Novel saturated 1,2,4-trioxanes and their antimalarial activity against multidrug resistant Plasmodium yoelii nigeriensis in Swiss mice model via oral route.

Novel saturated 6-(4'-aryloxy phenyl) vinyl 1,2,4-trioxanes 12a(1-3)-12d(1-3) and 13a(1-3)-13d(1-3) have been designed and synthesized, in one single step from diimide reduction of 11a(1-3)-11d(1-3). All the newly synthesized trioxanes were evaluated for their antimalarial activity against multi-drug resistant Plasmodium yoelii nigeriensis via oral route. Cyclopentane-based trioxanes 12b1, 12c1 and 12d1, provided 100 % protection to the infected mice at 24 mg/kg × 4 days. The most active compound of the series, trioxane 12b1, provided 100 % protection even at 12 mg/kg × 4 days and 60 % protection at 6 mg/kg × 4 days. The currently used drug, ß-arteether provides only 20 % protection at 24 mg/kg × 4 days.

Identification of novel hit molecules targeting M. tuberculosis polyketide synthase 13 by combining generative AI and physics-based methods.

In this work we investigated the Pks13-TE domain, which plays a critical role in the viability of the mycobacteria. In this report, we have used a series of AI and Physics-based tools to identify Pks13-TE inhibitors. The Reinvent 4, pKCSM, KDeep, and SwissADME are AI-ML-based tools. AutoDock Vina, PLANTS, MDS, and MM-GBSA are physics-based methods. A combination of these methods yields powerful support in the drug discovery cycle. Known inhibitors of Pks13-TE were collected, curated, and used as input for the AI-based tools, and Mol2Mol molecular optimisation methods generated novel inhibitors. These ligands were filtered based on physics-based methods like molecular docking and molecular dynamics using multiple tools for consensus generation. Rigorous analysis was performed on the selected compounds to reduce the chemical space while retaining the most promising compounds. The molecule interactions, stability of the protein-ligand complexes and the comparable binding energies with the native ligand were essential factors for narrowing the ligands set. The filtered ligands from docking, MDS, and binding energy colocations were further tested for their ADMET properties since they are among the essential criteria for this series of molecules. It was found that ligands Mt1 to Mt6 have excellent predicted pharmacokinetic, pharmacodynamic and toxicity profiles and good synthesisability.

Identification of Mycobacterium tuberculosis transcriptional repressor EthR inhibitors: Shape-based search and machine learning studies.

Tuberculosis has been a challenge to the world since prehistoric times, and with the advent of drug-resistant strains, it has become more challenging to treat this infection. Ethionamide (ETH), a second-line drug, acts as a prodrug and targets mycolic acid synthesis by targeting the enoyl-acyl carrier protein reductase (InhA) enzyme. Mycobacterium tuberculosis (Mtb) EthR is an ethA gene repressor required to activate prodrug ETH. Recent studies suggest targeting the EthR could lead to newer drug molecules that would help better activate the ETH or complement this process. In this report, we have attempted and successfully identified three new molecules from the drug repurposing library that can target EthR protein and function as ETH boosters. These molecules were obtained after rigorous filtering of the database for their physicochemical, toxicological properties and safety. The molecular docking, molecular dynamics simulations and binding energy studies yielded three compounds, Ethyl (2-amino-4-((4-fluorobenzyl)amino)phenyl)carbamate) (L1), 2-((2,2-Difluorobenzo [d] [1,3]dioxol-5-yl)amino)-2-oxoethyl (E)-3-(5-bromofuran-2-yl)acrylate (L2), and N-(2,3-Dihydrobenzo [b] [1,4]dioxin-6-yl)-4-(2-((4-fluorophenyl)amino)-2-oxoethoxy)-3-methoxy benzamide (L3) are potential EthR inhibitors. We applied machine learning methods to evaluate these molecules for toxicity and synthesisability, suggesting safety and ease of synthesis for these molecules. These molecules are known for other pharmacological activities and can be repurposed faster as adjuvant therapy for tuberculosis.

Deciphering the functional landscape and therapeutic implications of noncoding RNAs in the TGF-ß signaling pathway in colorectal cancer: A comprehensive review.

