Computational insights into allosteric inhibition of focal adhesion kinase: A combined pharmacophore modeling and molecular dynamics approach.

Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that modulates integrin and growth factor signaling pathways and is implicated in cancer cell migration, proliferation, and survival. Over the past decade various, FAK kinase, FERM, and FAT domain inhibitors have been reported and a few kinase domain inhibitors are under clinical consideration. However, few of them were identified as multikinase inhibitors. In kinase drug design selectivity is always a point of concern, to improve selectivity allosteric inhibitor development is the best choice. The current research utilized a pharmacophore modeling (PM) approach to identify novel allosteric inhibitors of FAK. The all-available allosteric inhibitor bound 3D structures with PDB ids 4EBV, 4EBW, and 4I4F were utilized for the pharmacophore modeling. The validated PM models were utilized to map a database of 770,550 compounds prepared from ZINC, EXIMED, SPECS, ASINEX, and InterBioScreen, aiming to identify potential allosteric inhibitors. The obtained compounds from screening step were forwarded to molecular docking (MD) for the prediction of binding orientation inside the allosteric site and the results were evaluated with the known FAK allosteric inhibitor (REF). Finally, 14 FAK-inhibitor complexes were selected from the docking study and were studied under molecular dynamics simulations (MDS) for 500 ns. The complexes were ranked according to binding free energy (BFE) and those demonstrated higher affinity for allosteric site of FAK than REF inhibitors were selected. The selected complexes were further analyzed for intermolecular interactions and finally, three potential allosteric inhibitor candidates for the inhibition of FAK protein were identified. We believe that identified scaffolds may help in drug development against FAK as an anticancer agent.

Exploring the abundance of microplastics in Indian landfill leachate: An analytical study.

Landfills are a major source of many emerging pollutants, including microplastics (MPs). This makes them a potential threat to human and environmental health and calls for a more detailed analysis of their hazard potential. India is a developing country with multiple unscientific waste dumping sites. In spite of their hazardous nature, detailed studies on the abundance of microplastics in landfills in India are scanty. Current work investigates the abundance and diversity of MPs in two landfills of India, Uruli Devachi in Pune (S1) and Deonar in Mumbai (S2). MPs collected from landfill leachate using multiple filters were analyzed using an optical microscope and categorized on the basis of shape, color and size to give information on their distribution. MP abundance in S1 was 1473 ± 273.01 items/L while 2067 ± 593.75 items/L were found in leachate from S2. Film and fragment were the dominant shape and black was the dominant color of MP found in both the landfills. Maximum number of MPs were in the size range below 100 µm in both the landfills necessitating the study of small sized particles. Chemical characterization revealed the prevalence of four types of MPs (polyethylene terephthalate, polypropylene, cellulose acetate and polyvinyl chloride). This study sheds light on the prevalence, characteristics, abundance and distribution of MPs in landfill leachate in Western India, sparking more research into the processes followed for capturing the factual small sized microplastic abundance data. This study is vital for a detailed management of landfill leachate enabling a sustainable waste management and targeted actions for ecosystem preservation.

Characterization of a CrPME indicates its possible role in determining vindoline accumulation in Catharanthus roseus leaves.

The leaf-specific Catharanthus roseus alkaloid, vindoline, is the major bottleneck precursor in the production of scarce and costly anticancer bisindoles (vincristine and vinblastine). The final steps of its biosynthesis and storage occur in the laticifers. Earlier, we have shown that vindoline content is directly related to laticifer number. Pectin remodeling enzymes, like pectin methylesterase (PME), are known to be involved in laticifer development. A search in the croFGD yielded a leaf-abundant CrPME isoform that co-expressed with a few vindoline biosynthetic genes. Full-length cloning, tissue-specific expression profiling, and in silico analysis of CrPME were carried out. It was found to possess all the specific characteristics of a typical plant PME. Transient silencing (through VIGS) and overexpression of CrPME in C. roseus indicated a direct relationship between its expression and vindoline content. Comparative analysis of transcript abundance and enzyme activity in three familial C. roseus genotypes differing significantly in their vindoline content and laticifer count (CIM-Sushil > Dhawal > Nirmal) also corroborated the positive relationship of CrPME expression with vindoline content. This study highlights the possible role of CrPME, a cell wall remodeling enzyme, in modulating laticifer-associated secondary metabolism.

