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Leukemic stromal hematopoietic microenvironment negatively regulates the normal hematopoiesis in mouse model of leukemia

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Chinese Journal of Cancer 2010年第12期29卷 969-979页

作者： Pratima Basak Sumanta Chatterjee Prosun Das Madhurima Das Jacintha Archana Pereira Ranjan Kumar Dutta Malay Chaklader Samaresh Chaudhuri sujata law Department of Biochemistry and Medical Biotechnology Stem Cell Research and Application Unit Calcutta School of Tropical Medicine

Background and Objective: Leukemic microenvironment has a major role in the progression of leukemia. Leukemic cells can induce reversible changes in microenvironmental components, especially the stromal function which results in improved growth conditions for maintaining the malignant leukemic cells. This study aimed to investigate the survival advantage of leukemic cells over normal hematopoietic cells in stromal microenvironment in long term. Methods: The mice were injected intraperitoneally with N-N’ ethylnitrosourea (ENU) to induce leukemia; the mice received injection of normal saline were used as control. At 180 days after ENU induction, the mice were killed and the bone marrows were cultured for 19 days. Colony-forming assays were used to analyze the formation of various cell colonies. The expression of Sca-1, CD146, VEGFR2, CD95, pStat3, pStat5, and Bcl-xL in marrow cells were detected by flow cytometry. Results: Long-term leukemic bone marrow culture showed abnormal elongated stromal fibroblasts with almost absence of normal hematopoietic cells. Adherent cell colonies were increased, but CFU-F and other hematopoietic cell colonies were significantly decreased in leukemia group (P< 0.001). Primitive progenitor-specific Sca-1 receptor expression was decreased with subsequent increased expression of CD146 and VEGFR-2 in leukemic bone marrow cells. Decreased Fas antigen expression with increased intracellular pStat3, pStat5 and Bcl-xL proteins were observed in leukemic bone marrow cells. Conclusions: Stromal microenvironment shows altered morphology and decreased maturation in leukemia. Effective progenitor cells are decreased in leukemia with increased leukemia-specific cell population. Leukemic microenvironment plays a role in promoting and maintaining the leukemic cell proliferation and survivability in long term.

关键词：白血病细胞环境基质造血功能小鼠负调控造血微环境骨髓细胞集落形成

Use of subword tokenization for domain generation algorithm classification

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Cybersecurity 2024年第2期7卷 1-12页

作者： Sea Ran Cleon Liew Ngai Fong law University of Waterloo WaterlooCanada Department of Electrical and Electronic Engineering The Hong Kong Polytechnic UniversityKowloonHong Kong

Domain name generation algorithm(DGA)classification is an essential but challenging *** feature-extract-ing machine learning(ML)methods and deep learning(DL)models such as convolutional neural networks and long short-term memory have been ***,the performance of these approaches varies with different types of *** features in the ML methods can characterize random-looking DGAs better than Word-looking *** improve the classification performance on word-looking DGAs,subword tokenization is employed for the DL *** experimental results proved that the subword tokenization can provide excellent classification performance on the word-looking *** then propose an integrated scheme that chooses an appropriate method for DGA classification depending on the nature of the *** show that the integrated scheme outperformed existing ML and DL methods,and also the subword DL methods.

关键词： Botnet detection Domain names Network security Machine learning-based botnet detection

Targeting calcium signaling in Alzheimer’s disease: challenges and promising therapeutic avenues

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Neural Regeneration Research 2024年第3期19卷 501-502页

作者： LinLin Song YongPei Tang Betty Yuen Kwan law Neher’s Biophysics Laboratory for Innovative Drug Discovery State Key Laboratory of Quality Research in Chinese MedicineMacao University of Science and TechnologyMacao Special Administration RegionChina

The critical role of calcium dyshomeostasis in the pathogenesis of Alzheimer’s disease(AD):AD is a progressive neurodegenerative disease characterized by cognitive decline,memory impairment,and behavioral *** an estimated 50 million people being affected worldwide,the incidence of AD is constantly increasing *** hallmark of AD is the accumulation of amyloid-beta protein(Aβ)in the form of amyloid plaques and hyperphosphorylated tau protein in the form of neurofibrillary ***,increasing evidence suggests that calcium ion(Ca2+)dysregulation also plays a crucial role in the pathogenesis of AD(Calvo-Rodriguez and Bacskai,2021).As a key second messenger,Ca2+regulates a wide range of cellular processes,including the release of neurotransmitters,gene expression,and cell ***^(2+)also regulates the activity of Calcium/calmodulin-dependent protein kinase II,which is critical for synaptic plasticity,learning,and memory(Kaushik et al.,2022).Alternation in the Ca^(2+)signal is an early event in the pathogenesis of AD,which can lead to synaptic dysfunction,neuronal loss,and cognitive impairment.

