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Drug resistance mechanisms in cancers:Execution of prosurvival strategies

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Journal of Biomedical Research 2024年第2期38卷 95-121页

作者： pavan Kumar Dhanyamraju Fels Cancer Institute of Personalized Medicine Lewis-Katz School of MedicineTemple UniversityPhiladelphiaPA 19140USA

One of the quintessential challenges in cancer treatment is drug *** mechanisms of drug resistance have been described to date,and new modes of drug resistance continue to be *** phenomenon of cancer drug resistance is now widespread,with approximately 90% of cancer-related deaths associated with drug *** significant advances in the drug discovery process,the emergence of innate and acquired mechanisms of drug resistance has impeded the progress in cancer ***,understanding the mechanisms of drug resistance and the various pathways involved is integral to treatment *** the present review,I discuss the different mechanisms of drug resistance in cancer cells,including DNA damage repair,epithelial to mesenchymal transition,inhibition of cell death,alteration of drug targets,inactivation of drugs,deregulation of cellular energetics,immune evasion,tumor-promoting inflammation,genome instability,and other contributing epigenetic ***,I highlight available treatment options and conclude with future directions.

关键词： cancer drug resistance mechanisms microRNAs treatment strategies

Coupled bio-chemo-hydro-mechanical modeling of microbially induced calcite precipitation process considering biomass encapsulation using a micro-scale relationship

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Journal of Rock Mechanics and Geotechnical Engineering 2024年第7期16卷 2775-2789页

作者： pavan Kumar Bhukya Nandini Adla Dali Naidu Arnepalli Department of Civil Engineering Indian Institute of Technology MadrasChennai600036Tamil NaduIndia

Geomaterials with inferior hydraulic and strength characteristics often need improvement to enhance their engineering *** ground improvement techniques require enormous mechanical effort or synthetic *** stabilization technique such as microbially induced calcite precipitation(MICP)utilizes bacterial metabolic processes to precipitate cementitious calcium *** reactive transport of biochemical species in the soil mass initiates the precipitation of biocement during the MICP *** precipitated biocement alters the hydro-mechanical performance of the soil ***,the flow,deformation,and transport phenomena regulate the biocementation technique via coupled bio-chemo-hydro-mechanical(BCHM)*** all,one crucial phenomenon controlling the precipitation mechanism is the encapsulation of biomass by calcium *** encapsulation can potentially reduce the biochemical reaction rate and decelerate *** examination of the encapsulation process demands a thorough analysis of associated coupled *** this,a numerical model can assist in capturing the coupled processes influencing encapsulation during the MICP ***,most numerical models did not consider biochemical reaction rate kinetics accounting for the influence of bacterial *** this,the current study developed a coupled BCHM model to evaluate the effect of encapsulation on the precipitated calcite content using a micro-scale semiempirical ***,the developed BCHM model was verified and validated using numerical and experimental observations of soil column ***,the encapsulation phenomenon was investigated in the soil columns of variable maximum calcite crystal *** results depict altered reaction rates due to the encapsulation phenomenon and an observable change in the precipitated calcite content for each maximum crystal ***,the permeability and defor

关键词： Biocementation process Bio-chemo-hydro-mechanical(BCHM) model Reactive transport Encapsulation Micro-scale

Coupled multiphysical model for investigation of influence factors in the application of microbially induced calcite precipitation

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Journal of Rock Mechanics and Geotechnical Engineering 2024年第6期16卷 2232-2249页

作者： Xuerui Wang pavan Kumar Bhukya Dali Naidu Arnepalli Shuang Chen Gesellschaft für Anlagen-und Reaktorsicherheit(GRS)GGmbH Braunschweig38122Germany Department of Civil Engineering Indian Institute of Technology MadrasChennai600036India Federal Institute for Geosciences and Natural Resources(BGR) Hannover30655Germany

The study presents a comprehensive coupled thermo-bio-chemo-hydraulic(T-BCH)modeling framework for stabilizing soils using microbially induced calcite precipitation(MICP).The numerical model considers relevant multiphysics involved in MICP,such as bacterial ureolytic activities,biochemical reactions,multiphase and multicomponent transport,and alteration of the porosity and *** model incorporates multiphysical coupling effects through well-established constitutive relations that connect parameters and variables from different physical *** was implemented in the open-source finite element code OpenGeoSys(OGS),and a semi-staggered solution strategy was designed to solve the couplings,allowing for flexible model ***,the developed model can be easily adapted to simulate MICP applications in different *** numerical model was employed to analyze the effect of various factors,including temperature,injection strategies,and application ***,a TBCH modeling study was conducted on the laboratory-scale domain to analyze the effects of temperature on urease activity and precipitated calcium *** understand the scale dependency of MICP treatment,a large-scale heterogeneous domain was subjected to variable biochemical injection *** simulations conducted at the field-scale guided the selection of an injection strategy to achieve the desired type and amount of ***,the study emphasized the potential of numerical models as reliable tools for optimizing future developments in field-scale MICP *** present study demonstrates the potential of this numerical framework for designing and optimizing the MICP applications in laboratory-,prototype-,and field-scale scenarios.

