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Endoplasmic reticulum (ER) is one of the most important sub‐cellular organelles which controls myriads of biological functions including protein biosynthesis with proper functional folded form, protein misfolding, protein transport into Golgi body for secretion, Ca2+ homeostasis and so on. Subsequently, dysregulation in ER function leads to ER stress followed by disease pathology like cancer. Hence, targeting ER in the cancer cells emerged as one of the futuristic strategies for cancer treatment. However, the major challenge is to selectively and specifically target ER in the sub‐cellular milieu in the cancer tissues, due to the lack of ER targeting chemical moieties to recognize the ER markers. To address this, in the last decade, numerous biomaterials were explored to selectively impair and image ER in cancer cells to induce ER stress. This review outlines those biomaterials which consists of carbon and silicon materials, lipid nanoparticles (liposomes and micelles), supramolecular self‐assembled nanostructures, cell membrane‐coated nanoparticles and metallic nanoparticles. Moreover, we also discuss the challenges and possible solutions of this promising field to usher the readers towards next‐generation ER targeted cancer therapy. [ABSTRACT FROM AUTHOR]

Marchantia polymorpha L. (Marchantiaceae), a thalloid liverwort, is cosmopolitan in distribution. It has various medicinal properties by exhibiting antimicrobial activity, cytotoxic activity, antifungal activity, antipyretic activity, and diuretic activity. In the present study, chemical profiling of M. polymorpha by using GC–MS has been carried out and fifty-five compounds have been identified in hexane and ethyl acetate extract of wild and cultured plants. Significant constituents of hexane extract of wild plants viz., Aromadendrene oxide, Norlinolenic Acid, Geranyl isovalerate, 1,2-Dihydrocuparene, Cedrene, epoxide (6.57%), whereas in the cultured plant (MCH) Palmitic Acid, α-Linolenic Acid, Oleic Acid, Campesterol, Stigmasterol have been identified. Extract of M. polymorpha has been found significantly effective against colon, Head, and Neck cancer cell lines. A comparative study of in vitro cytotoxicity of wild and cultured plants exhibited the medicinal potential of the plants grown fully in laboratory conditions. The cytotoxic activity of cultured plants is an important finding for its possible use as herbal formulation on the one hand and conservation of this species in nature by preventing its overharvesting in wild on the other hand. [Display omitted] • Marchantia polymorpha already reported for cytotoxic activity against liver and breast cancer cell lines and known for their potential chemical constituents. • The present study showed cytotoxic activity of M. polymorpha against colon and head & neck cancer cell lines that too for wild plants as well as cultured plants. • M. polymorpha cultured and grown in the laboratory and further wild plants as well as cultured plants tested for cytotoxic activities and for their chemical constituents. • The present study exhibited the medicinal potential and component profiling of the plant grown fully in the laboratory conditions. The study has paved the way for successful use of cultured plants for extraction of potential cytotoxic chemical compounds for herbal formulation in future. [ABSTRACT FROM AUTHOR]

Osteoporosis is a major health problem in postmenopausal women globally. This study determined the mechanism through which coelogin stimulates osteoblastogenesis and its osteoprotective and bone regenerating potential. Coelogin effect on primary calvarial osteoblast cells was determined by measuring alkaline phosphatase activity, mineralization, osteoblast survival, and apoptosis and protein expression studies. The osteoprotective effect of coelogin was also evaluated on osteopenic adult female Swiss mice. At autopsy, bones were collected for dynamic and histomorphometry studies. Serum samples were also collected for assessment of serum parameters. Coelogin treatment led to increased osteoblast proliferation, survival, differentiation, and mineralization in osteoblast cells. Coelogin supplementation to Ovx mice promoted new bone formation, prevented Ovx-induced deterioration of bone microarchitecture, and enhanced bone regeneration. In addition, signaling studies revealed that coelogin treatment activates the ER-Erk and Akt-dependent signaling pathways which stimulate the osteoblastogenesis in osteoblast cells. [ABSTRACT FROM AUTHOR]

The sparsely populated hilly areas are most prone to the power cuts and low voltage power supplies if the national grids fall any short of electricity demand. Therefore the present study evaluates the decadal efficiency of state-owned electric utility facilities from 2009 to 20019, situated in different geographic terrains, in Uttarakhand state of India. The productive efficiency of the Electricity Distribution Divisions (EDDs) of Uttarakhand state was evaluated in a nonparametric method of Data Envelopment Analysis (DEA). The obtained results indicate the performances of some EDDs are not up to the mark and suffer from low technical efficiency. The average Technical efficiencies are recorded as low as 0.5 in 2014–15; lowest for the EDDs located in hilly terrain with a value of 0.23 in 2014–15. An improvement trend in efficiency was noted with rearrangement of EDD during 2015–2017. Based on these findings, this study identifies potential for improvement. The recommendations and policies framed should keep geographical location into consideration. Region-specific policy interventions can help the state to achieve the efficient power goals by reducing electricity losses and improving overall efficiency. [ABSTRACT FROM AUTHOR]

Obesity is a chronic disorder with multifactorial etiology, including genetic, medical, dietary and other environmental factors. Both natural and synthetic heterocyclic compounds, especially oxazoles, represent an interesting group of compounds and have gained much attention due to their remarkable biological activities. Therefore, a library of 3,3-DMAH (3,3-dimethylallylhalfordinol) inspired N -alkylated oxazole bromide salts with varied substitutions were prepared and screened using the 3T3-L1 model of adipogenesis and HFD-induced obesity model in Syrian golden hamsters. Several compounds in the synthesized series displayed remarkable anti-adipogenic potential on the differentiation of 3T3-L1 preadipocytes. Compound 19e , displayed the most potent activity of all and selected for further studies. Compound 19e inhibited mitotic clonal expansion of 3T3-L1 cells and enhanced the mitochondrial oxygen consumption rate of the cells during early phase of differentiation via AMPK activation. 19e also improved the dyslipidaemia in high calorie diet fed Syrian Golden Hamsters. Therefore, compound 19e can serve as a potential lead against adipogenesis and dyslipidaemia models and could be further investigated to affirm its significance as a drug candidate. [Display omitted] • Thirty-one novel derivatives of naturally occurring halfordinol were synthesized. • All compounds were evaluated for their anti-adipogenesis activity. • Compound 19e showed potent anti-adipogenic activity. • 19e activates AMPK phosphorylation and boost mitochondrial function. • Compound 19e improves HFD induced obesity and dyslipidaemia in Hamsters. [ABSTRACT FROM AUTHOR]

