an acceptable relative standard deviation (<20.0%). Recovery was assessed at the limit of quantification level and was observed to fall within the range of 70%-120%, with relative standard deviations below 5.45%. The validated method presented here can be applied to analyze pesticide residues in various other vegetables, fruits, and cereals. It is essential for ongoing monitoring of pesticide residues to ensure public safety., (© 2023 John Wiley & Sons, Ltd.)

Metallosurfactants, defined here as hydrophobic metal-containing groups embedded in hydrophilic units when dispersed in water, emanate in the formation of metallomicelles. This approach continues to attract great interest for its ability to serve as micellar catalysts for various metal-mediated chemical transformations in water. Indeed, relevant to green chemistry, micellar catalysis plays a preeminent function as a replacement for organic solvents in a variety of chemical reactions. There are several methods for the interaction of metal complexes (catalysts or catalyst precursors) and surfactants for producing micellar aggregates. A very effective manner for achieving this involves the direct bonding of the metal center to the amphiphilic polymeric materials. Herein, we describe the synthesis of a metallosurfactant containing a palladium complex covalently incorporated into a CO 2 -based triblock polycarbonate derived using a dicarboxylic acid chain-transfer agent. This amphiphilic polycarbonate was shown to self-assemble in water to provide uniform and spherical micelles, where the catalytic metal center is located in the hydrophobic portion of the micelle. The resulting metallosurfactant was demonstrated to effectively catalyze carbon-carbon coupling reactions at very low catalyst loadings.

During infection, virus-specific CD8 + T cells undergo rapid bursts of proliferation and differentiate into effector cells that kill virus-infected cells and reduce viral load. This rapid clonal expansion can put T cells at significant risk for replication-induced DNA damage. Here, we find that c-Myc links CD8 + T cell expansion to DNA damage response pathways though the E3 ubiquitin ligase, Cullin 4b (Cul4b). Following activation, c-Myc increases the levels of Cul4b and other members of the Cullin RING Ligase 4 (CRL4) complex. Despite expressing c-Myc at high levels, Cul4b-deficient CD8 + T cells do not expand and clear the Armstrong strain of lymphocytic choriomeningitis virus (LCMV) in vivo. Cul4b-deficient CD8 + T cells accrue DNA damage and succumb to proliferative catastrophe early after antigen encounter. Mechanistically, Cul4b knockout induces an accumulation of p21 and Cyclin E2, resulting in replication stress. Our data show that c-Myc supports cell proliferation by maintaining genome stability via Cul4b, thereby directly coupling these two interdependent pathways. These data clarify how CD8 + T cells use c-Myc and Cul4b to sustain their potential for extraordinary population expansion, longevity and antiviral responses., (© 2023. The Author(s).)

A pH controlled cleavability unfolds the 3-in-1 surfactant feature of an ester-bonded gemini surfactant, 2, 2'-[(oxybis (ethane-1,2-diyl))bis (oxy)]bis (N-hexadecyl-N,Ndimethyl-2-oxoethanaminium) dichloride (C16-C4O2-C16), by reinforcing in-situ mixed micellization between cleaved components at non-neutral pH (pH 3,12). The triplicity is assigned to two mixed-micelle variants at pH 3 and pH 12 besides the unhydrolyzed C16-C4O2-C16 at pH 7. The pH-controlled aggregation of such trichotomic surfactant dramatically enhances the micellar solubilization/cosolubilization of PAHs viz. naphthalene (Np), phenanthrene (Ph), pyrene (Py), perylene (Pe). The cosolubilization of binary/ternary PAH mixtures in such remarkable micellar assemblies at pH 3, 7 and 12 yields intriguing synergistic or antagonistic solubility outcomes correlated to PAH-PAH and PAH-micelle interactions. This study provides valuable insights into the potential applications of the ester-bonded gemini surfactant for the cosolubilization of undesirable hydrophobic compounds at natural sites having variable pH., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

In the present study, a series of benzotriazole-based β-amino alcohols were efficiently synthesized in excellent yields via aminolysis of benzotriazolated epoxides under catalyst- and solvent-free conditions. Further these β-amino alcohols were successfully utilized to synthesize the corresponding benzotriazole-based oxazolidine heterocyclic derivatives. All the synthesized compounds were characterized by various spectroscopic techniques such as 1 H NMR, 13 C NMR, and mass spectroscopy for structure elucidation. The compounds were subjected to a microtiter plate-based antimicrobial assay. The antimicrobial activity results reveal that the compounds 4a , 4e , and 5f were found to be active against Staphylococcus aureus (ATCC-25923) with minimum inhibitory concentrations (MICs) of 32, 8, and 64 μM, respectively. Also, the compounds 4a , 4e , 4k , 4i , 4m , 4n , 4o , 5d , 5e , 5f , 5g , and 5h showed effective activity against Bacillus subtilis (ATCC 6633) with MICs of 64, 16, 16, 16, 64, 16, 64, 64, 32, 64, 8, and 16 μM, respectively. A biological investigation was conducted, including molecular docking of two compounds with several receptors to identify and confirm the best ligand-protein interactions. Hence, this study found a significant strategy to diversify the chemical molecules. The synthesized compounds play a potential role as an antibacterial intensifier against some pathogenic bacteria for the development of antibacterial substances., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Herein, we report a novel, simple, specific, accurate and cost-friendly validated reverse phase-high performance liquid chromatographic (RP-HPLC) method for the quantification of second generation sulphonylurea based antidiabetic drug, glibenclamide (GLB) in rat plasma and its application to calculate pharmacokinetic parameters in wistar rats. The internal standard used was flufenamic acid. The chromatographic separation was conducted on C 18 column (250 mm × 4.6 mm x 5 μm, Agilent-Zorbax, SB) using isocratic elution with mobile phase containing Acetonitrile: Water (1:1; v/v) pH adjusted to 4.0 with 0.03 % glacial acetic acid and detected by photo-diode array as detector. Calibration curves made in the rat plasma were linear in the range of 50-1200 ng/ml with r 2  = 0.998. The LLOQ was 40 ng/ml. This method was effectively applied for pharmacokinetic studies of Glibenclamide following administration through oral route as solid dispersion formulation to Wistar rats. Several methods are available in the literature which can be employed for the quantification of Glibenclamide but such methods are tedious, provide lower sensitivity, less simultaneous resolution and are time-consuming. Therefore the present methods suits best for the quantification of Glibenclamide from Wistar rats., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Published by Elsevier Ltd.)

