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Context-dependent role of sirtuin 2 in inflammation

Neural Regeneration Research 2025年第3期20卷 682-694页

作者： NoemíSola-Sevilla Maider Garmendia-Berges MCarmen Mera-Delgado Elena Puerta Department of Pharmaceutical sciences Division of PharmacologySchool of Pharmacy and NutritionUniversity of NavarraPamplonaSpain Navarra Institute for health Research(IdiSNA) PamplonaSpain

Sirtuin 2 is a member of the sirtuin family nicotinamide adenine dinucleotide(NAD~+)-dependent deacetylases, known for its regulatory role in different processes, including inflammation. In this context, sirtuin 2 has been involved in the modulation of key inflammatory signaling pathways and transcription factors by deacetylating specific targets, such as nuclear factor κB and nucleotide-binding oligomerization domain-leucine-rich-repeat and pyrin domain-containing protein 3(NLRP3). However, whether sirtuin 2-mediated pathways induce a pro-or an anti-inflammatory response remains controversial. Sirtuin 2 has been implicated in promoting inflammation in conditions such as asthma and neurodegenerative diseases, suggesting that its inhibition in these conditions could be a potential therapeutic strategy. Conversely, arthritis and type 2 diabetes mellitus studies suggest that sirtuin 2 is essential at the peripheral level and, thus, its inhibition in these pathologies would not be recommended. Overall, the precise role of sirtuin 2 in inflammation appears to be context-dependent, and further investigation is needed to determine the specific molecular mechanisms and downstream targets through which sirtuin 2 influences inflammatory processes in various tissues and pathological conditions. The present review explores the involvement of sirtuin 2 in the inflammation associated with different pathologies to elucidate whether its pharmacological modulation could serve as an effective strategy for treating this prevalent symptom across various diseases.

关键词： interferon inflammation lipopolysaccharide neuroinflammation NLRP3 nuclear factorκB sirtuin 2

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Cobalamin-dependent radical S-adenosyl-L-methionine protein functions with a partner to successively methylate tricyclic indole alkaloid for chuangxinmycin maturation and derivatization

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Science China Chemistry 2025年第1期68卷 308-316页

作者： Sili Wang Jiancheng Huang Yanan Du Wei Huang Yufeng Xue Xiaokun Xu Guannan Zhong Yuanyuan Shi Bin Hong Xiaoying Bian Wen Liu State Key Laboratory of Chemical Biology Shanghai Institute of Organic Chemistry University of Chinese Academy of SciencesChinese Academy of Sciences State Key Laboratory of Microbial Technology Shandong University National health Commission (NHC) Key Laboratory of Biotechnology for Microbial Drugs Institute of Medicinal BiotechnologyChinese Academy of Medical Science & Peking Union Medical College

Cobalamin(Cbl)-dependent radical S-adenosyl-L-methionine(SAM) proteins constitute the largest collection of the radical SAM superfamily that has hundreds of thousands of individual members. Many of these proteins are involved in the biosynthesis of pharmaceutically important natural products to catalyze chemically demanding reactions. In the biosynthetic pathway of chuangxinmycin(CXM), a unique indole alkaloid antibiotic with potent anti-infective activity, functionalization of the characteristic thiopyrano[4,3,2-cd]indole scaffold by regio-and stereoselective C3-methylation is believed to rely on a Cbl-dependent radical process, which, however, remained to be reconstituted biochemically. We here report the dissection of this enzymatic process, which requires the incorporation of Cxm8, a Cbl-dependent radical SAM protein, with Cxm9, a DUF5825family protein that shares no homology to any proteins of known functions. Cxm8 and Cxm9 function together by forming an unexpected heterodimeric complex that selectively catalyzes C3-methylation of the tricyclic indole-S-hetero ring system in a successive manner, achieving CXM and a recently identified, C3-dimethylated congener. Detailed biochemical characterization,isotope labeling, structural simulation and bioinformatics analysis rationalized the catalysis of the Cxm8/Cxm9 complex and particularly the necessity of the DUF5825 protein for C3-methylase activity. This is the first example that a Cbl-dependent protein acts with a partner to exhibit radical SAM activity.