Triple‐negative breast cancers (TNBC) are highly aggressive and drug resistant accounting for majority of cases with poor outcome. Purified natural compounds display substantial anticancer activity with reduced cytotoxicity providing a new avenue to combat TNBC. Chebulinic acid (CA), a polyphenol derived from the fruits of various medicinal plants has potent anticancer activity. Here, we demonstrate that CA shows significant cytotoxicity against triple negative MDA‐MB‐231 cells. CA exhibited cytotoxicity to MDA‐MB‐231 cells in 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay. Further, CA mitigated MDA‐MB‐231 cells viability and proliferation as shown by reduced live cell count, crystal violet staining, colony formation assay, soft agar assay and cell cycle analysis. Wound healing assay and trans‐well migration assay demonstrated that CA significantly inhibited migration of MDA‐MB‐231 cells. Also reduced MMP9 expression was observed in CA‐treated cells by gelatin zymography. CA negatively regulated mesenchymal characteristics of MDA‐MB‐231 cells demonstrated by F‐actin staining and reduced expression of N‐cadherin by confocal microscopy and western blot analysis. Annexin V/propidium iodide (PI) and active caspase‐3 staining showed that CA was able to induce apoptosis in MDA‐MB‐231 cells but did not activate caspase‐3. Two‐dimensional gel electrophoresis based proteomic analysis demonstrated that CA regulated proteins belonging to the oxidative stress pathway, apoptotic pathway and proteins with antiproliferative activity. Western blot analysis analysis revealed that CA negatively regulated superoxide dismutase 1 (SOD1) and enhanced oxidative stress in MDA‐MB‐231 cells. SOD1 in‐gel activity assay also showed reduced SOD1 activity upon CA treatment. Overexpression studies with GFP‐LC3 and tandem tagged RFP‐GFP‐LC‐3 also demonstrated enhanced autophagy upon CA treatment. [ABSTRACT FROM AUTHOR]

Artemisia absinthium is a herbaceous perennial plant with fibrous root and it belongs to the family Asteraceae. Due to having strong fragrance and pungent taste it has ability to defend itself from the herbivore animals. Essential oil extracted from leaves, stem and seeds of A. absinthium were analyzed for termite mortality as well as termite repellency. Chemical constituents of essential oil from all three parts were identified and compared by gas chromatography-mass spectroscopy. Total 16 compounds identified in the essential oil of leaves, stem and seeds in which boronyl acetate was present in major amount 26.59 %, 27.17 % and 26.63 % respectively. L-terpenen-4-ol was also identified in higher amount in leaves, stem and seeds; 18.24 %, 17.07 % and 17.3 % respectively. Leaf, stem and seed essential oil tested for termite mortality and repellency against Microcerotermes beesoni. Leaf essential oil showed significant and seed essential oil all were found to have moderate activity. [ABSTRACT FROM AUTHOR]

A field study was carried out on fly ash (FA) dumps of Panki Thermal Power Station to assess the phytoaccumulation of elements in various plant parts of edible fruit tree Ziziphus mauritiana. Of the twelve analyzed elements, the highest concentration was found for Fe followed by Mn > Se > Zn > Mo > Cu > Cr > Pb > Cd >Ni > As > Co in rhizospheric substrate of Z. mauritiana grown on FA dumps. Metal accumulation, bioconcentration factor, and translocation factor for each metal were calculated in various parts of the edible fruit tree. Significant variations of metal accumulations were observed among various plant parts. Accumulation of toxic elements was higher in roots, and it gradually declined toward the aerial parts of the plant corresponding to its distance from the ground. The concentration of some elements in fruit tree was found to be above prescribed limits in edible parts. Therefore, the present study suggested that additional care should be undertaken, if edible fruit trees are considered for phytoremediation or afforestation programs of FA dumps. [ABSTRACT FROM AUTHOR]

Plant extracts may provide natural alternative to crop pest control because of their bioactive components. Moreover they are biodegradable and seem to resolve problems associated with synthetic pesticides. Punica granatum fruit rind extracted in methanol and fractionated with hexane, ethyl acetate, chloroform and water. All the solvent extracts along with partially purified column fractions were evaluated for termite mortality against Microcerotermes beesoni termite species. Methanolic, ethyl acetate extract were found to be effective however column fraction (PGR) found to be significantly effective. Moreover five compounds have also been identified from the Punica granatum fruit rind and evaluated for termite mortality against Microcerotermes beesoni termite species with Chlorpyriphos 20% TC. Although Chlorpyriphos found to be very effective none of the compound had shown comparable results but Quercetin is found to be moderately active comparative to other compounds. Five known marker compounds have been quantified in the column fraction PGR via HPLC and GC–MS. Fraction PGR has shown significant activity may be because of Quercetin found to be present in the higher amount in the column fraction PGR analyzed by HPLC and GC–MS. Punica granatum fruit rind is a waste material which can be utilized as natural termite managing agent easily available to the farmers around the world. [ABSTRACT FROM AUTHOR]

The present study deals with the remediation of red mud deposits through the naturally growing native grass species. On the basis of visual observation we noticed that Saccharum bengalense Retz. is a dominant grass species of vegetation on red mud deposits. The results showed that most of the elements are stabilized in root part of the plant except Fe, Zn and Cd. Therefore, it reveals that S . bengalense has the capability for phytostabilization of red mud deposits, is a promising species for the remediation and management of red mud deposits. [ABSTRACT FROM AUTHOR]