关键词： Multiphysics Microbially induced calcite precipitation(MICP) Coupled thermo-bio-chemo-hydraulic(TBCH) model OpenGeoSys(OGS) Influence factors

Evolution, divergence, and convergence in the mandibles of opossums (Didelphidae, Didelphimorphia)

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Current Zoology 2024年第4期70卷 488-504页

作者： Franciscodas Chagas Silva-Neto Silvia E.pavan Diego Astua Laboratorio de Mastozoologia Departamento de ZoologiaUniversidade Federal de Pernambuco.Av.Prof.Moraes Regos.n.Cidade Universitaria.50670-901RecifePEBrazil Department of Biological Sciences California State Polytechnic UniversityHumboldt1Harpst StreetArcataCA95521USA

Didelphid marsupials are considered a morphologically unspecialized group with a generalist diet that includes vertebrates,invertebrates,and plant *** cranium and scapula variation has alreadybeen examined within Didelphidae,variation inmandible shape,usually associated with diet or phylogeny in other mammalian groups,has not yet been properly assessed in the *** evaluated the variation in mandible shape and size of didelphids(2470 specimens belonging to 94 species)using 2D geometric *** classified the diet of the didel-phids into four broad categories to assess whether morphospace ordination relates to dietary *** also provided the most comprehensive phylogeny for the family(i23 out of the 126 living species)using 10 nuclear and mitochondrial *** then mapped mandible size and shape onto that phylogeny for 93 selected taxa and ancestral size and shapes were reconstructed by *** found phylogenetically structured variation in mandible morphology between didelphid groups,and our results indicate that they have a significant phylogenetic *** main axis of shape variation is poorly related to size,but the second is strongly allometric,indicating that allometry is not the main factor in shaping morphological diversity on their *** results indicate that the shape and size of the ancestral mandible of didelphids would be similar to that of the current species of the genus Marmosa.

关键词： mandible Didelphimorphia morphological evolution allometry phylogeny diet.

Advancements in nanotechnology for the delivery of phytochemicals

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Journal of Integrative Medicine 2024年第4期22卷 385-398页

作者： Divya Chauhan pavan K.Yadav Nazneen Sultana Arun Agarwal Saurabh Verma Manish K.Chourasia Jiaur R.Gayen Division of Pharmaceutics and Pharmacokinetics Central Drug Research InstituteCouncil of Scientific and Industrial ResearchLucknow 226031Uttar PradeshIndia Academy of Scientific and Innovative Research Ghaziabad 201002Uttar PradeshIndia

Phytosomes(phytophospholipid complex) are dosage forms that have recently been introduced to increase the stability and therapeutic effect of herbal medicine. Currently, bioactive herbs and the phytochemicals they contain are considered to be the best remedies for chronic diseases. One promising approach to increase the efficacy of plant-based therapies is to improve the stability and bioavailability of their bio-active ingredients. Phytosomes employ phospholipids as their active ingredients, and use their amphiphilic properties to solubilize and protect herbal extracts. The unique properties of phospholipids in drug delivery and their use in herbal medicines to improve bioavailability results in significantly enhanced health benefits. The introduction of phytosome nanotechnology can alter and revolutionize the current state of drug delivery. The goal of this review is to explain the application of phytosomes, their future prospects in drug delivery, and their advantages over conventional formulations.

关键词： Phytochemical Bioavailability Drug delivery system Phytosome Plant extracts

BIKAS:Bio-Inspired Knowledge Acquisition and Simulacrum-A Knowledge Database to Support Multifunctional Design Concept Generation

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Data Intelligence 2024年第2期6卷 531-558页

作者： pavan Tejaswi Velivela Yaoyao Fiona Zhao Department of Mechanical Engineering McGill UniversityQuebecCanada H3A 0G4

A detailed acquisition,analysis,and representation of biological systems exhibiting different functions is required to develop unique bio-inspired multifunctional conceptual designs and *** paper presents BIKAS:Bio-inspired Knowledge Acquisition and Simulacrum,a knowledge database of biological systems exhibiting various functionalities,developed based on case-based bio-inspired examples from *** knowledge database represents the biological features,their characteristics,and the function exhibited by the biological feature as a combination of its integrated structure and structural ***,this knowledge database is utilized by the Expandable Domain Integrated Design(xDID)model that works on classifying,mapping,and representing biological features into their respective geometric designations called *** combination of features from the Domains results in the generation of multifunctional conceptual *** addition,Meta-level design factors are proposed to aid designers in filtering the biological features and their respective functions having a similar structural strategy,thus aiding designers in rapidly selecting and emulating biological functions.