Postoperative Outcomes After Emergency Surgery in COVID-19 Patients: An Ambispective Matched Cohort Study.

Purpose There is limited data from the Indian subcontinent regarding the surgical outcomes of coronavirus disease (COVID-19) patients. In this observational study, we aimed to evaluate the postoperative outcomes after emergency surgery in COVID-19 patients compared to concurrent age and gender-matched controls. We also sought to analyze the possible predictors of postoperative mortality in COVID-19 patients. Methods This matched cohort study was conducted in a tertiary care teaching hospital in central India, between 1st July 2021 and 30th June 2022. COVID-19-positive patients undergoing emergency surgery under anesthesia were recruited as cases. Age and gender-matched COVID-19-negative patients undergoing a similar nature of surgery in the same period served as concurrent controls. The cases and controls were compared for the 30-day mortality and perioperative complications. Results The COVID-19-positive surgical cohort had a 12.3 times greater 30-day postoperative overall mortality risk as compared to a matched cohort of patients with a negative COVID-19 test. A positive COVID-19 status was associated with more postoperative complications of acute respiratory distress syndrome (ARDS), sepsis, shock, and persistent hyperglycemia. On analysis of predictors of mortality, the presence of preoperative dyspnea, ARDS, American Society of Anesthesiologists Physical Status (ASA-PS) Class IIIE/IVE, increase in sequential organ failure assessment (SOFA) score, Quick SOFA>1, higher creatinine, bilirubin, and lower albumin were observed to be associated with increased mortality. Conclusions Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients undergoing emergency surgery is significantly associated with higher postoperative complications and increased 30-day postoperative mortality.

Modulating cultivation regimes of Messastrum gracile SVMIICT7 for biomass productivity integrated with resource recovery via hydrothermal liquefaction.

The present study was designed to assess Messastrum gracile SVMIICT7 potential in treating dairy wastewater (autoclaved (ADWW) and raw (DWW)) with relation to nutrient removal, in-vivo Chl-a-based biomass, and bio-oil synthesis. Chlorophyll a fluorescence kinetics revealed improved photochemical efficiency (0.639, Fv/Fm) in M. gracile when grown with DWW. This may be owing to enhanced electron transport being mediated by an effective water-splitting complex at photosystem (PSII) of thylakoids. The increase in ABS/RC observed in DWW can be attributed to the elevated chlorophyll content and reduced light dissipation, as evident by higher values of ETo/RC and a decrease in non-photochemical quenching (NPQ). M. gracile inoculated in DWW had the highest Chl-a-biomass yield (1.8 g L-1) and biomolecules while maximum nutrient removal efficiency was observed in ADWW (83.7% TN and 60.07% TP). M. gracile exhibited substantial bio-oil yield of 29.6% and high calorific value of 37.19 MJ kg-1, predominantly composed of hydrocarbons along with nitrogen and oxygen cyclic compounds. This research offers a thorough investigation into wastewater treatment, illustrating the conversion of algal biomass into valuable energy sources and chemical intermediates within the framework of a biorefinery.

Neuroprotective effect of taxifolin against aluminum chloride-induced dementia and pathological alterations in the brain of rats: possible involvement of toll-like receptor 4.

Aluminum (Al) overexposure damages various organ systems, especially the nervous system. Regularly administered aluminum chloride (AlCl3) to rats causes dementia and pathophysiological alterations linked to Alzheimer's disease (AD). Taxifolin's neuroprotective effects against AlCl3-induced neurotoxicity in vitro and in vivo studies were studied. Taxifolin (0.1, 0.3, 1, 3, and 10 µM) was tested against AlCl3 (5 mM)-induced neurotoxicity in C6 and SH-SY5Y cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays. Additionally, neural morphology was examined by confocal microscopy. Additionally, taxifolin's mode of binding with the co-receptor of toll-like receptor 4 (TLR4), human myeloid differentiation-2 (hMD-2) was investigated. AlCl3 (25 mg/kg/d, i.p.) was administered to rats for 14 d, and from the eighth day, taxifolin (1, 2, and 5 mg/kg/d, i.p.) was given along with AlCl3. This study assessed memory impairment using the Morris water maze, plus maze, and pole tests. This study also performed measurement of oxidant (malondialdehyde [MDA] and nitrite), antioxidant (reduced glutathione), and inflammatory (myeloperoxidase [MPO] activity, TLR4 expression) parameters in rats' brain in addition to histopathology. The docking score for taxifolin with hMD-2 was found to be -4.38 kcal/mol. Taxifolin treatment reduced the neurotoxicity brought on by AlCl3 in both C6 and SH-SY5Y cells. Treatment with 10 µM taxifolin restored AlCl3-induced altered cell morphology. AlCl3 administration caused memory loss, oxidative stress, inflammation (increased MPO activity and TLR4 expression), and brain atrophy. Taxifolin treatment significantly improved the AlCl3-induced memory impairment. Taxifolin treatment also mitigated the histopathological and neurochemical consequences of repeated AlCl3 administration in rats. Thus, taxifolin may protect the brain against AD.