关键词： cbl-dependent radical SAM protein biosynthesis chuangxinmycin stereoselective methylation

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Sky location of massive black hole binaries in the foreground of Galactic white dwarf binaries

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Science China(Physics,Mechanics & Astronomy) 2025年第1期Mechanics & Astronomy) .卷 97-108页

作者： Pan Guo Hong-Bo Jin Cong-Feng Qiao Yue-Liang Wu The International Centre for Theoretical Physics Asia-Pacific University of Chinese Academy of Sciences The School of Physical sciences University of Chinese Academy of Sciences Institute for Frontiers in Astronomy and Astrophysics Beijing Normal University National Astronomical Observatories Chinese Academy of Sciences Institute of Theoretical Physics Chinese Academy of Sciences

For space-based gravitational wave （GW） detection,the main noise source for massive black hole binaries （MBHBs） is attributed to approximately 10～7double white dwarf binaries in the *** a GW source,the amplitude of the detector response,recorded by a space-based gravitational wave detector,exhibits a modulation effect with a year period when observing the source from various orbital *** the adverse conditions mentioned above,where there is a strong foreground noise and annual modulation in the signals,we employed the wavelet transform and the strong-amplitude relevant orbital position search methods,which allows the weak MBHB sources to achieve higher locating *** detail,for two MBHB sources of lower intensity,the precision of luminosity distance,represented by the ratio ?DL/DLat the 95%confidence level,is enhanced by factors of ～*** angular resolutions,denoted by??s,are enhanced by a factor of ～*** improvements increase the number of detectable GW sources,facilitate multi-messenger follow-up observations and provide constraints on the cosmological constant.

关键词： space-based gravitational wave detection gravitational waves massive black hole binaries

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Crustal magma oxidation state and endowments in porphyry copper deposits

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Science China Earth sciences 2025年第1期68卷 226-236页

作者： Yumin AI Massimo CHIARADIA Chao WU Huayong CHEN Key Laboratory of Mineralogy and Metallogeny Guangzhou Institute of Geochemistry Chinese Academy of Sciences university of Chinese Academy of sciences Department of Earth sciences University of Geneva Guangdong Provincial Key Laboratory of Mineral Physics and Materials

Porphyry copper deposits（PCDs） supply the majority of the world's copper（Cu） as well as significant amounts of molybdenum（Mo） and gold（Au）. The formation of these deposits is controlled by a variety of geological factors, among which the magmatic oxidation is one of the focuses of current research. This study investigates the redox characteristics of arc magmas by analyzing the ratio of vanadium（V） to scandium（Sc） and its correlation with the oxygen fugacity （fO2） of magmas from arcs of various crustal thicknesses globally. We compiled an extensive dataset of published V/Sc values and studied the partition coefficients of Vand Sc between minerals and silicate melts across various magmatic environments. The results demonstrate that fractional crystallization of magnetite markedly reduces V/Sc values of the residual melt. Furthermore, magnesium number（Mg#） at the onset of magnetite fractionation is strongly positively correlated with fO2of the equilibrium magma. Based on this,the oxidation of arc magmas from different crustal thicknesses can be evaluated. The result suggests that magmas generated in crusts thicker than 20 km tend to be more oxidized with increasing crust thickness. This trend is attributed to enhanced intracrustal differentiation processes involving garnet and amphibole, particularly in mature island and continental arcs. In contrast,magmas in thinner arc crusts（<20 km）, which are significantly influenced by subducted slab materials, display higher oxidation states than most of their thicker crust counterparts. These findings suggest that both subduction dynamics and crustal thickness play a vital role in determining the oxidation state of arc magmas and, consequently, their capacity to generate PCDs. Highly oxidized, primitive arc magmas are less favorable for PCD formation due to that they tend to experience magnetite fractionation and thus sulfide saturation in the early stage of magma evolution, a process leading to copper depletion. On the contra

