The prominence of potential biomarkers in the diagnosis and management of hepatocellular carcinoma: Current scenario and future anticipation.

Hepatocellular carcinoma (HCC) is one of the most aggressive and truculent types of cancer. Early detection of HCC is a massive concern that can boost the overall survival rates of HCC patients. As a result, there is a continual quest for advancements in screening, diagnosis, and treatment strategies to enhance the prognosis at its early stages. However, the confluence of inflammation and cirrhosis hampers the early detection of HCC. The analysis of different types of biomarkers such as tissue biomarkers, serum biomarkers, protein biomarkers, autoantibody markers, and improved imaging techniques has played a vital role in ameliorating HCC monitoring responses. Therefore biomarkers that can identify HCC early with a high degree of sensitivity and specificity might be prodigiously serviceable in the diagnosis and treatment of this notorious disorder. This study offers an overview of the contemporary understanding of several types of biomarkers implicated in hepatocarcinogenesis and their applications in monitoring, diagnosis, and prognosis presage. In additament, we address the role of image techniques associated with HCC diagnosis.

Effect of Hypochlorites on the Compressive Strength and Surface Hardness of Type V Dental Stone: An In Vitro Study.

AIM: The study aimed to evaluate the compressive strength and surface hardness of a type V dental stone after hypochlorite disinfection. MATERIALS AND METHODS: Two types of specimens were made according to the American Dental Association (ADA) specification no. 25 for each wet compressive strength, dry compressive strength, and surface hardness. The specimens were split into three groups with 30 samples each according to the type of disinfection. All specimens were immersed in their respective disinfecting solutions for 30 minutes at room temperature and after removal, they were left to dry for 24 hours at room temperature. Total five cycles of immersion and drying were followed. A compressive strength test was done using a universal testing machine. Wet compressive strength was tested one hour after the last cycle and dry compressive strength was tested 7 days after the last cycle. Surface hardness was measured after 48 hours using Vickers hardness test. The results were statistically analyzed. RESULTS: There was a statistical difference between the calcium hypochlorite and sodium hypochlorite groups for both dry and wet compressive strength. The mean wet compressive strength of calcium hypochlorite was higher when compared to the sodium hypochlorite group and it was statistically significant (p = 0.042). The results were similar and statistically significant (p = 0.003) for dry compressive strength. When the mean surface hardness of the sodium hypochlorite (As) group was compared to calcium hypochlorite the results were highly significant (p = 0.0001) with the mean surface hardness of the calcium hypochlorite group more than the sodium hypochlorite group. CONCLUSION: Calcium hypochlorite used as a disinfectant showed better compressive strength and surface hardness when compared to sodium hypochlorite as a disinfectant. CLINICAL SIGNIFICANCE: Dental casts poured in the contaminated impressions which might not be disinfected at all or properly. They also come in contact with the prosthesis that might be tried inside the patient's mouth and sent to a lab for corrections without disinfecting the cast causing cross-contamination between patients, dentists, and laboratory personnel. However, immersion disinfection with sodium or calcium hypochlorite might affect important properties of the cast. Any negative effect on the mechanical or physical properties of the cast will affect the final outcome of the prosthesis.

Development of improved strain in species of Pleurotus by gamma irradiation.

The oyster mushroom (Pleurotus spp.) is the second important edible mushroom in the world, with 19 per cent contribution to total mushroom production (Sharma et al., Mushroom Res 26(2):111-120, 2017). The cultivated mushrooms face the problems like loss of genetic diversity and strain degeneration (Wang et al., Curr Microbiol 65(4):424-431, 2012). Thus to enhance the productivity within short duration, three species of Pleurotus namely Pleurotus djamor, Pleurotus florida and Pleurotus ostreatus were gamma irradiated at 20 and 25 Gy at 9.779 kGy/h and performance of mutants followed by three generation of selection in paddy straw substrate were observed. Biological efficiency (BE) of P. djamor mutants irradiated at 20 Gy was increased by 9.25 per cent. The number of days taken for primordial initiation was also reduced by 1 day compared to P. djamor. P. florida irradiated at 25 Gy recorded increase in sporocarp size over P. florida. The biological efficiency of P. ostreatus irradiated at 25 Gy was improved by 12.89 per cent and there was earliness in primordial initiation by 3 days compared to P. ostreatus. The polymorphism per cent was analysed by Random Amplified Polymorphic DNA (RAPD) and revealed that P. djamor, P. florida and P. ostreatus had 16.70%, 25% and 22% polymorphism with their respective improved strains.