Exploring the Relation Between Interstitial Lung Diseases and Chronic Periodontitis: A Systematic Review.

The objective of this systematic review is to determine the association between interstitial lung diseases and chronic periodontitis from various aspects such as microbial, biomarker, genetic, and environmental levels. A systematic review was carried out from 2000 to 2021 following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations including studies searched in PubMed-Medline, Google Scholar, and Cochrane databases. A total of more than 100 articles were obtained in the initial screening process. Out of these 42 studies fulfilled the inclusion criteria and were included in the study. According to the extracted data, there is mounting evidence suggesting the association between these two diseases. Our systematic review raises the prospect of a connection between chronic periodontitis and interstitial lung diseases, within the limitations of the studies we included.

Zinc nitride quantum dots as an efficient probe for simultaneous fluorescence detection of Cu2+ and Mn2+ ions in water samples.

The exceptional ascending heights of graphene (carbon) and boron nitride nanostructures have invited scientists to explore metal nitride nanomaterials. Herein, Zn3N2 quantum dots (QDs) were prepared via a simple hydrothermal route from the reaction between zinc nitrate hexahydrate and ammonia solution that possess efficient strength towards sensing applications of metal ions (Cu2+ and Mn2+). The as-prepared Zn3N2 QDs show bright fluorescence, displaying an emission peak at 408 nm upon excitation at 320 nm, with a quantum yield (QY) of 29.56%. It was noticed that the fluorescence intensity of Zn3N2 QDs linearly decreases with the independent addition of Cu2+ and Mn2+ ions, displaying good linearity in the ranges 2.5-50 µM and 0.05-5 µM with detection limits of 21.77 nM and of 63.82 nM for Cu2+ and Mn2+ ions, respectively. The probe was successfully tested for quantifying Cu2+ and Mn2+ in real samples including river, canal, and tap water, providing good recoveries with a relative standard deviation < 2%. Furthermore, the masking proposition can successfully eliminate the interference if the two metal ions exist together. It was found that thiourea is efficiently able to mask Cu2+ and selectively quenches Mn2+, and L-cysteine is able to halt the quenching potential of Mn2+ and is selectively able to sense Cu2+. The Zn3N2 QDs provide a simple way for the simultaneous detection of both Cu2+ and Mn2+ ions in environmental samples at low sample preparations requirements.

Low dose cadmium exposure regulates miR-381-ANO1 interaction in airway epithelial cells.

Chronic obstructive pulmonary disease (COPD) is the 3rd leading cause of death worldwide. Cigarette smoke which has approximately 2-3 µg of Cadmium (Cd) per cigarette contributes to the environmental exposure and development and severity of COPD. With the lack of a cadmium elimination mechanism in humans, the contribution of cadmium induced stress to lung epithelial cells remains unclear. Studies on cadmium responsive miRNAs suggest regulation of target genes with an emphasis on the critical role of miRNA-mRNA interaction for cellular homeostasis. Mir-381, the target miRNA in this study is negatively regulated by cadmium in airway epithelial cells. miR-381 is reported to also regulate ANO1 (Anoctamin 1) expression negatively and in this study low dose cadmium exposure to airway epithelial cells was observed to upregulate ANO1 mRNA expression via mir-381 inhibition. ANO1 which is a Ca2+-activated chloride channel has multiple effects on cellular functions such as proliferation, mucus hypersecretion and fibroblast differentiation in inflamed airways in chronic respiratory diseases. In vitro studies with cadmium at a high concentration range of 100-500 µM is reported to activate chloride channel, ANO1. The secretory epithelial cells are regulated by chloride channels like CFTR, ANO1 and SLC26A9. We examined "ever" smokers with COPD (n = 13) lung tissue sections compared to "never" smoker without COPD (n = 9). We found that "ever" smokers with COPD had higher ANO1 expression. Using mir-381 mimic to inhibit ANO1, we demonstrate here that ANO1 expression is significantly (p < 0.001) downregulated in COPD derived airway epithelial cells exposed to cadmium. Exposure to environmental cadmium contributes significantly to ANO1 expression.