关键词： Magma evolution V/Sc systematics Magnetite Oxygen fugacity Porphyry copper deposits

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Genetic signatures of ERCC1 and ERCC2 expression,along with SNPs variants,unveil favorable prognosis in SCLC patients undergoing platinum-based chemotherapy

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Oncology Research 2025年第1期33卷 45-55页

作者： ENRICO CALIMAN SARA FANCELLI FEDERICO SCOLARI ADRIANO PASQUI CLARA MANNESCHI DANIELE LAVACCHI FRANCESCA MAZZONI FRANCESCA GENSINI VALERIA PASINI CAMILLA EVA COMIN LUCA VOLTOLINI SERENA PILLOZZI LORENZO ANTONUZZO Clinical Oncology Unit Careggi University HospitalFlorence50134Italy Department of Experimental and Clinical Medicine University of FlorenceFlorence50134Italy Department of health sciences University of FlorenceFlorence50134Italy Medical Oncology Unit Careggi University HospitalFlorence50134Italy Department of Experimental and Clinical Biomedical sciences“Mario Serio” University of FlorenceFlorence50134Italy Section of Anatomic Pathology Department of Health SciencesUniversity of FlorenceFlorence50139Italy Section of Surgery Histopathology and Molecular PathologyUniversity of FlorenceFlorence50139Italy Thoracic Surgery Unit Careggi University HospitalFlorence50134Italy

Background:Platinum chemotherapy(CT)remains the backbone of systemic therapy for patients with smallcell lung cancer(SCLC).The nucleotide excision repair(NER)pathway plays a central role in the repair of the DNA damage exerted by platinum *** in this repair mechanism may affect patients’*** and Methods:We conducted a retrospective analysis of data from 38 patients with extensive disease(ED)-SCLC who underwent platinum-CT at the Clinical Oncology Unit,Careggi university Hospital,Florence(Italy),from 2015 to *** expression analysis and single nucleotide polymorphism(SNP)characterization of three NER pathway genes—namely ERCC1,ERCC2,and ERCC5—were performed on patient tumor ***:Overall,elevated expression of ERCC genes was observed in SCLC patients compared to healthy *** with low ERCC1 and ERCC5 expression levels exhibited a better median progression-free survival(mPFS=7.1 vs.4.9 months,p=0.39 for ERCC1 and mPFS=6.9 vs.4.8 months,p=0.093 for ERCC5)and overall survival(mOS=8.7 vs.6.0 months,p=0.4 for ERCC1 and mOS=7.2 vs.6.2 months,p=0.13 for ERCC5).Genotyping analysis of five SNPs of ERCC genes showed a longer survival in patients harboring the wild-type genotype or the heterozygous variant of the ERCC1 rs11615 SNP(p=0.24 for PFS and p=0.14 for OS)and of the rs13181 and rs1799793 ERCC2 SNPs(p=0.43 and p=0.26 for PFS and p=0.21 and p=0.16 for OS,respectively)compared to patients with homozygous mutant ***:The comprehensive analysis of ERCC gene expression and SNP variants appears to identify patients who derive greater survival benefits from platinum-CT.

