Predicting the bioactive compounds of Lentinula edodes and elucidating its interaction with genes associated to obesity through network pharmacology and in-vitro cell-based assay.

Mushrooms are traditionally used for various medicinal purposes in traditional oriental medicine. The Japanese and Chinese are familiar with the medicinal macro fungus Lentinula edodes (Shiitake mushroom). This study aims to evaluate the role of chemical compounds from L. edodes using network pharmacology and in-vitro studies for management of Obesity. Bioactive compounds in extracts of L. edodes were identified by GC-MS analysis. Compounds were later screened for their drug-like property by Lipinski's rule. In addition, public databases (SEA, STP, Omim and DisGenet) were searched to identify genes associated with selected molecules and obesity, as well as genes that overlap obesity target genes with genes related to L. edodes. Additionally, analysis was performed using Enrichr KG to predict the disease targets of L. edodes. Finally, network was constructed between the overlapping genes and bioactive molecules using Rstudio. Further in-vitro studies were carried out using 3T3-L1 cell line. The genes related to the selected compounds and obesity were identified and overlapped. The disease targets of L. edodes was predicted by enrichment analysis and was found to be linked to obesity. Furthermore, the hub gene was found to be fatty acid amide hydrolase, and the key bioactive compound was hexadecanoic acid methyl ester. The in-vitro cell culture studies confirmed the inhibition of adipogenesis in mushroom extract-treated 3T3-L1 cells and the augmentation of adiponectin. The study suggests that the hub gene fatty acid amide hydrolase might alleviate obesity by inhibiting arachidonoyl ethanolamide signaling, which would enhance the action of fatty acid amide hydrolase and limit appetite in L. edodes extract.

Long-term health consequences of COVID-19 in survivors hospitalised at a tertiary care hospital and their correlation with acute COVID-19 severity and associated risk factors.

OBJECTIVES: To determine post-COVID syndromes in the Indian population, correlating a wide spectrum of post-COVID manifestations with acute disease severity and associated risk factors. BACKGROUND: Post-COVID Syndrome (PCS) is defined as signs and symptoms that develop during or after acute COVID-19 infection. DESIGN OF STUDY: This is a prospective observational cohort with repetitive measurements. METHODS: The study followed RT-PCR confirmed COVID-19-positive survivors discharged from HAHC Hospital, New Delhi, for a period of 12 weeks. The patients were interviewed over the phone at 4 weeks and 12 weeks from the onset of symptoms for evaluation of clinical symptoms and health-related quality of life parameters. RESULTS: A total of 200 patients completed the study. At the baseline, 50% of the patients were categorised as severe based on their acute infection assessment. At 12 weeks after symptom onset, fatigue (23.5%), hair loss (12.5%) and dyspnea (9%) were the main persistent symptoms. The incidence of hair loss (12.5%), memory loss (4.5%) and brain fog (5%) were found to be increased as compared to the acute infection period. Severity of the acute COVID infection behaved as an independent predictor for the development of PCS, with high odds of experiencing persistent cough (OR = 13.1), memory loss (OR = 5.2) and fatigue (OR = 3.3). Further, 30% of subjects in the severe group experienced statistically significant fatigue at 12 weeks (p < .05). CONCLUSION: From the results of our study, it can be concluded that there is a huge disease burden of post-COVID Syndrome (PCS). The PCS comprised multisystem symptoms ranging from serious complaints of dyspnea, memory loss and brain fog to non-serious complaints of fatigue and hair loss. Severity of the acute COVID infection behaved as an independent predictor for the development of PCS. Our findings strongly recommend vaccination against COVID-19, for protection from disease severity as well as prevention of PCS. RELEVANCE TO CLINICAL PRACTICE: The findings of our study support the multidisciplinary approach required for the management of PCS with a team comprising of physicians, nurses, physiotherapists and psychiatrists working in close coordination for the rehabilitation of these patients. As nurses are considered the most trusted professionals in the community and the class of health workers associated with rehabilitation, focus should be given to educating them on PCS, which would prove to be an important strategy for efficient monitoring and long-term management of COVID-19 survivors.