Background: Renal cell carcinoma is among the most prevalent malignancies. It is generally sporadic. However, genetic studies of rare familial forms have led to the identification of mutations in causative genes such as VHL and FLCN. Mutations in the FLCN gene are the cause of Birt-Hogg-Dubé syndrome, a rare tumor syndrome which is characterized by the combination of renal cell carcinoma, pneumothorax and skin tumors. Methods: Using Sanger sequencing we identify a heterozygous splice-site mutation in FLCN in lymphocyte DNA of a patient suffering from renal cell carcinoma. Furthermore, both tumor DNA and DNA from a metastasis are analyzed regarding this mutation. The pathogenic effect of the sequence alteration is confirmed by minigene assays and the biochemical consequences on the protein are examined using TALEN-mediated transgenesis in cultured cells. Results: Here we describe an FLCN mutation in a 55-year-old patient who presented himself with progressive weight loss, bilateral kidney cysts and renal tumors. He and members of his family had a history of recurrent pneumothorax during the last few decades. Histology after tumor nephrectomy showed a mixed kidney cancer consisting of elements of a chromophobe renal cell carcinoma and dedifferentiated small cell carcinoma component. Subsequent FLCN sequencing identified an intronic c.1177-5_-3delCTC alteration that most likely affected the correct splicing of exon 11 of the FLCN gene. We demonstrate skipping of exon 11 to be the consequence of this mutation leading to a shift in the reading frame and the insertion of a premature stop codon. Interestingly, the truncated protein was still expressed both in cell culture and in tumor tissue, though it was strongly destabilized and its subcellular localization differed from wild-type FLCN. Both, altered protein stability and subcellular localization could be partly reversed by blocking proteasomal and lysosomal degradation. Conclusions: Identification of disease-causing mutations in BHD syndrome requires the analysis of intronic sequences. However, biochemical validation of the consecutive alterations of the resulting protein is especially important in these cases. Functional characterization of the disease-causing mutations in BHD syndrome may guide further research for the development of novel diagnostic and therapeutic strategies. [ABSTRACT FROM AUTHOR]

Disposal of red mud (RM) poses serious environmental problems such as wind erosion, air and water pollution. To overcome these problems, effective restoration of the disposal land through naturally growing vegetation is a sustainable and economical approach. The present study involved estimation of frequency (F), density (D), abundance (Ab), and important value index (IVI) of natural flora on abandoned RM sites in order to assess their metal toxicity tolerance capacity. Based on visual observations and highest IVI,S. AsperandS. puniceawere identified as effective ecological tools for the restoration of barren RM sites. From the study, remarkable differences were observed between non-rhizospheric and rhizospheric RM of both species. These rhizospheric RM analyses confirm the ability ofS. asperandS. puniceafor enhancing the biological activities of abandoned RM. Translocation factor (TF) of iron was maximum (2.58) inS. asper, and bioconcentration factor (BCF) was found maximum (1.25) inS. punicea, but both TF (2.58) and BCF (1.35) were high inS. asper. Therefore, this plant could be reported as an iron hyperaccumulator plant. These results suggest that these plant species can be exploited for effective restoration of RM deposited land without any inputs or maintenance. [ABSTRACT FROM PUBLISHER]

Essential oil ofArtemisia nilagiricaisolated from aerial parts was analyzed for antitermite activity. Chemical constituents were identified by gas chromatography-mass spectroscopy. Total forty constituents have been identified which is 93.55 % of the essential oil. Major constituents of the oil were α-thujone (33.78 %), germacrene-D (9.31 %), β-thujone (6.01 %), caryophyllene (5.86 %), caryophyllene oxide (6.17 %), borneol (2.16 %). The essential oil consist of 41.34 % monoterpene hydrocarbon, 30.9 % sesquiterpene hydrocarbon, 10.24 % monoterpene alcohol, 8.33 % sesquiterpene oxide along with 2.74 % sesquiterpene alcohol. The essential oil exhibited significant antitermite activity againstMicrotermes beesonithe termite. ED50for termite repellency was found 4.44 mg/g and 5.81 mg/g for termite mortality. Chlorpyriphos 20 % TC was taken as control, ED50of chlorpyriphos was found 1.53 mg/g. This study indicated thatA. nilagiricaessential oil can be used as a wood preservative to control the termites infesting wooden material and commodities. [ABSTRACT FROM PUBLISHER]

Objective: The present study investigated the comparative analysis of fatty acid and antioxidant activity from the bark of Betula utilis, collected from Kashmir and Sikkim coded as BUK and BUS respectively. Methods: Fatty acid constituents were analyzed by GCMS (gas chromatography mass spectroscopy) in BUK and BUS bark. B. utilis bark extracts of both the locations were phytochemically investigated and radical scavenging activity was evaluated by DPPH in all solvent fractions. Results: Phenolic content were found to be higher in methanolic extracts of BUK bark, 5.8 ± 0.1 mg/gm and flavonoid content were higher in the water extract of BUK bark, 6.16 ± 0.2 mg/gm. The radical scavenging activity was found to be higher methanolic, alcoholic and water extracts of BUK bark. The lowest IC50 value for radical scavenging activity of methanolic and water extracts of B. utilis bark collected from Kashmir were found 18.7 ± 1.1 and 18.2 ± 0.3 µg/mL, respectively. Thirteen fatty acids were identified in the sample BUK as well as BUS in which the major fatty acids were found-Palmitic acid, linoleic acid and oleic acid. BUK possess the highest amount of Palmitic acid (18.07%) in oily portion of the bark. Conclusion: The present study concluded that BUK and BUS extracts have shown significant antioxidant activity in comparison to standard but BUK possess potent radical scavenging activity over BUS, and higher amounts palmitic acid, linoleic acid and oleic acid was present in the extract, and may a play an important role in nutritional and pharmaceutical applications. [ABSTRACT FROM AUTHOR]

Recent progress on studies of labdane diterpenoids is compiled. Seventy seven biologically active labdane diterpenes isolated from various higher plants, mosses, liverworts, algae, etc. are reported. The absolute configurations of compounds 1 - 77 were established using extensive spectroscopic techniques. The wide range of biological activities possessed by these diterpenoids suggests that thorough evaluation of some structure-activity relationships is overdue. In this review, data on the natural sources, isolation, structure and biological activities of labdane diterpenoids isolated from various plants are summarized. [ABSTRACT FROM AUTHOR]