The present study on "acephate persistence on green pea" was conducted in SKUAST-Kashmir. The study aimed to determine the persistence, dissipation kinetics and waiting period of acephate on green pea. Acephate was sprayed at 75% soluble powder (SP) at 560 g a.i.ha -1 at the fruiting stage followed by another application at a 10 day interval. A rapid and accurate method (quick, easy, cheap, effective, rugged and safe, QuEChERS) was used for extraction and the residue was determined by gas chromatography-electron capture detection on a CPSIL-8CB capillary column (0.25um film thickness, 0.25 mm i.d, 30 m length). At the fortification levels of 0.05, 0.1 and 0.5 mg kg -1 , the percentage recovery of acephate on green pea was found in the range of 71-107%. The initial deposit of green pea was estimated to be 0.37 mg kg -1 . At the indicated dose, the residue of acephate on green pea dissipated below the limit of quantification of 0.05 mg kg -1 after 10 days. Acephate degradation was quick in green pea, with a half-life of 4.07 days. For safe eating of green peas, a 10 day waiting period is recommended. The gas chromatography-electron capture detection technique was validated by following the SANTE standards., (© 2023 John Wiley & Sons, Ltd.)

As a result of tumor heterogeneity and solid cancers harboring multiple molecular defects, precision medicine platforms in oncology are most effective when both genetic and pharmacologic determinants of a tumor are evaluated. Expandable patient-derived xenograft (PDX) mouse tumor and corresponding PDX culture (PDXC) models recapitulate many of the biological and genetic characteristics of the original patient tumor, allowing for a comprehensive pharmacogenomic analysis. Here, the somatic mutations of 23 matched patient tumor and PDX samples encompassing four cancers were first evaluated using next-generation sequencing (NGS). 19 antitumor agents were evaluated across 78 patient-derived tumor cultures using clinically relevant drug exposures. A binarization threshold sensitivity classification determined in culture (PDXC) was used to identify tumors that best respond to drug in vivo (PDX). Using this sensitivity classification, logic models of DNA mutations were developed for 19 antitumor agents to predict drug response. We determined that the concordance of somatic mutations across patient and corresponding PDX samples increased as variant allele frequency increased. Notable individual PDXC responses to specific drugs, as well as lineage-specific drug responses were identified. Robust responses identified in PDXC were recapitulated in vivo in PDX-bearing mice and logic modeling determined somatic gene mutation(s) defining response to specific antitumor agents. In conclusion, combining NGS of primary patient tumors, high-throughput drug screen using clinically relevant doses, and logic modeling, can provide a platform for understanding response to therapeutic drugs targeting cancer., (©2023 American Association for Cancer Research.)

The present study was carried out to analyze the leaf functional traits of co-occurring evergreen and deciduous tree species in a tropical dry scrub forest. This study also intended to check whether the species with contrasting leaf habits differ in their leaf trait plasticity, responding to the canopy infestation by lianas. A total of 11 leaf functional traits were studied for eight tree species with contrasting leaf habits (evergreen and deciduous) and liana-colonization status (with or without liana). In the liana-free environment (L - ), evergreen trees had significantly higher leaf tissue density (LTD) and total chlorophyll (CHL t ) than the deciduous species. Whereas the deciduous trees had higher specific leaf area (SLA) and mass-based leaf nitrogen concentration (N mass ). The leaf trait-pair relationship in the present study agreed with the well-established global trait-pair relationships (leaf thickness (LT) vs. SLA, N mass vs. LT, SLA vs. N mass , and LDMC vs. SLA). There was a significant difference between L + and L - individuals in leaf area (LA), petiole length (PL), SLA, LDMC, and CHL t in the deciduous species. On the other hand, evergreen species showed marked differences across LT, SLA, LTD, N mass, and chlorophyll components between L + and L - individuals of the same species. The results revealed the differential impact of liana colonization on the host trees with contrasting leaf habits. The deciduous species with the acquisitive strategy can have a competitive advantage over evergreen species in the exposed environments (L - ), whereas evergreen species with shade-tolerant properties were better acclimated to the shaded environments (L + ). Therefore, liana colonization can significantly impact the C-fixation strategies of the host trees by altering their light environment and further, the magnitude of such impact may vary among species of different leaf habits. The result also indicated the patterns of convergence and divergence in some of the leaf functional traits between evergreen and deciduous species explaining the patterns of species co-existence., (© 2023. The Author(s).)

In this study, the oxidation of 1-naphthol (1-NAP) and 2-naphthol (2-NAP) by Fe(VI) was investigated. The impacts of operating factors were investigated through a series of kinetic experiments, including Fe(VI) dosages, pH and coexisting ions (Ca 2+ , Mg 2+ , Cu2 + , Fe 3+ , Cl - , SO 4 2- , NO 3 - and CO 3 2- ). Almost 100% elimination of both 1-NAP and 2-NAP could be achieved within 300 s at pH 9.0 and 25 °C. Cu 2+ could significantly improve the degradation efficiency of 1-NAP and 2-NAP, but the impacts of other ions were negligible. The liquid chromatography-mass spectrometry was used to identify the transformation products of 1-NAP and 2-NAP in Fe(VI) system, and the degradation pathways were proposed accordingly. Electron transfer mediated polymerization reaction was the dominant transformation pathway in the elimination of NAP by Fe(VI) oxidation. After 300 s of oxidation, heptamers and hexamers were found as the final coupling products during the removal of 1-NAP and 2-NAP, respectively. Theoretical calculations demonstrated that the hydrogen abstraction and electron transfer reaction would easily occur at the hydroxyl groups of 1-NAP and 2-NAP, producing NAP phenoxy radicals for subsequent coupling reaction. Moreover, since the electron transfer reactions between Fe(VI) and NAP molecules were barrierless and could occur spontaneously, the theoretical calculation results also confirmed the priority of coupling reaction in Fe(VI) system. This work indicated that the Fe(VI) oxidation was an effective way for removing naphthol, which may help us understand the reaction mechanism between phenolic compounds with Fe(VI)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Oxybenzone (OXB), a very widely used sunscreen ingredient has the potential to block both UVA and UVB but can penetrate through skin. Studies have revealed its presence in the blood and urine of most humans, which may lead to long-term health effects. As the confined cavities of macrocycles can alter the physical and chemical properties of encapsulated guests, in this study, we investigated the formation of host-guest complexes between C -methylresorcin[4]arene and OXB. Combined experimental (NMR spectroscopy, UV/vis absorption, and fluorescence spectroscopy) and theoretical investigation confirmed the formation of a weak host-guest complex that had a 1 : 1 stoichiometry. Furthermore, skin permeation testing revealed that complexation by C -methylresorcin[4]arene significantly reduced the skin permeation of OXB which can potentially limit the harmful effects of this organic sunscreen., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Endocrine-disrupting chemicals (EDCs) are of interest in human physiopathology and have been extensively studied for their effects on the endocrine system. Research also focuses on the environmental impact of EDCs, including pesticides and engineered nanoparticles, and their toxicity to organisms. Green nanofabrication has surfaced as an environmentally conscious and sustainable approach to manufacture antimicrobial agents that can effectively manage phytopathogens. In this study, we examined the current understanding of the pathogenic activities of Azadirachta indica aqueous formulated green synthesized copper oxide nanoparticles (CuONPs) against phytopathogens. The CuONPs were analyzed and studied using a range of analytical and microscopic techniques, such as UV-visible spectrophotometer, Transmission electron microscope (TEM), Scanning electron microscope (SEM), X-ray diffraction (XRD) and Fourier transformed infrared spectroscopy (FTIR). The XRD spectral results revealed that the particles had a high crystal size, with an average size ranging from 40 to 100 nm. TEM and SEM images were utilized to verify the size and shape of the CuONPs, revealing that they varied between 20 and 80 nm. The existence of potential functional molecules involved in the reduction of the nanoparticles was confirmed by FTIR spectra and UV analysis. Biogenically synthesized CuONPs revealed significantly enhanced antimicrobial activities at 100 mg/L concentration in vitro by the biological method. The synthesized CuONPs at 500 μg/ml had a strong antioxidant activity which was examined through the free radicle scavenging method. Overall results of the green synthesized CuONPs have demonstrated significant synergetic effects in biological activities which can play a crucial impact in plant pathology against numerous phytopathogens., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

