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SBL-JP-0004: A promising dual inhibitor of JAK2 and PI3KCD against gastric cancer

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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) remains 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

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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A note on circle packing

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Journal of Zhejiang University-Science C(Computers and Electronics) 2012年第8期13卷 559-564页

作者： Young Joon AHN Christoph m. HOFFmANN Paul rosen Department of mathematics Education Chosun University Gwangju 501-759 Korea Department of Computer Science Purdue University West Lafayette IN 47907 USA Scientific Computing and Imaging Institute University of Utah Salt Lake City UT 84112 USA

The problem of packing circles into a domain of prescribed topology is considered. The circles need not have equal radii. The Collins-Stephenson algorithm computes such a circle packing. This algorithm is parmlelized in two different ways and its performance is reported for a triangular, planar domain test case. The implementation uses the highly parallel graphics processing unit （GPU） on commodity hardware. The speedups so achieved are discussed based on a number of experiments.

关键词： Circle packing Algorithm performance Parallel computation Graphics processing unit (GPU)

BRCA mutated pancreatic cancer:A change is coming

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World Journal of Gastroenterology 2021年第17期27卷 1943-1958页

作者： michael N rosen Rachel A Goodwin michael m Vickers Faculty of medicine The University of OttawaOttawa K1H 8L6OntarioCanada The Ottawa Hospital Cancer Center The University of OttawaOttawa K1H 8L6OntarioCanada

Pancreatic cancer remains a leading cause of cancer-related death with few available therapies for advanced ***,patients with germline BRCA mutations have received increased attention due to advances in the management of BRCA mutated ovarian and breast *** BRCA mutations significantly increase risk of developing pancreatic cancer and can be found in up to 8%of patients with sporadic pancreatic *** patients with germline BRCA mutations,platinum-based chemotherapies and poly(ADP-ribose)polymerase inhibitors are effective treatment options which may offer survival *** review will focus on the molecular biology,epidemiology,and management of BRCA-mutated pancreatic ***-more,we will discuss future directions for this area of research and promising active areas of research.

关键词： Pancreatic cancer Systemic therapy Platinum chemotherapy BRCA Deoxyribonucleic acid repair Poly(ADP-ribose)polymerase inhibitors

Glia-to-neuron reprogramming 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： programming passing proof

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

Fresnel incoherent correlation hologram-a review(Invited Paper)

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Chinese Optics Letters 2009年第12期7卷 1134-1141页

作者： Joseph rosen Barak Katz Gary Brooker Department of Electrical and Computer Engineering Ben-Gurion University of the NegevP.O. Box 653 Beer-Sheva 84105 Israel Johns Hopkins University microscopy Center Montgomery County Campus Advanced Technology Laboratory Whiting School of Engineering 9605 Medical Center Drive Suite 240Rockville MD 20850 USA

Holographic imaging offers a reliable and fast method to capture the complete three-dimensional （3D） information of the scene from a single perspective. We review our recently proposed single-channel optical system for generating digital Fresnel holograms of 3D real-existing objects illuminated by incoherent light. In this motionless holographic technique, light is reflected, or emitted from a 3D object, propagates through a spatial light modulator （SLm）, and is recorded by a digital camera. The SLm is used as a beamsplitter of the single-channel incoherent interferometer, such that each spherical beam originated from each object point is split into two spherical beams with two different curve radii. Incoherent sum of the entire interferences between all the couples of spherical beams creates the Fresnel hologram of the observed 3D object. When this hologram is reconstructed in the computer, the 3D properties of the object are revealed.

关键词： Color holography Digital holographic imaging Holographic techniques Spatial light modulators Three dimensional imaging Zone plates

Finding stable multi-component materials by combining cluster expansion and crystal structure predictions

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npj Computational materials 2023年第1期9卷 2137-2146页

作者： Adam Carlsson Johanna rosen martin Dahlqvist materials Design Department of PhysicsChemistryand Biology(IFM)Linköping UniversitySE-58183 LinköpingSweden

A desired prerequisite when performing a quantum mechanical calculation is to have an initial idea of the atomic positions within an approximate crystal *** atomic positions combined should result in a system located in,or close to,an energy ***,designing low-energy structures may be a challenging task when prior knowledge is scarce,specifically for large multi-component systems where the degrees of freedom are close to *** this paper,we propose a method for identification of low-energy crystal structures within multi-component systems by combining cluster expansion and crystal structure predictions with density-functional theory *** structure prediction searches are applied to the mo_(2)AlB_(2) and Sc2AlB_(2) ternary systems to identify candidate structures,which are subsequently used to explore the quaternary(pseudo-binary)(mo_(x)Sc_(1–x))2AlB_(2) system through the cluster expansion formalism utilizing the ground-state search ***,we show that utilizing low-energy structures found within the cluster expansion ground-state search as seed structures within crystal structure predictions of(mo_(x)Sc_(1–x))2AlB_(2) can significantly reduce the computational *** this combined approach,we not only correctly identified the recently discovered mo_(4/3)Sc_(2/3)AlB_(2) i-mAB phase,comprised of in-plane chemical ordering of mo and Sc and with Al in a Kagomélattice,but also predict additional low-energy structures at various *** result demonstrates that combining crystal structure prediction with cluster expansion provides a path for identifying low-energy crystal structures in multi-component systems by employing the strengths from both frameworks.

关键词： structure cluster crystal

Transition metal carbides as cathode supports for PEm fuel cells

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Nano Research 2022年第12期15卷 10218-10233页

作者： Eliran R.Hamo Brian A.rosen Department of materials Science and Engineering Tel Aviv UniversityRamat Aviv69987001Israel

As energy demands increase and environmental issues loom,fuel cells(FCs)have attracted significant attention as an alternative to conventional energy *** use encompasses portable applications,transportation,and a stationary grid-power mainly due to their low-temperature operation and quick ***,the primary challenge is improving fuel cell durability to meet 2025 *** of Energy targets(e.g.,8,000+h for automotive drive cycle).Proton exchange membrane fuel cell(PEmFC)catalysts currently suffer from low durability,undermining their wide-scale deployment into the consumer and industrial *** group metals(PGms)are still the most common catalysts used in PEmFCs as they provide among the highest activity for electrode reactions and lifetime *** effective way to decrease Pt loading is the adoption of supports to enhance both Pt dispersion and its *** of the carbon-based support was identified to be the major contributor to performance degradation as they suffer from parasitic oxidation to CO_(2)(at the cathode).Therefore,there is a significant interest in exploring stable alternatives to replace carbon supports in *** metal carbides(TmCs)have attracted significant attention over the last several years as a possible candidate to replace carbon-based catalyst supports in fuel *** these advantages over carbon supports,the large-scale deployment of TmC-based supports in fuel cells is still hindered by concerns of durability at the high potential on the cathode during start-up and shutdown ***,we address the most relevant studies concerning TmCs as supports for acidic oxygen reduction reaction(ORR)catalysis,including viewpoints about the surface and bulk design of the support,as well as the design of the catalyst itself to enhance the interaction and dispersion with the support.

关键词： carbides fuel cells catalysis durability corrosion