Betula utilis, also known as Himalayan silver birch has been used as a traditional medicine for many health ailments like inflammatation, HIV, renal and bladder disorders as well as many cancers from ages. Here, we performed bio-guided fractionation of Betula utilis Bark (BUB), in which it was extracted in methanol and fractionated with hexane, ethyl acetate, chloroform, n-butanol and water. All six fractions were evaluated for their in-vitro anticancer activity in nine different cancer cell lines and ethyl acetate fraction was found to be one of the most potent fractions in terms of inducing cytotoxic activity against various cancer cell lines. By utilizing column chromatography, six triterpenes namely betulin, betulinic acid, lupeol, ursolic acid (UA), oleanolic acid and β-amyrin have been isolated from the ethyl acetate extract of BUB and structures of these compounds were unraveled by spectroscopic methods. β-amyrin and UA were isolated for the first time from Betula utilis. Isolated triterpenes were tested for in-vitro cytotoxic activity against six different cancer cell lines where UA was found to be selective for breast cancer cells over non-tumorigenic breast epithelial cells (MCF 10A). Tumor cell selective apoptotic action of UA was mainly attributed due to the activation of extrinsic apoptosis pathway via up regulation of DR4, DR5 and PARP cleavage in MCF-7 cells over non-tumorigenic MCF-10A cells. Moreover, UA mediated intracellular ROS generation and mitochondrial membrane potential disruption also play a key role for its anti cancer effect. UA also inhibits breast cancer migration. Altogether, we discovered novel source of UA having potent tumor cell specific cytotoxic property, indicating its therapeutic potential against breast cancer. [ABSTRACT FROM AUTHOR]

Compounds having antimicrobial activity obtained from plant sources are useful because they are new sources against antibiotic resistance. The present study is based on the evaluation of antimicrobial activity of the essential oil of the fresh bark ofBetula utilisand to identify the chemical constituents responsible for antimicrobial potential, grown in high altitude of Himalaya, India. The chemical constituents of essential oil were identified by gas chromatography-mass spectrometry (GC-MS). The essential oil was evaluated for the antimicrobial potential against human pathogenic bacteria and fungi by using a micro-dilution assay. GC-MS analysis revealed that the major constituents of the essential oil were geranic acid (11.38 %), β-seleneol (10.98 %), β-linalool (10.91 %), terragon (10.61 %), β-sesquiphellendrene (8.02 %), champacol (6.33 %) and 1,8-cineol (5.49 %). Result showed thatB. utilisessential oil has a strong antimicrobial activity against the fungusCandida albicansand Gram (+) and Gram (-) human pathogenic bacteria (MIC: 60.5-240 µg/ml). [ABSTRACT FROM AUTHOR]

Obesity and associated metabolic disorders are heading up with an alarming rate in developing nations. One of highly sought solution for metabolic disorders is to identify natural molecule with an ability to reduce obesity and increase insulin sensitivity. Coelogin (CLN) is a phenanthrene derivative isolated from the ethanolic extract of Coelogyne cristata. In our constant efforts to identify novel anti-dyslipidemic and anti-adipogenic compounds using CFPMA (common feature pharmacophore model using known anti-adipogenic compounds) model, predicted possible anti-adipogenic activity of CLN. In vitro results showed significant inhibition of adipogenesis in 3T3-L1 and C3H10T1/2 cell by CLN. It arrests the cell cycle in G1 phase of interphase and inhibits mitotic clonal expansion to regulate adipogenesis. CLN elicits insulin sensitizing effect in mature adipocytes. During extracellular flux assessment studies, it increases oxidative respiration and energy expenditure in adipocytes. In vivo, CLN reversed HFD-induced dyslipidemia as well as insulin resistance in C57BL/6 mice. It promoted the expression of genes involved in improved mitochondrial function and fatty acid oxidation in eWAT. CLN restored energy expenditure and increased the capacity of energy utilization in HFD fed mice. Taken together, the study indicated beneficial effects of CLN in combating obesity-associated metabolic complications. [Display omitted] [ABSTRACT FROM AUTHOR]

The article offers information on the study regarding the fatty acid characterization in Himalayan silver birch's (Betula utilis) bark. The study extracted the bark using petroleum ether wherein fatty acid methyl esters (FAME) of the bark were analyzed and separated through gas chromatography (GC) and gas chromatography/mass spectrometry (GC-MS). Result shows that 19 fatty acids were found in the tree which include betulin, oleanolic acid, and lupeol.

Odorant receptors (ORs) obey mutual exclusivity and monoallelic mode of expression. Efforts are ongoing to decipher the molecular mechanism that drives the 'one-neuron-one-receptor' rule of olfaction. Recently, single-cell profiling of olfactory sensory neurons (OSNs) revealed the expression of multiple ORs in the immature neurons, suggesting that the OR gene choice mechanism is much more complex than previously described by the silence-all-and-activate-one model. These results also led to the genesis of two possible mechanistic models i.e. winner-takes-all and stochastic selection. We developed Reverse Cell Tracking (RCT), a novel computational framework that facilitates OR-guided cellular backtracking by leveraging Uniform Manifold Approximation and Projection embeddings from RNA Velocity Workflow. RCT-based trajectory backtracking, coupled with statistical analysis, revealed the OR gene choice bias for the transcriptionally advanced (highest expressed) OR during neuronal differentiation. Interestingly, the observed selection bias was uniform for all ORs across different spatial zones or their relative expression within the olfactory organ. We validated these findings on independent datasets and further confirmed that the OR gene selection may be regulated by Upf3b. Lastly, our RNA dynamics-based tracking of the differentiation cascade revealed a transition cell state that harbors mixed molecular identities of immature and mature OSNs, and their relative abundance is regulated by Upf3b. [ABSTRACT FROM AUTHOR]