A modified quick, easy, cheap, efficient, rugged, and safe (QuEChERS) method coupled to gas chromatography with electron capture detection was developed for the simultaneous determination of selected electronegative pesticides, namely, chlorpyrifos-methyl (1), chlorpyrifos (2), quinolphos (3), profenofos (4), myclobutanil (5), ethion (6), fenpropathrin (7), and cypermethrin (8), in vegetables with high water content. The selected compounds and some of their metabolites have even been found in human body fluids. In addition, some of them are known or suspected carcinogens according to the World Health Organization. Extraction and cleanup parameters were optimized; thus, the original QuEChERS method was modified to minimize solvent usage by making the study eco-friendly. The developed method was validated for selectivity, specificity, linearity, precision, and accuracy using SANTE guidelines. Calibration curves showed good linearity (r > 0.99) within the test range. Precision was evaluated by intra- and inter-day experiments with an acceptable range of less than 20.0% of relative standard deviation. Recovery was evaluated at limit of quantification and was found to be in the range of 70-120%, with relative standard deviations lower than 4.21%. The proposed method is applicable for detection and monitoring of selected pesticides in one run not only in fruits and vegetables with high water content but also in samples containing large quantities of pigments/dyes., (© 2023 John Wiley & Sons Ltd.)

Herein, we report a novel, accurate and cost-effective validated analytical method for the quantification of losartan potassium and its active metabolite, EXP 3174, in rabbit plasma by reversed-phase high-performance liquid chromatography. Valsartan was used as an internal standard. The method was validated as per International Conference on Harmonization guidelines. The analytes were extracted in rabbit plasma using liquid-liquid extraction technique and analyzed at 247 nm after separation through a reverse-phase C 18 column. The isocratic mobile phase used is a mixture of acetonitrile, water and glacial acetic acid in the ratio of 60:40:1 v/v/v maintained at pH 3.4. All calibration curves showed a good linear relationship (r > 0.995) within the test range. Precision was evaluated by intra- and interday tests with RSDs <1.91% and accuracy showed validated recoveries of 86.20-101.11%. Based on our results, the developed method features good quantification parameters and can serve as an effective quality control method for the standardization of drugs., (© 2023 John Wiley & Sons Ltd.)

This innovative study was carried out to determine the presence of the mineral oil Arbofine in apple and soil at four locations. Arbofine kills the vast majority of dormant insects and mites (mite and asphid eggs, scales and psyllids) on fruit trees (cherry, apple, plum and peach) and thus reduces the plant diseases in summer. In this study, the mineral oil was sprayed at recommended doses of 2.0 and 0.75%, and the doses were doubled to 4.0 and 1.5% in dormant and summer seasons, respectively. The soil samples were taken for observation during the dormant season, whereas both soil and apple samples were taken during the summer season after treatment for 0, 1, 3 and 5 days. The recovery study of all the 11 paraffinic constituents (n-pentane, n-hexane, n-heptane, n-octane, n-nonane, n-decane, n-undecane, n-dodecane, n-tridecane, n-tetradecane and n-pentadecane) in soil and apple samples which constitutes 60% of mineral oil in soil and apple was carried out at the fortification level of 1.0 μg/ml, which was found to be between 72.1% and 99.0%. No residue of all the 11 paraffinic compounds of Arbofine mineral oil was detected in soil and apple samples at day 0 after the recommended doses, and the recommended doses were doubled in both seasons at four locations. Therefore, mineral oil can be used on apples without any risk., (© 2023 John Wiley & Sons Ltd.)

Crystal engineering is one green alternative to organic synthesis that can be used to manipulate molecular behavior promptly and economically. We report the preparation and characterization of the pharmaceutical organic salt (FLC-C) of fluconazole (FLC) and organosulfonate (NDSA-2H), based on the sulfonate-pyridinium supramolecular synthon. Structural studies validate the crystallization of the two-component stoichiometric crystal with two molecules of water in the triclinic P 1̅ space group. The anticipated proton transfer between the crystal forms leads to ionic interactions, augmenting the organic salt's thermal stability. Hirshfeld studies of FLC-C help to understand the role and significance of different types of intermolecular interactions responsible for crystal packing. The structural and theoretical studies indicate the absence of π-π interactions in FLC-C, which account for the incipience of solid-state emission in the product. The solubility studies establish augmented aqueous solubility of FLC-C over pristine FLC at physiological pH values of 2 and 7. Interestingly, in in vitro studies, FLC-C appears to serve as a potential alternative to FLC, displaying a wide spectrum of antifungal activity. FLC-C is active against several human pathogenic yeast strains, including the leading and emerging Candida strains ( Candida albicans and Candida auris, respectively), at comparable and/or lower drug concentrations without showing any enhanced host cell toxicity. Interestingly, the pharmaceutical co-crystal also displays fluorescence properties inside the Candida cells.