Colorectal cancer (CRC) remains a major global health concern, necessitating an in-depth exploration of the intricate molecular mechanisms underlying its progression and potential therapeutic interventions. Transforming Growth Factor-ß (TGF-ß) signaling, a pivotal pathway implicated in CRC plays a dual role as a tumor suppressor in the early stages and a promoter of tumor progression in later stages. Recent research has shed light on the critical involvement of noncoding RNAs (ncRNAs) in modulating the TGF-ß signaling pathway, introducing a new layer of complexity to our understanding of CRC pathogenesis. This comprehensive review synthesizes the current state of knowledge regarding the function and therapeutic potential of various classes of ncRNAs, including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), in the context of TGF-ß signaling in CRC. The intricate interplay between these ncRNAs and key components of the TGF-ß pathway is dissected, revealing regulatory networks that contribute to the dynamic balance between tumor suppression and promotion. Emphasis is placed on how dysregulation of specific ncRNAs can disrupt this delicate equilibrium, fostering CRC initiation, progression, and metastasis. Moreover, the review provides a critical appraisal of the emerging therapeutic strategies targeting ncRNAs associated with TGF-ß signaling in CRC. The potential of these ncRNAs as diagnostic and prognostic biomarkers is discussed, highlighting their clinical relevance. Additionally, the challenges and prospects of developing RNA-based therapeutics, such as RNA interference and CRISPR/Cas-based approaches, are explored in the context of modulating TGF-ß signaling for CRC treatment. In conclusion, this review offers a comprehensive overview of the intricate interplay between ncRNAs and the TGF-ß signaling pathway in CRC. By unraveling the functional significance of these regulatory elements, we gain valuable insights into the molecular landscape of CRC, paving the way for the development of novel and targeted therapeutic interventions aimed at modulating the TGF-ß signaling cascade through the manipulation of ncRNAs.

Effects of vermicompost on soil microbiological properties in lettuce rhizosphere: An environmentally friendly approach for sustainable green future.

The aim of this study is to investigate the effects of vermicompost on the biological and microbial properties of lettuce rhizosphere in an agricultural field in Samsun, Turkey. The experiment was conducted in a completely randomised design (CRD) and included four vermicompost dosages (0%, 1%, 2%, and 4%) and two application methods (with and without plants). Batavia lettuce was selected as the test plant due to its sensitivity to environmental conditions and nutrient deficiencies. The study evaluated the changes in organic matter (OM), pH, electrical conductivity (EC), carbon dioxide (CO2), dehydrogenase activity (DHA), microbial biomass carbon (MBC), and catalase activity (CA) in the rhizosphere of lettuce plants treated with different vermicompost levels (0%, 1%, 2%, and 4%). The findings showed that vermicompost application significantly increased chlorophyll content in lettuce plants, with the highest content observed in plants treated with V1 compared to the control. Different vermicompost concentrations also influenced chlorophyll b and total chlorophyll levels, with positive effects observed at lower concentrations than the control. Plant height and fresh weight were highest in plants treated with V2, indicating the positive impact of vermicompost on plant growth. Additionally, vermicompost application increased plant dry weight and improved soil properties such as pH, organic matter content, and microbial activity. The findings showed that vermicompost increased the rhizosphere's microbial biomass and metabolic activity, which can be beneficial for plant growth and disease suppression. The study highlights the importance of understanding the effects of organic amendments on soil properties and the microbial community in the rhizosphere, which can contribute to sustainable agricultural practices. Overall, the results suggest that vermicompost can be used as an effective organic amendment for enhancing plant growth and improving soil properties in agricultural fields. Moreover, based on the data, it can be suggested that a dose between 1% and 2% vermicompost is beneficial for the overall growth of plants.

Combination Therapy with Enalapril and Paricalcitol Ameliorates Streptozotocin Diabetes-Induced Testicular Dysfunction in Rats via Mitigation of Inflammation, Apoptosis, and Oxidative Stress.

