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Targeting NAD Metabolism for the Therapy of Age-Related Neurodegenerative Diseases

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Neuroscience Bulletin 2024年第2期40卷 218-240页

作者： Feifei Li Chou wu Gelin Wang School of Pharmaceutical Sciences Ministry of Education Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical BiologyTsinghua UniversityBeijing 100084China Tsinghua-Peking Joint Center for Life Sciences Tsinghua UniversityBeijing 100084China

As the aging population continues to grow rapidly, age-related diseases are becoming an increasing burden on the healthcare system and a major concern for the well-being of elderly individuals. While aging is an inevitable process for all humans, it can be slowed down and age-related diseases can be treated or alleviated. Nicotinamide adenine dinucleotide (NAD) is a critical coenzyme or cofactor that plays a central role in metabolism and is involved in various cellular processes including the maintenance of metabolic homeostasis, post-translational protein modifications, DNA repair, and immune responses. As individuals age, their NAD levels decline, and this decrease has been suggested to be a contributing factor to the development of numerous age-related diseases, such as cancer, diabetes, cardiovascular diseases, and neurodegenerative diseases. In pursuit of healthy aging, researchers have investigated approaches to boost or maintain NAD levels. Here, we provide an overview of NAD metabolism and the role of NAD in age-related diseases and summarize recent progress in the development of strategies that target NAD metabolism for the treatment of age-related diseases, particularly neurodegenerative diseases.

关键词： Ageing Neuroprotection NAD metabolism Therapeutic strategy Neurodegenerative diseases

Demixing microwave signals using system-on-chip photonic processor

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Light(Science & Applications) 2024年第3期13卷 399-401页

作者： Sheng Gao Chu wu Xing Lin Department of Electronic Engineering Tsinghua University100084 BeijingChina Beijing National Research Center for Information Science and Technology Tsinghua University100084 BeijingChina

The integrated photonic processor,co-packaged with electronic peripherals,is proposed for blind source separation of microwave signals,which separates signal-of-interest from dynamic interference with real-time adapta... 详细信息

关键词： processor microwave mixing

Flotation separation of scheelite from calcite using luteolin as a novel depressant

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International Journal of Minerals,Metallurgy and Materials 2024年第3期31卷 462-472页

作者： Xiaokang Li Ying Zhang Haiyang He Yu wu Danyu wu Zhenhao Guan Faculty of Land and Resources Engineering Kunming University of Science and TechnologyKunming 650093China State Key Laboratory of Clean Utilization of Complex Non-Ferrous Metal Resources Kunming University of Science and TechnologyKunming 650093China

This paper proposes luteolin(LUT)as a novel depressant for the flotation-based separation of scheelite and calcite in a sodium oleate(NaOL)system.The suitability of LUT as a calcite depressant is confirmed through micro-flotation testing.At pH=9,with LUT concentration of 50 mg·L^(-1) and NaOL concentration of 50 mg·L^(-1),scheelite recovery reaches 80.3%.Calcite,on the other hand,exhibits a recovery rate of 17.6%,indicating a significant difference in floatability between the two minerals.Subsequently,the surface modifica-tions of scheelite and calcite following LUT treatment are characterized using adsorption capacity testing,Zeta potential analysis,Fourier transform infrared spectroscopy(FT-IR),X-ray photoelectron spectroscopy(XPS),and atomic force microscopy(AFM).The study in-vestigates the selective depressant mechanism of LUT on calcite.Adsorption capacity testing and Zeta potential analysis demonstrate sub-stantial absorption of LUT on the surface of calcite,impeding the further adsorption of sodium oleate,while its impact on scheelite is min-imal.FT-IR and XPS analyses reveal the selective adsorption of LUT onto the surface of calcite,forming strong chemisorption bonds between the hydroxyl group and calcium ions present.AFM directly illustrates the distinct adsorption densities of LUT on the two miner-al types.Consequently,LUT can effectively serve as a depressant for calcite,enabling the successful separation of scheelite and calcite.

关键词： scheelite calcite luteolin flotation depressant separation

Complicated target recognition by archaeal box C/D guide RNAs

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Science China(Life Sciences) 2024年第4期67卷 631-644页

作者： Jiayin Wang Songlin wu Keqiong Ye Key Laboratory of RNA Science and Engineering CAS Center for Excellence in BiomacromoleculesInstitute of BiophysicsChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China

Box C/D RNAs guide the site-specific formation of 2′-O-methylated nucleotides(Nm)of RNAs in eukaryotes and archaea.Although C/D RNAs have been profiled in several archaea,their targets have not been experimentally determined.Here,we mapped Nm in r RNAs,t RNAs,and abundant small RNAs(s RNAs)and profiled C/D RNAs in the crenarchaeon Sulfolobus islandicus.The targets of C/D RNAs were assigned by analysis of base-pairing interactions,in vitro modification assays,and gene deletion experiments,revealing a complicated landscape of C/D RNA-target interactions.C/D RNAs widely use dual antisense elements to target adjacent sites in r RNAs,enhancing modification at weakly bound sites.Two consecutive sites can be guided with the same antisense element upstream of box D or D′,a phenomenon known as doublespecificity that is exclusive to internal box D′in eukaryotic C/D RNAs.Several C/D RNAs guide modification at a single non-canonical site.This study reveals the global landscape of RNA-guided 2′-O-methylation in an archaeon and unexpected targeting rules employed by C/D RNA.