Chebulinic acid (CA), a polyphenolic compound extracted from the fruits of Terminalia chebula, has been recently reported as a novel neuraminidase inhibitor against the influenza A virus and also for various biological activities that require pharmacokinetic estimation. We report a proposed fragmentation pathway for the formation and selection of sodium and ammonium adducts using molecular thermodynamics. The chebulinic acid ammonium adduct was reproducible and stable compared to the earlier reported sodium adduct to quantify chebulinic acid by liquid chromatography‐tandem mass spectrometry. Chebulinic acid was extracted from plasma by protein precipitation followed by single‐step liquid‐liquid extraction by removing interfering metal adducts such as sodium. chebulinic acid resolution was achieved from the C18 column with mobile phase acetonitrile: methanol mixture and ammonium acetate buffer at a flow rate of 0.5 ml/min. The linear calibration curve (r2 ≥ 0.995) range was 3.52–1800 ng/ml. Finally, we report the oral pharmacokinetic profile of chebulinic acid in male Swiss albino mice plasma using the developed method. [ABSTRACT FROM AUTHOR]

Chebulinic acid (CA), a plant ellagitannin derived from Triphala, is reported to exhibit both anti-inflammatory & anti-oxidant activity apart from anti-tumour property. However, its role in inflammatory bone loss conditions was unexplored. We hypothesized that CA may prevent the bone loss under inflammatory conditions induced by lipopolysaccharide (LPS) in 10-week-old male C57BL/6J mice. Micro-CT analysis and histomorphometric evaluations were carried out where it was found that CA significantly improved the bone micro-architectures by enhancing trabecular connectivity and strength of the bone. CA also increased the bone regeneration as examined by calcein labelling and ex-vivo mineralisation along with maintaining the bone serum markers. Further, CA ameliorated the reduction in osteoblast cell differentiation, proliferation and viability after LPS stimulation. DCFDA and Mitosox staining revealed that CA presented remarkable protective effects against LPS treatment by attenuating oxidative stress, both at cellular & mitochondrial levels. In addition, CA significantly decreased the production of pro-inflammatory cytokines, and down-regulated the phosphorylation of NFκB and IκBα, indicating that CA could attenuate the inflammatory impairment to primary osteoblast cells by suppressing the NFkB signalling pathway. Taken together, the protective role of CA against LPS-induced bone loss & inhibitory effect on total ROS levels hold promise as a potential novel therapeutic strategy for the inflammatory diseases in bones. [Display omitted] • Chebulinic acid attenuated LPS induced osteoblast dysfunction. • Chebulinic acid ameliorates the oxidative stress generated by LPS. • Chebulinic acid inhibited the LPS stimulated activation of NFkB pathway in osteoblast cells. • Chebulinic acid protects against LPS induced inflammatory bone loss in C57BL/6J mice. [ABSTRACT FROM AUTHOR]

Dramatic genomic alterations, either inducible or in a pathological state, dismantle the core regulatory networks, leading to the activation of normally silent genes. Despite possessing immense therapeutic potential, accurate detection of these transcripts is an ever-challenging task, as it requires prior knowledge of the physiological gene expression levels. Here, we introduce EcTracker, an R-/Shiny-based single-cell data analysis web server that bestows a plethora of functionalities that collectively enable the quantitative and qualitative assessments of bona fide cell types or tissue-specific transcripts and, conversely, the ectopically expressed genes in the single-cell ribonucleic acid sequencing datasets. Moreover, it also allows regulon analysis to identify the key transcriptional factors regulating the user-selected gene signatures. To demonstrate the EcTracker functionality, we reanalyzed the CRISPR interference (CRISPRi) dataset of the human embryonic stem cells differentiated into endoderm lineage and identified the prominent enrichment of a specific gene signature in the SMAD2 knockout cells whose identity was ambiguous in the original study. The key distinguishing features of EcTracker lie within its processing speed, availability of multiple add-on modules, interactive graphical user interface and comprehensiveness. In summary, EcTracker provides an easy-to-perform, integrative and end-to-end single-cell data analysis platform that allows decoding of cellular identities, identification of ectopically expressed genes and their regulatory networks, and therefore, collectively imparts a novel dimension for analyzing single-cell datasets. [ABSTRACT FROM AUTHOR]

The molecular mechanisms of olfaction, or the sense of smell, are relatively underexplored compared with other sensory systems, primarily because of its underlying molecular complexity and the limited availability of dedicated predictive computational tools. Odorant receptors (ORs) allow the detection and discrimination of a myriad of odorant molecules and therefore mediate the first step of the olfactory signaling cascade. To date, odorant (or agonist) information for the majority of these receptors is still unknown, limiting our understanding of their functional relevance in odor-induced behavioral responses. In this study, we introduce OdoriFy, a Web server featuring powerful deep neural network-based prediction engines. OdoriFy enables (1) identification of odorant molecules for wildtype or mutant human ORs (Odor Finder); (2) classification of user-provided chemicals as odorants/nonodorants (Odorant Predictor); (3) identification of responsive ORs for a query odorant (OR Finder); and (4) interaction validation using Odorant-OR Pair Analysis. In addition, OdoriFy provides the rationale behind every prediction it makes by leveraging explainable artificial intelligence. This module highlights the basis of the prediction of odorants/nonodorants at atomic resolution and for the ORs at amino acid levels. A key distinguishing feature of OdoriFy is that it is built on a comprehensive repertoire of manually curated information of human ORs with their known agonists and nonagonists, making it a highly interactive and resource-enriched Web server. Moreover, comparative analysis of OdoriFy predictions with an alternative structure-based ligand interaction method revealed comparable results. OdoriFy is available freely as a web service at https://odorify.ahujalab.iiitd.edu.in/olfy/. [ABSTRACT FROM AUTHOR]

