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Target-based anticancer indole derivatives and insight into structure-activity relationship:A mechanistic review update(2018—2021)

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Acta Pharmaceutica Sinica B 2022年第7期12卷 3006-3027页

作者： Ashima Dhiman Rupam Sharma rajesh k.singh Department of Pharmaceutical Chemistry Shivalik College of PharmacyIKG Punjab Technical UniversityJalandhar 140126India

Cancer,which is the uncontrolled growth of cells,is the second leading cause of death after heart disease.Targeting drugs,especially to specific genes and proteins involved in growth and survival of cancer cells,is the prime need of research world-wide.Indole moiety,which is a combination of aromatic-heterocyclic compounds,is a constructive scaffold for the development of novel leads.Owing to its bioavailability,high unique chemical properties and significant pharmacological behaviours,indole is considered as the most inquisitive scaffold for anticancer drug research.This is illustrated by the fact that the U.S.Food and Drug Administration(FDA)has recently approved several indole-based anticancer agents such as panobinostat,alectinib,sunitinib,osimertinib,anlotinib and nintedanib for clinical use.Furthermore,hundreds of studies on the synthesis and activity of the indole ring have been published in the last three years.Taking into account the facts stated above,we have presented the most recent advances in medicinal chemistry of indole derivatives,encompassing hot articles published between 2018and 2021 in anticancer drug research.The recent advances made towards the synthesis of promising indole-based anticancer compounds that may act via various targets such as topoisomerase,tubulin,apoptosis,aromatase,kinases,etc.,have been discussed.This review also summarizes some of the recent efficient green chemical synthesis for indole rings using various catalysts for the period during 2018—2021.The review also covers the synthesis,structure-activity relationship,and mechanism by which these leads have demonstrated improved and promising anticancer activity.Indole molecules under clinical and preclinical stages are classified into groups based on their cancer targets and presented in tabular form,along with their mechanism of action.The goal of this review article is to point the way for medicinal chemists to design and develop effective indole-based anticancer agents.

关键词： Indole Synthesis Anticancer Structure-activity relationship Topoisomerase Apoptosis Aromatase inhibitors Tubulin inhibitors

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R2R3-MYB transcription factors, StmiR858 and sucrose mediate potato flavonol biosynthesis

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Horticulture Research 2021年第1期8卷 378-390页

作者： Sen Lin rajesh k.singh Moehninsi Duroy A.Navarre Irrigated Agriculture Research and Extension Center Washington State UniversityProsserWAUSA USDA-Agricultural Research Service ProsserWAUSA Present address:Department of Biotechnology CSIR-Institute of Himalayan Bioresource TechnologyPalampurHimachal Pradesh 176061India

Flavonols and other phenylpropanoids protect plants from biotic and abiotic stress and are dietarily desirable because of their health-promoting properties.The ability to develop new potatoes(Solanum tuberosum)with optimal types and amounts of phenylpropanoids is limited by lack of knowledge about the regulatory mechanisms.Exogenous sucrose increased flavonols,whereas overexpression of the MYB StAN1 induced sucrolytic gene expression.Heterologous StAN1 protein bound promoter fragments from sucrolytic genes(SUSY1 and INV1).Two additional MYBs and one microRNA were identified that regulated potato flavonols.Overexpression analysis showed MYB12A and C increased amounts of flavonols and other phenylpropanoids.Endogenous flavonol amounts in light-exposed organs were much higher those in the dark.Expression levels of StMYB12A and C were high in flowers but low in tubers.Transient overexpression of miR858 altered potato flavonol metabolism.Endogenous StmiR858 expression was much lower in flowers than leaves and correlated with flavonol amounts in these organs.Collectively,these findings support the hypothesis that sucrose,MYBs,and miRNA control potato phenylpropanoid metabolism in a finely tuned manner that includes a feedback loop between sucrose and StAN1.These findings will aid in the development of potatoes with phenylpropanoid profiles optimized for crop performance and human health.