Phenotyping of lymphocyte subsets, Th-1/Th-2 cytokines and other parameters in high-risk contacts of SARS-CoV-2.

Background: The information on the pathophysiology of infection in high-risk contacts of SARS-CoV-2 is limited. Aims: The aim of the present study was to assess the various factors and their elucidation in the protection of SARS- CoV-2 infection in high-risk contacts. Settings and Design: Cross-sectional descriptive clinical study. Materials and Methods: A total of 136 subjects were recruited in the present study including 100 high-risk subjects and 36 control subjects. Out of 100 high-risk subjects, 44 subjects were found positive for SARS-CoV-2 RNA. Further, absolute blood counts of total T-cells (CD3+), T-helper cells (CD4+), T-cytotoxic cells (CD8+), B lymphocytes (CD19+) Natural Killer (NK) Cells (CD16+, CD56+), cytokines, and other parameters were measured in the samples of study subjects. Statistical Analysis Used: The continuous variables were analyzed by unpaired 't' test, analysis of variance and 'Tukey test' for multiple comparisons. Results: A significant reduction of total leukocyte counts and absolute lymphocyte count was found in the acute SARS-CoV-2 positive group as compared to control group (<0.05). Interestingly, IL-4 level was significantly elevated in SARS-CoV-2 negative high-risk subjects as compared to control and acute SARS-CoV-2 positive group (p < 0.05). A significant decrease of T-cytotoxic, B-cells, and NK cells were found in acute SARS-CoV-2 positive subjects as compared to control groups. Conclusion: The findings of this study may augment our knowledge about the pathogenesis of SARS-CoV-2 infection that could help in making future strategies to control its infection.

Landscape genetics identified conservation priority areas for blue sheep (Pseudois nayaur) in the Indian Trans-Himalayan Region.

The trans-Himalayan region of India, although have xeric features, still supports a unique assemblage of biodiversity, including some of the charismatic and endemic species. In the present study, we studied blue sheep (Pseudois nayaur) across the distribution range in the Western trans Himalayas of India and found about 18,775 km2 area suitable for blue sheep. The explicit Bayesian based spatial and non-spatial population structure analysis assigned blue sheep into two genetic populations, i.e., Ladakh and Lahaul-Spiti. We found relatively high genetic divergence in blue sheep which is also supported by the low current flow in Circuitscape model. With the multiple evidences, we explain landscape resistance facilitated by the landscape heterogeneity, and large patches of unsuitable habitats forced population divergence and poor functional connectivity. We found that blue sheep population has been demographically stable in the past, but showed a slight decline within the last few decades. This study is the first range-wide attempt to exhibit landscape features in shaping the spatial distribution, genetic structure and demography patterns of blue sheep in Western Himalayas, and will be of use in the conservation and management planning of blue sheep.

Mid-Pleistocene Transitions Forced Himalayan ibex to Evolve Independently after Split into an Allopatric Refugium.

Pleistocene glaciations had profound impact on the spatial distribution and genetic makeup of species in temperate ecosystems. While the glacial period trapped several species into glacial refugia and caused abrupt decline in large populations, the interglacial period facilitated population growth and range expansion leading to allopatric speciation. Here, we analyzed 40 genomes of four species of ibex and found that Himalayan ibex in the Pamir Mountains evolved independently after splitting from its main range about 0.1 mya following the Pleistocene species pump concept. Demographic trajectories showed Himalayan ibex experienced two historic bottlenecks, one each c. 0.8-0.5 mya and c. 50-30 kya, with an intermediate large population expansion c. 0.2-0.16 mya coinciding with Mid-Pleistocene Transitions. We substantiate with multi-dimensional evidence that Himalayan ibex is an evolutionary distinct phylogenetic species of Siberian ibex which need to be prioritized as Capra himalayensis for taxonomic revision and conservation planning at a regional and global scale.

Visiting Ladakh Himalaya for a better knowledge of butterflies: new faunistic data with annotations (Lepidoptera, Papilionoidea).