Turn-on fluorogenic probes are commonly utilized for an efficient estimation of reactive oxygen species such as H 2 O 2. In the present study, three different sets of turn-on fluorogenic probes for sensing H 2 O 2 were rationally designed by coupling boronate ester group with three important fluorescent dyes either by linking directly or via self-immolative linkers. Interestingly, our results reveal that directly-linked boronate ester probes are superior and sensitive than the self-immolative linker-containing probes in detecting traces of exogenous and endogenous levels of H 2 O 2. The difference in probe efficiency was also dependent on the nature of fluorophore unit being used. Considering these aspects, our detailed studies reveal that the directly-linked boronate ester-based fluorescein probe 19 is the best probe for efficiently sensing H 2 O 2 both in aqueous as well as cellular medium with very high level of sensitivity. The present observation would be useful while designing the fluorogenic sensors for ROS as well as during their utilization in ROS-associated pathologies. [Display omitted] • Peroxide sensing abilities of turn-on fluorogenic probes having boronate ester linkers are described. • Our results reveal superiority of direct boronate ester linker over the self-immolative linkers for sensing peroxide. • Fluorescein-based directly-linked boronate ester probe was found to be the best probe among nine probes studied herein. • The probe can be used both in aqueous and cellular medium for sensing traces of peroxide effectively. [ABSTRACT FROM AUTHOR]

Olfactory receptors are primarily known to be expressed in the olfactory epithelium of the nasal cavity and therefore assist in odor perception. With the advent of high‐throughput omics technologies such as tissue microarray or RNA sequencing, a large number of olfactory receptors have been reported to be expressed in the nonolfactory tissues. Although these technologies uncovered the expression of these olfactory receptors in the nonchemosensory tissues, unfortunately, they failed to reveal the information about their cell type of origin. Accurate characterization of the cell types should be the first step towards devising cell type‐specific assays for their functional evaluation. Single‐cell RNA‐sequencing technology resolved some of these apparent limitations and opened new means to interrogate the expression of these extranasal olfactory receptors at the single‐cell resolution. Moreover, the availability of large‐scale, multi‐organ/species single‐cell expression atlases offer ample resources for the systematic reannotation of these receptors in a cell type‐specific manner. In this Viewpoint article, we discuss some of the technical limitations that impede the in‐depth understanding of these extranasal olfactory receptors, with a special focus on odorant receptors. Moreover, we also propose a list of single cell‐based omics technologies that could further promulgate the opportunity to decipher the regulatory network that drives the odorant receptors expression at atypical locations. [ABSTRACT FROM AUTHOR]

A prominent clinical symptom of 2019-novel coronavirus (nCoV) infection is hyposmia/anosmia (decrease or loss of sense of smell), along with general symptoms such as fatigue, shortness of breath, fever and cough. The identity of the cell lineages that underpin the infection-associated loss of olfaction could be critical for the clinical management of 2019-nCoV-infected individuals. Recent research has confirmed the role of angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) as key host-specific cellular moieties responsible for the cellular entry of the virus. Accordingly, the ongoing medical examinations and the autopsy reports of the deceased individuals indicate that organs/tissues with high expression levels of ACE2 , TMPRSS2 and other putative viral entry-associated genes are most vulnerable to the infection. We studied if anosmia in 2019-nCoV-infected individuals can be explained by the expression patterns associated with these host-specific moieties across the known olfactory epithelial cell types, identified from a recently published single-cell expression study. Our findings underscore selective expression of these viral entry-associated genes in a subset of sustentacular cells (SUSs), Bowman's gland cells (BGCs) and stem cells of the olfactory epithelium. Co-expression analysis of ACE2 and TMPRSS2 and protein–protein interaction among the host and viral proteins elected regulatory cytoskeleton protein-enriched SUSs as the most vulnerable cell type of the olfactory epithelium. Furthermore, expression, structural and docking analyses of ACE2 revealed the potential risk of olfactory dysfunction in four additional mammalian species, revealing an evolutionarily conserved infection susceptibility. In summary, our findings provide a plausible cellular basis for the loss of smell in 2019-nCoV-infected patients. [ABSTRACT FROM AUTHOR]

Cardamom, known by the botanical name Elettaria cardamomum , is a well-known spice which is increasingly used in the field of cosmetics and industrial applications in the form of dried powders and oil. However, usage of cardamom is limited by its moisture content (around 80% in wet basis) and for effective oil extraction and usage, cardamom needs to be dried to a moisture content of less than 10% (in wet basis) prior to usage. Solar driers are traditionally used for cardamom drying and fluidized bed driers and tray driers are also used for industrial-level large-scale drying. During drying, loss of bioactive like phenolics, flavonoids and antioxidants become inevitable. Under such a scenario, this study explores the performance of low-temperature, low-humidity dryers namely refrigeration adsorption dehumidified dryers (RADD), designed and developed by CSIR-NIIST, for retention of bioactives during drying. To assess and compare the RADD with traditional dryers, experiments were performed in a tray dryer, solar dryer and fluidized bed dryer and the results are compared with RADD. It was found that cardamom dried in RADD retained around 70–75% of total phenolic, flavonoid and anti-oxidant compounds, whereas retention in other conventional drying methods was in the range 35–60% only. Advanced analysis such as SEM, FTIR and GC-MS was also done to evaluate the morphological changes, functional group changes and difference in essential oil composition due to different drying methods. Considering the overall result it has been proved that RADD has several advantages over the conventional dryers (due to low temperature and low humidity inside RADD) and thus can be used for drying cardamom which will promise good quality cardamom with maximum retention or preservation of all the bioactives. Thus, RADD is found to be a promising alternative for fluidized bed dryers and also it performs better than other conventional drying methods. • Dried cardamom powders & oils are widely used in cosmetics, food, and therapeutics. • However, drying at elevated temperatures leads to bioactive losses. • Drying at controlled low humidity ensures better retention of bioactive during drying. • Refrigerated Adsorption Dehumidified Drier (RADD) ensures better retention. • RADD dried samples showed better oil yield and minimized the loss of bioactive. [ABSTRACT FROM AUTHOR]