Ru(II)-Catalyzed C-H Activation/Alkylation of 3-Formylbenzofurans with Conjugated Olefins: Product Divergence.

Ru-catalyzed alkylation of 3-formylbenzofuran with acrylates and acrylamides has been described. Branched selectivity with unsubstituted or ß-substituted acrylates/acrylamides and linear selectivity with α-substituted acrylates have been observed. However, in all of the cases, the intermediate alkylation products seem to undergo further reactions, either cycloannulation or deformylation, depending on the substrate employed. For example, with methyl acrylate, the intermediate branched alkylation product underwent cycloannulation with another molecule of methyl acrylate, resulting in a densely functionalized cyclohexene ring formation. On the other hand, in the case of N-monosubstituted acrylamides, the branched alkylation proceeded with intramolecular aldehyde-amide condensation, leading to pyridin-2-one ring annulation. However, with both methacrylate and crotonate, deformylation of the initially formed alkylation products was observed.

Needs and perceptions regarding healthy eating among people at risk of food insecurity: a qualitative analysis.

BACKGROUND: Healthy eating behaviour is an essential determinant of overall health. This behaviour is generally poor among people at risk of experiencing food insecurity, which may be caused by many factors including perceived higher costs of healthy foods, financial stress, inadequate nutritional knowledge, and inadequate skills required for healthy food preparation. Few studies have examined how these factors influence eating behaviour among people at risk of experiencing food insecurity. We therefore aimed to gain a better understanding of the needs and perceptions regarding healthy eating in this target group. METHODS: We conducted a qualitative exploration grounded in data using inductive analyses with 10 participants at risk of experiencing food insecurity. The analysis using an inductive approach identified four core factors influencing eating behaviour: Health related topics; Social and cultural influences; Influences by the physical environment; and Financial influences. RESULTS: Overall, participants showed adequate nutrition knowledge. However, eating behaviour was strongly influenced by both social factors (e.g. child food preferences and cultural food habits), and physical environmental factors (e.g. temptations in the local food environment). Perceived barriers for healthy eating behaviour included poor mental health, financial stress, and high food prices. Participants had a generally conscious attitude towards their financial situation, reflected in their strategies to cope with a limited budget. Food insecurity was mostly mentioned in reference to the past or to others and not to participants' own current experiences. Participants were familiar with several existing resources to reduce food-related financial strain (e.g. debt assistance) and generally had a positive attitude towards these resources. An exception was the Food Bank, of which the food parcel content was not well appreciated. Proposed interventions to reduce food-related financial strain included distributing free meals, facilitating social contacts, increasing healthy food supply in the neighbourhood, and lowering prices of healthy foods. CONCLUSION: The insights from this study increase understanding of factors influencing eating behaviour of people at risk of food insecurity. Therefore, this study could inform future development of potential interventions aiming at helping people at risk of experiencing food insecurity to improve healthy eating, thereby decreasing the risk of diet-related diseases.

Nanoparticle encapsidation of Flock house virus by auto assembly of Tobacco mosaic virus coat protein.