Periodontal health status in patients with lung cancer: Case-control study.

Objective: The objective of this study was to assess the periodontal health status of individuals with lung cancer in the North Indian population. In addition, the study aimed to determine the levels of human beta-defensin2 (Hbd-2) in the gingival crevicular fluid (GCF) and serum samples collected from the participants. Methods: The study consisted of a total of 90 participants, who were categorized into three groups: Group 1 included 30 healthy individuals, Group 2 comprised 30 patients with chronic periodontitis, and Group 3 involved 30 patients diagnosed with both lung cancer and chronic periodontitis. Various periodontal parameters, including plaque index, gingival index, probing pocket depth, and clinical attachment level (CAL), were assessed in addition to the analysis of human beta defensin2 levels in both the GCF and serum samples of all participants. Results: The study results revealed that all clinical parameters assessed were higher in Group 3 compared to both Group 2 and Group 1. Specifically, the levels of hBD-2 in the GCF were measured as 52.29 ± 46.41 pg/mL in Group 1, 27.15 ± 28.76 pg/mL in Group 2, and 86.01 ± 68.82 pg/mL in Group 3. When comparing the hBD-2 levels in serum, the values were found to be 813.72 ± 269.43 pg/mL in Group 1, 591.50 ± 263.91 pg/mL in Group 2, and 1093.04 ± 674.55 pg/mL in Group 3. These intergroup comparisons indicate variations in hBD-2 levels among the different groups. Conclusions: The study findings demonstrated significantly higher clinical and biochemical markers in patients with both lung cancer and chronic periodontitis, in comparison to individuals with chronic periodontitis alone and healthy participants. These results suggest that Hbd-2 could potentially serve as a valuable diagnostic biomarker for identifying and distinguishing individuals with both lung cancer and chronic periodontitis.

Tumor hypoxia and role of hypoxia-inducible factor in oral cancer.

BACKGROUND: Head and neck cancer (HNC) is one of the most frequent malignancies in Asian males with a poor prognosis. Apart from well-known prognostic indicators, markers of tumor hypoxia can help us predict response to treatment and survival. METHODS: A review of the literature on the present evidence and potential clinical importance of tumor hypoxia in head and neck cancer was carried out. The data obtained from the literature search is presented as a narrative review. RESULTS: The literature shows possible associations between prognosis and low tumor oxygenation. Intermediate hypoxia biomarkers like HIF-1, GLUT-1, miRNA, and lactate, can help in predicting the response to therapy and survival as their altered expression is related to prognosis. CONCLUSIONS: Hypoxia is common in HNC and can be detected by use of biomarkers. The tumors that show expression of hypoxia biomarkers have poor prognosis except for patients with human papilloma virus-associated or VHL-associated cancers. Therapeutic targeting of hypoxia is emerging; however, it is still in its nascent stage, with increasing clinical trials hypoxia is set to emerge as an attractive therapeutic target in HNC.

Aberrant Lipid Metabolic Signatures in Acute Myeloid Leukemia.