BACKGROUND: As the impacts of diabetes-induced reproductive damage are now evident in young people, we are now in urgent need to devise new ways to protect and enhance the reproductive health of diabetic people. The present study aimed to evaluate the protective effects of enalapril (an ACE inhibitor) and paricalcitol (a vitamin D analog), individually or in combination, on streptozotocin (STZ)-diabetes-induced testicular dysfunction in rats and to identify the possible mechanisms for this protection. MATERIAL AND METHODS: This study was carried out on 50 male Sprague-Dawley rats; 10 normal rats were allocated as a non-diabetic control group. A total of 40 rats developed diabetes after receiving a single dose of STZ; then, the diabetic rats were divided into four groups of equivalent numbers assigned as diabetic control, enalapril-treated, paricalcitol-treated, and combined enalapril-and-paricalcitol-treated groups. The effects of mono and combined therapy with paricalcitol and enalapril on testicular functions, sperm activity, glycemic state oxidative stress, and inflammatory parameters, as well as histopathological examinations, were assessed in comparison with the normal and diabetic control rats. RESULTS: As a result of diabetes induction, epididymal sperm count, sperm motility, serum levels of testosterone, follicle-stimulating hormone (FSH) as well as luteinizing hormone (LH), and the antioxidant enzyme activities, were significantly decreased, while abnormal sperm (%), insulin resistance, nitric oxide (NO), malondialdehyde (MDA), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were significantly increased, along with severe distortion of the testicular structure. Interestingly, treatment with paricalcitol and enalapril, either alone or in combination, significantly improved the sperm parameters, increased antioxidant enzyme activities in addition to serum levels of testosterone, FSH, and LH, reduced insulin resistance, IL-6, and TNF-α levels, and finally ameliorated the diabetes-induced testicular oxidative stress and histopathological damage, with somewhat superior effect for paricalcitol monotherapy and combined therapy with both drugs compared to monotherapy with enalapril alone. CONCLUSIONS: Monotherapy with paricalcitol and its combination therapy with enalapril has a somewhat superior effect in improving diabetes-induced testicular dysfunction (most probably as a result of their hypoglycemic, antioxidant, anti-inflammatory, and anti-apoptotic properties) compared with monotherapy with enalapril alone in male rats, recommending a synergistic impact of both drugs.

Management of COPD and Comorbidities in COPD patients by Dispensing Pharmaceutical Care following Global Initiative for chronic Obstructive Lung Disease-Guidelines (GOLD guidelines 2020): A study protocol for a Prospective Randomized Clinical Trial.

COPD (chronic obstructive pulmonary disease) is a medical condition that encompasses several chronic, progressive, and severe respiratory illnesses, such as emphysema and chronic bronchitis. COPD is the 4th most deadly disease in the world and its prevalence is expected to increase. Despite the abundance of information on the disease's etiology, pathophysiology, and treatment possibilities, it has long been underdiagnosed and underreported for a long time, particularly in developing countries. The symptoms of COPD result in significant impairments and significant impact on quality of life. COPD is the third leading cause of death in Pakistan. According to the published literature, COPD has been found to be associated with a serious economic burden, either the direct cost to healthcare systems in the form of frequent hospital admissions or indirect costs to patients suffering from COPD. Despite the availability of excellent medication, COPD treatment goals are frequently not achieved resulting in poor management of COPD. The recent studies revealed that due to the missing role of Pharmacists in most of the public sector hospitals of Pakistan, the COPD disease management protocols are not being properly followed. Pharmacists can help the healthcare system by implementing these management protocols that focus on patient education about the disease, prescribed medications, and proper inhalation techniques. Furthermore, the pharmacists as an effective healthcare's team member properly educate the patients about the ongoing assessments and their willingness to follow treatment recommendations and quit smoking, while referring them to smoking cessation programs as needed, following the GOLD guidelines. This aim of this clinical trial is to evaluate the impact of implementing standard treatment guidelines and the role of pharmacists in implementing GOLD guidelines for COPD management.

A novel MWCNT-encapsulated (2-aminoethyl)piperazine-decorated zinc(II) phthalocyanine composite: development of an electrochemical sensor for detecting the antipsychotic drug promazine in environmental samples.

A nanocomposite of (2-aminoethyl)piperazine ligand substituted with zinc(II) tetra carboxylic acid phthalocyanine (ZnTEPZCAPC) and MWCNTs was constructed and employed to develop an electrochemical sensor with outstanding sensitivity and a low detection limit. The macrocyclic complex ZnTEPZCAPC was first synthesized and then employed for the electrochemical determination of the antipsychotic drug promazine (PMZ). The as-prepared ZnTEPZCAPC and MWCNT nanocomposite was characterized using different techniques, such as Fourier-transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), UV-visible spectroscopy (UV-Vis), field emission scanning electron microscopy (FE-SEM), and thermogravimetric analysis (TGA). Further, the prepared ZnTEPZCAPC@MWCNT nanocomposites were modified on a glassy carbon electrode (GCE) surface, and the electrochemical activity was investigated using cyclic voltammetry (CV), differential pulse voltammetry (DPV), and chronoamperometry (CA) tests in pH 7.0 phosphate buffer solution (PBS) in the potential window of 0.0-1 V. The ZnTEPZCAPC@MWCNTs displayed a superior electrochemical performance because of their high electrochemical active surface area (0.453 cm2), good conductivity, and a synergetic effect. The developed electrochemical sensor exhibited a broad linear range of 0.05-635 µM and the lowest detection limit of 0.0125 nM, as well as excellent sensitivity, repeatability, and reproducibility. Finally, the fabricated sensor was successively used for the real-time detection of PMZ in environmental and biological samples and displayed feasible recoveries.