Tobacco Mosaic virus (TMV) coat protein is well known for its ability to self-assemble into supramolecular nanoparticles, either as protein discs or as rods originating from the ~300 bp genomic RNA origin-of-assembly (OA). We have utilized TMV self-assembly characteristics to create a novel Flock House virus (FHV) RNA nanoparticle. FHV encodes a viral polymerase supporting autonomous replication of the FHV genome, which makes it an attractive candidate for viral transgene expression studies and targeted RNA delivery into host cells. However, FHV viral genome size is strictly limited by native FHV capsid. To determine if this packaging restriction could be eliminated, FHV was adapted to express enhanced green fluorescent protein (GFP), to allow for monitoring of functional FHV RNA activity. Then TMV OA was introduced in six 3' insertion sites, with only site one supporting functional FHV GFP expression. To create nanoparticles, FHV GFP-OA modified genomic RNA was mixed in vitro with TMV coat protein and monitored for encapsidation by agarose electrophoresis and electron microscopy. The production of TMV-like rod shaped nanoparticles indicated that modified FHV RNA can be encapsidated by purified TMV coat protein by self-assembly. This is the first demonstration of replication-independent packaging of the FHV genome by protein self-assembly.

Mitochondria-targeted antioxidant MitoQ ameliorates experimental mouse colitis by suppressing NLRP3 inflammasome-mediated inflammatory cytokines.

BACKGROUND: MitoQ is a mitochondria-targeted derivative of the antioxidant ubiquinone, with antioxidant and anti-apoptotic functions. Reactive oxygen species are involved in many inflammatory diseases including inflammatory bowel disease. In this study, we assessed the therapeutic effects of MitoQ in a mouse model of experimental colitis and investigated the possible mechanisms underlying its effects on intestinal inflammation. METHODS: Reactive oxygen species levels and mitochondrial function were measured in blood mononuclear cells of patients with inflammatory bowel disease. The effects of MitoQ were evaluated in a dextran sulfate sodium-induced colitis mouse model. Clinical and pathological markers of disease severity and oxidative injury, and levels of inflammatory cytokines in mouse colonic tissue were measured. The effect of MitoQ on inflammatory cytokines released in the human macrophage-like cell line THP-1 was also analyzed. RESULTS: Cellular and mitochondrial reactive oxygen species levels in mononuclear cells were significantly higher in patients with inflammatory bowel disease (P <0.003, cellular reactive oxygen species; P <0.001, mitochondrial reactive oxygen species). MitoQ significantly ameliorated colitis in the dextran sulfate sodium-induced mouse model in vivo, reduced the increased oxidative stress response (malondialdehyde and 3-nitrotyrosine formation), and suppressed mitochondrial and histopathological injury by decreasing levels of inflammatory cytokines IL-1 beta and IL-18 (P <0.001 and P <0.01 respectively). By decreasing mitochondrial reactive oxygen species, MitoQ also suppressed activation of the NLRP3 inflammasome that was responsible for maturation of IL-1 beta and IL-18. In vitro studies demonstrated that MitoQ decreases IL-1 beta and IL-18 production in human THP-1 cells. CONCLUSION: Taken together, our results suggest that MitoQ may have potential as a novel therapeutic agent for the treatment of acute phases of inflammatory bowel disease.

Corrosion inhibition study of 6061 aluminium alloy in the presence of ethyl 5-methyl-1-(4-nitrophenyl)-1H-1,2,3-triazole-4-carboxylate (NTE) in hydrochloric acid.

The inhibitory effect of an ethyl 5-methyl-1-(4-nitrophenyl)-1H-1,2,3-triazole-4-carboxylate (NTE) was investigated on the corrosion of Al (AA6061) alloy at different temperatures (303-333 K) by Electrochemical impedance spectroscopy (EIS), Potentiodynamic polarization (PDP), and weight loss techniques. It was found that NTE molecules protect the aluminium against corrosion and its ability increases with increasing concentrations, and temperature resulting in better inhibitory performance. At all concentrations and temperature ranges, NTE exhibited mixed inhibitor action and complied with the Langmuir isotherm. At 100 ppm and 333 K, NTE demonstrated the highest inhibition efficiency (94%). The EIS results and the PDP results had a good level of concordance. A suitable mechanism for the corrosion prevention of AA6061 alloy was proposed. Atomic force microscopy (AFM) and scanning electron microscopy (SEM) were used to confirm the adsorption of an inhibitor onto the aluminium alloy surface. The electrochemical results were validated by morphological examination, which demonstrated that NTE prevents uniform corrosion of aluminium alloy in acid chloride solutions. The activation energy and thermodynamic parameters were computed, and the results were discussed.