The present study enumerates 65 species of Papilionoidea from the Ladakh Himalaya with the geographical locations and adult flight data. All the species are documented by museum vouchers. Most of the species recorded, have restricted distribution or they are endemic to the Pamir-NW Himalaya region. Sixteen species are protected in the Indian Wildlife (Protection) Act, 1972; three species highly protected under schedule I: Baltia butleri, Pieris krueperi, Lasiommata menava; and others under schedule II: Papilio machaon, Parnassius charltonius, Parnassius epaphus, Colias ladakensis, Colias eogene, Colias stoliczkana, Pieris deota, Pontia chloridice, Alpherakya devanica, Pamiria metallica, Paralasa mani, Paralasa kalinda and Polygonia c-album. We report lower occurrences for the endemic Pieris deota, where the migrant Pontia chloridice is reported to fly at more than 600 m higher than earlier records indicated. Lastly, the male and female genitalia of some endemic and rare species are illustrated, including Euchloe daphalis.

Environmental predictors may change at fine scale habitat suitability modelling: implications for conservation of Kashmir musk deer in three protected areas of Uttarakhand, India.

The Kashmir musk deer (Moschus cupreus, hereafter KMD) is one of the top conservation priority species which is facing population decline due to poaching, habitat loss, and climate change. Therefore, the long-term survival and viability of KMD populations in their natural habitat require conservation and management of suitable habitats. Hence, the present study attempted to assess the suitable habitat of KMD in three protected areas (PAs) of the Western Himalayan region of Uttarakhand using the Maxent modelling algorithm. Our results suggest that Kedarnath wildlife sanctuary (KWLS) possesses the maximum highly suitable habitats (22.55%) of KMD, followed by Govind Pashu Vihar National Park & Sanctuary (GPVNP&S; 8.33%) and Gangotri National Park (GNP; 5%). Among the environmental variables, altitude was the major contributing factor governing the distribution of KMD in KWLS. In contrast, human footprint in GPVNP&S and precipitation in GNP were the major contributing factors governing the distribution of KMD in these respective PAs. The response curve indicated that habitats with less disturbance falling in the altitudinal zone of 2000-4000 m were the most suitable habitat range for the distribution of KMD in all three PAs. However, in the case of GNP suitable habitat of KMD increases with an increase in the value of variables bio_13 (precipitation of wettest month). Further, based on our results, we believe that the predictors of suitable habitat change are site specific and cannot be generalized in the entire distribution range of the species. Therefore, the present study will be helpful in making proper habitat management actions at fine scale for the conservation of KMD.

A new distributional range of Abraxas antipusilla Inoue, 1995 (Lepidoptera: Geometridae) from Eastern Himalaya, India.

Based on Indian Himalayan expeditions, the species Abraxas antipusilla Inoue, 1995 is reported for the first time from Eastern Himalaya, India. After two decades, differential diagnoses of males and females are presented in comparison to Abraxas pusilla Butler, 1880. Redescriptions of male and female genitalia are given. An annotated summary on habitat preference and distributional ranges for both species is emphasized within the Indian Himalayan Region.

Review of Melolontha Fabricius, 1775 (Coleoptera: Scarabaeidae: Melolonthinae) from India with the description of two new species.

The genus Melolontha Fabricius, 1775 (Coleoptera: Scarabaeidae: Melolonthinae) from India is reviewed. Two new species, Melolontha arunachalensis Gupta, Keith, Bhunia, Das, Ghosh & Chandra, new species and Melolontha lachungensis Gupta, Keith, Bhunia, Das, Ghosh & Chandra, new species are described. Melolontha chinensis Guérin-Méneville, 1838 is reported for the first time from India. Taxonomic notes on the identification of previously known species of Melolontha from India are provided, together with a key to the species (males).

Amemboa Esaki (Hemiptera: Gerromorpha: Gerridae) of India, with descriptions of two new species and establishment of species groups of world species.

Two new species of Gerridae, Amemboa latoae Jehamalar & Dash, new species and A. zetteli Jehamalar & Dash, new species, are described from India. Amemboa latoae is described from Meghalaya and can be recognised by the presence of the two setal tufts on the flexor region of the male fore femur and the slightly dilated midlateral region of the main part of the proctiger. Amemboa zetteli Jehamalar & Dash, new species, is described from Andaman Island and can be identified by the presence of the three setal tufts on the flexor region of the male fore femur; the rhombus-shaped main part of the proctiger of the male and the shape of the posterior region of the pygophore. Eleven species groups of Amemboa are also recognized in the present paper.