Leukemogenesis is a complex process that involves multiple stages of mutation in either hematopoietic stem or progenitor cells, leading to cancer development over time. Acute myeloid leukemia (AML) is an aggressive malignancy that affects myeloid cells. The major disease burden is caused by immature blast cells, which are eliminated using conventional chemotherapies. Unfortunately, relapse is a leading cause of death in AML patients, with 30%-80% experiencing it within 2 years of initial treatment. The dominant cause of relapse in leukemia is the presence of therapy-resistant leukemic stem cells (LSCs). These cells express genes related to stemness that are frequently difficult to eradicate and tend to survive standard treatments. Studies have demonstrated that by targeting the metabolic pathways of LSCs, it is possible to improve outcomes and extend the survival of those afflicted by leukemia. The overwhelming evidence suggests that lipid metabolism is reprogrammed in LSCs, leading to an increase in fatty acid uptake and de novo lipogenesis. Genes regulating this process also play a crucial role in therapy evasion. In this concise review, we summarize the lipid metabolism in normal hematopoietic cells, AML blast cells, and AML LSCs. We also compare the lipid metabolic signatures in de novo versus therapy-resistant AML blast and LSCs. We further discuss the metabolic switches, cellular crosstalk, potential targets, and inhibitors of lipid metabolism that could alleviate treatment resistance and relapse.

Aspirin and Cancer Survival: An Analysis of Molecular Mechanisms.

The benefit of aspirin on cancer survival is debated. Data from randomized clinical trials and cohort studies are discordant, although a meta-analysis shows a clear survival advantage when aspirin is added to the standard of care. However, the mechanism by which aspirin improves cancer survival is not clear. A PubMed search was carried out to identify articles reporting genes and pathways that are associated with aspirin and cancer survival. Gene ontology and pathway enrichment analysis was carried out using web-based tools. Gene-gene and protein-protein interactions were evaluated. Crosstalk between pathways was identified and plotted. Forty-one genes were identified and classified into primary genes (PTGS2 and PTGES2), genes regulating cellular proliferation, interleukin and cytokine genes, and DNA repair genes. The network analysis showed a rich gene-gene and protein-protein interaction between these genes and proteins. Pathway enrichment showed the interleukin and cellular transduction pathways as the main pathways involved in aspirin-related survival, in addition to DNA repair, autophagy, extracellular matrix, and apoptosis pathways. Crosstalk of PTGS2 with EGFR, JAK/AKT, TP53, interleukin/TNFα/NFκB, GSK3B/BRCA/PARP, CXCR/MUC1, and WNT/CTNNB pathways was identified. The results of the present study demonstrate that aspirin improves cancer survival by the interplay of 41 genes through a complex mechanism. PTGS2 is the primary target of aspirin and impacts cancer survival through six primary pathways: the interleukin pathway, extracellular matrix pathway, signal transduction pathway, apoptosis pathway, autophagy pathway, and DNA repair pathway.

Identifying potential neuroprotective polyphenols targeting endoplasmic reticulum stress through an in silico approach.

The endoplasmic reticulum (ER) is essential in many cellular processes, including protein processing, lipid metabolism, and calcium storage. Dysregulation of ER function has been linked with neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, etc. The primary pathological alteration explicated in the diseases is the accumulation of misfolded proteins in the neuronal cells. ER stress-associated activation of PERK-mediated pro-apoptotic cell death leads to neurodegeneration. In this study, we have primarily screened the potential polyphenols evidenced for neuroprotective activity. The 24 polyphenols were selected to explore their binding affinity towards various proteins of ER cascade such as pPERK (phospho-PERK), EIF2 (Eukaryotic Initiation Factor 2), and ATF4 (Activating Transcription Factor 4). On the basis of binding affinity, four phytopolyphenols were further selected for in-silico ADMET and molecular dynamic simulation. Among them curcumin found to be the most promising and serve as a potential hit against all three targets of ER cascade. The selected proteins' active site has demonstrated high stability of curcumin binding according to molecular dynamics findings. Though curcumin exhibited a significant hit in interaction with targets but needs to be further improved in drug-ability criteria. Thus, seventy derivatives of curcumin scaffold (from the published literature) were also screened with improve in druggability criteria, which showed good interaction with unfolded protein response related targets. The new scaffolds serve considerable potential to be developed as novel polyphenolic lead for neurodegenerative disorders.Communicated by Ramaswamy H. Sarma.