The role of p53 and ki67 in predicting clinical outcome in breast cancer patients.

Background: ">ki67 may be used as a proliferative index in addition to estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) negative status. p53 gene expression is a well-known biomarker in breast cancer and its role in predicting clinical outcome remains unclear. The current study aimed to determine the relationship between p53 gene mutation and ki67 expression, their clinical characteristics, and overall survival (OS), and to differentiate the significance of p53 and ki67 as the prognostic value in breast cancer patients. Methods: ">In this study, 135 patients were enrolled in the study from December 2015 to May 2017. Medical records for all patients were reviewed prospectively. The inclusion criteria included age more than 18 years with histologically proven breast cancer and willingness to be enrolled in p53 genetic study. Exclusion criteria included dual malignancy, male breast cancer, with a loss to follow-up during the study. Results: ">The mean survival of patients with ki67 ≤20 index was 42.7 months (95% confidence interval [CI] 38.7-46.7) and 129 months (95% CI 101.3-157.2) in patients with ki67 >20. The mean OS was 145 months (95% CI 105.6-185.5) in the p53 wild-type group and 106 months (95% CI 78.0-133.0) in the p53 mutated group, as illustrated. Conclusion: ">Our results indicated that p53 mutational status and high ki67 might have an essential impact on overall survival, with p53 mutated patients having a poorer outcome than p53 wild type patients.

N-[(4-Methyl-phen-yl)sulfon-yl]acetamide.

In the title compound, C(9)H(11)NO(3)S, the dihedral angle between the benzene ring and the amide group is 76.7 (3)°. In the crystal, mol-ecules are linked by pairs of C-H⋯O hydrogen bonds into inversion dimers with R(2) (2)(8) ring motifs. The dimers are further connected by N-H⋯O and C-H⋯O hydrogen bonds into an infinite tape running parallel to the b-axis direction.

N-[(4-Chloro-phen-yl)sulfon-yl]acetamide.

The asymmetric unit of the title compound, C(8)H(8)ClNO(3)S, consists of two crystallographically independent mol-ecules (A and B). The dihedral angles between the benzene ring and amide C-C(=O)-NH- plane are 87.6 (3) (mol-ecule A) and 86.0 (3)° (mol-ecule B). In the crystal, the independent mol-ecules are alternately linked by N-H⋯O hydrogen bonds into an infinite chain along the b axis. Short inter-molecular Cl⋯Cl contacts [3.2882 (5) and 3.2812 (5) Å] are also observed.

Long-acting and extended-release implant and nanoformulations with a synergistic antiretroviral two-drug combination controls HIV-1 infection in a humanized mouse model.

The HIV pandemic has affected over 38 million people worldwide with close to 26 million currently accessing antiretroviral therapy (ART). A major challenge in the long-term treatment of HIV-1 infection is nonadherence to ART. Long-acting antiretroviral (LA-ARV) formulations, that reduce dosing frequency to less than once a day, are an urgent need that could tackle the adherence issue. Here, we have developed two LA-ART interventions, one an injectable nanoformulation, and the other, a removable implant, for the delivery of a synergistic two-drug ARV combination comprising a pre-clinical nonnucleoside reverse transcriptase inhibitor (NNRTI), Compound I, and the nucleoside reverse transcriptase inhibitor (NRTI), 4'-ethynyl-2-fluoro-2'-deoxyadenosine. The nanoformulation is poly(lactide-co-glycolide)-based and the implant is a copolymer of ω-pentadecalactone and p-dioxanone, poly(PDL-co-DO), a novel class of biocompatible, biodegradable materials. Both the interventions, packaged independently with each ARV, released sustained levels of the drugs, maintaining plasma therapeutic indices for over a month, and suppressed viremia in HIV-1-infected humanized mice for up to 42 days with maintenance of CD4+ T cells. These data suggest promise in the use of these new drugs as LA-ART formulations in subdermal implant and injectable mode.

