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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： ha.sa. 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

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SYNTHESIS OF SOLUBLE POLY(3,4-DIHYDROXY-o-TOLYLENE):REDOX POLYmER

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Chinese Journal of Polymer Science 2006年第1期24卷 41-46页

作者： sad moulay Fatima m'zyène Laboratoire de Chimie-Physique moléculaire et macromoléculaire Faculté des Sciences de l'Ingénieur Département de Chimie Industrielle Université de BlidaRoute de SoumèaB.P.270Blida 09000Algeria. Laboratoire de Chimie-Physique moléculaire et macromoléculaire Faculté des Sciences de l'Ingénieur Département de Chimie Industrielle Université de BlidaRoute de SoumaB.P.270Blida 09000Algeria.

Conventional chloromethylation, paraformaldehyde/hydrogen chloride in acetic acid medium, was applied to 1,2- dimethoxybenzene. Chloroform-soluble poly（3,4-dimethoxy-o-tolylene） was obtained with an intrinsic viscosity of 0.034 dL g^-1. The polymer was evaluated as a condensation redox polymer precursor formed by a Friedel-Crafts reaction. Cleavage of the methoxy groups present in this polymer resulted in poly（3,4-dihydroxy-o-tolylene） which manifested a great air-oxidation resistance. The redox property of the latter polymer was found to be 1017 mV by potentiometric titration with 0.05 N ceric ammonium nitrate at 25℃. This midpotential was compared to that of catechol, a monomeric analogue, under the same titration conditions.

关键词： Poly(3,4-dimethoxy-o-tolylene) Poly(3,4-dihydroxy-o-tolylene) Redox polymer.

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Effects of human disturbance on nest placement of the woodpigeon (Columba palumbus): a case study from the middle Atlas, morocco

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Integrative Zoology 2014年第3期9卷 349-359页

作者： saâd haNANE Forest Research Center High Commissariat for WaterForests and Desertification ControlRabat-AgdalMorocco

The woodpigeon(Columba palumbus)is a common and widespread bird in morocco(North Africa).I examined,over 2 years(2010 and 2011),the breeding density and nest placement of this game species in relation to nest site habitat and degree of human *** study area was in the middle Atlas Tighboula mountain forest,morocco,in a disturbed and an undisturbed *** data collected in the 2 study sites,I aimed to identify the factors influencing the placement of nests within holm oak trees(Quercus rotundifolia)and their densities.I found that habitat structures,influenced by grazing disturbance,have affected nesting density and the location of nests of this *** place their nests in a higher position(3.42±0.19 m)when disturbance intensity is high and lower(1.68±0.1 m)when disturbance intensity is low,and show higher nesting density in less disturbed zone(3.1±0.4 nests/ha)than in highly disturbed zones(1.4±0.2 nests/ha).Grazing disturbance could pose a threat to population persistence at a broader scale and could potentially reduce the abundance of this species by altering the composition and the structure of the forest nesting *** multi-scale studies are needed to assess the effects of different levels of grazing disturbance on woodpigeon nest density and placement,and to enhance our knowledge of the breeding behavior of this game species under variable environments.

关键词： breeding density Columba palumbus holm oak middle Atlas morocco nest location woodpigeon

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Changes in plant community diversity and aboveground biomass along with altitude within an alpine meadow on the Three-River source region

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Chinese Science Bulletin 2012年第27期57卷 3573-3577页

作者： sa WenJun AN LiZhe sa Wei Institute of Botany Science School of Life SciencesLanzhou UniversityLanzhou 730000China School of Life Science Qinghai UniversityXining 810008China

The grassland is an important component of terrestrial ecosystems and plays a significant role in biodiversity and ecosystem *** the present study,the changes of plant species diversity and aboveground biomass productivity were examined along with the altitude in natural alpine grassland in the source region of three rivers on the Qinghai-Tibetan *** experimental locations were selected with altitudes ranging from 3862 to 4450 m above sea level(a.s.l.).The results indicated that Kobresia pygmaea meadow,Kobresia humilis meadow and salix cupularis shrub meadow had higher indices of diversity and aboveground *** distribution of species diversity,richness and aboveground biomass showed similarly unimodal patterns across the altitude gradient with the highest indices appeared at mid-altitudes *** changing trend of species diversity,richness and evenness also showed significant unimodal patterns with total aboveground biomass,and the highest species diversity occurred at intermediate level of *** research would provide a valuable reference for the protection of grassland biodiversity and maintaining of the grazing ecosystem function in the source region of the Three Rivers.

