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Advances in genotypic antimicrobialresistance testing: a comprehensive review

Science China Life sciences 2025年第1期68卷 130-143页

作者： Boheng Duan Xianjun Zeng Junping Peng Huan Kui College of Nanchang University Department of Imaging The Second Affiliated Hospital of Nanchang University NHC Key laboratory of Systems Biology of Pathogens National Institute of Pathogen BiologyChinese Academy of Medical Sciences & Peking Union Medical College Key laboratory of Respiratory Disease Pathogenomics Chinese Academy of Medical Sciences & Peking Union Medical College Key laboratory of Pathogen Infection Prevention and Control (Ministry of Education) State Key Laboratory of Respiratory Health and MultimorbidityNational Institute of Pathogen BiologyChinese Academy of Medical Sciences & Peking Union Medical College

Antimicrobial resistance(AMR) represents a substantial threat to global public health, complicating the treatment of common infections and leading to prolonged illness and escalated healthcare expenses. To effectively combat AMR, timely and accurate detection is crucial for AMR surveillance and individual-based therapy. Phenotypic antibiotic resistance testing(AST) has long been considered the gold standard in clinical applications, serving as the foundation for clinical AMR diagnosis and optimized therapy. It has significantly contributed to ensuring patients′ health and the development of novel antimicrobials. Despite advancements in automated culture-based AST technologies,inherent limitations impede the widespread use of phenotypic AST in AMR surveillance. Genotypic AST technologies offer a promising alternative option, exhibiting advantages of rapidity, high sensitivity, and specificity. With the continuous advancement and expanding applications of genotypic AST technologies, such as microfluidics, mass spectrometry, and high-resolution melting curve analysis, new vigor has been injected into the development and clinical implementation of genotypic AST technologies. In this narrative review, we discuss the principles, applications, and advancements of emerging genotypic AST methods in clinical settings. The comprehensive review aims to highlight the significant scientific potential of emerging genotypic AST technologies in clinical AMR diagnosis, providing insights to enhance existing methods and explore novel approaches.

关键词： antimicrobial resistance (AMR) genotypic antibiotic resistance testing (AST) AST technologies review

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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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The complex roles of m^(6)A modifications in neural stem cell proliferation, differentiation, and self-renewal and implications for memory and neurodegenerative diseases

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Neural Regeneration Research 2025年第6期20卷 1582-1598页

作者： Yanxi Li Jing Xue Yuejia Ma Ke Ye Xue Zhao Fangliang Ge Feifei Zheng Lulu Liu Xu Gao Dayong Wang Qing Xia Department of biochemistry and Molecular Biology College of Basic Medical SciencesHarbin Medical UniversityHarbinHeilongjiang ProvinceChina College of Basic medical sciences Harbin Medical UniversityHarbinHeilongjiang ProvinceChina Basic medical Institute Heilongjiang Academy of Medical SciencesHarbinHeilongjiang ProvinceChina Key laboratory of Heilongjiang Province for Genetically Modified Animals Harbin Medical UniversityHarbinHeilongjiang ProvinceChina Translational Medicine Research and Cooperation Center of Northern China Heilongjiang Academy of Medical SciencesHarbinHeilongjiang ProvinceChina Dongzhimen Hospital Beijing University of Chinese MedicineBeijingChina