关键词： C/D RNA 2′-O-methylation archaea guide RNA RNA modification

Phase-field lattice-Boltzmann study on fully coupled thermal-solute-convection dendrite growth of Al-Cu alloy

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China Foundry 2024年第2期21卷 125-136页

作者： Yin-qi Qiu Meng-wu wu Xun-peng Qin Shou-mei Xiong Hubei Key Laboratory of Advanced Technology for Automotive Components Wuhan University of TechnologyWuhan 430070China Hubei Longzhong Laboratory Xiangyang 441000HubeiChina School of Materials Science and Engineering Tsinghua UniversityBeijing 100084China

Dendrite growth is a complex liquid-solid phase transition process involving multiple physical factors.A phase-field lattice-Boltzmann method was developed to simulate the two-and three-dimension dendrite growth of Al-Cu alloy.The effect of fully coupled thermal-solute-convection interaction on the dendrite growth was investigated by incorporating a parallel-adaptive mesh refinement algorithm into the numerical model.By accurately reproducing the latent heat release,solute diffusion and convective transport behaviors at the liquidsolid interface,the interaction mechanism among thermal-solute-convection transport as well as their coupling effects on the dendrite growth dynamics were discussed.The simulation results show that the release of latent heat slows down the dendrite growth rate,and both natural and forced convection disrupt the symmetrical growth of dendrites.Their combination makes the growth of dendrites more complex,capturing important physical aspects such as recalescence,dendrite tip splitting,dendrite tilting,dendrite remelting,and solute plume in the simulation case.Based on the robustness and powerful ability of the numerical model,the formation mechanisms of these physical aspects were revealed.

关键词： simulation phase field dendrite growth thermal-solute-convection interaction

Discovering deaminases using AlphaFold2:a strategy to search for tool proteins for gene editing

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Signal Transduction and Targeted Therapy 2024年第3期9卷 822-824页

作者： Yongye Huang Jianxin Jiang Min wu Key Laboratory of Bioresource Research and Development of Liaoning Province College of Life and Health SciencesNortheastern UniversityShenyang 110169China Wound Trauma Medical Center State Key Laboratory of TraumaBurns and Combined InjuryDaping HospitalArmy Medical UniversityChongqing 400042China Wenzhou Traditional Chinese Medicine Hospital of Zhejiang Chinese Medical University WenzhouZhejiang 325000China Wenzhou Institute University of Chinese Academy of SciencesWenzhou 325000China The Joint Research Center Affiliated Xiangshan Hospital of Wenzhou Medical UniversityNingboChina

A recent study by Huang et al.published in Cell reported the application of AlphaFold2 to forecast the structures of deaminase proteins and cluster them based on structural similarity,creating a truncated Sdd that can be used as a cytosine base editor(CBE)to be integrated into a single adeno-associated virus(AAV)1 This ground-breaking study aided by the artificial intelligence system would largely broaden the utility of tool proteins for gene editing.

关键词： CBE Alpha editor

Ultrafast optical modulation of the fluorescence from a single-photon emitter in silicon carbide

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Photonics Research 2024年第5期12卷 941-946页

作者： MENGTING HE YUJING CAO JUNJIE LIN ZHIPING JU BOTAO wu E wu State Key Laboratory of Precision Spectroscopy East China Normal UniversityShanghai 200241China Photon Technology(Zhejiang)Co. Ltd.Jiaxing 314100China National Key Laboratory of Materials for Integrated Circuits Shanghai Institute of Microsystem and Information TechnologyChinese Academy of SciencesShanghai 200000China Department of Physics and Shanghai Key Laboratory for Magnetic Resonance East China Normal UniversityShanghai 200241China Chongqing Key Laboratory of Precision Optics Chongqing Institute of East China Normal UniversityChongqing 401120China Collaborative Innovation Center of Extreme Optics Shanxi UniversityTaiyuan 030006China

The quest for the room-temperature optical transistor based on nonlinearities in single atoms or molecules is attracting a lot of attention.In this work,a single-photon emitter in cubic silicon carbide is verified that can operate as an optical switch at room temperature under pulsed green laser illumination with a near-infrared pulsed laser as the control gate.We demonstrated an ultrafast and reversible optical modulation with a high photoluminescence intensity suppression ratio up to 97.9%and a response time as short as 287.9±5.7 ps.The current development provides insights for high-precision and ultrafast optical switches,with possibilities for integration with emerging electronic installations to realize more intelligent photoelectric integrated devices.