Infectious causes of acute encephalitis syndrome hospitalizations in Central India, 2018-20.

BACKGROUND: We enhanced surveillance of hospitalizations of all ages for acute encephalitis syndrome (AES) along with infectious aetiologies, including the Japanese encephalitis virus (JEV). METHODS: From October 2018 to September 2020, we screened neurological patients for AES in all age groups in Maharashtra and Telangana States. AES cases were enrolled at study hospitals along with other referrals and sampled with cerebrospinal fluid, acute and convalescent sera. We tested specimens for non-viral aetiologies viz. leptospirosis, typhoid, scrub typhus, malaria and acute bacterial meningitis, along with viruses - JEV, Dengue virus (DENV), Chikungunya virus (CHIKV), Chandipura virus (CHPV) and Herpes simplex virus (HSV). RESULTS: Among 4977 neurological hospitalizations at three study site hospitals over two years period, 857 (17.2%) were AES. However, only 287 (33.5%) AES cases were eligible. Among 278 (96.9%) enrolled AES cases, infectious aetiologies were identified in 115 (41.4%) cases, including non-viral in 17 (6.1%) cases - leptospirosis (8), scrub-typhus (3) and typhoid (6); and viral in 98 (35.3%) cases - JEV (58, 20.9%), HSV (22, 7.9%), DENV (15, 5.4%) and CHPV (3, 1.1%). JEV confirmation was significantly higher in enrolled cases than referred cases (10.2%) (p < 0.05). However, the contribution of JEV in AES cases was similar in both children and adults. JE was reported year-round and from adjacent non-endemic districts. CONCLUSIONS: The Japanese encephalitis virus continues to be the leading cause of acute encephalitis syndrome in central India despite vaccination among children. Surveillance needs to be strengthened along with advanced diagnostic testing for assessing the impact of vaccination.

Ability to delay neuropathological events associated with astrocytic MAO-B increase in a Parkinsonian mouse model: implications for early intervention on disease progression.

We previously demonstrated that elevation of astrocytic monoamine oxidase B (MAO-B) levels in adoxycycline (dox)-inducible transgenic mouse model following 14 days of dox induction results in several neuropathologic features similar to those observed in the Parkinsonian midbrain (Mallajosyula et al., 2008).These include a specific, selective and progressive loss of dopaminergic neurons of the substantia nigra (SN),selective decreases in mitochondrial complex I (CI) activity and increased oxidative stress. Here, we report that the temporal sequence of events following MAO-B elevation initially involves increased oxidative stress followed by CI inhibition and finally neurodegeneration. Furthermore, dox removal (DR) at days 3 and 5 of MAO-B induction was sufficient to arrest further increases in oxidative stress as well as subsequent neurodegenerative events. In order to assess the contribution of MAO-B-induced oxidative stress to later events, we compared the impact of DR which reverses the MAO-B increase with treatment of animals with the lipophilic antioxidant compound EUK-189. EUK-189 was found to be as effective as DR in halting downstream CI inhibition and also significantly attenuated SN DA cell loss as a result of astrocytic MAO-B induction. This suggests that MAO-B-mediated ROS contributes to neuropathology associated with this model and that antioxidant treatment can arrest further progression of dopaminergic cell death. This has implications for early intervention therapies.

Antioxidant enzymes induced by repeated intake of excess energy in the form of high-fat, high-carbohydrate meals are not sufficient to block oxidative stress in healthy lean individuals.