N6-methyladenosine(m^(6)A), the most prevalent and conserved RNA modification in eukaryotic cells, profoundly influences virtually all aspects of mRNA metabolism. mRNA plays crucial roles in neural stem cell genesis and neural regeneration, where it is highly concentrated and actively involved in these processes. Changes in m^(6)A modification levels and the expression levels of related enzymatic proteins can lead to neurological dysfunction and contribute to the development of neurological diseases. Furthermore, the proliferation and differentiation of neural stem cells, as well as nerve regeneration, are intimately linked to memory function and neurodegenerative diseases. This paper presents a comprehensive review of the roles of m^(6)A in neural stem cell proliferation, differentiation, and self-renewal, as well as its implications in memory and neurodegenerative diseases. m^(6)A has demonstrated divergent effects on the proliferation and differentiation of neural stem cells. These observed contradictions may arise from the time-specific nature of m^(6)A and its differential impact on neural stem cells across various stages of development. Similarly, the diverse effects of m^(6)A on distinct types of memory could be attributed to the involvement of specific brain regions in memory formation and recall. Inconsistencies in m^(6)A levels across different models of neurodegenerative disease, particularly Alzheimer's disease and Parkinson's disease, suggest that these disparities are linked to variations in the affected brain regions. Notably, the opposing changes in m^(6)A levels observed in Parkinson's disease models exposed to manganese compared to normal Parkinson's disease models further underscore the complexity of m^(6)A's role in neurodegenerative processes. The roles of m^(6)A in neural stem cell proliferation, differentiation, and self-renewal, and its implications in memory and neurodegenerative diseases, appear contradictory. These inconsistencies may be a

关键词： Alzheimer's disease cell self-renewal central nervous system memory microglia nerve regeneration neurodegenerative diseases neurogenesis RNA methylation

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Deciphering fungal metabolon coupling tandem inverse-electrondemand Diels-Alder reaction and semipinacol rearrangement for the biosynthesis of spiro polycyclic alkaloids

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Science China Chemistry 2025年第1期68卷 288-296页

作者： Shuai Liu Wen-Qiang Xu Ying-Tong Di Man-Cheng Tang Ding-Kang Chen Ming-Ming Cao Yao-Wen Chang Hong-Yu Tang Chun-Mao Yuan Jun-Bo Yang Zhi-Li Zuo Han Guo Zi-Fei Xu Ying Zeng Yun-Dong Wu Xiao-Jiang Hao Key laboratory of Phytochemistry and Natural Medicines (Chinese Academy of sciences) Kunming Institute of Botany Chinese Academy of Sciences University of Chinese Academy of sciences Lab of Computational Chemistry and Drug Design State Key Laboratory of Chemical Oncogenomics Peking University Shenzhen Graduate School Shenzhen Bay laboratory State Key laboratory of Microbial Metabolism School of Life Sciences & Biotechnology Shanghai Jiao Tong University State Key laboratory of Functions and Applications of Medicinal Plants Guizhou Medical University Molecular Biology Experimental Center Germplasm Bank of Wild Species in Southwest China Kunming Institute of Botany Chinese Academy of Sciences Yunnan Key laboratory for Wild Plant Resources Kunming Institute of Botany Chinese Academy of Sciences Research Unit of Chemical Biology of Natural Anti-Virus Products Chinese Academy of Medical Sciences

In the intricate process of natural product biosynthesis, a metabolon can enhance metabolic flux by associating sequential enzymes. A fungal metabolon, comprising of flavin-dependent monooxygenase Spe F and P450 monooxygenase Spe G, is identified in the biosynthesis of spiro polycyclic alkaloids(+)-notoamide B and its diastereomer(+)-versicolamide B. Using notoamide E as a substance, Spe F/Spe G metabolon can control the stereoselectivity of its 2,3-epoxidation, followed by hydrogen atom ion at C-17 to generate reactive epoxide tau-m A with dienyl iminium unit. Subsequently,(+)-notoamide B and(+)-versicolamide B are produced via tandem nonenzymatic inverse-electron-demand Diels-Alder reaction and semipinacol rearrangement. This provides the first example of metabolon in the biosynthesis of spiro-prenylated indole alkaloids.