关键词： properties. finding media

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Precision phenotyping of contrasting potato(Solanum tuberosum L.) varieties in a novel aeroponics system for improving nitrogen use efficiency: In search of key traits and genes

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Journal of Integrative Agriculture 2020年第1期19卷 51-61页

作者： Jagesh k.TIWARI Sapna DEVI Tanuja BUCkSETH Nilofer ALI rajesh k.singh Rasna ZINTA Vijay k.DUA Swarup k.CHAkRABARTI Indian Council of Agricultural Research-Central Potato Research Institute

With increasing population, degrading soil health, limited arable land area, and high cost of nitrogen(N) fertilizers, improving nitrogen use efficiency(NUE) of potato is an inevitable approach to save the environment and achieve sufficient tuber yields with less N fertilizer supply. Recently, we have developed an aeroponics system to study NUE in potato using genomics, physiology, and breeding approaches. This study aims on precision phenotyping of plants of two distinct potato varieties(kufri Gaurav, N efficient;kufri Jyoti, N inefficient) in the novel aeroponics system. Plants were grown in aeroponics under controlled conditions with low N(0.75 mmol L^-1NO3^-) and high N(7.5 mmol L^-1NO3^-) levels. Plant biomass, root traits, total chlorophyll content, and plant N were increased with increasing N supply, whereas higher NUE parameters namely NUE, agronomic NUE(Ag NUE), N uptake efficiency(NUp E), harvest index(HI), and N harvest index(NHI) were observed at low N. An NUE efficient cv. kufri Gaurav showed higher tuber dry weight, fresh tuber yield, tuber number per plant, early start of tuber harvesting, root traits, stolon traits, NUE parameters, and higher amino acid(aspartic acid and asparagine) content at low N supply. Higher expression of nitrate reductase(NR), nitrite reductase(NIR), and asparagine synthetase(AS) genes was observed in the leaf tissues of kufri Gaurav at high N. Thus, aeroponics-based precision phenotyping enables identification of NUE efficient genotypes based on key traits and genes involved in improving NUE in potato. Further, this study suggests that the potential of aeroponics can be utilized to investigate N biology in potato under different N regimes.

关键词： aeroponics precision phenotyping potato nitrogen use efficiency

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Dual PPAR delta/gamma agonist offer therapeutic potential for Alzheimer's disease

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Neural Regeneration Research 2024年第6期19卷 1175-1176页

作者： Ian Steinke Meenakshi singh rajesh Amin Department of Drug Discovery and Development Auburn University

The increasing incidence of Alzheimer’s disease(AD) in the aging population, indicates the critical need for the development of novel targeted molecular therapies for ameliorating AD pathology. Moreover, clinical and preclinical evidence demonstrates that peroxisomal proliferator activating receptors(PPAR) agonists regulate energy and lipid homeostasis in models of diabetes, as well as improve spatial memory in animal models of AD(khan et al., 2019).

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Designing of tragacanth gum-poly(2-(methacryloyloxy) ethyl] dimethyl-(3-sulfopropyl) ammonium hydroxide) and poly(acrylamide) based hydrogels for drug delivery and wound dressing applications

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Medicine in Novel Technology and Devices 2024年第2期22卷 90-101页

作者： kavita Devi Ashima Sharma rajesh kumar Baljit singh Department of Chemistry Himachal Pradesh UniversityShimla171005India Department of Physiology Indira Gandhi Medical CollegeShimlaIndia