关键词： Alzheimer homeostasis globally

Supergravity effects on flame propagation and structure in hydrogen/air mixtures

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Acta Mechanica Sinica 2024年第6期40卷 31-38页

作者： Wenkai Liang Chung K.law Center for Combustion Energy Department of Energy and Power EngineeringTsinghua UniversityBeijing100080China Department of Mechanical and Aerospace Engineering Princeton UniversityPrinceton08544USA

In the current work,we investigated hydrogen/air flame propagation under supergravity *** show that when gravity is in the same/opposite direction as flame propagation,it leads to acceleration/deceleration of the flame,and that such an effect could substantially modify the flame propagation and structure at high gravity ***,for the absolute and relative flame propagation speeds,the gravity-affected flame speed shows opposite trends as the absolute flame speed is more affected by the local induced flow field,while the relative flame speeds are controlled by the super-adiabatic or sub-adiabatic flame *** gravity-affected thermal and chemical flame structures are also examined through the influence of the mixture equivalence ratio,pressure,and flame stretch.

关键词： Supergravity Flame acceleration Laminar flame speed Flame stretch Hydrogen

Interactions between maternal parity and feed additives drive the composition of pig gut microbiomes in the post‑weaning period

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Journal of Animal Science and Biotechnology 2024年第3期15卷 1241-1257页

作者： Kayla law Eduardo Rosa Medina Garcia Chad Hastad Deborah Murray Pedro E.Urriola Andres Gomez Department of Animal Science University of Minnesota1364 Eckles AvenueSaint PaulMN 55108USA New Fashion Pork 164 Industrial ParkwayJacksonMN 56143USA

Background Nursery pigs undergo stressors in the post-weaning period that result in production and welfare *** challenges disproportionately impact the offspring of primiparous sows compared to those of mul-tiparous *** is known regarding potential interactions between parity and feed additives in the post-weaning period and their effects on nursery pig ***,the objective of this study was to investigate the effects of maternal parity on sow and offspring microbiomes and the influence of sow parity on pig fecal microbi-ome and performance in response to a prebiotic *** weaning,piglets were allotted into three treat-ment groups:a standard nursery diet including pharmacological doses of Zn and Cu(Con),a group fed a commercial prebiotic only(Preb)based on an Aspergillus oryzae fermentation extract,and a group fed the same prebiotic plus Zn and Cu(Preb+ZnCu).Results Although there were no differences in vaginal microbiome composition between primiparous and mul-tiparous sows,fecal microbiome composition was different(R^(2)=0.02,P=0.03).The fecal microbiomes of primiparous offspring displayed significantly higher bacterial diversity compared to multiparous offspring at d 0 and d 21 post-weaning(P<0.01),with differences in community composition observed at d 21(R^(2)=0.03,P=0.04).When analyzing the effects of maternal parity within each treatment,only the Preb diet triggered significant microbiome distinc-tions between primiparous and multiparous offspring(d 21:R^(2)=0.13,P=0.01;d 42:R^(2)=0.19,P=0.001).Composi-tional differences in pig fecal microbiomes between treatments were observed only at d 21(R^(2)=0.12,P=0.001).Pigs in the Con group gained significantly more weight throughout the nursery period when compared to those in the Preb+ZnCu *** Nursery pig gut microbiome composition was influenced by supplementation with an Aspergillus oryzae fermentation extract,with varying effects on performance

关键词： Aspergillus prebiotic Copper Feed additives Maternal Nursery pig microbiome Parity Swine microbiome Trace minerals Zinc

A Multi-Channel CMOS Analog Front-End Interface IC with 157.8 d B Current Detection Dynamic Range

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Chinese Journal of Electronics 2024年第2期33卷 393-402页

作者： Kunyu WANG Wenjing XU Chengbin ZHANG Yanjun YANG Man-Kay law Li ZHOU Jie CHEN Ming CHEN Institute of Microelectronics of the Chinese Academy of Science University of Chinese Academy of Sciences Zunyi Normal University Institute of Microelectronics and Dept.of ECE FST University of Macau

A high dynamic range and low-noise CMOS(complementary metal-oxide-semiconductor transistor)front-end interface integrated circuit(IC) with multi-channel detection is presented in this paper. Two different current detection channels, composed of a trans-impedance amplifier(TIA) and an integrator-differentiator TIA, are used to boost the current detection range. A capacitance-coupled instrument amplifier(CCIA) is also included to realize high precision voltage detection. A fourth-order sigma-delta modulator using a second-order loop filter and a second-order noise shaping integral quantizer is adopted to realize effective number of bits above 16 bits. The presented interface IC is implemented in 0.18-μm CMOS process with supply voltage of 3.3 V, and a proto-type electrochemical sensor platform with miniaturized sensor array is developed to verify the functionality of the interface IC. Measurement results indicate that the designed interface IC achieves 157.8 d B current detection dynamic range, and the measured input-referred current noise and voltage noise floor are 1.04 p A and 58.4 n V within 10 k Hz integration bandwidths,respectively.