关键词： Bio-inspired design(BID) Knowledge database Conceptual design Multifunctional bio-inspired design Agile innovation

Physical insights into trapping effects on vertical GaN-on-Si trench MOSFETs from TCAD

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Journal of Semiconductors 2024年第3期45卷 45-52页

作者： NicolòZagni Manuel Fregolent Andrea Del Fiol Davide Favero Francesco Bergamin Giovanni Verzellesi Carlo De Santi Gaudenzio Meneghesso Enrico Zanoni Christian Huber Matteo Meneghini Paolo pavan Department of Engineering“Enzo Ferrari” University of Modena and Reggio EmiliaModena 41125Italy Department of Information Engineering University of PadovaPadova 35131Italy Department of Sciences and Methods for Engineering(DISMI) University of Modena and Reggio EmiliaReggio Emilia 42122Italy EN&TECH Center University of Modena and Reggio EmiliaReggio Emilia 42122Italy Advanced Technologies and Micro Systems Department Robert Bosch GmbHRenningen 71272Germany

Vertical GaN power MOSFET is a novel technology that offers great potential for power switching *** still in an early development phase,vertical GaN devices are yet to be fully optimized and require careful studies to foster their *** this work,we report on the physical insights into device performance improvements obtained during the development of vertical GaN-on-Si trench MOSFETs(TMOS’s)provided by TCAD simulations,enhancing the dependability of the adopted process optimization ***,two different TMOS devices are compared in terms of transfer-curve hysteresis(H)and subthreshold slope(SS),showing a≈75%H reduction along with a≈30%SS *** allow attributing the achieved improvements to a decrease in the border and interface traps,respectively.A sensitivity analysis is also carried out,allowing to quantify the additional trap density reduction required to minimize both figures of merit.

关键词： vertical GaN trench MOSFET SiO_(2) interface traps border traps hysteresis BTI

Dietary Green Tea Extract and Antioxidants Improve Insulin Secretory Functions of Pancreatic β-Cells in Mild and Severe Experimental Rodent Model of Chronic Pancreatitis

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Open Journal of Endocrine and Metabolic Diseases 2024年第2期14卷 53-72页

作者： Galande Sheethal Ranjeet K. Tokala pavan.pon.ugala Krishna Vemula Vijayalakshmi Venkatesan Pothani Suresh Surya Satyanarayana Singh Guduru Venkat Rao Duvvur Nageshwar Reddy Mitnala Sasikala Basic Science and Translational Research Division Asian Healthcare Foundation AIG Hospitals Hyderabad India Division of Cell and Molecular Biology National institute of Nutrition Hyderabad India National Animal Resource Facility for Biomedical Research Hyderabad India Department of Biochemistry Osmania University Hyderabad India Department of Surgical Gastroenterology Asian Institute of Gastroenterology Hyderabad India Department of Gastroenterology Asian Institute of Gastroenterology Hyderabad India

Chronic pancreatitis (CP) is a progressive inflammatory disorder of the pancreas. It is predominantly idiopathic (with an unknown cause) in India and mostly due to alcohol in the West. Diabetes that occur secondary to chronic pancreatitis (T3c Diabetes) is often brittle, and is difficult to attain normoglycemia with conventional treatment requiring multiple doses of insulin. Mild and severe model of CP was induced in mice by repeated intraperitoneal injections of cerulein and L-arginine respectively with an intent to study islet dysfunction and develop therapeutic strategy in animal models of CP. Dietary intervention of epigallocatechin-3-gallate (EGCG) was tested in both the models of CP for its beneficial effects on insulin secretory functions. Pancreata collected upon euthanasia were used to study alterations in the morphology of pancreatic parenchyma and inflammation by staining with H&E and fibrotic changes by Masson’s trichrome and picrosirius staining. Insulin secretory functions of islets were evaluated to test the efficacy of the dietary intervention on β-cell functions. Intraperitoneal glucose tolerance test was performed to monitor the glucose homeostasis before and after the dietary intervention. Both the models resulted in CP with dispersed acini, inflammation and fibrosis. The loss of acini and extent of fibrosis was more in L-arginine model. 2-fold improvement in glucose-stimulated insulin secretory functions of islets was observed with 0.5% EGCG dietary intervention in cerulein model of CP and 1.6-fold in L-arginine model of CP. A further improvement in insulin secretion by 3.2-fold was observed with additional dietary supplements like N-acetyl cysteine, curcumin in combination with EGCG. Our results thus demonstrate and highlight the therapeutic potential of dietary green tea (EGCG) supplementation in reversing islet dysfunction and improving glucose homeostasis in experimental chronic pancreatitis in mice.

关键词： Dietary Intervention C57BL6/J Mice Epigallocatechin-3-Gallate N-Acetyl Cysteine Curcumin Chronic Pancreatitis Islets Glucose Stimulated Insulin Secretion

Targeting metabolism to treat multiple sclerosis

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Neural Regeneration Research 2021年第3期16卷 502-503页

作者： pavan Bhargava Department of Neurology Johns Hopkins University School of MedicineBaltimoreMDUSA

Multiple sclerosis(MS)is a chronic autoimmune disorder of the central nervous system(CNS)that has both inflammatory and neurodegenerative com *** genetic and environmental factors confer risk for developing the ***,gut microbiota appears to play an important role in the risk for MS and potentially also in affecting disease severity,though our understanding of these interactions are still incomplete(Bhargava and Mowry,2014).

关键词： metabolism sclerosis autoimmune