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SBL-JP-0004: A promising dual inhibitor of JAK2 and Pi3KCD against gastric cancer

Oncology research 2025年第1期33卷 235-243页

作者： Hassan m Otifi Department of Pathology College of Medicine King Khalid University Abha 62521 Saudi Arabia.

Background:Gastric cancer (GC) rem.ins a global health burden and is often characterized by heterogeneous molecular profiles and resistance to conventional therapies. The phosphoinositide 3-kinase and Pi3K and Janus kinase (JAK) signal transducer and activator of transcription (JAK-STAT) pathways play pivotal roles in GC progression, making them attractive targets for therapeutic interventions.methods:This study applied a computational and molecular dynamics simulation approach to identify and characterize SBL-JP-0004 as a potential dual inhibitor of JAK2 and Pi3KCD kinases. KATOiii and SNU-5 GC cells were used for evaluation.Results:SBL-JP-0004 exhibited a robust binding affinity for JAK2 and Pi3KCD kinases, as evidenced by molecular docking scores and molecular dynamics simulations. Binding interactions and Gibbs binding free energy estimates confirmed stable and favorable interactions with target proteins. SBL-JP-0004 displayed an half-maximal inhibitory concentration (iC) value of 118.9 nm against JAK2 kinase and 200.9 nm against Pi3KCD enzymes. SBL-JP-0004 exhibited potent inhibition of cell proliferation in KATOiii and SNU-5 cells, with half-maximal growth inhibitory concentration (Gi) values of 250.8 and 516.3 nm, respectively. A significant elevation in the early phase apoptosis (28.53% in KATOiii cells and 26.85% in SNU-5 cells) and late phase apoptosis (17.37% in KATOiii cells and 10.05% in SNU-5 cells) were observed with SBL-JP-0004 treatment compared to 2.1% and 2.83% in their respective controls.Conclusion:The results highlight SBL-JP-0004 as a promising dual inhibitor targeting JAK2 and Pi3KCD kinases for treating GC and warrant further preclinical and clinical investigations to validate its utility in clinical settings.

关键词： Dual inhibition Gastric cancer (GC) JAK2 molecular docking molecular dynamics simulation Pi3KCD SBL-JP-0004

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Nonlinear forced vibration in a subcritical regime of a porous functionally graded pipe conveying fluid with a retaining clip

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Applied mathematics and mechanics(English Edition) 2025年第1期46卷 101-122页

作者： m.GHOLAmi m.EFTEKHARi Department of mechanical Engineering Shahid Bahonar University of Kerman

This study examines the nonlinear behaviors of a clamped-clamped porous pipe made of a functionally graded material(FGm) that conveys fluids and is equipped with a retaining clip, focusing on primary resonance and subcritical dynamics. The nonlinear governing equations for the FGm pipe are derived by the extended Hamilton's principle, and subsequently discretized through the application of the Galerkin *** direct method of multi-scales is then used to solve the derived equations. A thorough analysis of various parameters, including the clip stiffness, the power-law index, the porosity, and the clip location, is conducted to gain a comprehensive understanding of the system's nonlinear dynamics. Through the analysis of the first natural frequency, the study highlights the influence of the flow velocity and the clip stiffness, while the comparisons with metallic pipes emphasize the role of FGm composition. The examination of the forced response curves reveals saddle-node bifurcations and their dependence on parameters such as the detuning parameter and the power-law index, offering valuable insights into the system's nonlinear resonant behavior. Furthermore, the frequency-response curves illustrate the hardening nonlinearities influenced by factors such as the porosity and the clip stiffness, revealing nuanced effects on the system response and resonance characteristics. This comprehensive analysis enhances the understanding of nonlinear behaviors in FGm porous pipes with a retaining clip, providing key insights for practical engineering applications in system design and optimization.

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Glia-to-neuron reprogram.ing to the rescue?

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Neural Regeneration Research 2025年第5期20卷 1395-1396页

作者： Jack W.Hickmott Cindi m.morshead Department of Surgery University of TorontoTorontoONCanada Donnelly Centre for Cellular and Biomolecular Research TorontoONCanada institute of Biomedical Engineering University of TorontoTorontoONCanada The KiTE Research institute Toronto Rehabilitation InstituteUniversity Health NetworkTorontoONCanada

Over the last two decades,the dogma that cell fate is immutable has been increasingly challenged,with important implications for regenerative *** brea kth rough discovery that induced pluripotent stem cells could be generated from adult mouse fibroblasts is powerful proof that cell fate can be *** exciting extension of the discovery of cell fate impermanence is the direct cellular reprogram ming hypothesis-that terminally differentiated cells can be reprogrammed into other adult cell fates without first passing through a stem cell state.