Summary Machine Learning-based techniques are emerging as state-of-the-art methods in chemoinformatics to selectively, effectively and speedily identify biologically relevant molecules from large databases. So far, a multitude of such techniques have been proposed, but unfortunately due to their sparse availability, and the dependency on high-end computational literacy, their wider adaptation faces challenges, at least in the context of G-Protein Coupled Receptors (GPCRs)-associated chemosensory research. Here, we report Machine-OlF-Action (MOA), a user-friendly, open-source computational framework, that utilizes user-supplied SMILES (simplified molecular input line entry system) of the chemicals, along with their activation status, to synthesize classification models. MOA integrates a number of popular chemical databases collectively harboring approximately 103 million chemical moieties. MOA also facilitates customized screening of user-supplied chemical datasets. A key feature of MOA is its ability to embed molecules based on the similarity of their local neighborhood, by utilizing a state-of-the-art model interpretability framework LIME. We demonstrate the utility of MOA in identifying previously unreported agonists for human and mouse olfactory receptors OR1A1 and MOR174-9 by leveraging the chemical features of their known agonists and non-agonists. In summary, here we develop an ML-powered software playground for performing supervisory learning tasks involving chemical compounds. Availability and implementation MOA is available for Windows, Mac and Linux operating systems. It's accessible at (https://ahuja-lab.in/). Source code, user manual, step-by-step guide and support is available at GitHub (https://github.com/the-ahuja-lab/Machine-Olf-Action). For results, reproducibility and hyperparameters, refer to Supplementary Notes. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Objective/Backgrounds: Inflammation, a common phase during bone healing is reported to negatively affect bone regeneration. Inflammatory bone loss conditions like periodontitis, inflammatory arthritis and periprosthetic osteolysis, all driven by Lipopolysaccharide (LPS), which has been identified as a key pathogenic agent. Infact, inflammatory bone diseases not only associated with generation of inflammatory cytokines but also produce local oxidative stress by intracellular reactive oxygen species (ROS). Till date, there are limited therapeutic approaches for inflammation triggered osteoblast differentiation inhibition. Chebulinic acid (CA), a plant ellagitannin derived from fruits of Triphala (Terminalia Chebula) reported to exhibits anti-inflammatory & anti-oxidant activity. However, its role in preventing inflammatory bone loss condition induced by lipopolysaccharide (LPS) remains unknown. Methods: For LPS induced inflammatory bone loss model, 10wk old male C57BL/6J mice were taken & divided into Control (PBS), LPS, and LPS (5 mg/kg; IP injection) +CA (10 mg/kg; orally) groups. After 21 days, bones and serum were collected; micro-CT analysis, Elisa and histomorphometric evaluation were conducted. In vitro, murine osteoblasts were treated with vehicle, LPS (800 ng) and LPS+CA (10 nM). Thereafter, cell differentiation, viability and proliferation, Inflammatory behaviour, Cellular & mitochondrial oxidative stress, and NFkBsignalling were determined. Results: Our results shows that LPS inhibited bone remodelling, formation& regeneration, and also promoted oxidative stress accumulation within cell by producing inflammatory cytokines. Upon Chebulinic acid (CA) administration, LPS-induced bone destruction &biochemical changes ameliorated with marked protective effect by enhancing bone formation invivo. In osteoblast cells, LPS treatment causes osteoblast dysfunction by increased ROS at cellular & mitochondria levels with enhanced expression of inflammatory cytokines. Chebulinic acid (CA) improves the inhibitory effect of LPS on osteoblast functions by enhancing cell differentiation and proliferation. Moreover, CA inhibited the oxidative stress & mitochondrial dysfunction stimulated by LPS treatment by blocking increased secretion of inflammatory cytokines Mechanistically, CA presented remarkable protective effects against LPS treatment by blocking NFkBsignalling. Discussion/Conclusions: Our results proclaim the protective role of CA against LPS-induced inflammatory bone loss & inhibitory effect on total ROS levels and inflammation. Collectively, Chebulinic acid holds as a potential novel therapeutic strategy for inflammatory diseases in bones. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Zn-Ag nanoparticle act as elicitor to synthesis secondary metabolites in W. somnifera.. • Nanoparticles increase photosynthesis and upregulates Calvin cycle genes. • Zn-Ag nanoparticles increase light absorption and oxidative stress. • Nanoparticles increase transcripts of withanolide biosynthesis and sterol content. • Quantum dots show increased ETR and did not impart withanolide biosynthesis. Abstract Withania somnifera is an important medicinal plant due to the presence of secondary metabolites. Nanoparticles (NPs) have elicitor activity for the enhancement of secondary metabolites biosynthesis in plants. W. somnifera plants were grown in-vitro and in-vivo and treated with homologous series of Zn-Ag NPs, Ni, and CdSe. Four NPs having different molar ratio of Zn and Ag have been used for the treatment. NP1, NP2, NP3, and NP4 Exhibit 19:1, 9:1, 3:1 and 1:1 molar ratios between Zn and Ag. Among all the treated NPs NP1 showed maximum enhancement in photosynthesis rate, transpiration rate, withanolide content and increase in some carbohydrates. Genes involved in photosynthesis, Calvin cycle, carbohydrate metabolism, and withanolide biosynthesis showed up regulation in NP1 and NP3 treatments. Zn-Ag NPs showed the photocatalytic and elicitor activity which helped in the light absorption and increased oxidative stress. NP2, NP4, Ni, and CdSe treatments showed the negative impact on withanolide biosynthesis and withanolide content. NP2, NP4, Ni, CdSe treated samples showed down regulation of most of the carbohydrate and withanolide pathway genes and lower withanolide content in comparison with water treated plants. CdSe caused excess cell damage, therefore, decrease in withanolide content was recorded. Gas exchange and electron transfer rate increased in CdSe and NP1 increases due to their semiconducting properties. CdSe and NP1 can liberate significant number of electrons under the light exposure, which behaves like carriers. Cyclic electron flux was observed in all the treatments but lowest in control condition. Cyclic electron flux not only manages the electron flow around PSI under stress but also considered as essential for photosynthesis and plant growth under control condition. [ABSTRACT FROM AUTHOR]