It has been reported that high-fat, high-carbohydrate (HFHC) meals increase oxidative stress and inflammation. We examined whether repeated intake of excess energy in the form of HFHC meals alters reactive oxygen species (ROS) generation and the expression levels of antioxidant enzymes and mitochondrial proteins in mononuclear cells, and to determine whether this is associated with insulin resistance. We recruited healthy lean individuals (n 10). The individuals were divided into two groups: one group (n 5) ingested 10878·4 kJ/d (2600 kcal/d; 55-70 % carbohydrate, 9·5-16 % fat, 7-20 % protein) recommended by the Dietary Reference Intake for Koreans for 4 d and the other group (n 5) ingested a HFHC meal containing 14 644 kJ/d (3500 kcal/d). Then, measurements of blood insulin and glucose levels, together with suppressor of cytokine signalling-3 (SOCS-3) expression levels, were performed in both groups. Also, cellular and mitochondrial ROS levels as well as malondialdehyde (MDA) levels were measured. Expression levels of cytosolic and mitochondrial antioxidant enzymes, and mitochondrial complex proteins were analysed. Repeated intake of HFHC meals induced an increase in homeostasis model of assessment-insulin resistance (HOMA-IR), together with an increase in SOCS-3 expression levels. While a single intake of the HFHC meal increased cytosolic and mitochondrial ROS, repeated intake of HFHC meals reduced them and increased the levels of MDA, cytosolic and mitochondrial antioxidant enzymes, and several mitochondrial complex proteins. Repeated intake of HFHC meals induced cellular antioxidant mechanisms, which in turn increased lipid peroxidation (MDA) and SOCS-3 expression levels, induced hyperinsulinaemia and increased HOMA-IR, an index of insulin resistance. In conclusion, excess energy added to a diet can generate detrimental effects in a short period.

Modulating HIV-1 envelope glycoprotein conformation to decrease the HIV-1 reservoir.

Small CD4-mimetic compounds (CD4mc) sensitize HIV-1-infected cells to antibody-dependent cellular cytotoxicity (ADCC) by facilitating antibody recognition of epitopes that are otherwise occluded on the unliganded viral envelope (Env). Combining CD4mc with two families of CD4-induced (CD4i) antibodies, which are frequently found in plasma of HIV-1-infected individuals, stabilizes Env in a conformation that is vulnerable to ADCC. We employed new-generation SRG-15 humanized mice, supporting natural killer (NK) cell and Fc-effector functions to demonstrate that brief treatment with CD4mc and CD4i-Abs significantly decreases HIV-1 replication, the virus reservoir and viral rebound after ART interruption. These effects required Fc-effector functions and NK cells, highlighting the importance of ADCC. Viral rebound was also suppressed in HIV-1+-donor cell-derived humanized mice supplemented with autologous HIV-1+-donor-derived plasma and CD4mc. These results indicate that CD4mc could have therapeutic utility in infected individuals for decreasing the size of the HIV-1 reservoir and/or achieving a functional cure.

Ability to delay neuropathological events associated with astrocytic MAO-B increase in a Parkinsonian mouse model: implications for early intervention on disease progression.

We previously demonstrated that elevation of astrocytic monoamine oxidase B (MAO-B) levels in a doxycycline (dox)-inducible transgenic mouse model following 14 days of dox induction results in several neuropathologic features similar to those observed in the Parkinsonian midbrain (Mallajosyula et al., 2008). These include a specific, selective and progressive loss of dopaminergic neurons of the substantia nigra (SN), selective decreases in mitochondrial complex I (CI) activity and increased oxidative stress. Here, we report that the temporal sequence of events following MAO-B elevation initially involves increased oxidative stress followed by CI inhibition and finally neurodegeneration. Furthermore, dox removal (DR) at days 3 and 5 of MAO-B induction was sufficient to arrest further increases in oxidative stress as well as subsequent neurodegenerative events. In order to assess the contribution of MAO-B-induced oxidative stress to later events, we compared the impact of DR which reverses the MAO-B increase with treatment of animals with the lipophilic antioxidant compound EUK-189. EUK-189 was found to be as effective as DR in halting downstream CI inhibition and also significantly attenuated SN DA cell loss as a result of astrocytic MAO-B induction. This suggests that MAO-B-mediated ROS contributes to neuropathology associated with this model and that antioxidant treatment can arrest further progression of dopaminergic cell death. This has implications for early intervention therapies.

Delaying clozapine: how long is too long?