关键词： program.ing passing proof

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impact of Zika virus non-structural protein mutations on hippocampal damage

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Neural Regeneration Research 2025年第8期20卷 2307-2308页

作者： Larissa m.G.Cassiano Roney S.Coimbra Neurogenômica/imunopatologia Instituto RenéRachouFiocruzBelo HorizonteBrazil Departamento de Bioquímica e imunologia Instituto de Ciências BiológicasUniversidade Federal de Minas GeraisBelo HorizonteBrazil

The Zika virus(ZiKV),a member of the Flaviviridae family,attracted worldwide attention for its connection to severe neurological effects,notably microcephaly in newborns,first reported during the 2015 epidemic in ***,its impact goes beyond fetal and neonatal abnormalities,also affecting the central nervous system(CNS)in both children and adults,leading to enduring cognitive and behavioral impairments.

关键词： damage fetal neonatal

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insights from an academic endeavor into central nervous system drug discovery

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Neural Regeneration Research 2025年第6期20卷 1717-1718页

作者： Lieve van Veggel An m.Voets Tim Vanmierlo Rudy Schreiber BiOmED Biomedical Research institute Faculty of Medicine and Life SciencesHasselt UniversityHasseltBelgium Department of Psychiatry and Neuropsychology Division of Translational NeuroscienceEuropean Graduate School of NeuroscienceSchool for Mental Health and NeuroscienceMaastricht UniversityMaastrichtThe Netherlands Section of Psychopharmacology Neuropsychology and PsychopharmacologyFaculty of Psychology and NeuroscienceMaastricht UniversityMaastrichtThe Netherlands University mS Center(UmSC) Hasselt-PeltBelgium

Historically,"big pharma"did most central nervous system drug discovery R&D ***,in modern times their"management reductionism"resulted in disappointing pipelines and pharma resided to(late)development,regulatory approval,and marketing(Thong,2015).This had significant consequences for financing and executing research,resulting in a larger role for funding by governments and patient-organizations and a shift of research to academia(mazzucato,2013).

关键词： academic approval consequences

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Neurocircuit regeneration by extracellular matrix reprogram.ing

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Neural Regeneration Research 2025年第8期20卷 2300-2301页

作者： Shengzhang Su ian N.Levasseur Kimberly m.Alonge Department of medicinal Chemistry University of WashingtonSeattleWAUSA Department of Chemistry University of WashingtonSeattleWAUSA Department of medicine University of Washington Medicine Diabetes InstituteSeattleWAUSA

The brain's extracellular matrix(ECm),which is comprised of protein and glycosaminoglycan(GAG)scaffolds,constitutes 20%-40% of the human brain and is considered one of the largest influencers on brain cell functioning(Soles et al.,2023).Synthesized by neural and glial cells,the brain's ECm regulates a myriad of homeostatic cellular processes,including neuronal plasticity and firing(miyata et al.,2012),cation buffering(moraws ki et al.,2015),and glia-neuron interactions(Anderson et al.,2016).Considering the diversity of functions,dynamic remodeling of the brain's ECm.indicates that this understudied medium.is an active participant in both normal physiology and neurological diseases.

关键词： matrix program.ing

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Crossover of large to small radius polaron in ionic crystals

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Chinese Physics B 2016年第11期25卷 434-440页

作者： m.i Umo Department of Physics University of Calabar PMB 1115 Nigeria

The crossover of large to small radius polaron is studied in terms of the inverse-relaxation time and *** is found that the small radius polaron exists at higher temperature than the large radius polaron.A formula which relates the inverse-relaxation time to the ratio of arbitrary temperature and Debye temperature of the crystal is *** polaron crossover temperatures in NaCl and KBr are found from plotted *** straight line emerging at the Debye temperature T_d of a graph reflects the increase of the inverse relaxation time for increasing temperature up to the collapse of the small radius *** relationship between the small and large radius polarons is found and known ratios of the effective and the bare masses of the electrons for the two substances are used to validate our *** small radius polaron＇s mass is later compared with the mass obtained from the hopping formula and is found to be approximately ***,we point out that the crossover temperature is material-specific since it depends on the Debye and the effective dielectric function.

关键词： relaxation radius crossover inverse straight ionic validate arbitrary phonon dielectric

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Transport mechanism.in chemically reactive hybrid nanofluid flow containing gyrotactic micro-organisms over a curved oscillatory surface

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Applied mathematics and mechanics(English Edition) 2025年第1期46卷 177-192页

作者： m.NAVEED m.imRAN T.ASGHAR Z.ABBAS Department of mathematics Division of Science and TechnologyUniversity of Education Department of mathematics The Islamia University of Bahawalpur