Mapping the genetic architecture of idiopathic pulmonary fibrosis: Meta-analysis and epidemiological evidence of case-control studies.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a rare and devastating fibrotic lung disorder with unknown etiology. Although it is believed that genetic component is an important risk factor for IPF, a comprehensive understanding of its genetic landscape is lacking. Hence, we aimed to highlight the susceptibility genes and pathways implicated in IPF pathogenesis through a two-staged systematic literature search of genetic association studies on IPF, followed by meta-analysis and pathway enrichment analysis. METHODS: This study was performed based on PRISMA guidelines (PROSPERO, registration number: CRD42022297970). The first search was performed (using PubMed and Web of Science) retrieving a total of 5642 articles, of which 52 were eligible for inclusion in the first stage. The second search was performed (using PubMed, Web of Science and Scopus) for ten polymorphisms, identified from the first search, with 2 or more studies. Finally, seven polymorphisms, [rs35705950/MUC5B, rs2736100/TERT, rs2609255/FAM13A, rs2076295/DSP, rs12610495/DPP9, rs111521887/TOLLIP and rs1800470/TGF-ß1] qualified for meta-analyses. The epidemiological credibility was evaluated using Venice criteria. RESULTS: From the systematic review, 222 polymorphisms in 118 genes showed a significant association with IPF susceptibility. Meta-analyses findings revealed significant association of rs35705950/T [OR = 3.92(3.26-4.57)], rs2609255/G [OR = 1.50(1.18-1.82)], rs2076295/G [OR = 1.19(0.82-1.756)], rs12610495/G [OR = 1.28(1.12-1.44)], rs2736100/C [OR = 0.68(0.54-0.82), rs111521887/G [OR = 1.34(1.06-1.61)] and suggestive evidence for rs1800470/T [OR = 1.08(0.82-1.34)] with IPF susceptibility. Four polymorphisms- rs35705950/MUC5B, rs2736100/TERT, rs2076295/DSP and rs111521887/TOLLIP, exhibited substantial epidemiological evidence supporting their association with IPF risk. Gene ontology and pathway enrichment analysis performed on IPF risk-associated genes identified a critical role of genes in mucin production, immune response and inflammation, host defence, cell-cell adhesion and telomere maintenance. CONCLUSIONS: Our findings present the most prominent IPF-associated genetic risk variants involved in alveolar epithelial injuries (MUC5B, TERT, FAM13A, DSP, DPP9) and epithelial-mesenchymal transition (TOLLIP, TGF-ß1), providing genetic and biological insights into IPF pathogenesis. However, further experimental research and human studies with larger sample sizes, diverse ethnic representation, and rigorous design are warranted.

Regioselective synthesis and molecular docking studies of functionalized imidazo [1,2-a]pyridine derivatives through MCRs.

A efficient protocol has been developed for the synthesis of regioselective imidazo[1,2-a]pyridine and imidazo[1,2-a]pyrimidine derivatives through cascade reaction between 2-aminopyridine, arylelglyoxal, and 4-hydroxypyran via three-component reaction to prepare targeted compounds with good to excellent yields. The advantages of this transformation are a catalyst-free reaction, green solvent, operationally simple, scalable, and eco-friendly. The product collects with simple filtration which avoided tedious and expensive purification techniques. In addition, computational studies like molecular docking were conducted to provide the theoretical possibilities of binding these types of synthesized compounds to the VEGFR2 receptors as potential key inhibitors of tumor cell growth and angiogenesis.

Stress-mitigating behavior of glycine betaine to enhance growth performance by suppressing the oxidative stress in Pb-stressed barley genotypes.

The toxicity of lead (Pb) in agricultural soil is constantly increasing as a result of anthropogenic activities. Pb is one of the most phytotoxic metals in soil that accumulates in plant tissue, resulting in yield loss. It is currently becoming more popular to supplement glycine betaine (GB) for Pb-induced stress tolerance in crop plants. Currently, no report describes the use of GB as a stress mitigator for growth attributes and stress-specific biomarkers in barley plants under Pb stress conditions. Hence, the present research was designed to examine the stress-mitigating behavior of GB on various growth attributes including germination percentage, seed vigor index (SVI), radicle length, plant biomass (fresh and dry), shoot and root length, physiological attributes such as relative water content (RWC), and stress-specific biomarkers like electrolyte leakage (EL), and H2O2 content of two barley varieties viz. BH959 and BH946 at three Pb stress treatments (15 mM, 25 mM, and 35 mM), with and without GB (2 mM) supplementation in natural conditions. The present investigation showed that at the highest Pb stress (35 mM), the germination rate was reduced to zero, and the growth attributes and RWC of both barley varieties were also reduced as compared to the non-stressed plants (control) with an increase in Pb treatment. However, EL up to 70% and H2O2 content up to 30% increased with an increase in Pb stress concentration indicated by ROS accumulation, resulting in more oxidative stress. Additionally, GB application alleviated the toxic effect of Pb stress by improving the rate of germination by 33.3% and growth performance by reducing the ROS accumulation in terms of reducing stress biomarkers H2O2 by 25%, and EL by 12%. It has been revealed that the application of GB can minimize or reduce the toxic effects caused by Pb toxicity in both varieties, positively modulating plant growth performances and lowering oxidative stress. This research may provide a scientific basis for assessing Pb tolerance in barley plants and developing alternative approaches to protecting them from the severe effects of Pb toxicity.