关键词：植物群落多样性地上生物量海拔高度高寒草甸三江源地区植物物种多样性生态系统功能生物多样性

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Coprophilous contributions to the phylogeny of Lasiosphaeriaceae and allied taxa within Sordariales(Ascomycota,Fungi)

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Fungal Diversity 2015年第1期70卷 101-113页

作者： Åsa Kruys sabine m.Huhndorf Andrew N.miller Systematic Biology Department of Organismal BiologyEvolutionary Biology CentreUppsala UniversityNorbyvägen 18DSE-75236 UppsalaSweden Botany Department Field MuseumChicagoIL 60605USA Illinois Natural History Survey University of IllinoisChampaignIL 61820US

The phylogenetic relationships of Lasiosphaeriaceae are complicated in that the family is paraphyletic and includes Sordariaceae and Chaetomiaceae,as well as several polyphyletic *** study focuses on the phylogenetic relationships of the coprophilous genera,Anopodium,Apodospora,Arnium,Fimetariella and *** are traditionally circumscribed based on ascospore characters,which have proven homoplasious in other genera within the *** results based on LSU nrDNA andß–tubulin sequences distinguish four lineages of Lasiosphaeriaceae *** joins the clade of mor-phologically similar,yellow-pigmented species of Cercophora and *** is monophyletic and joins a larger group of taxa with unclear affinities to each other,while Arnium is polyphyletic being scattered throughout three of the four major clades of *** is represented by a single collection and joins the clade containing Cercophora scortea and Podospora *** shows affinities to the Lasiosphaeris *** on a combination of morphological and molecular data,Echria *** recognized at the genus level for the former Arnium section and two new combinations are proposed:*** and ***.

关键词： Ascomal wall Ascomycete β-tubulin LSU nrDNA Systematics,Taxonom

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Laser irradiation effects and its possible mechanisms of action on spermatozoa functions in domestic animals

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Asian pacific Journal of Reproduction 2017年第3期6卷 97-103页

作者： Lone sa mohanty TK Kumaresan A Bhakat m Artificial Breeding Research Centre ICAR-National Dairy Research InstituteKarnal132001HaryanaIndia Livestock Research Centre ICAR-National Dairy Research InstituteKarnal132001HaryanaIndia

This article presents a review pertains the laser irradiation effects and its possible mechanisms of action on spermatozoa functions in domestic animals. To improve artificial insemination, laser is sensitive and cost effective technique, when compared to other conventional methods. Laser may have both positive and negative effects on spermatozoa functions. Since the effects of light are mediated by reactive oxygen species, and the levels of these reactive oxygen species following irradiating spermatozoa with laser may be responsible for determining the effects of laser on sperm. Dose of laser may be regarded as of great significance and this dosage of laser may be responsible for determining its effects on spermatozoa. Optimum dosage of laser for improving seminal attributes may vary among various species and this need to be standardized in each of them. The beneficial effects include improving sperm livability, acrosomal integrity, hypo-osmotic swelling response, mitochondrial function and computer-aided sperm analysis parameters. The increase in cytochrome c oxidase activity, ATP levels and mitochondrial membrane potential, in laser irradiated cells may be responsible for enhanced sperm quality parameters. Improving fertility with laser irradiated spermatozoa has been reported in few species like boar and need to be elaborated in other species. In conclusion laser may be regarded as an easy, cheap and time saving technology for improving artificial insemination;in addition, laser may have various potential applications in the field of reproductive biotechnology as well as in livestock farms and veterinary polyclinics.

关键词： Laser Irradiation Spermatozoa Function mechanism

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salinity Distribution at Canal Istanbul and Its Possible Impacts on the Northern marmara Sea

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China Ocean Engineering 2020年第6期34卷 881-888页

作者： Şehriban saÇU Tarkan ERDIK OlgayŞEN Istanbul Technical University MaslakIstanbul 34467Turkey

Turkey has announced its plan to construct a new waterway, Canal Istanbul, parallel to the Bosphorus. In this study,the influence of Canal Istanbul on salinity distribution in the northern marmara Sea is investigated using a previously calibrated 3 D hydrodynamic and salinity model. moreover, the salinity field of the canal and its propagation are examined based on various meteorological cases. Finally, the flow structure of the canal is determined. It is calculated that at the southern end of the canal, mainly unidirectional flow(from the Black Sea to the marmara Sea)occurs during 68% of the simulation period. A two-layer flow is seen only 28% of the time with a weak lower layer flow, whereas this value decreases to 4% at the north end of the canal. In the southward direction(to the marmara Sea), velocities higher than 1.5 m/s are rarely observed along the canal. The average surface salinity difference in the northern marmara Sea due to the construction of the canal is calculated to be smaller than 0.50 ppt. The salinity difference gradually diminishes as water depth increases and after 25 m(from the surface) almost no difference is observed.