Introduction: Chromatography and spectroscopy are nowadays well-validated techniques allowing to isolate and purify different class of natural products from the genus Codonopsis. Several categories of phytochemicals with drug like properties have been selectively extracted, isolated, characterised by this methodology., Objectives: The present review aims to provide up-to-date and comprehensive information on the chromatography, phytochemistry and pharmacology of natural products of Codonopsis with an emphasis on the search for natural products having various biological activities and the semi-synthetic derivatives of bioactive ones and to highlight current gaps in knowledge., Materials and Methods: A literature search was performed in the SciFinder Scholar, PubMed, Medline, and Scopus databases., Results: During the period covered in this review, several classes of compounds have been reported from genus Codonopsis. Codonopsis pilosula and Codonopsis lanceolata are the most popular in the genus especially as per phytochemical and bioactive studies. Phytochemical investigation demonstrates that Codonopsis species contain mainly xanthones, flavonoids, alkaloids, polyacetylenes, phenylpropanoids, triterpenoids and polysaccharides, which contribute to numerous bioactivities. The major bioactive compounds isolated were used for semi-synthetic modification to increase the chance to discover lead compound., Conclusions: It can be concluded that genus Codonopsis has been used as traditional medicines and food materials around the world over years due to chemical constituents with diverse structural types, exhibiting extensive pharmacological activities in immune system, blood system, cardiovascular system, central nervous system, digestive system, and so forth, with almost no obvious toxicity and side effect. Therefore, Codonopsis can be used as a promising ethnopharmacological plant source., (© 2023 John Wiley & Sons Ltd.)

Background: Obstructive sleep apnea (OSA) is a sleep disorder characterized by periodic and repetitive partial or complete collapse of the upper airway during sleep, resulting in reduced ventilation (hypopnea) or absent ventilation (apnea)., Materials and Methods: The present study was conducted on 100 adult OSA patients attending hospitals of Jodhpur and the dental clinic in Vyas Dental College and Hospital in Jodhpur city. The sample consisted of 65.0% males and 35.0% females, belonging to 18 years ≥60 years of age with a mean age of 47.61 ± 8.53., Results: In our study, we have used AHI for the assessment of OSA, the major significant association ( P = 0.001) was seen between AHI and periodontitis. The finding suggest that the prevalence of periodontitis is greater among patient with OSA with almost 39 patients with AHI value between 11to15 having loss of attachment between 4 mm ≥8 mm., Conclusion: Obstructive sleep apnea is acting as a significant risk factor for major Dental diseases. The study concludes that there was a significant association found between oral health status and OSA patients., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Pharmacy and Bioallied Sciences.)

Biopolymers have received widespread attention due to their beneficial characteristics, such as like easy processing, biodegradability and biocompatibility. Concurrently, inorganic polyoxometalates (POMs), a class of metal-oxygen anionic and nanosized clusters of early transition metals, have a wide range of attractive functions and are used in biomedical and industrial fields. In this communication, we report a simple approach to create ammonium metavanadate (AMV)-biopolymer composite hydrogel beads that combine the advantages of biopolymers and POM clusters. Crosslinking was achieved through electrostatic interactions between cationic chitosan, chitosan/gelatin, chitosan/methylcellulose and AMV (NH 4 VO 3 ). The as-prepared hydrogel beads were yellow in colour and exhibited a high mechanical strength. They were characterized using FT-IR spectroscopy and SEM, to confirm hydrogel formation and evaluate their surface morphology. It was demonstrated that the fabricated hydrogel blend possessed tuneable physicochemical properties, good swelling behaviour (with a maximum swelling of 432%), excellent luminescence and adsorption, and remarkable biomedical properties. Batch adsorption experiments demonstrated that the beads had an equilibrium adsorption capacity of 539 mg g -1 for the removal of Congo red dye from aqueous solutions, which was more efficient than the most reported natural biosorbents. Due to their luminescence properties these hydrogel beads showed excellent selective sensing behaviour toward ascorbic acid with a LOD of 1.06 μM. The hydrogels were also assessed for their antibacterial activity, and were tested against Staphylococcus aureus , Escherichia coli , Streptococcus anginosus , and Klebsiella pneumoniae . The cytotoxicity results showed that the embedded POMs exhibited dose-dependent cytotoxicity against the embryonic kidney cell line (HEK).

Current study was conducted to evaluate the effect of important land uses and soil depth on soil organic carbon pools viz. total organic carbon, Walkley and black carbon, labile organic carbon, particulate organic carbon, microbial biomass carbon and carbon management index (CMI) in the north Western Himalayas, India. Soil samples from five different land uses viz. forest, pasture, apple, saffron and paddy-oilseed were collected up to a depth of 1 m (0-30, 30-60, 60-90 cm). The results revealed that regardless of soil depth, all the carbon pools differed significantly ( p  < 0.05) among studied land use systems with maximum values observed under forest soils and lowest under paddy-oilseed soils. Further, upon evaluating the impact of soil depth, a significant ( p  < 0.05) decline and variation in all the carbon pools was observed with maximum values recorded in surface (0-30 cm) soils and least in sub-surface (60-90 cm) layers. CMI was higher in forest soils and lowest in paddy-oilseed. From regression analysis, a positive significant association (high R-squared values) between CMI and soil organic carbon pools was also observed at all three depths. Therefore, land use changes and soil depth had a significant impact on soil organic carbon pools and eventually on CMI, which is used as deterioration indicator or soil carbon rehabilitation that influences the universal goal of sustainability in the long run., Competing Interests: The authors declare there are no competing interests., (©2023 Mir et al.)