关键词： metabolon Diels-Alder reaction semipinacol rearrangement biosynthesis notoamides spiro polycyclic alkaloids

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Establishing a new testing protocol of the electrochemical stability window for electric double-layer capacitors

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Science China Chemistry 2025年第1期68卷 217-225页

作者： Ruilin Hou Xiaoxi Zhao Tingting Liang Qingyun Dou Shan Xu Xingbin Yan School of Materials Science and Engineering Sun Yat-sen University laboratory of Clean Energy Chemistry and Materials Lanzhou Institute of Chemical Physics Chinese Academy of Sciences College of Engineering and applied sciences Nanjing University Center of Industrial Analysis and Testing Guangdong Academy of Science

The electrochemical stability window(ESW) is crucial for determining the energy density of electric double-layer capacitors(EDLCs). However, current ESW testing protocols of EDLCs are strongly affected by artificial factors, thereby leading to unreliable result. To solve this problem, we first identify the key shortcomings of the traditional protocols by analyzing their test principles. Subsequently, taking an aqueous carbon-based EDLC as an example, we design a side reaction descriptor to represent the response difference in the charging capacitance to side reactions between the cyclic voltammetry and galvanostatic chargedischarge methods. With the aid of this descriptor, we propose a new ESW testing protocol, which is not only able to completely avoid the adverse influence of subjective factors but also fully consider the operating condition limitations. The protocol can be extended from the single electrode to the full device. This work proposes a more rigorous definition of ESW and provides a reliable protocol for evaluating the ESW of EDLCs.

关键词： electric double-layer capacitors electrochemical stability window testing protocol side reaction descriptor operating limitation

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De novo synthesis of atropisomeric benzofurans via Cu/SPDO complex catalyzed asymmetric formal [3 + 2] annulation

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Science China Chemistry 2025年第1期68卷 174-180页

作者： Fan-Xiao Meng Xing-Yu Wang Ka Lu Ju-Song Yang Fu-Min Zhang Ai-Jun Ma Bao Du Yong-Qiang Tu State Key laboratory of applied Organic Chemistry College of Chemistry and Chemical Engineering Lanzhou University School of Chemistry and Chemical Engineering Shanghai Jiao Tong University School of Biotechnology and Health sciences Wuyi University

Herein, the de novo synthesis of atropisomeric benzofurans through the Cu/spirocyclic-pyrrolidine-oxazoline(SPDO) complex catalyze asymmetric formal [3 + 2] cycloaddition between quinones and ynamides is explored, producing a range of structurally diverse axially chiral benzofurans in satisfactory yields with good to excellent enantioselectivities. Furthermore, density functional theory calculations were applied to explain the possible reaction mechanism.

关键词： benzofuran atropisomers novel de novo synthetic strategy asymmetric formal [3 + 2] cycladdition Cu/SPDO complex DFT calculations

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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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Lipid droplets in the nervous system:involvement in cell metabolic homeostasis

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Neural Regeneration Research 2025年第3期20卷 740-750页

作者： Yuchen Zhang Yiqing Chen Cheng Zhuang Jingxuan Qi Robert Chunhua Zhao Jiao Wang School of Life sciences Shanghai UniversityShanghaiChina School of Medicine Shanghai UniversityShanghaiChina Institute of Basic medical sciences Chinese Academy of medical sciences School of Basic MedicinePeking Union Medical CollegeBeijingChina Center of Excellence in Tissue Engineering Chinese Academy of Medical SciencesBeijingChina Beijing Key laboratory of New Drug Development and Clinical Trial of Stem Cell Therapy BeijingChina

Lipid droplets serve as primary storage organelles for neutral lipids in neurons,glial cells,and other cells in the nervous *** droplet formation begins with the synthesis of neutral lipids in the endoplasmic ***,lipid droplets were recognized for their role in maintaining lipid metabolism and energy homeostasis;however,recent research has shown that lipid droplets are highly adaptive organelles with diverse functions in the nervous *** addition to their role in regulating cell metabolism,lipid droplets play a protective role in various cellular stress ***,lipid droplets exhibit specific functions in neurons and glial *** of lipid droplet formation leads to cellular dysfunction,metabolic abnormalities,and nervous system *** review aims to provide an overview of the role of lipid droplets in the nervous system,covering topics such as biogenesis,cellular specificity,and ***,it will explore the association between lipid droplets and neurodegenerative *** the involvement of lipid droplets in cell metabolic homeostasis related to the nervous system is crucial to determine the underlying causes and in exploring potential therapeutic approaches for these diseases.