This paper examines the transport analysis, including both heat transfer and mass transfer, in hybrid nanofluid flow containing gyrotactic microorganisms towards a curved oscillatory surface. The influence of magnetic fields is also inspected in terms of their physical characteristics. To depict the phenomena of transport, modified versions of both Fick's and Fourier's laws are used. Additionally, the characteristics of both heterogeneous and homogeneous chemical reactions are also incorporated. Utilizing a curvilinear coordinate system, the flow problem.is formulated as partial differential equations(PDEs)for momentum, concentration, microorganism field, and energy. An analytical solution to the obtained flow equations is achieved utilizing the homotopy analysis method(HAm).The effects of significant flow parameters on the pressure and microorganism fields, velocity, oscillation velocity, concentration, and temperature distributions are shown via graphs. Furthermore, the variations in skin friction, mass transfer rate, heat transfer rate, and local motile number due to different involved parameters are presented in tables and are analyzed in detail. Graphical results indicate that the curves of velocity and temperature fields are enhanced as the values of the solid volume fraction variables *** is also verified that the concentration rate field decreases as the values of the homogeneous reaction strength parameter and the radius of curvature parameter increase, and it increases with the Schmidt number and the heterogeneous reaction strength *** outcomes show a favorable response of the motile number to advanced values of the Peclet number, the Schmidt number, the microorganism difference parameter, and the bio-convective Lewis number.

关键词： hybrid nanofluid oscillating curved stretchable sheet gyrotactic microorganism Cattaneo-Christov heat and mass flux chemical reaction analytical solution O368

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Regression analysis of squeezing-induced hybrid nanofluid flow in Darcy-Forchheimer porous medium

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Applied mathematics and mechanics(English Edition) 2025年第1期46卷 193-208页

作者： K.mUHAmmAD m.SARFRAZ Department of Humanities and Sciences School of Electrical Engineering and Computer Science National University of Sciences and Technology Department of mathematics Quaid-i-Azam University

This article presents a mathematical model addressing a scenario involving a hybrid nanofluid flow between two infinite parallel plates. One plate rem.ins stationary, while the other moves downward at a squeezing velocity. The space between these plates contains a Darcy-Forchheimer porous medium. A mixture of water-based fluid with gold(Au) and silicon dioxide(Si O2) nanoparticles is formulated. in contrast to the conventional Fourier's heat flux equation, this study employs the Cattaneo-Christov heat flux equation. A uniform magnetic field is applied perpendicular to the flow direction, invoking magnetohydrodynamic(mHD) effects. Further, the model accounts for Joule heating, which is the heat generated when an electric current passes through the fluid. The problem.is solved via NDSolve in mATHEmATiCA. Numerical and statistical analyses are conducted to provide insights into the behavior of the nanomaterials between the parallel plates with respect to the flow, energy transport, and skin *** findings of this study have potential applications in enhancing cooling systems and optimizing thermal management strategies. it is observed that the squeezing motion generates additional pressure gradients within the fluid, which enhances the flow rate but reduces the frictional drag. Consequently, the fluid is pushed more vigorously between the plates, increasing the flow velocity. As the fluid experiences higher flow rates due to the increased squeezing effect, it spends less time in the region between the plates. The thermal relaxation, however, abruptly changes the temperature, leading to a decrease in the temperature fluctuations.

关键词： convective boundary condition Darcy-Forchheimer medium hybrid nanofluid Joule heating magnetohydrodynamic (mHD) numerical solution squeezing flow regression analysis O361 O175.2

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Vertical seismic absorber utilizing inertance and negative stiffness implemented with gas springs

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Earthquake Engineering and Engineering Vibration 2023年第1期22卷 225-241页

作者： Kalogerakou m Paradeisiotis A Antoniadis i Dynamics and Structures Laboratory School of Mechanical EngineeringNational Technical University of Athens15780 AthensGreece

A novel implementation of negative stiffness elements(NSEs)is proposed,utilizing industrial grade nitrogen gas springs as pre-stressed stiffness elements in a configuration with lever *** NSE is com.ined with an inerter to form a stiff dynamic absorber(SDA)for vertical seismic protection of structures with base *** SDA is optimized to minimize vertical accelerations while ensuring static structural integrity,excellent dam.ing performance and containment of relative *** introduction of gas springs in place of conventional linear springs addresses important practical limitations through features of non-linearity and industrial grade *** proposed implementation is dimensioned for a 50-ton structure and evaluated numerically for 25 actual earthquake records,in comparison with a linear SDA model and an equivalent conventional damper(CD).individual and averaged results of acceleration and displacement time histories demonstrate vastly superior response compared to CD regarding induced accelerations for similar *** equivalency with the linear SDA model indicates the stability of the gas spring implementation while guaranteeing predictability,tested endurance,proper tolerances,and off-axis motion resistance without requiring additional guiding components,as opposed to conventional *** features render the proposed implementation a promising solution for the realization of NSEs in seismic protection.

关键词： negative stiffness gas springs vertical seismic protection KDamper inerter

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