BACKGROUND: Although clozapine is the most effective drug for treatment-resistant schizophrenia, its use remains restricted in clinical practice in India. The delay in initiating treatment with clozapine and its impact on disease outcome needs evaluation. AIM: To identify the implications of delaying clozapine initiation in clinical outcomes among people with treatment-resistant schizophrenia. METHODS: Subjects with treatment-resistant schizophrenia, stabilised on clozapine monotherapy, were recruited from the outpatient clinic of a general hospital psychiatry unit offering tertiary care services in Thrissur district, Kerala, India. A retrospective cohort design was employed, and information on duration of illness, total duration of treatment and duration of treatment with clozapine was collected. Present symptom status was measured using the Positive and Negative Syndrome Scale. Factors associated with higher symptom scores were analysed using an independent sample t test, Spearman correlation and multiple linear regression. RESULTS: Forty subjects stabilised on long-term clozapine therapy formed the study sample. The mean dose of clozapine used in the study population was 200 mg. The mean duration of antipsychotic treatment before starting clozapine was 89.3 months (7.4 years). The duration of treatment before starting clozapine was found to have a significant positive association with the total Positive and Negative Syndrome Scale score (correlation coefficient 0.40; p=0.01) and negative symptom score (correlation coefficient 0.33; p=0.04). The multiple regression analysis adjusting for covariates showed that the duration of treatment before starting clozapine was an independent factor associated with a higher negative symptom score in the Positive and Negative Syndrome Scale (slope ß=0.05; p=0.02; R2=0.27). CONCLUSION: Poor treatment outcomes in treatment-resistant schizophrenia could be secondary to a delay in initiating clozapine therapy.

Microwave-assisted synthesis, biological evaluation and molecular docking studies of new coumarin-based 1,2,3-triazoles.

Coumarin-based 1,4-disubstituted 1,2,3-triazole derivatives were synthesized using a highly efficient, eco-friendly protocol via a copper(i)-catalyzed click reaction between various substituted arylazides and terminal alkynes. The synthetic route was easy to access and gave excellent yields under microwave irradiation conditions compared to the conventional heating route. The structures of all the compounds were characterized by IR, 1H NMR, 13C NMR spectroscopy and mass spectrometry. All the synthesized compounds were screened for their in vitro antimicrobial, antioxidant and anti-inflammatory activities; among all compounds, 8a, 8j, 8k and 8l exhibited better results with respect to standard drugs. Furthermore, molecular docking studies have been carried out with PDB IDs 2VCX (anti-inflammatory), 3VXI (antioxidant), 4GEE (antimicrobial) and 2XFH (antifungal) using the Glide module of the Schrödinger suite. The final compounds 8d, 8e, 8h, and 8k showed the highest hydrogen bond interactions with His-88 and Val-191 proteins and with water in all the proteins.

Comparative assessment in enzyme activities and microbial populations during normal and vermicomposting.

Changes in extracellular enzyme activities and microbial populations were studied during the normal composting and vermicomposting of fruitpulp, vegetable waste, groundnut husk and cowdung. The microbial numbers and their extracellular enzyme profiles showed relative variation and were found increasingly more abundant in vermicompost than in normal compost leading to the conversion of agricultural waste into value added product. In vermicompost, the maximum enzyme activities (cellulase, amylase, invertase, protease and urease) were observed during 21-35 days. The cellulase, amylase and protease activities of vermicompost reached the maximum values by 28th day of 1175, 825 microg reducing sugar g(-1) hr(-1) and 28 micro mol of aminoacid g(-1) hr(-1) of vermicompost samples respectively. Similarly the invertase and urease activities reached to peak values of 876 microg reducing sugar g(-1) hr(-1) and 197 microg NH4(+)-N g(-1) ha(-1) sample on 35th day respectively. Most of the enzymes showed correlation with change in number and types of different microbial groups like bacteria, fungi and actinomycetes during vermicomposting with maximum number of 126 x 10(6), 28 x 10(4) and 93 x 10(5) CFU g(-1) sample respectively. In contrast delayed greatest enzyme activities were observed on 42-49th day i.e., last days of normal composting. Earthworms stimulated biochemical activity and nutrient cycling by 40-45% contributing to the reduction of period of degradation of agricultural wastes resulting in maturation of vermicompost by 28th day.