关键词： Canal Istanbul marmara Sea salinity distribution hydrodynamic modeling

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Computational Prediction of micro RNAs from Toxoplasma gondii Potentially Regulating the Hosts' Gene Expression

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Genomics, Proteomics & Bioinformatics 2014年第5期12卷 228-238页

作者： müs?erref Duygu saar Caner Bagc? Jens Allmer molecular Biology and Genetics Izmir Institute of Technology Urla Izmir 35430 Turkey Biotechnology Izmir Institute of Technology Urla Izmir 35430 Turkey Bionia Incorporated IZTEKGEB A8 Urla Izmir 35430 Turkey

microRNAs （miRNAs） were discovered two decades ago, yet there is still a great need for further studies elucidating their genesis and targeting in different phyla. Since experimental discovery and validation of miRNAs is difficult, computational predictions are indispensable and today most computational approaches employ machine learning. Toxoplasma gondii, a parasite residing within the cells of its hosts like human, uses miRNAs for its post-transcriptional gene reg- ulation. It may also regulate its hosts＇ gene expression, which has been shown in brain cancer. Since previous studies have shown that overexpressed miRNAs within the host are causal for disease onset, we hypothesized that T. gondii could export miRNAs into its host cell. We computationally predicted all hairpins from the genome of T. gondii and used mouse and human models to filter possible candidates. These were then further compared to known miRNAs in human and rodents and their expression was examined for T. gondii grown in mouse and human hosts, respectively. We found that among the millions of potential hairpins in T. gondii, only a few thousand pass filtering using a human or mouse model and that even fewer of those are expressed. Since they are expressed and differentially expressed in rodents and human, we suggest that there is a chance that T. gondii may export miRNAs into its hosts for direct regulation.

关键词： Toxoplasma gondii microRNA Regulation Host interaction Parasite

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Seasonal variability in CDOm absorption and fluorescence properties in the Barataria Basin,Louisiana,Usa

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Journal of Environmental Sciences 2010年第10期22卷 1481-1490页

作者： Shatrughan Singh Eurico D'sa Erick Swenson Department of Oceanography and Coastal Sciences Louisiana State University

Absorption and fluorescence properties of chromophoric dissolved organic matter （CDOm） along a 124 km transect in the Barataria Basin, a large estuary located in Louisiana, Usa, were investigated during high and low flow periods of the mississippi River in the spring and winter of 2008-2009. mean CDOm absorption at 355 nm from the marine to the freshwater end member stations ranged from （3.25 ± 0.56） to （20.76 ± 2.43） m^-1 for the three month high flow period whereas it varied from （1.48 ± 1.08） to （25.45 ± 7.03） m^-1 for the same stations during low flow period. Corresponding salinity values at these stations indicated the influence of river and shelf exchanges in the lower basin and precipitation and runoff in the upper basin. An inverse relationship of CDOm absorbance and fluorescence with salinity observed in the basin could he a useful indicator of salinity. CDOm fluorescence also varied over a large range showing an approximately 8 to 12-fold increase between the marine and freshwater end members for the two flow seasons. Excitation-emission matrix spectral plots indicated the presence of various fluorescence components with highest being the A-peak, lowest the T-peak, and the C and m-peaks showing similar trends along the transect. During low flow season the A/C ratio were well correlated with station locations indicating increased terrestrial influence towards the upper basin. CDOm absorption and fluorescence at 355 nm were highly correlated and independent of CDOm sources suggesting that fluorescence could be used to characterize CDOm in the basin.

关键词： Barataria Basin chromophoric dissolved organic matter CDOm fluorescence excitation-emission matrix

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Analysis and optimal synthesis of single loop spatial mechanisms

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Journal of Zhejiang University-Science A(Applied Physics & Engineering) 2011年第9期12卷 665-679页

作者： med Amine LARIBI Lotfi ROmDhaNE sad ZEGHLOUL Laboratoire de Génie mécanique LAB-MA-05 Ecole Nationale d'Ingénieurs de Sousse Institut Pprime-UPR 3346 CNRS-Université de Poitiers-ENSMA Département Génie Mécanique et Systémes Complexes SP2MIBP30179 86962 Futuroscope France

In this work, a systematic approach is presented to obtain the input-output equations of a single loop 4-bar spatial mechanisms. The dialytic method along with Denavit-hartenberg parameters can be used to obtain these equations efficiently. A genetic algorithm （GA） has been used to solve the problem of spatial mechanisms synthesis. Two types of mechanisms, e.g., RSCR and RSPC （R： revolute; S： spherical; C： cylindrical; P： prismatic）, have illustrated the application of the GA to solve the problem of function generation and path generation. In some cases, the GA method becomes trapped in a local minimum. A combined GA-fuzzy logic （GA-FL） method is then used to improve the final result. The results show that GAs, combined with an adequate description of the mechanism, are well suited for spatial mechanism synthesis problems and have neither difficulties inherent to the choice of the initial feasible guess, nor a problem of convergence, as it is the case for deterministic methods.

关键词： Spatial mechanisms Genetic algorithm-fuzzy logic (GA-FL) method Denevit-hartenberg parameters mechanism synthesis

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