关键词： Small cell lung cancer(SCLC) Nucleotide excision repair(NER)pathway ERCC genes Single nucleotide polymorphisms(SNPs) Platinumchemotherapy(CT)

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Emerging role of A-kinase anchoring protein 5 signaling in reward circuit function

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Neural Regeneration Research 2025年第10期20卷 2913-2914页

作者： William J.Flerlage Mark L.Dell’Acqua Brian M.Cox Fereshteh S.Nugent Uniformed Services university of the health sciences Department of Pharmacology and Molecular TherapeuticsBethesdaMDUSA Department of Pharmacology University of Colorado School of MedicineAnschutz Medical CampusAuroraCOUSA

There is a strong evidence supporting the hypothesis of synaptic dysfunction as a major contributor to neural circuit and network disruption underlying emotional and mood dysregulation in psychiatric disorders(Simmons et al.,2024).Diverse sets of distinct molecular signaling pathways converge on the synapse to regulate synaptogenesis,synaptic function,and synaptic plasticity in brain regions and circuits through complex interactions organized by numerous multivalent protein scaffolds,including the family of proteins known as A-kinase anchoring proteins(AKAPs).

关键词： function supporting

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Reconstructing forest and grassland cover changes in China over the past millennium

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Science China Earth sciences 2025年第1期68卷 94-110页

作者： Fanneng HE Fan YANG Yafei WANG Key Laboratory of Land Surface Pattern and Simulation Institute of Geographic Sciences and Natural Resources Research Chinese Academy of Sciences Key Research Institute of Yellow River Civilization and Sustainable Development Henan University university of Chinese Academy of sciences

Historical forest and grassland cover changes not only are critical indicators for quantifying ecological and environmental change processes but also serve as fundamental data for long-term climate change simulations and terrestrial ecosystem carbon emission assessments. However, because of limitations in historical data, quantitative estimations and spatially gridded reconstructions of these changes remain challenging, necessitating further methodological exploration. This study focused on China's present-day land area over the past millennium, objectively capturing the characteristics and drivers of forest and grassland cover changes. On this basis, using the forest transition theory and the space-for-time substitution method, we depicted the historical deforestation process as an inverted “S” curve and developed a model to reconstruct historical forest area changes based on the functional relationship between the forest area and population size dynamics. Subsequently, a gridded forest allocation model was established on the basis of deforestation tendencies. For the grassland cover, we implemented regionspecific methods, such as the cropland area deduction method and the habitat constraint method, to quantitatively reconstruct historical changes. Consequently, we obtained provincial forest and grassland area changes over the past millennium and mapped 10-km-resolution gridded data of forest and grassland cover. The results indicated the following.(1) The methods developed using population data as a proxy objectively reproduced the spatiotemporal evolution of forest and grassland cover in China over the past millennium. These feasible methods offer a novel pathway for the quantitative reconstruction of historical forest and grassland cover changes.(2) The data indicated that China's forest area generally decreased over the past millennium, characterized by a “decrease-then-increase” pattern. The forest area experienced three distinct phases: a slow decline(AD 1000

关键词： Land use and land cover change Forest Grassland Quantitative reconstruction Gridded reconstruction China historical period

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Formation and evolution of supercritical geofluid

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Science China Earth sciences 2025年第1期68卷 39-51页

作者： Huaiwei NI Yilin XIAO Xiaolin XIONG Xiandong LIU Chunxiao GAO Yi-Xiang CHEN Yunguo LI Wan-Cai LI Xuan GUO Yang-Yang WANG Dong-Bo TAN Li ZHANG State Key Laboratory of Lithospheric and Environmental Coevolution University of Science and Technology of China Deep Space Exploration Laboratory/School of Earth and Space sciences University of Science and Technology of China Guangzhou Institute of Geochemistry Chinese Academy of Sciences School of Earth sciences and Engineering Nanjing University State Key Lab of Superhard Materials Jilin University