An ultra-stretchable, quickly self-healable, adhesive hydrogel with efficient anti-oxidant and anti-bacterial activities makes it potential wound dressing material, particularly in healing skin wounds. However, it is highly challenging to prepare such hydrogels with a facile and efficient material design. Given this, we opine the synthesis of medicinal plant Bergenia stracheyi extract-loaded hybrid hydrogels of biocompatible and biodegradable polymers like Gelatin, Hydroxypropyl cellulose, and Polyethylene glycol with acrylic acid via in situ free radical polymerization reaction. The selected plant extract is rich in phenols, flavonoids, and tannins and found to have important therapeutic benefits such as anti-ulcer, anti-Human Immunodeficiency Virus, anti-inflammatory, and burn wound healing effects. The polyphenolic compounds in the plant extract interacted strongly via hydrogen bonding with -OH, -NH 2 , -COOH, and C-O-C groups of the macromolecules. The synthesized hydrogels were characterized by fourier transform infrared spectroscopy and rheology. The as-prepared hydrogels demonstrate ideal tissue adhesion, excellent stretchability, good mechanical strength, broad-band anti-bacterial capability, and efficient anti-oxidant properties, in addition to quick self-healing and moderate swelling properties. Thus, the aforementioned properties attract the potential use of these materials in the biomedical field., Competing Interests: Declaration of competing interest There are no conflicts of interest to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Soil carbon (SC) heterogeneity in mountain ecosystems is ascertained by a complex interdependency of topography, climate, edaphic features, and biotic elements, which may incite uncertainties in regional SC estimation. However, quantitative evaluations of the interplay between SC and these determinants as well as underlying possible link networks, are uncommon. Using the data set of SC along with soil properties at 0-10 and 10-20 cm depths from 135 plots under three coniferous forests, we aimed to ascertain SC heterogeneity and to elucidate how these interactions affect the SC storage, operating data-driven models (Least Absolute Shrinkage and Selection Operator [LASSO] regression and structural equation modeling [SEM]) to identify the dominant explanatory factors affecting the distribution of SC in Kashmir Himalayan forests. Average SC stocks at 0-10 cm and 10-20 cm depth intervals range from 32.41 Mg ha -1 in sub-alpine (SA) forest to 48.50 Mg ha -1 in mixed conifer (MC) forest. The findings show that SC declines significantly from 0 - 10 cm to 10-20 cm strata, consistent with other soil physico-chemical determinants other than bulk density. SEM renders better model fit (0-10 cm: R 2  = 0.61; 10-20cm: R 2  = 0.46) with lesser uncertainties compared to LASSO (0-10 cm: R 2  = 0.55; 10-20cm: R 2  = 0.37). Soil properties and topography play a key role in modulating SC stocks, with total nitrogen (TN), soil moisture (SM), and elevation being principal drivers with contrasting effects on SC storage, while climate and vegetation parameters are of lesser influence. The relative effect of majority of explanatory drivers reduces with depth while that of temperature increases. Our analyses indicate that shifts in floristic composition could have long-lasting implications on soil structure and C storage, providing valuable data for C sink management., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Biomass and carbon stock assessments in data-deficient plantations and identifying the factors influencing tree growth, distribution, and carbon stocks are extremely important for implementing sound silvicultural management and monitoring practices to achieve REDD+ goals. We conducted carbon stock assessments in five major plantation types in a regional landscape in the central Western Ghats, India, by establishing fifty 0.1-ha plots across the landscape. We quantified the overall carbon stocks by summing the carbon pools across mature trees, deadwood, and soil (0 -15 cm) components. Allometric equations were compared to address the uncertainty in the tree biomass carbon. The tree biomass carbon and soil organic carbon varied significantly across the plantation types (F = 55.23, p < 0.00). The present study yielded the highest carbon stocks in Pinus plantation (201.91 ± 9.52 Mg ha -1 ) and the least in Eucalyptus (122.63 ± 9.73 Mg ha -1 ). The correlation analysis displayed a strong influence of mean annual precipitation and edaphic factors on soil organic carbon, while basal area and elevation were good predictors of tree biomass carbon. The principal component analysis revealed an association of predictor variables in the distribution of plantation types. We found a strong association between mean annual precipitation on Pinus plantation and mean annual temperature on Eucalyptus and Acacia plantations. On the other hand, teak pure plantation was associated with structural and topographic variables, while edaphic factors mainly influenced the distribution of teak mixed plantations. The findings of the present study conclude substantial carbon storage ability of the plantations in the studied landscape which can play a significant role in mitigating the effects of climate change and reaching carbon neutrality., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Globally growing demand for agricultural and farm foods has more or less become dependent on chemical pesticides to maintain the supply chain, which undoubtedly boosts agricultural production. However, pesticides not only impact the target pests but cause hazard to human health. Pesticides are ubiquitous and can be found in almost every component of the environment. They can therefore impair human and biota health when present over the threshold level. The present study assessed the concentration of commonly used pesticides for agricultural purposes but get mixed in different sources of water, as such fifteen sampling sites along the upper Jhelum basin of Kashmir valley were chosen. For the analysis, 60 water samples were obtained from different water sources. Gas chromatography coupled with tandem mass spectrometry (GC-MS/MS) was used to determine pesticide residues in water samples. Pesticide residues from 10 of the 26 commonly used pesticides were detected in water samples. Difenoconazole had the highest concentration among the pesticides detected, with a mean concentration of 0.412 ± 0.424  μ g/L ranging from 0.0  μ g/L to 0.8196  μ g/L. The target hazards quotient (THQ) was used to quantify the possible noncarcinogenic health risks associated with drinking pesticide-contaminated water. Only chlorpyrifos and quinalphos were detected >1 in RWS3 (1.6571), RWS4 (1.0285), RWS14 (1.2571), and RWS15 (1.2000) sample sites, implying that the drinking water poses a health risk to humans. Hence, pesticide hazards should be mitigated and rigorous monitoring is needed to reduce pesticide residues in drinking water., Competing Interests: All authors declare no potential conflicts of interest., (Copyright © 2023 M. Imran Ganaie et al.)

This work describes the syntheses, structural characterization, and biological profile of Mn(II)- and Zn(II)-based complexes 1 and 2 derived from the aroyl-hydrazone Schiff base ligand ( L1 ). The synthesized compounds were thoroughly characterized by elemental analysis, Fourier transform infrared spectroscopy (FTIR), UV-vis, electron paramagnetic resonance (EPR), nuclear magnetic resonance (NMR), and single-crystal X-ray diffraction (s-XRD). Density functional theory (DFT) studies of complexes 1 and 2 were performed to ascertain the structural and electronic properties. Hirshfeld surface analysis was used to investigate different intermolecular interactions that define the stability of crystal lattice structures. To ascertain the therapeutic potential of complexes 1 and 2 , in vitro interaction studies were carried out with ct-DNA and bovine serum albumin (BSA) using analytical and multispectroscopic techniques, and the results showed more avid binding of complex 2 than complex 1 and L1 . The antioxidant potential of complexes 1 and 2 was examined against the 2,2-diphenyl picrylhydrazyl (DPPH) free radical, which revealed better antioxidant ability of the Mn(II) complex. Moreover, the antibacterial activity of synthesized complexes 1 and 2 was tested against Gram-positive and Gram-negative bacteria in which complex 2 demonstrated more effective bactericidal activity than L1 and complex 1 toward Gram-positive bacteria. Furthermore, the in vitro cytotoxicity assessment of L1 and complexes 1 and 2 was carried out against MDA-MB-231 (triple negative breast cancer) and A549 (lung) cancer cell lines. The cytotoxic results revealed that the polymeric Zn(II) complex exhibited better and selective cytotoxicity against the A549 cancer cell line as was evidenced by its low IC 50 value., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