Ex vivo fluorescence imaging for the identification of rhodamine-labeled bovine serum albumin and chitosan-coated gold and silver nanoparticles.

Therapeutic potential and toxic effects of in vivo administered gold nanoparticles (GNPs) and silver nanoparticles (SNP) depend on distribution in tissues. Rhodamine (Rho) labeled bovine serum albumin (BSA) and chitosan (Chi) were prepared by covalent conjugation and were characterized by fluorescence spectral analysis. GNP and SNP were coated with the labeled conjugates of BSA and chitosan by adsorption. The soluble Rho-BSA or Rho-Chi conjugates, uncoated, and conjugate-coated GNP, and SNP were orally administered into 8-week-old rats. After 24 h, rats were euthanized and the liver, kidney, spleen, and thymus were dissected. The tissues were examined ex vivo using a small animal in vivo imaging system. The liver, kidney, and thymus displayed higher fluorescence due to increased accumulation of Rho-BSA or Rho-Chi conjugate-coated nanoparticles (NPs) in the tissues as compared to the spleen where lower fluorescence was noticed. Tissues obtained from rats that were administered Rho-BSA or Rho-Chi conjugate-coated GNP and SNP showed tenfold higher fluorescence intensity as compared to tissues from rats that were given soluble conjugates or NP alone. The results strongly suggest significant tissue distribution of NP following oral administration.

Glutathione treatment suppresses the adverse effects of microplastics in rice.

Oryza sativa is grown worldwide and exhibit sensitivity to different stresses. Exponential increase in microplastics in agroecosystems is damaging and demand pragmatic strategies to protect growth and yield losses. We evaluated exogenous application of different doses of glutathione (GSH) for mediation of physiological traits of rice plants experiencing two different MPs i.e. PET and HDPE in root zone. All the rice seedlings exhibited MP-induced significant (P ≤ 0.001) growth inhibition compared to the control plants. GSH application (T3) significantly increased the shoot fresh weight (8.80%), root fresh weight (19.22%), shoot dry weight (13.705%), root dry weight (25.52%), plant height (5.75%) and 100-grain weight (9.36%), compared to control plants. GSH treated plants (T4) showed a recovery mechanism by managing the marginal rate of reduction of all photosynthetic and gas exchange attributes by showing 34.44, 20.98, 34.83, 42.16, 39.70, and 51.38% reduction for Chl-a, Chl-b, total cholophyll, photosynthetic rate (A), transpiration rate (E), and stomatal conductance (Gs), respectively, compared to control plants. Under 5 mg L-1 HDPE and PET, rice seedlings without GSH treatment responded in terms of increase in total soluble sugar, total free amino acid, glutathione, glutathione disulfide contents, while total soluble protein and ascorbic acid contents decreased significantly, compared with control plants. Corrleation matrix revealed positive relationship between GSH and improvement in studied attributes. Moreover, exogenous GSH improved rice growth and productivity to counter the negative role of MPs. This unique study examined the effects of GSH on rice plants growing in MP-contaminated media and revealed how exogenous GSH helps plants survive MP-stress.

Phytotoxic responses of wheat to an imidazolium based ionic liquid in absence and presence of biochar.