Bioactive tragacanth gum(TG)was functionalized by covalent crosslinking of poly[2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide(PMEDSAH)to design network structure in form of hydrogel wound dressings(HWD).These copolymers were encapsulated with antibiotic drug vancomycin to enhance wound healing potential of the dressings.The copolymers were characterized by SEM,AFM,FTIR,13C NMR,XRD,and TGA-DSC analysis.SEM demonstrated uneven heterogeneous morphology and AFM revealed rough surface of copolymer.Inclusion of synthetic component into HD was confirmed by FTIR and 13C NMR.Hydrogel dressings absorbed 8.491.03 g/g simulated wound fluid and exhibited non-hemolytic(3.70.02%hemolytic potential)and antioxidant(37.421.54%free radical scavenging in DPPH assay)properties.Polymers required 35.05.0 mN detachment force to get it detach from the mucosal surface during mucoadhesive test.Tensile strength was found to be 1.880.13 N/mm2 during mechanical stability test.Hydrogel dressings were permeable to O2/H2O and impermeable to microbes.Release of drug vancomycin occurred through non-Fickian diffusion mechanism and release profile was best described by korsmeyer-Peppas kinetic model.Overall,these results revealed that these hydrogels could be explored as materials for hydrogel wound dressings.

关键词： Hydrogel dressings Drug delivery Wound dressings Vancomycin

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Multimodality Medical Image Fusion Based on Pixel Significance with Edge-Preserving Processing for Clinical Applications

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Computers, Materials & Continua 2024年第3期78卷 4317-4342页

作者： Bhawna Goyal Ayush Dogra Dawa Chyophel Lepcha rajesh singh Hemant Sharma Ahmed Alkhayyat Manob Jyoti Saikia Department of ECE and UCRD Chandigarh UniversityMohaliPunjab140413India Chitkara University Institute of Engineering and Technology Chitkara UniversityPunjab140401India Department of ECE Uttaranchal Institute of TechnologyUttaranchal UniversityDehradun248007India IES College of Technology IES UniversityBhopal462044India College of Technical Engineering The Islamic UniversityNajaf54001Iraq Department of Electrical Engineering University of North FloridaJacksonvilleFL32224USA

Multimodal medical image fusion has attained immense popularity in recent years due to its robust technology for clinical diagnosis.It fuses multiple images into a single image to improve the quality of images by retaining significant information and aiding diagnostic practitioners in diagnosing and treating many diseases.However,recent image fusion techniques have encountered several challenges,including fusion artifacts,algorithm complexity,and high computing costs.To solve these problems,this study presents a novel medical image fusion strategy by combining the benefits of pixel significance with edge-preserving processing to achieve the best fusion performance.First,the method employs a cross-bilateral filter(CBF)that utilizes one image to determine the kernel and the other for filtering,and vice versa,by considering both geometric closeness and the gray-level similarities of neighboring pixels of the images without smoothing edges.The outputs of CBF are then subtracted from the original images to obtain detailed images.It further proposes to use edge-preserving processing that combines linear lowpass filtering with a non-linear technique that enables the selection of relevant regions in detailed images while maintaining structural properties.These regions are selected using morphologically processed linear filter residuals to identify the significant regions with high-amplitude edges and adequate size.The outputs of low-pass filtering are fused with meaningfully restored regions to reconstruct the original shape of the edges.In addition,weight computations are performed using these reconstructed images,and these weights are then fused with the original input images to produce a final fusion result by estimating the strength of horizontal and vertical details.Numerous standard quality evaluation metrics with complementary properties are used for comparison with existing,well-known algorithms objectively to validate the fusion results.Experimental results from the proposed research article exhibit superior per

关键词： Image fusion fractal data analysis biomedical diseases research multiresolution analysis numerical analysis

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Robust Facial Biometric Authentication System Using Pupillary Light Reflex for Liveness Detection of Facial Images

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Computer Modeling in Engineering & Sciences 2024年第4期139卷 725-739页