The bulk and interfacial shear rheological behavior of aqueous solutions of biocompatible polymer HPC has been investigated in the presence of cationic CTAB and nonionic Tween 40 having the same chain length but different head groups. Steady-state bulk experiments depict two distinct regions in the rheogram (Newtonian followed by pseudoplastic). Dynamic experiments suggest that the stability of HPC hydrogels decreases with the increase in surfactant concentration. Interfacial steady shear tests of 2D monolayers of 1 wt % HPC and 1 wt % HPC with varying concentrations of Tween 40/CTAB show a non-Newtonian dilatant behavior at the solution-air interface. However, two distinct dilatant regions separated by a Newtonian region were observed for the same films at the solution-soya oil interface. The strength of films formed at the two interfaces decreases with the increase of surfactant concentration as observed from oscillatory interfacial tests. HPC interacts more strongly with CTAB than Tween 40 both in bulk as well as at the interfaces studied.

Recent global health concern motivated the exploration of natural medicinal plant resources as an alternative target for treating COVID-19 infection and associated inflammation. In the current study, a phytochemical, 6-shogaol [1-(4-hydroxy-3-methoxyphenyl)dec-4-en-3-one; 6-SHO] was investigated as a potential anti-inflammatory and anti-COVID-19 agent. In virus release assay, 6-SHO efficiently (94.5%) inhibited SARS-CoV2 replication. When tested in the inflammasome activation model, 6-SHO displayed mechanistic action by regulating the expression of the inflammasome pathway molecules. In comparison to the existing drugs, remdesivir and hydroxy-chloroquine, 6-SHO was not only found to be as effective as the standard anti-viral drugs but also much superior and safe in terms of predicted physicochemical properties and clinical toxicity. Comparative molecular dynamics simulation demonstrated a stable interaction of 6-SHO with NLRP3 (the key inflammasome regulator) in the explicit water environment. Overall, this study provides important cues for further development of 6-SHO as potential anti-inflammatory and anti-viral therapeutic agents., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Objective: Studies on the prevalence of adverse childhood experiences (ACEs) in Kashmir, India, are yet to be conducted. This study aims to estimate the prevalence of ACEs among young adults across all the ten districts of Kashmir Valley., Methods: A cross-sectional research strategy was used to assess the prevalence of ACEs by employing a multi-stage sampling method. Data were collected from 800 students studying in different colleges and universities in Kashmir with the help of the "Adverse Childhood Experiences" (ACEs) scale., Results: Findings disclosed that less than a quarter of the respondents reported high exposure to ACEs (15.4 %), more than one-tenth of the participants reported extremely high exposure to ACEs (13.4 %), over a quarter of the sample reported moderate exposure to ACEs (26.3 %), one-third of the youth reported low exposure to ACEs (33.0 %) and over one-tenth of the respondents reported no exposure to ACEs (11.8 %). The prevalence of ACEs was found to be 88.2 % (females: 82.7 % and males: 90.8 %) in Kashmir. The ACEs with the highest level of prevalence were "often or very often sworn at, insulted, or put down" (49.8 %), followed by "often or very often acted in a way that made them afraid that they would be physically hurt" (47.6 %), "often or very often pushed, grabbed, shoved, or slapped" (41.6 %), "often or very often hit so hard that they had marks or were injured" (28.3 %) and "touched or sexually fondled" (25.3 %). Thirteen out of 21 adverse events during childhood were significantly associated with gender., Conclusion: The findings suggest the need to advocate early targeted interventions, reduce ACEs and their impact, and design efficient measures to improve the health and well-being of young adults in Kashmir., Competing Interests: Declaration of competing interest The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Purpose: To assess the biomarker and functional role of the chromatin remodeling factor, bromodomain PHD finger transcription factor (BPTF), in breast cancer progression., Methods: BPTF copy number was assessed using fluorescence in situ hybridization. BPTF expression was regulated in breast cancer cells by shRNA/siRNA-mediated gene silencing and BPTF cDNA overexpression. The effects of regulating BPTF expression were examined on key oncogenic signaling pathways and on breast cancer cell proliferation, apoptosis, and cell cycle progression, as well as in xenograft models. The consequences of pharmacological bromodomain inhibition, alone or in combination with other targeted agents, on breast cancer progression were assessed in culture and in xenograft models., Results: BPTF copy number was gained in 34.1% and separately amplified in 8.2% of a breast cancer tissue cohort. Elevated BPTF copy number was significantly associated with increasing patient age and tumor grade and observed in both ER-positive and triple-negative breast cancer (TNBC) subtypes. BPTF copy number gain and amplification were also observed in The Cancer Genome Atlas (TCGA) breast cancer cohort. Stable shRNA-mediated silencing of BPTF significantly inhibited cell proliferation and induced apoptosis in TNBC and ER-positive human breast cancer cell lines. BPTF knockdown suppressed signaling through the phosphoinositide 3 kinase (PI3K) pathway, including reduced expression of phosphorylated AKT (Ser473), phosphorylated GSK-β (Ser9), and CCND1. These findings were confirmed following transient BPTF knockdown by a distinct siRNA in TNBC and ER-positive breast cancer cells. Stable suppression of BPTF expression significantly inhibited the in vivo growth of TNBC cells. Conversely, BPTF cDNA overexpression in TNBC and ER-positive breast cancer cells enhanced breast cancer cell proliferation and reduced apoptosis. BPTF targeting with the bromodomain inhibitor bromosporine, alone or in combination with the PI3K pathway inhibitor gedatolisib, produced significant anti-tumor effects against TNBC cells in vitro and in vivo ., Conclusion: These studies demonstrate BPTF activation in distinct breast cancer subtypes, identify pathways by which BPTF promotes breast cancer progression, and suggest BPTF as a rational target for breast cancer therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bezrookove, Khan, Nosrati, Miller, McAllister, Dar and Kashani-Sabet.)