Research on ionic liquids (ILs) and biochars (BCs) is a novel site of scientific interest. An experiment was designed to assess the effect of 1-propanenitrile imidazolium trifluoro methane sulfonate ([C2NIM][CF3SO3]) ionic liquid (IL) and IL-BC combination on the wheat plant. Three working standards of the IL; 50, 250, 500 and 1000 mg/L, prepared in deionized water, were tested in the absence and presence of BC on wheat seedling. Results indicated significant decrease in seed germination (%), length, fresh weight, chlorophyll a, b and carotenoid contents of wheat seedlings at 250, 500 and 1000 mg/L of the IL. An admirable increase in phenolic and 2,2-diphenyl-1-picrylhydrazyl (DPPH) contents of wheat seedlings was noted at 250, 500 and 1000 mg/L of the IL. The application of BC significantly ameliorated the negative effects of IL on the selected parameters of wheat. It is inferred that the undesirable effects of the IL on wheat growth can be positively restored by addition of BC.

Plant-soil-microbe interactions in maintaining ecosystem stability and coordinated turnover under changing environmental conditions.

Ecosystem functions directly depend upon biophysical as well as biogeochemical reactions occurring at the soil-microbe-plant interface. Environment is considered as a major driver of any ecosystem and for the distributions of living organisms. Any changes in climate may potentially alter the composition of communities i.e., plants, soil microbes and the interactions between them. Since the impacts of global climate change are not short-term, it is indispensable to appraise its effects on different life forms including soil-microbe-plant interactions. This article highlights the crucial role that microbial communities play in interacting with plants under environmental disturbances, especially thermal and water stress. We reviewed that in response to the environmental changes, actions and reactions of plants and microbes vary markedly within an ecosystem. Changes in environment and climate like warming, CO2 elevation, and moisture deficiency impact plant and microbial performance, their diversity and ultimately community structure. Plant and soil feedbacks also affect interacting species and modify community composition. The interactive relationship between plants and soil microbes is critically important for structuring terrestrial ecosystems. The anticipated climate change is aggravating the living conditions for soil microbes and plants. The environmental insecurity and complications are not short-term and limited to any particular type of organism. We have appraised effects of climate change on the soil inhabiting microbes and plants in a broader prospect. This article highlights the unique qualities of tripartite interaction between plant-soil-microbe under climate change.

One-pot green synthesis of ZnO nanoparticles using Scoparia Dulcis plant extract for antimicrobial and antioxidant activities.

Nanostructured Zinc oxide (ZnO) materials have attained exciting research interests among various metal oxide nanoparticles due to their unique features. Thus, the scope of applications for ZnO nanoparticles (ZnO NPs) is vast and efficient. The current study demonstrates a simple and environmental-friendly approach for the synthesis of ZnO NPs using the extract of the Scoparia Dulcis. Scoparia Dulcis is a common medicinal plant in Kerala (India) that is traditionally used for its medicinal properties. Morphological characterizations of the as-synthesized ZnO NPs were evaluated using X-ray diffraction, Fourier transform infrared spectroscopy (FTIR), and field-emission scanning electron microscopy (FESEM). The results revealed that ZnO NPs showed pebble-like morphology and possessed an average particle size of ~ 20 nm. Further, antibacterial and antifungal activities of as-prepared ZnO NPs were investigated against E. coli, Staphylococcus aureus, as well as Candida albicans, and Aspergillus niger, respectively, using the agar-well diffusion method. The results revealed that the prepared ZnO NPs shows excellent antimicrobial activity against the examined microorganisms. Moreover, the antioxidant activity of the as-synthesized ZnO NPs was evaluated using the DPPH assay, which indicated an excellent IC50 value of 1.78 µg/mL that shows high antioxidant activity. All these results proved that the S. dulcis plant extract-mediated synthesis method is a simple, low-cost, eco-friendly procedure for preparing efficient ZnO NPs for biomedical applications.

Binder-Free Zinc-Iron Oxide as a High-Performance Negative Electrode Material for Pseudocapacitors.

The interaction between cathode and anode materials is critical for developing a high-performance asymmetric supercapacitor (SC). Significant advances have been made for cathode materials, while the anode is comparatively less explored for SC applications. Herein, we proposed a high-performance binder-free anode material composed of two-dimensional ZnFe2O4 nanoflakes supported on carbon cloth (ZFO-NF@CC). The electrochemical performance of ZFO-NF@CC as an anode material for supercapacitor application was examined in a KOH solution via a three-electrode configuration. The ZFO-NF@CC electrode demonstrated a specific capacitance of 509 F g-1 at 1.5 A g-1 and was retained 94.2% after 10,000 GCD cycles. The ZFO-NF@CC electrode showed exceptional charge storage properties by attaining high pseudocapacitive-type storage. Furthermore, an asymmetric SC device was fabricated using ZFO-NF@CC as an anode and activated carbon on CC (AC@CC) as a cathode with a KOH-based aqueous electrolyte (ZFO-NF@CC||AC@CC). The ZFO-NF@CC||AC@CC yielded a high specific capacitance of 122.2 F g-1 at a current density of 2 A g-1, a high energy density of 55.044 Wh kg-1 at a power density of 1801.44 W kg-1, with a remarkable retention rate of 96.5% even after 4000 cycles was attained. Thus, our results showed that the enhanced electrochemical performance of ZFO-NF@CC used as an anode in high-performance SC applications can open new research directions for replacing carbon-based anode materials.