作者： Puja S.Prasad Adepu Sree Lakshmi Sandeep kautish Simar Preet singh rajesh kumar Shrivastava Abdulaziz S.Almazyad Hossam M.Zawbaa Ali Wagdy Mohamed CSE Department Geethanjali College of EngineeringHyderabadTelangana501301India Department of Computer Science LBEF CampusKathmandu44600Nepal School of Computer Science Engineering and Technology(SCSET) Bennett UniversityGreater Noida201310India Department of Computer Engineering College of Computer and Information SciencesKing Saud UniversityP.O.Box 51178Riyadh11543Saudi Arabia CeADAR Ireland’s Centre for AI Technological University DublinDublinD07 EWV4Ireland Operations Research Department Faculty of Graduate Studies for Statistical ResearchCairo UniversityGiza12613Egypt Applied Science Research Center Applied Science Private UniversityAmman11937Jordan

Pupil dynamics are the important characteristics of face spoofing detection.The face recognition system is one of the most used biometrics for authenticating individual identity.The main threats to the facial recognition system are different types of presentation attacks like print attacks,3D mask attacks,replay attacks,etc.The proposed model uses pupil characteristics for liveness detection during the authentication process.The pupillary light reflex is an involuntary reaction controlling the pupil’s diameter at different light intensities.The proposed framework consists of two-phase methodologies.In the first phase,the pupil’s diameter is calculated by applying stimulus(light)in one eye of the subject and calculating the constriction of the pupil size on both eyes in different video frames.The above measurement is converted into feature space using kohn and Clynes model-defined parameters.The Support Vector Machine is used to classify legitimate subjects when the diameter change is normal(or when the eye is alive)or illegitimate subjects when there is no change or abnormal oscillations of pupil behavior due to the presence of printed photograph,video,or 3D mask of the subject in front of the camera.In the second phase,we perform the facial recognition process.Scale-invariant feature transform(SIFT)is used to find the features from the facial images,with each feature having a size of a 128-dimensional vector.These features are scale,rotation,and orientation invariant and are used for recognizing facial images.The brute force matching algorithm is used for matching features of two different images.The threshold value we considered is 0.08 for good matches.To analyze the performance of the framework,we tested our model in two Face antispoofing datasets named Replay attack datasets and CASIA-SURF datasets,which were used because they contain the videos of the subjects in each sample having three modalities(RGB,IR,Depth).The CASIA-SURF datasets showed an 89.9%Equal Error Rate,while the Replay Attack datasets showed

关键词： SIFT pupil CASIA-SURF pupillary light reflex replay attack dataset brute force

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Effects of supplemental xylanase and xylooligosaccharides on production performance and gut health variables of broiler chickens

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Journal of Animal Science and Biotechnology 2022年第1期13卷 166-180页

作者： Amit k.singh Birendra Mishra Michael R.Bedford rajesh Jha Department of Human Nutrition Food and Animal SciencesUniversity of Hawaii at ManoaHonoluluHI 96822USA AB Vista Feed Ingredients MarlboroughWiltshireUK

Background:This study evaluated the effects of supplemental xylanase and xylooligosaccharides(XOS)in a cornsoybean meal(SBM)-based diet on growth performance and intestinal health of broilers.A total of 288 day-old chicks(Cobb 500)were allocated to 36 floor pens(8 birds/pen)equally in 9 dietary treatments in a 3×3 factorial arrangement.The treatments were combinations of 3 levels of xylanase(0,0.005% and 0.01% Econase XT)and 3 levels of prebiotics(0,0.005% and 0.01% XOS)added to basal mash diets formulated in three phases(starter,d 0-14;grower,d 15-28;finisher,d 29-42).The feed intake and body weights were recorded weekly.On d 42,ileal sections were collected for histomorphometric and gene expression analysis,and cecal content was collected for determining short-chain fatty acids(SCFA)and microbiota.Results:Xylanase linearly(P0.05).Supplemental xylanase and XOS did not affect average daily feed intake and feed conversion ratio(P>0.05).Xylanase and XOS did not change villus height(VH)or crypt depth(CD)ratio(P>0.05).However,xylanase exhibited a trend(P=0.097)on VH:CD ratio.The inclusion of 0.01%XOS without xylanase increased the level of IL-10(a marker of anti-inflammatory cytokine)and IL-4(a T-cell differentiation cytokine)genes compared with control(P0.05).However,the mean proportion of family Ruminococcaceae was increased by the supplemental 0.01% xylanase(P<0.01).Conclusion:It can be concluded that XOS can enhance cecal fermentation,while xylanase can increase the body weight gain along with the fermentation metabolites in the ceca of broilers fed th