We describe our institutional experience of developing a liquid biopsy approach using circulating tumor DNA (ctDNA) analysis for personalized medicine in cancer patients, focusing on the hurdles encountered during the multistep process in order to benefit other investigators wishing to set up this type of study in their institution. Blood samples were collected at the time of cancer surgery from 209 patients with one of nine different cancer types. Extracted tumor DNA and circulating cell-free DNA were sequenced using cancer-specific panels and the Illumina MiSeq machine. Almost half of the pairs investigated were uninformative, mostly because there was no trackable pathogenic mutation detected in the original tumor. The pairs with interpretable data corresponded to 107 patients. Analysis of 48 gene sequences common to both panels was performed and revealed that about 40% of these pairs contained at least one driver mutation detected in the DNA extracted from plasma. Here, we describe the choice of our overall approach, the selection of the cancer panels, and the difficulties encountered during the multistep process, including the use of several tumor types and in the data analysis. We also describe some case reports using longitudinal samples, illustrating the potential advantages and rewards in performing ctDNA sequencing to monitor tumor burden or guide treatment for cancer patients., Competing Interests: The authors declare no conflict of interest.

Air is a diverse mixture of gaseous and suspended solid particles. Several new substances are being added to the air daily, polluting it and causing human health effects. Particulate matter (PM) is the primary health concern among these air toxins. The World Health Organization (WHO) addressed the fact that particulate pollution affects human health more severely than other air pollutants. The spread of air pollution and viruses, two of our millennium's most serious concerns, have been linked closely. Coronavirus disease 2019 (COVID-19) can spread through the air, and PM could act as a host to spread the virus beyond those in close contact. Studies on COVID-19 cover diverse environmental segments and become complicated with time. As PM pollution is related to everyday life, an essential awareness regarding PM-impacted COVID-19 among the masses is required, which can help researchers understand the various features of ambient particulate pollution, particularly in the era of COVID-19. Given this, the present work provides an overview of the recent developments in COVID-19 research linked to ambient particulate studies. This review summarizes the effect of the lockdown on the characteristics of ambient particulate matter pollution, the transmission mechanism of COVID-19, and the combined health repercussions of PM pollution. In addition to a comprehensive evaluation of the implementation of the lockdown, its rationales-based on topographic and socioeconomic dynamics-are also discussed in detail. The current review is expected to encourage and motivate academics to concentrate on improving air quality management and COVID-19 control.

This study was conducted on ewes with pregnancy toxemia (PT) with an attempt to evaluate metabolic and oxidative profile in subclinical and clinical ovine pregnancy toxemia and to determine their association with diagnosis and prognosis of the disease. A total of 20 ewes having beta-hydroxy butyric acid (β-HBA) > 2.5 mmol/L and proven clinical sings of PT, categorized as clinical PT (CPT); 12 ewes having β-HBA 0.8-2.5 mmol/L and no clinical signs of PT, categorized at subclinical PT (SPT); and 10 ewes having β-HBA ≤ 0.8 mmol/L, categorized as healthy control (CON) were enrolled. Among 20 CPT ewes, 11 had negative outcomes (non-survivors), six ewes had positive outcomes (survivors), and three were lost during follow-up. A significant increase in non-esterified fatty acid, β-HBA, triglycerides, gamma-glutamyl transferase, lactate dehydrogenase, and malondialdehyde levels and a significant decrease in fructosamine were observed in CPT and SPT compared to CON. A significant increase in cholesterol, aspartate amino transferase, and creatinine kinase and a significant decrease in albumin, potassium, calcium, superoxide dismutase, and catalase were observed in CPT only. Glucose was significantly decreased in SPT only. The highest area under the curve (AUC) was observed for fructosamine (89.7% and 87.5% for CPT and SPT, respectively) with the optimum cutoff point calculated on the basis of maximum sensitivity (SE) and specificity (SP) being 0.607 mmol/L (SE: 89.3% and SP: 72.2%) and 1.005 mmol/L (SE: 90.0% and SP: 75.3%) for CPT and SPT, respectively. At the cutoff limit of 0.607 mmol/L and 1.005 mmol/L, the odds ratio was 10.8 and 8.0 for CPT and SPT, respectively. A significant decrease in fructosamine and potassium and a significant increase in creatinine, lactate dehydrogenase, and malondialdehyde were observed in non-survivors compared to survivors. It was thus concluded that fructosamine was the best diagnostic indicator of both CPT and SPT followed by non-esterified fatty acid. Fructosamine, creatinine, potassium, lactate dehydrogenase, and malondialdehyde were the best prognostic indicators of PT., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

The novel coronavirus (COVID-19) has become a cause for global concern. Apart from a multitude of symptoms, the virus is known for its ability to cause loss of taste and smell that can be irreversible in a few cases. In fact, even after recovery, post-covid syndrome can still lead to devastating outcomes, specifically with reference to loss of smell and taste. A number of mechanisms that have been postulated include receptor-mediated uptake, increased inflammation, transneuronal migration, and direct damage to the olfactory pathway. Considering how important these two senses are, many psychological, social, and emotional repercussions can be expected. These repercussions include lowering of self-esteem and developmental of mental health issues. Long-term altered taste sensation can also lead to the development of unhealthy eating habits that can result in increasing risk for diabetes and hypertension. A few solutions have been investigated for treating these chemosensory dysfunctions, such as olfactory training, corticosteroids, theophylline and acupuncture. Although the results have been promising but a new modality, virtual reality, requires more in-depth exploration because it targets not only the dysfunction but also the mental health issues being experienced. It is important that affected individuals be provided with strong emotional and family support. Additionally, physicians can help the patients through support groups, cognitive behavioural therapy, olfactory, and virtual reality training., Competing Interests: The authors declare no competing interests., (Copyright: Nismat Javed et al.)

COVID-19 pandemic caused global epidemic infections, which is one of the most severe infections in human medical history. In the absence of proper medications and vaccines, handling the pandemic has been challenging for governments and major health facilities. Additionally, tracing COVID-19 cases and handling data generated from the pandemic are also extremely challenging. Data privacy access and collection are also a challenge when handling COVID-19 data. Blockchain technology provides various features such as decentralization, anonymity, cryptographic security, smart contracts, and a distributed framework that allows users and entities to handle COVID-19 data better. Since the outbreak has made the moral crisis in the clinical and administrative centers worse than any other that has resulted in the decline in the supply of the exact information, however, it is vital to provide fast and accurate insight into the situation. As a result of all these concerns, this study emphasizes the need for COVID-19 data processing to acquire aspects such as data security, data integrity, real-time data handling, and data management to provide patients with all benefits from which they had been denied owing to misinformation. Hence, the management of COVID-19 data through the use of the blockchain framework is crucial. Therefore, this paper illustrates how blockchain technology can be implemented in the COVID-19 data handling process. The paper also proposes a framework with three main layers: data collection layer; data access and privacy layer; and data storage layer., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Arshad Ahmad Dar et al.)