In silico identification of small molecule modulators for disruption of Hsp90-Cdc37 protein-protein interaction interface for cancer therapeutic application.

The protein-protein interactions (PPIs) in the biological systems are important to maintain a number of cellular processes. Several disorders including cancer may be developed due to dysfunction in the assembly of PPI networks. Hence, targeting intracellular PPIs can be considered as a crucial drug target for cancer therapy. Among the enormous and diverse group of cancer-enabling PPIs, the Hsp90-Cdc37 is prominent for cancer therapeutic development. The successful inhibition of Hsp90-Cdc37 PPI interface can be an important therapeutic option for cancer management. In the current study, a set of more than sixty thousand compounds belong to four databases were screened through a multi-steps molecular docking study in Glide against the Hsp90-Cdc37 interaction interface. The Glide-score and Prime-MM-GBSA based binding free energy of DCZ3112, standard Hsp90-Cdc37 inhibitor were found to be -6.96 and -40.46 kcal/mol, respectively. The above two parameters were used as cut-off score to reduce the chemical space from all successfully docked molecules. Furthermore, the in-silico pharmacokinetics parameters, common-feature pharmacophore analyses and the molecular binding interactions were used to wipe out the inactive molecules. Finally, four molecules were found to be important to modulate the Hsp90-Cdc37 interface. The potentiality of the final four molecules was checked through several drug-likeness characteristics. The molecular dynamics (MD) simulation study explained that all four molecules retained inside the interface of Hsp90-Cdc37. The binding free energy of each molecule obtained from the MD simulation trajectory was clearly explained the strong affection towards the Hsp90-Cdc37. Hence, the proposed molecule might be crucial for successful inhibition of the Hsp90-Cdc37 interface.Communicated by Ramaswamy H. Sarma.

Electrochemical sensing base for hazardous herbicide aclonifen using gadolinium niobate (GdNbO4) nanoparticles-actual river water and soil sample analysis.

The present work scrutinized the voltammetric analysis of hazardous herbicide aclonifen (ACF) in actual soil and river water samples utilizing the electrochemical method. The electrochemical sensing device was fabricated for the determination of ACF using gadolinium niobate (GdNbO4) nanoparticles modified glassy carbon electrode (GCE). The novel GdNbO4 sensing material was prepared via a simple co-precipitation method. Several characterization techniques (TEM, EDS, XRD, XPS, and BET) were utilized to analyze the structural features of the GdNbO4. The enhanced electrochemical behavior of GdNbO4 modified GCE towards ACF was observed compared to bare GCE. The cyclic voltammetry response revealed that the prepared sensor shows the lower negative potential with a dramatic increase in the peak current of ACF compared to bare GCE. In the differential pulse voltammetry, the limit of detection (1.15 nM) and sensitivity (23 µA µM-1 cm-2) of the ACF on the GdNbO4 modified GCE was comparatively superior to the formerly proposed ACF based sensor. This sensor reveals good selectivity, repeatability, reproducibility, and long-term stability. The reliability of the sensor exhibits satisfactory recovery results for ACF detection in river water and soil samples.

Temperature-enabled reversible "On/Off" switch-like hazardous herbicide picloram voltammetric sensor in agricultural and environmental samples based on thermo-responsive PVCL-tethered MWCNT@Au catalyst.