Lahaul-Zanskar-Sham Valley Corridor in Indian Trans Himalayan Region Facilitates Dispersal and Gene Flow in Himalayan Ibex.

Wildlife corridors that connect mosaic habitats in heterogeneous mountainous landscapes can be of high significance as they facilitate the genetic and demographic stability of free-ranging populations. Peripheral populations of widespread species are usually ignored in conservation planning. However, these populations retain locally common alleles and are genetic reservoir under the changing climatic conditions. Capra sibirica has widespread distribution, and its southern peripheral population is distributed in the Indian trans-Himalayan region (ITR). In the present study, we studied the spatial distribution and genetic make-up of Himalayan ibex from the ITR following the landscape genetics approach. We obtained 16 haplotypes at the mitochondrial d-loop region and found a stable demography in the past with a recent decline. With 10 nuclear microsatellites, we ascertained 111 unique individuals assigned into two clusters following Bayesian and non-Bayesian clustering analysis with several admixed individuals. We also recorded 25 first-generation migrants that reflected relatively high dispersal and gene-flow across the range. We identified a 19,835 sq.km suitable area with 13,311 sq.km in Ladakh and 6524 sq.km in Lahaul-Spiti. We identified a novel movement corridor for Himalayan ibex across the Lahaul-Zanskar-Sham valley (L-Z-SV) that displayed a fairly good conductance with low genetic divergence among the samples collected on the L-Z-SV corridor. We propose declaring a protected area in the Lahaul and Kargil districts to prioritize dedicated conservation efforts for the Himalayan ibex and other sympatric ungulates that impart a major role in the diet of large carnivore and balancing ecosystem services in the trans-Himalayan region.

Pyrazole scaffold-based derivatives: A glimpse of α-glucosidase inhibitory activity, SAR, and route of synthesis.

The α-glucosidase is a validated target to develop drugs for treating type 2 diabetes mellitus. The existing α-glucosidase inhibitors have certain shortcomings related to side effects and route of synthesis. Accordingly, it is inevitable to develop new chemical templates as α-glucosidase inhibitors. Pyrazole derivatives have a special place in medicinal chemistry because of various biological activities. Recently, pyrazole-based heterocyclic compounds have emerged as a promising scaffold to develop α-glucosidase inhibitors. This study focuses on the recently reported pyrazole-based α-glucosidase inhibitors, including their biological activity (in vivo, in vitro, and in silico), structure-activity relationship, and ways of synthesis. The literature revealed the development of several promising pyrazole-based α-glucosidase inhibitors and new synthetic routes for their preparation. The encouraging α-glucosidase inhibitory results of the pyrazole-based heterocyclic compounds make them an attractive target for further research. The authors also foresee the arrival of the pyrazole-based α-glucosidase inhibitors in clinical practice.

Whether curse or blessing: A counterintuitive perspective on global pest thrips infestation under climatic change with implications to agricultural economics.

The improvement and application of pest models to predict yield losses is still a challenge for the scientific community. However, pest models were targeted chiefly towards scheduling scouting or pesticide applications to deal with pest infestation. Thysanoptera (thrips) significantly impact the productivity of many economically important crops worldwide. Until now, no comprehensive study is available on the global distribution of pest thrips, as well as on the extent of cropland vulnerability worldwide. Further, nothing is known about the climate change impacts on these insects. Thus the present study was designed to map the global distribution and quantify the extent of cropland vulnerability in the present and future climate scenarios using data of identified pest thrips within the genus, i.e., Thrips, Frankliniella, and Scirtothrips. Our found significant niche contraction under the climate change scenarios and thrips may reside primarily in their thermal tolerance thresholds. About 3,98,160 km2 of cropland globally was found to be affected in the present scenario. However, it may significantly reduce to 5530 Km2 by 2050 and 1990 km2 by 2070. Further, the thrips distribution mostly getting restricted to Eastern North America, the North-western of the Indian sub-continent, and the north of Europe. Among all realms, thrips may lose ground in the Indo-Malayan realm at the most and get restricted to only 27 out of 825 terrestrial ecoregions. The agrarian communities of the infested regions may get benefit if these pests get wiped out, but on the contrary, we may lose species diversity. Moreover, the vacated niche may attract other invasive species, which may seriously impact the species composition and agricultural productivity. The present study findings can be used in making informed decisions about prioritizing future economic and research investments on the thrips in light of anticipated climate change impacts.