Therapy of BRAF -mutant melanoma with selective inhibitors of BRAF (BRAFi) and MEK (MEKi) represents a major clinical advance but acquired resistance to therapy has emerged as a key obstacle. To date, no clinical approaches successfully resensitize to BRAF/MEK inhibition. Here, we develop a therapeutic strategy for melanoma using bromosporine, a bromodomain inhibitor. Bromosporine (bromo) monotherapy produced significant anti-tumor effects against established melanoma cell lines and patient-derived xenografts (PDXs). Combinatorial therapy involving bromosporine and cobimetinib (bromo/cobi) showed synergistic anti-tumor effects in multiple BRAFi-resistant PDX models. The bromo/cobi combination was superior in vivo to standard BRAFi/MEKi therapy in the treatment-naive BRAF -mutant setting and to MEKi alone in the setting of immunotherapy-resistant NRAS - and NF1 -mutant melanoma. RNA sequencing of xenografts treated with bromo/cobi revealed profound down-regulation of genes critical to cell division and mitotic progression. Bromo/cobi treatment resulted in marked DNA damage and cell-cycle arrest, resulting in induction of apoptosis. These studies introduce bromodomain inhibition, alone or combined with agents targeting the mitogen activated protein kinase pathway, as a rational therapeutic approach for melanoma refractory to standard targeted or immunotherapeutic approaches.

In India the genus Plicigastra is represented by single species Plicigastra himalayana Cigliano et al. (2022). Uvarov (1924) reported the species from the Punjab region of India, based on only female specimens. The authors in the present paper described both male and female. Also, SEM images of male stridulatory file are given. The dark flightless Bush-cricket species is widespread in the forested region of northern part of Kashmir, which starts from Baramulla to Bandipora, situated at an elevation of 3200 m a.s.l and is part of the Western Himalayan Mountain mixed forest Eco region.

Herein, a novel, rapid, reliable, simple method validation and simultaneous quantification of 11 bioactive compounds (mostly xanthones) have been described. International Conference on Harmonization guidelines were used for the analytical method validation. Good linearity, repeatability, intra- and inter-day precision, accuracy and reliability were well-illuminated in the method validation procedure. The calibration curves showed a good linear relationship (r > 0.999) within test range. Precision was evaluated by intra- and inter-day tests with relative standard deviation <2.79% and accuracy validation recovery of 74.16%-91.84%. On quantification study, the validated method described the high content of bioactive xanthone derivatives, including 1-hydroxy-3, 5-dimethoxyxanthone (7), 2-(allyloxy)-8-hydroxy-1, 6-dimethoxyxanthone (6) 1, 7, 8-trihydroxy-3-methoxyxanthone (9) and Coxanthone E (5) in Codonopsis ovata, which is advantageous given the numerous pharmacological and biological effects associated with these compounds, which mostly exhibit anti-cancerous, antioxidant, anti-inflammatory, anti-mutagenic and anti-obesity effects. The bulk abundance of these compounds can also be used for further modification to produce better lead molecules for drug discovery with low toxicity and high potency. The proposed method makes it possible to simultaneously determine all bioactive compounds in one run and can be extended to marker-based standardization of herbal formulations in medicinal and pharmaceutical industries., (© 2022 John Wiley & Sons Ltd.)

We report a promising strategy based on chitosan (CS) hydrogels and dual temperature- and pH-responsive poly( N -isopropylacrylamide- co -methacrylic acid) (PNIPAM- co -MAA) microgels to facilitate release of a model drug, moxifloxacin (MFX). In this protocol, first, the microgels were prepared using a free radical copolymerization method, and subsequently, these carboxyl-group-rich soft particles were incorporated inside the hydrogel matrix using an EDC-NHS amidation method. Interestingly, the resulting microgel-embedded hydrogel composites (MG-HG) acting as a double barrier system largely reduced the drug release rate and prolonged the delivery time for up to 68 h, which was significantly longer than that obtained using microgels or hydrogels alone (20 h). On account of the dual-responsive features of the embedded microgels and the variation of water-solubility of drug molecules as a function of pH, MFX could be released in a controllable manner by regulating the temperature and pH of the delivery medium. The release kinetics followed a Korsmeyer-Peppas model, and the drug delivery mechanism was described by Fickian diffusion. Both the gel precursors and the hydrogel composites exhibited low cytotoxicity against mammalian cell lines (HeLa and HEK-293) and no deleterious hemolytic activity up to a certain higher concentration, indicating excellent biocompatibility of the materials. Thus, the unprecedented combination of modularity of physical properties caused by soft particle entrapment, unique macromolecular architecture, biocompatibility, and the general utility of the stimuli-responsive polymers offers a great promise to use these composite materials in drug delivery applications.

Background: The present study was designed to develop an improved in vitro regeneration system for Dioscorea bulbifera using mature nodal explants. Direct organogenesis from nodal segments was achieved by culturing the nodal explants on Murashige and Skoog medium supplemented with 3.5 mgl -1 6-benzylaminopurine (BAP). Shoot multiplication was widely affected by the kind and concentration of plant growth regulators, and the sub-culturing of in vitro regenerated shootlets on fresh medium. After incubation for 4 weeks at optimum BAP concentration, cultures were transferred to secondary medium with BAP (optimized concentration) supplemented with different auxins., Results: On medium with 3.5 mgl -1 6-benzylaminopurine, maximum regeneration (87 ± 1.85%) with an average shoot number of 2.0 ± 0.08, and length of 3.5 ± 0.04 cm were observed after 4 weeks of incubation. Maximum number of shoots (3.9 ± 0.21) was observed with 3.5 mgl -1 BAP in combination with 0.75 mgl -1 indole-3-acetic acid. The best root formation was observed on ½ MS medium supplemented with 0.75 mgl -1 α-naphthalene acetic acid, with 4.7 ± 0.03 roots per shoot. The well-rooted plantlets were successfully acclimatized in with 100% survival rate. The plantlets grew well with normal growth, flowering and showed, by High performance thin layer chromatography, almost same number of phytoconstituents compared with the mother plant., Conclusions: This is the first study on comparative phytochemical analysis of wild growing and in vitro regenerated plants of D. bulbifera which validates the medicinal and nutritional properties of in vitro raised plants., (© 2022. The Author(s).)