关键词： Gene expression Histomorphology Microbiota Poultry Prebiotics Short-chain fatty acid Xylooligosaccharide

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Bioremediation of Textile Azo Dyes Amido Black 10B, Reactive Black 5, Reactive Blue 160 by Lentinus squarrosulus AF5 and Assessment of Toxicity of the Degraded Metabolites

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Advances in Microbiology 2024年第2期14卷 137-161页

作者： Anshu Mathur Chandrachur Ghosh Partha Roy Ramasare Prasad rajesh Pratap singh Department of Biosciences and Bioengineering Indian Institute of Technology Roorkee Roorkee India

Bioremediation is an eco-compatible and economical approach to counter textile dye menace. The isolated Lentinus squarrosulus AF5 was assessed for decolourization of textile azo dyes, and had shown ~93%, 88% and 70% decolorization of Reactive blue 160 (RB160), Reactive black 5 (RB5) and Amido black 10B (AB10B) respectively. Further analysis using UV-vis, HPLC, and FTIR, 1H NMR had shown the degradation of the dyes. Toxicity analysis of the metabolites was performed using seed germination and plant growth on two agriculturally important plants Guar (Cyamopsis tetragonoloba) and wheat (Triticum aestivum) as well as cytotoxicity analysis using the human keratinocyte cell line (HaCaT). The dye mix appeared inhibitory for seed germination (20% - 40%), whereas metabolites were non-inhibitory for germination. Treatment of HaCaT cells with of dye mix and metabolites led into 45% and ~100% of cell viability of HaCaT cells respectively. Therefore, metabolites following degradation of the dye mix were observed to be non-toxic.

关键词： Lentinus squarrosulus AF5 Azo Dyes FTIR 1H NMR Catabolism Cytotoxicity

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Thermal and Oxygen Barrier Properties of Chitosan Bionanocomposites by Reinforcement of Calcium Carbonate Nanopowder

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Journal of Materials Science & Technology 2014年第8期30卷 791-795页

作者： Sarat k. Swain Satyabrata Dash Sudhir k. kisku rajesh k. singh Department of Chemistry Veer Surendra Sai University of TechnologyBurlaSambalpur 768018India Department of Chemistry North Orissa UniversityTakatpurBaripada 757003India

Chitosan and calcium carbonate nanopowder（chitosan/CaCO3） bionanocomposites were prepared by solution method.Interaction between chitosan and CaCO3 was studied by Fourier transform infrared spectroscopy（FTIR）.Structure and surface morphology of chitosan/CaCO3 bionanocomposites were investigated by X-ray diffraction（XRD） and field emission scanning electron microscopy（FESEM）,respectively.The energy dispersive X-ray spectroscopy（EDS） of chitosan/CaCO3 bionanocomposites was studied in order to establish the elements of composition.Thermal stability of prepared bionanocomposites was studied by thermogravimetric analysis（TGA） and a substantial increase of thermal stability of virgin chitosan was noticed due to incorporation of CaCO3 nanopowder.The oxygen permeability was reduced by three times as compared to the raw chitosan due to the dispersion of nano CaCO3 filler.Biodegradability and resistance towards dilute acid and alkali of the prepared bionanocomposite were investigated.The bionanocomposite having gas barrier and thermal stable property may be suitable for packaging and biomedical applications.

关键词： Chitosan Nanocomposites Thermal properties Oxygen permeability

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