Picloram (PCR), a vastly utilized chlorinated herbicide, is very stable in water and soil with severe ecological and health impacts. It is necessary to establish a fast and highly sensitive technique for accurately detecting trace level PCR in agricultural and environmental samples. We employed a temperature-responsive poly(N-vinylcaprolactam)-tethered multiwalled carbon nanotubes (MWCNT-PVCL) decorated gold nanoparticles (Au@MWCNT-PVCL) catalyst on the electrochemical sensor for the sensitive "On/Off" switch-like detection of PCR. The effect of temperature-sensitive catalyst surface chemistry on electrocatalytic activity was scrutinized. Results showed that the hydrophilic surface of PVCL at 25 °C (LCST) that immensely upgraded PCR oxidation on the catalyst in the electrochemical reaction, signifying the "On" state. The detection of the Au@MWCNT-PVCL modified electrode ranged from 0.02-183 µM with a low detection limit (LOD) of 1.5 nM at 40 °C toward PCR. The proposed sensor was successfully used to detect PCR in real agricultural and environmental samples.

Identification of potential anti-TMPRSS2 natural products through homology modelling, virtual screening and molecular dynamics simulation studies.

Recent outbreak of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to a pandemic of COVID-19. The absence of a therapeutic drug and vaccine is causing severe loss of life and economy worldwide. SARS-CoV and SARS-CoV-2 employ the host cellular serine protease TMPRSS2 for spike (S) protein priming for viral entry into host cells. A potential way to reduce the initial site of SARS-CoV-2 infection may be to inhibit the activity of TMPRSS2. In the current study, the three-dimensional structure of TMPRSS2 was generated by homology modelling and subsequently validated with a number of parameters. The structure-based virtual screening of Selleckchem database was performed through 'Virtual Work Flow' (VSW) to find out potential lead-like TMPRSS2 inhibitors. Camostat and bromhexine are known TMPRSS2 inhibitor drugs, hence these were used as control molecules throughout the study. Based on better dock score, binding-free energy and binding interactions compared to the control molecules, six molecules (Neohesperidin, Myricitrin, Quercitrin, Naringin, Icariin, and Ambroxol) were found to be promising against the TMPRSS2. Binding interactions analysis revealed a number of significant binding interactions with binding site amino residues of TMPRSS2. The all-atoms molecular dynamics (MD) simulation study indicated that all proposed molecules retain inside the receptor in dynamic states. The binding energy calculated from the MD simulation trajectories also favour the strong affinity of the molecules towards the TMPRSS2. Proposed molecules belong to the bioflavonoid class of phytochemicals and are reported to possess antiviral activity, our study indicates their possible potential for application in COVID-19.Communicated by Ramaswamy H. Sarma.

The fluorescence quenching of Ru(bipy)32+ : an application for the determination of bilirubin in biological samples.

A simple, sensitive and efficient fluorescence method has been established for the quantitative analysis of bilirubin. The fluorometric determination method was based on the kinetic quenching of ruthenium(II) fluorescence. The quenching effect may be due to the complexation reaction of bilirubin with ruthenium(II). Therefore, the effects of ruthenium concentrations and different surfactants have been studied. Under the optimized experimental parameters, the fluorescence intensity decreased proportionally with the bilirubin concentration and linearity was established in the range of 3.3 × 10-7 to 3.0 × 10-4  M bilirubin. The detection limit calculated from the calibration graph was found to be 5.2 × 10-8  M. The relative standard deviation (RSD) of 10 consecutive measurements of 8.0 × 10-6  M bilirubin was 3.0%, while the recoveries of bilirubin in both human serum and urine samples were obtained in the range 94.0-99.5%. The interference study shows that the developed fluorescence based technique is fast, easy to carry out and shows negligible interference. The developed technique was successfully applied for the analysis of bilirubin in human urine and serum samples. All the experimental results and quality parameters confirmed the sensitivity and reproducibility of the proposed technique for bilirubin determination in human urine and serum samples.

Chemiluminescence determination of folic acid by a flow injection analysis assembly.

A flow injection (FI) method is reported for the determination of folic acid by chemiluminescence method. This method is based on the reaction of folic acid with Ru(bipy)(3)(2+) and Ce(IV) to produce chemiluminescence. The calibration curve was linear over the range of 2.5×10(-5)-3.1×10(-7) mol/L with a detection limit of 2.3×10(-8) mol/L (S/N=3). The relative standard deviation of 1.0×10(-6) mol/L folic acid was found 3.5% (n=11). The influences of potential interfering substances were studied. The recovery was higher than 95.3%. The method was accurate, sensitive, and effective for assay of folic acid. This CL method was successfully applied to the determination of folic acid in pharmaceutical preparations. The mechanism of CL reaction was also studied.