关键词： Integrated circuits Sigma-delta modulation Semiconductor device measurement Voltage measurement Current measurement Noise Bandwidth

Mass-Based Environmental Factor and Energy Assessment of Microwave-Assisted Synthesized Transition Metal Nanostructures

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American Journal of Analytical Chemistry 2024年第6期15卷 201-218页

作者： Victor J. law School of Mechanical and Materials Engineering University College Dublin Dublin Ireland

This paper describes mass-based energy phase-space projection of microwave-assisted synthesis of transition metals (zinc oxide, palladium, silver, platinum, and gold) nanostructures. The projection uses process energy budget (measured in kJ) on the horizontal axes and process density (measured in kJg−1) on the vertical axes. These two axes allow both mass usage efficiency (Environmental-Factor) and energy efficiency to be evaluated for a range of microwave applicator and metal synthesis. The metrics are allied to the: second, sixth and eleventh principle of the twelve principle of Green Chemistry. This analytical approach to microwave synthesis (widely considered as a useful Green Chemistry energy source) allows a quantified dynamic environmental quotient to be given to renewable plant-based biomass associated with the reduction of the metal precursors. Thus allowing a degree of quantification of claimed “eco-friendly” and “sustainable” synthesis with regard to waste production and energy usage.

关键词： Microwave-Assisted Synthesis Transition Metals Nanostructures Allometry Scaling Power-law Signature Green Chemistry

Mitophagy and cGAS-STING crosstalk in neuroinflammation

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3327-3361页

作者： Xiaogang Zhou Jing Wang Lu Yu Gan Qiao Dalian Qin Betty Yuen-Kwan law Fang Ren Jianming Wu Anguo Wu Sichuan Key Medical Laboratory of New Drug Discovery and Drugability Evaluation Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia MedicaKey Laboratory of Medical Electrophysiology of Ministry of EducationSchool of PharmacySouthwest Medical UniversityLuzhou 646000China State Key Laboratory of Quality Research in Chinese Medicine Macao University of Science and TechnologyMacao SAR 999078China Chongqing Key Laboratory of Sichuan-Chongqing Co-construction for Diagnosis and Treatment of Infectious Diseases Integrated Traditional Chinese and Western Medicine Chongqing Traditional Chinese Medicine HospitalChongqing 400021China

Mitophagy,essential for mitochondrial health,selectively degrades damaged *** is intricately linked to the cGAS-STING pathway,which is crucial for innate *** pathway responds to mitochondrial DNA and is associated with cellular stress *** review explores the molecular details and regulatory mechanisms of mitophagy and the cGAS-STING *** critically evaluate the literature demonstrating how dysfunctional mitophagy leads to neuroinflammatory conditions,primarily through the accumulation of damaged mitochondria,which activates the cGAS-STING *** activation prompts the production of pro-inflammatory cytokines,exacerbating *** review emphasizes the interaction between mitophagy and the cGAS-STING *** mitophagy may suppress the cGAS-STING pathway,offering protection against ***,impaired mitophagy may activate the cGAS-STING pathway,leading to chronic ***,we explored how this interaction influences neurodegenerative disorders,suggesting a common mechanism underlying these *** conclusion,there is a need for additional targeted research to unravel the complexities of mitophagy-cGAS-STING interactions and their role in *** review highlights potential therapies targeting these pathways,potentially leading to new treatments for neuroinflammatory and neurodegenerative *** synthesis enhances our understanding of the cellular and molecular foundations of neuroinflammation and opens new therapeutic avenues for neurodegenerative disease research.

关键词： Neuroinflammation Mitophagy cGAS-STING Innate immunity Mitochondrial DNA Crosstalk Therapeutic avenues Neurodegenerative diseases

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灵光独耀:沈宗灵与中国法理学

中国法律评论 2024年第4期 149-154页

作者： Peking University law School 北京大学法学院

在其诸多弟子的追忆中,沈宗灵先生一生专心治学、淡泊名利,由此常常对世事保持一种有意的疏离。“灵光独耀,迥脱根尘”,或许便是这位法理学大家的灵魂写照。壹“经国济民”:沈宗灵的早年岁月1923年2月24日,沈宗灵出生于浙江杭州的一个... 详细信息

在其诸多弟子的追忆中,沈宗灵先生一生专心治学、淡泊名利,由此常常对世事保持一种有意的疏离。“灵光独耀,迥脱根尘”,或许便是这位法理学大家的灵魂写照。壹“经国济民”:沈宗灵的早年岁月1923年2月24日,沈宗灵出生于浙江杭州的一个商人家庭,后随家人迁居上海。

关键词：沈宗灵淡泊名利法理学浙江杭州灵光