Comparison of lung ultrasound technique versus clinical method to evaluate the accuracy of size and placement of left endobronchial double lumen tube in patients undergoing elective thoracic surgery: a prospective observational study.

Anthropometric measurements like height and gender have been frequently found to be inaccurate in prediction of size of double lumen tube (DLT). A tracheal ultrasonography (TUS) is a technique that can be used to predict the size of DLT and its correct placement for lung isolation. We aim to check the accuracy of ultrasound over clinical methods. This prospective study included 68 patients undergoing elective thoracic surgery requiring one-lung ventilation (OLV) with DLT. The groups were assessed for the size of DLT by either anthropometric measurement using height and gender (Group C) or ultrasound method (Group U). Further, the accuracy of placement of DLT was assessed through, either lung auscultation in group C or various ultrasonographic and ventilatory parameters such as lung isolation in the first attempt (lung sliding and lung pulse sign), oxygenation status and peak airway pressure, in group U. Surgeon satisfaction score was also compared in both the groups. The accuracy of predicted DLT size between Group C and Group U was statistically significant (p=0.044). In Group C, 56% of patients showed a mismatch between the predicted DLT size and the actual size required, while in Group U, the mismatch was only 32.4%. The accuracy of DLT placement through group C was 41% as compared to 79% in Group U. Surgeon satisfaction score was also significantly higher in Group U as compared to Group C (p=0.0028). Thus, our study suggests that tracheal and chest ultrasonography for DLT size selection and placement for lung isolation is superior to clinical methods.

Efficacy of analgesia using ilioinguinal-iliohypogastric (IIIH) nerve block, transversus abdominis plane (TAP) block and diclofenac after caesarean delivery under spinal anaesthesia: A non-randomised clinical trial.

Background and Aims: Our aim was to assess the efficacy of analgesia using ilioinguinal-iliohypogastric (IIIH) nerve block, transversus abdominis plane (TAP) block and diclofenac after caesarean delivery (CD) under spinal anaesthesia (SA).]. Methods: A total of 457 healthy parturients undergoing CD under SA were included in this prospective, observational study. Groups differed in the postoperative analgesic strategies received by the parturient at the end of surgery: group D (n = 148) received intramuscular diclofenac sodium, group I (n = 153) received bilateral IIIH block with bupivacaine plus clonidine and group T (n = 156) received bilateral TAP block with bupivacaine plus clonidine. Total duration of postoperative analgesia, numerical pain rating scale (NRS) scores, patient satisfaction score, rescue analgesics in the first 48 h postoperatively and adverse effects were observed. A value of P < 0.05 was taken as significant. Results: Total duration of analgesia was longest (18.2 ± 1.3 h) in group T and shortest in group D (6.3 ± 0.8 h) compared to group I (13.1 ± 1.2 h) (P < 0.001). Total analgesic requirement in postoperative 48 h was lowest in group T (152.1 ± 34.9 mg), highest in group D (355.0 ± 25.6 mg) and intermediate in group I (221.0 ± 30.0 mg) (P < 0.001). Mean NRS scores were lower in group T compared to those in groups D and I. The patients in group T were extremely satisfied, in group I were satisfied and in group D were dissatisfied (P < 0.001). Conclusion: Bilateral TAP block with bupivacaine and clonidine after CD under SA increases the duration of postoperative analgesia.