Identification of novel pyrazole containing ɑ-glucosidase inhibitors: insight into pharmacophore, 3D-QSAR, virtual screening, and molecular dynamics study.

Pharmacophore modelling, 3 D QSAR modelling, virtual screening, and molecular dynamics study, all-in-one combination were employed successfully design and develop an alpha-glucosidase inhibitor. To explain the structural prerequisites of biologically active components, 3 D-QSAR models were generated using the selected best hypothesis (AARRR) for compounds 55 included in the model C. The selection of 3 D-QSAR models showed that the Gaussian steric characteristic is crucial to alpha glucosidase's inhibitory potential. The alpha-glucosidase inhibitory potency of the compound is enhanced by other components, including Gaussian hydrophobic groups, Gaussian hydrogen bond acceptor or donor groups, Gaussian electrostatic characteristics, and a Gaussian steric feature. An identification of structure-activity relationships can be obtained from the developed 3 D-QSAR, C model, with R2 = 0.77 and SD = 0.02 for training set, and Q2 = 0.66, RMSE 0.02, and Pearson R = 0.81 for testing set, corresponding to elevated predictive ability. Additionally, docking and MM/GBSA experiments on 1146023 showed that it interacts with critical amino acids in the binding site when coupled with acarbose. Further, five compounds that display a high affinity for alpha-glucosidase were found, and these compounds may serve as potent leads for alpha-glucosidase inhibitor development. Biological activity will be tested for these compounds in the future.Communicated by Ramaswamy H. Sarma.

A new species of the genus Subniganda Kiriakoff, 1962 (Lepidoptera: Notodontidae) from India and Nepal.

The present paper describes a new species of Notodontidae Subniganda bambusoides Mazumder & Schintlmeister sp. nov. from the Himalayan and northeastern landscapes of India and Nepal. It also provides a comparative diagnosis with its congeners S. tristan (Schintlmeister, 1997) and S. isolde (Schintlmeister, 1997) along with detailed morphological and genitalic illustrations.

Fabrication and Characterization of Cu Nanoparticles Dispersed on ZnAl-Layered Double Hydroxide Nanocatalysts for the Oxidation of Cyclohexane.

In the chemical industry, designing high-performance catalysts for the oxidation of cyclohexane into value-added products such as cyclohexanol and cyclohexanone (the combination is known as KA oil) is critical. The catalytic activity of copper nanoparticles supported on layered double hydroxide (LDH) for the liquid phase oxidation of cyclohexane was examined in this study. In this work, we have developed Cu nanoparticles supported on layered double hydroxide nanocatalysts, abbreviated as CuNPs@LDH, by the chemical reduction approach. Various physical methods were used to characterize the resulting material, including ICP-AES, XRD, FTIR, SEM, EDX, HRTEM, and BET surface area. The catalytic activity of copper nanoparticles supported on LDH was examined for the liquid phase oxidation of cyclohexane with tert-butyl hydroperoxide. CuNPs@LDH nanocatalysts with an excellent 52.3% conversion of cyclohexane with 97.2% selectivity of KA oil was obtained after 6 h at 353 K. The hot filtration test further indicated that CuNPs@LDH was a heterogeneous catalyst that could be recycled at least six times without suffering a substantial reduction in its catalytic activity.

Coronary access following ACURATE neo implantation for transcatheter aortic valve-in-valve implantation: Ex vivo analysis in patient-specific anatomies.