In this work, we provide a comprehensive review on the formation, evolution, properties, and effects of supercritical geofluid. In Earth's interior, enhanced miscibility between H2O and silicate by the addition of special components or by the increase of pressure and temperature gives rise to supercritical geofluid with a significant amount of both H2O and silicate *** formation of supercritical geofluid in magmatic-hydrothermal systems, typified by pegmatite system, is governed by meltfluid critical curve. The formation of supercritical geofluid in metamorphic systems, typified by subducted slab, is governed by the second critical end point. Experimental results suggest that the presence of boron and fluorine in pegmatite system makes it possible to form supercritical geofluid at crustal depths, but the release of supercritical geofluid from subducted slab is withheld until almost 100 km depth. A major presence of both H2O and depolymerized structural units（monomers, dimers, etc.） endows supercritical geofluid with unique physical properties including low density, low elastic moduli, low viscosity, high diffusivity,and high electrical conductivity. Supercritical geofluid can effectively mobilize a variety of elements even including high field strength elements and heavy rare earth elements. The chemical signatures of supercritical geofluid can be inherited by metasomatized mantle and mantle-derived melts, and this could give an explanation of the oxidation of arc magmas. Phase separation of supercritical geofluid through the mechanism of spinodal decomposition leads to formation of a melt network. Multiphase fluid inclusions recovered from subduction zone rocks and pegmatites are possible relics of supercritical geofluid. Supercritical geofluid can cause electrical anomaly and low seismic velocity near the top of subducted slab, and can be linked with intermediate-focus earthquakes. Supercritical geofluid may have played a crucial role in the formation of pe

关键词： Supercritical geofluid Miscibility Subduction zone Pegmatite

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Miyaoka-type inequalities for terminal threefolds with nef anti-canonical divisors

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Science China Mathematics 2025年第1期68卷 1-18页

作者： Masataka Iwai Chen Jiang Haidong Liu Department of Mathematics Graduate School of ScienceOsaka University Shanghai Center for Mathematical sciences & School of Mathematical sciences Fudan University Department of mathematics Sun Yat-sen University

In this paper,we study Miyaoka-type inequalities on Chern classes of terminal projective 3-folds with nef anti-canonical *** X be a terminal projective 3-fold such that-KXis *** show that if c1（X） · c2（X）≠0,then c1（X） · c2（X） ≥ 1/252;if further X is not rationally connected,then c1（X） · c2（X） ≥ 4/5 and this inequality is *** order to prove this,we give a partial classification of such varieties along with many *** also study the nonvanishing of c1（X）dim X-2· c2（X） for terminal weak Fano varieties and prove a Miyaoka-Kawamata-type inequality.

关键词： terminal threefolds Miyaoka-type inequality boundedness

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Impact of Startup Strategy and Buffer Tank Volume on the Compressor Inlet State for a 3-MW sCO2 Brayton Cycle

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Journal of Thermal Science 2025年第1期34卷 159-175页

作者： ZHAO Decai WANG Bo Key Laboratory of Advanced Energy and Power Institute of Engineering Thermophysics(IET)Chinese Academy of Sciences (CAS) university of Chinese Academy of sciences

The supercritical carbon dioxide（sCO2） Brayton cycle system has become an emerging and highly promising method of thermal power conversion due to its efficiency advantage,system compactness,and excellent adaptability of the heat *** the low carbon sCO2Brayton cycle testbed with cycle output power approaching 3 MW,a relatively detailed dynamic simulation model of the entire system is constructed to explore the dynamic response characteristics of the system with different startup strategies and different buffer tank volumes during the startup *** simulation results indicate that the smaller the volume of the buffer tank,the more rapid and obvious the parameter fluctuation in the buffer tank during the *** the allowable relative deviation limit of density is 5%,then the ratio of the buffer tank volume to the volume of the entire closed loop should not be lower than 36.80%.The strategy of simultaneous temperature and speed increase during turbine bypass start can effectively reduce the fluctuation of compressor inlet parameters and reach the steady-state more *** paper provides the recommended matching table for the opening of the turbine bypass valve（TBV） and the main regulating valve（MGV） to reduce the parameter fluctuation during the bypass *** effectiveness of the proposed turbine bypass and bypass switching startup strategy is verified by simulation,which may be used as a reference for test bench's future debugging and operation.

关键词： buffer tank dynamic characteristic dynamic model sCO2 Brayton cycle startup strategy

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