关键词： emitter carbide photon

Functionalized selenium nanoparticles ameliorated acetaminophen-induced hepatotoxicity through synergistically triggering PKCδ/Nrf2 signaling pathway and inhibiting CYP 2E1

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Food Science and Human Wellness 2024年第2期13卷 932-945页

作者： Si Zou Yetao Gong Xiujie Li Yanbin wu Jinzhong wu Jianguo wu Ka-Hing Wong College of Pharmacy Fujian University of Traditional Chinese MedicineFuzhou 350122China Research Institute for Future Food The Hong Kong Polytechnic UniversityHong Kong 999077China Department of Food Science and Nutrition The Hong Kong Polytechnic UniversityHong Kong 999077China

Selenium nanoparticles(SeNPs)have been demonstrated potential for use in diseases associated with oxidative stress.Functionalized SeNPs with lower toxicity and higher biocompatibility could bring better therapeutic activity and clinical application value.Herein,this work was conducted to investigate the protective effect of Pleurotus tuber-regium polysaccharide-protein complex funtionnalized SeNPs(PTR-SeNPs)against acetaminophen(APAP)-induced oxidative injure in HepG2 cells and C57BL/6J mouse liver.Further elucidation of the underlying molecular mechanism,in particular their modulation of Nrf2 signaling pathway was also performed.The results showed that PTR-SeNPs could significantly ameliorate APAP-induced oxidative injury as evidenced by a range of biochemical analysis,histopathological examination and immunoblotting study.PTR-SeNPs could hosphorylate and activate PKCδ,depress Keap1,and increase nuclear accumulation of Nrf2,resulting in upregulation of GCLC,GCLM,HO-1 and NQO-1 expression.Besides,PTR-SeNPs suppressed the biotransformation of APAP to generate intracellular ROS through CYP 2E1 inhibition,restoring the mitochondrial morphology.Furthermore,the protective effect of PTR-SeNPs against APAP induced hepatotoxicity was weakened as Nrf2 was depleted in vivo,indicating the pivotal role of Nrf2 signaling pathway in PTR-SeNPs mediated hepatoprotective efficacy.Being a potential hepatic protectant,PTR-SeNPs could serve as a new source of selenium supplement for health-promoting and biomedical applications.

关键词： PTR-SeNPs(polysaccharide-proteincomplex functionalized selenium nanoparticles) Acetaminophen-induced hepatotoxicity Nuclear factor erythroid 2-related factor 2 Cytochrome P450 enzyme 2E1 Mitochondria

Structural effects of sulfonamides on the proliferation dynamics of sulfonamide resistance genes in the sequencing batch reactors and the mechanism

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Journal of Environmental Sciences 2024年第1期135卷 161-173页

作者： Ligui wu Mingyu Wang Lingling Rong Wenbiao Wang Linwei Chen Qiaofeng wu Haoyu Sun Xiangfeng Huang Xiaoming Zou College of Environmental Science and Engineering Tongji UniversityShanghai 200092China School of Life Science Jinggangshan UniversityJi’an 343009China Key Laboratory of Organic Compound Pollution Control Engineering(MOE) School of Environmental and Chemical EngineeringShanghai UniversityShanghai 200444China Fuzhou Urban and Rural Construction Group Co.Ltd. Fuzhou 350007China

Antibiotic resistance genes(ARGs)can be easily promoted by antibiotics,however,the structural effects of antibiotics on the proliferation of ARGs dynamic and the associated mechanisms remain obscure in,especially,activated sludge sequencing batch reactors.In the present study,the effects of 9 sulfonamides(SAs)with different structures on the proliferation dynamic of sulfonamide resistance genes(Suls)in the activated sludge sequencing batch reactors and the corresponding mechanisms were determined(30 days),and the results showed that the largest proliferation value(ΔA^(R))of Suls dynamic for SAs(sulfachloropyridazine)was approximately 2.9 times than that of the smallest one(sulfadiazine).The proliferation of Suls was significantly related to the structural features(minHBint6,SssNH,SHBd and SpMax2_Bhm)that represent the biological activity of SAs.To interpret the phenomenon,a mechanistic model was developed and the results indicated that the biodegradation of SAs(T_(1/2))rather than conjugative transfer frequency or mutation frequency tends to be the key process for affecting Suls proliferation.T_(1/2)was proved to be dependent on the interactions between SAs and receptors(E_(binding)),the cleavage mode(bond dissociation energy),and the site of nucleophilic assault.Besides,the metagenomic analysis showed that SAs posed significant effect on antibiotic resistome and Tnp31 played a vital role in the proliferation of Suls.Overall,our findings provide important insight into a theoretical basis for understanding the structural effects of SAs on the proliferation of ARGs in SBR systems.

关键词： Activated sludge Sulfonamides Suls Proliferation Mechanism