Background: Coronary access after transcatheter aortic valve implantation (TAVI) with supra-annular self-expandable valves may be challenging or un-feasible. There is little data concerning coronary access following transcatheter aortic valve-in-valve implantation (ViV-TAVI) for degenerated surgical bioprosthesis. Aims: To evaluate the feasibility and challenge of coronary access after ViV-TAVI with the supra-annular self-expandable ACURATE neo valve. Materials and methods: Sixteen patients underwent ViV-TAVI with the ACURATE neo valve. Post-procedural computed tomography (CT) was used to create 3D-printed life-sized patient-specific models for bench-testing of coronary cannulation. Primary endpoint was feasibility of diagnostic angiography and PCI. Secondary endpoints included incidence of challenging cannulation for both diagnostic catheters (DC) and guiding catheters (GC). The association between challenging cannulations with aortic and transcatheter/surgical valve geometry was evaluated using pre and post-procedural CT scans. Results: Diagnostic angiography and PCI were feasible for 97 and 95% of models respectively. All non-feasible procedures occurred in ostia that underwent prophylactic "chimney" stenting. DC cannulation was challenging in 17% of models and was associated with a narrower SoV width (30 vs. 35 mm, p < 0.01), STJ width (28 vs. 32 mm, p < 0.05) and shorter STJ height (15 vs. 17 mm, p < 0.05). GC cannulation was challenging in 23% of models and was associated with narrower STJ width (28 vs. 32 mm, p < 0.05), smaller transcatheter-to-coronary distance (5 vs. 9.2 mm, p < 0.05) and a worse coronary-commissural overlap angle (14.3° vs. 25.6 o , p < 0.01). Advanced techniques to achieve GC cannulation were required in 22/64 (34%) of cases. Conclusion: In this exploratory bench analysis, diagnostic angiography and PCI was feasible in almost all cases following ViV-TAVI with the ACURATE neo valve. Prophylactic coronary stenting, higher implantation, narrower aortic sinus dimensions and commissural misalignment were associated with an increased challenge of coronary cannulation.

Multi-species occupancy modeling suggests interspecific interaction among the three ungulate species.

Species with sympatric distribution influence ecosystem dynamics and are impacted by the presence of other co-existing species. Assessing the coexistence and the role of interspecific interactions with the landscape variables is necessary to know the species co-occurrence in space. In the Indian Himalayan region, such studies are completely lacking due to limited efforts being made, mainly because of complex terrains and inaccessible landscape features. We used camera trapping and sign survey in a multi-species occupancy framework to understand the influence of environmental variables on occupancy and detection probability of species-specific and pair-wise interaction of the three ungulates in Uttarkashi. Our results concluded that individual species' occupancy probabilities were related both to the environmental variables and the presence or absence of other interacting species. Our top model showed evidence of interspecific interaction among species pairs, and the occupancy probability of species one varied in the presence or absence of another species. The overall activity patterns were similar among all the three species and were found active throughout the day. The activity overlap between sambar-barking deer (Dhat1 value = 0.85) was considerably higher than barking deer-goral (Dhat1 value = 0.78). The findings of the present study will be useful for the conservation and management of ungulates in the Indian Himalayan and adjoining regions.

From poops to planning: A broad non-invasive genetic survey of large mammals from the Indian Himalayan Region.

Large forested landscapes often harbour significant amount of biodiversity and support mankind by rendering various livelihood opportunities and ecosystem services. Their periodic assessment for health and ecological integrity is essential for timely mitigation of any negative impact of human use due to over harvesting of natural resources or unsustainable developmental activities. In this context, monitoring of mega fauna may provide reasonable insights about the connectivity and quality of forested habitats. In the present study, we conducted a largest non-invasive genetic survey to explore mammalian diversity and genetically characterized 13 mammals from the Indian Himalayan Region (IHR). We analyzed 4806 faecal samples using 103 autosomal microsatellites and with three mitochondrial genes, we identified 37 species of mammal. We observed low to moderate level of genetic variability and most species exhibited stable demographic history. We estimated an unbiased population genetic account (PGAunbias) for 13 species that may be monitored after a fixed time interval to understand species performance in response to the landscape changes. The present study has been evident to show pragmatic permeability with the representative sampling in the IHR in order to facilitate the development of species-oriented conservation and management programmes.