In general medicinal plants grown under water limiting conditions show much higher concentrations of secondary metabolites in comparison to control plants. In the present study, Withania somnifera plants were subjected to water stress and data related to drought tolerance phenomenon was collected and a putative mechanistic concept considering growth responses, physiological behaviour, and metabolite content and gene expression aspects is presented. Drought induced metabolic and physiological responses as well as drastic decrease in CO 2 uptake due to stomatal limitations. As a result, the consumption of reduction equivalents (NADPH 2+ ) for CO 2 assimilation via the calvin cycle declines significantly resulting in the generation of a large oxidative stress and an oversupply of antioxidant enzymes. Drought also results in the shifting of metabolic processes towards biosynthetic activities that consume reduction equivalents. Thus, biosynthesis of reduced compounds (isoprenoids, phenols and alkaloids) is enhanced. The dynamics of various metabolites have been discussed in the light of gene expression analysis of control and drought treated leaves. Gene encoding enzymes of pathways leading to glucose, fructose and fructan production, conversion of triose phosphates to hexoses and hexose phosphorylation were up-regulated in the drought stressed leaves. The down-regulated Calvin cycle genes were co-ordinately regulated with the down-regulation of chloroplast triosephosphate/phosphate translocator, cytoplasmic fructose-1,6-bisphosphate aldolase and fructose bisphosphatase. Expression of gene encoding Squalene Synthase (SQS) was highly upregulated under drought stress which is responsible for the diversion of carbon flux towards withanolides biosynthesis from isoprenoid pathway. [ABSTRACT FROM AUTHOR]

Bergenia species are important medicinal plants used in indigenous systems of medicine for their antilithiatic and diuretic properties. An ultra-high performance liquid chromatography coupled to hybrid linear ion trap triple quadrupole mass spectrometry (UHPLC-QqQLIT-MS/MS) method has been developed and validated for the estimation of quantitative variation of eight major bioactive phenolics in the rhizomes (150 samples) of four species of this herb, Bergenia (B. ciliata, B. ligulata, B. purpurascens and B. stracheyi). Chromatographic separation was obtained on a Waters ACQUITY UPLCTM BEH (ethylene bridged hybrid) C18 column with a mobile phase consisting of 0.1% (v/v) formic acid aqueous solution and acetonitrile under a gradient elution manner. A hybrid linear ion trap triple quadrupole mass spectrometer was operated in negative electrospray ionization mode with multiple reactions monitoring for detection and quantification of the eight compounds. The validated method demonstrated good linearity (r2 ≥ 0.9991), precision (RSD ≤ 1.87%) and accuracy (95.16–102.11%, RSD ≤ 1.83%) for all reference analytes. The quantitative results revealed that B. ligulata contains the highest amount of the major active marker-bergenin. The results also suggest that sensitive UHPLC-QqQLIT-MS/MS method, a sensitive, accurate and convenient one, could be helpful in identification of potential accession(s), rapid quality control and establishing authenticity of Bergenia species as raw material for pharmaceutical industries. [ABSTRACT FROM AUTHOR]

[Display omitted] Mitochondrion emerged as an important therapeutic target for anti-cancer strategy due to its involvement in cancer progression and development. However, progress of novel small molecules for selective targeting of mitochondria in cancer cells remained a major challenge. To address this, herein, through a concise synthetic strategy, we have synthesized a small molecule library of indomethacin and ibuprofen (non-steroidal anti-inflammatory drugs, NSAIDs) derivatives having triarylphosphonium moiety for mitochondria localization. Two of the library members were identified to induce mitochondrial damage through outer membrane permeabilization (MOMP) followed by generation of reactive oxygen species (ROS) leading to the remarkable MCF7 breast cancer cell death through apoptosis. These novel mitochondria targeted NSAID derivatives could open a new direction in understanding mitochondrial biology towards anti-cancer therapeutics in future. [ABSTRACT FROM AUTHOR]

Ectopically expressed olfactory receptors (ORs) have been linked with multiple clinically-relevant physiological processes. Previously used tissue-level expression estimation largely shadowed the potential role of ORs due to their overall low expression levels. Even after the introduction of the single-cell transcriptomics, a comprehensive delineation of expression dynamics of ORs in tumors remained unexplored. Our targeted investigation into single malignant cells revealed a complex landscape of combinatorial OR expression events. We observed differentiation-dependent decline in expressed OR counts per cell as well as their expression intensities in malignant cells. Further, we constructed expression signatures based on a large spectrum of ORs and tracked their enrichment in bulk expression profiles of tumor samples from The Cancer Genome Atlas (TCGA). TCGA tumor samples stratified based on OR-centric signatures exhibited divergent survival probabilities. In summary, our comprehensive analysis positions ORs at the cross-road of tumor cell differentiation status and cancer prognosis. Through analyses of olfactory receptors in single-cell RNA sequencing dataset from different cancers, Kalra, Mittal et al. find that the number and expression levels of olfactory receptors vary by differentiation status. The study provides insights into an under-appreciated role for olfactory receptors in cancer pathogenesis. [ABSTRACT FROM AUTHOR]

• Hydrochar was aged microbially in a fermentation system from 0 to 60 days. • The specific surface area of microbially-aged hydrochar (MHC) was 2.2 times higher than fresh hydrochar. • MHC showed a 3.8-fold higher Cd2+ adsorption capacity than fresh hydrochar. • MHC displayed lower zeta potential and higher pH than fresh hydrochar. • Functional group binding, electrostatic interaction, and cation exchange facilitate Cd2+ adsorption. Microbially-aged hydrochar were prepared to investigate how aging affected their ability to remove Cd2+ from aqueous solutions. Based on aging time in an anaerobic fermenter, four samples were produced: HC, M20-HC, M40-HC, and M60-HC. Results indicated increases in specific surface area, pH, and negative charge on hydrochar surface with aging process. Also, there were a decrease in O/C and an increase in surface functional groups, such as –COOH. The adsorption experiments confirmed the positive correlation between aging time and adsorption performance. The 60-day-aged M60-HC treatment displayed the maximum adsorption capacity, which was 3.8 times higher than that of HC. The Langmuir and pseudo-second-order kinetic equations fitted well with isothermal and kinetic data, respectively. Thermodynamic study indicated that Cd2+ adsorption is dominated by chemisorption. This study showed that microbial aging process is an effective and promising measure to improve hydrochar adsorption capacity for Cd2+. [ABSTRACT FROM AUTHOR]