关键词： Alzheimer's disease lipid droplet biogenesis lipid droplets lipid metabolism nervous system neurodegenerative disorders oxidative stress Parkinson's disease

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Bifunctional bridging capping layer enables 24.5% efficiency of perovskite solar cells with polymer-based hole transport materials

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Science China Chemistry 2025年第1期68卷 350-359页

作者： Can Zhu Yiyang Wang Lei Meng Beibei Qiu Jing Li Shucheng Qin Ke Hu Xin Jiang Wenbin Lai Minchao Liu Zhe Liu Chenxing Lu Jinyuan Zhang Yongfang Li Beijing National laboratory for Molecular sciences CAS Key Laboratory of Organic Solids Institute of Chemistry Chinese Academy of Sciences School of Chemical Science University of Chinese Academy of Sciences Key laboratory of Solid State Optoelectronic Devices of Zhejiang Province College of Physics and Electronic Information Engineering Zhejiang Normal University Key laboratory of Photochemical Conversion and Optoelectronic Materials Technical Institute of Physics and ChemistryChinese Academy of Sciences laboratory of Advanced Optoelectronic Materials College of Chemistry Chemical Engineering and Materials ScienceSoochow University

Developing a bridge capping layer between perovskite and hole transport layer materials（HTMs） in the n-i-p perovskite solar cells（pero-SCs） is an effective approach to modify the morphology of HTMs and passivate the perovskite ***, we select the quinoxaline-based bifunctional passivation agent, quinoxalin-6-yl-methylamine hydrochloride（Qx MACl）,as the bridging layer, and a D-A copolymer PBQ12 containing the same quinoxaline unit as an HTM for the n-i-p pero-SCs. Due to the π-π stacking among the common quinoxaline units in the bridge layer and HTM, Qx MACl induces the π-π stacking of the PBQ12 film and improves the film morphology of HTMs with better conductivity. Additionally, Qx MACl can effectively passivate the perovskite surface, and PBQ12 possesses appropriate energy levels and high hole mobility. The pero-SCs based on FAPbI3with PBQ12/Qx MACl treatment showed a higher power conversion efficiency（PCE） of 24.05% and outstanding stability, maintaining 95.4% and 92.1% of its initial PCE after 750 h of storage and after over 800 h of thermal annealing at 85 °C, respectively. To further enhance the PCE of the PBQ12/Qx MACl-based devices, we developed a non-metal ion dopant for the PBQ12 HTM. Through trace doping of PBQ12 HTM by the non-metal ion dopant, the PCE of the PBQ12/Qx MACl-based devices reached 25.24%（the calibrated PCE of 24.55% by the National Institute of Metrology, China）.

关键词： D-A copolymer, hole transport materials, bifunctional bridge capping layer, passivation perovskite solar cells

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Selective G6PDH inactivation for Helicobacter pylori eradication with transformed polysulfide

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Science China Life sciences 2025年

作者： Xiaonan Wang Ning Zhou Xuejiao J.Gao Zijing Zhu Minmin Sun Qian Wang Haolin Cao Xuetong Wu Caiyu Zhou Qingkang Zheng Ye Yuan Yuan Liu Lei Chen Jing Jiang Pengcheng Bu Lizeng Gao CAS Engineering laboratory for Nanozyme Key Laboratory of Biomacromolecules Institute of Biophysics Chinese Academy of Sciences School of Life sciences University of Chinese Academy of Sciences College of Chemistry and Chemical Engineering Jiangxi Normal University Key laboratory of Epigenetic Regulation and Intervention Institute of Biophysics Chinese Academy of Sciences Nanozyme laboratory in Zhongyuan School of Basic Medical Sciences Zhengzhou University Nanozyme laboratory in Zhongyuan Henan Academy of Innovations in Medical Science

Alternative treatment for the highly prevalent Helicobacter pylori infection is imperative due to rising antibiotic resistance. We unexpectedly discovered that the anti-H. pylori component in garlic is hydrogen polysulfide（H2S_n, n≥2）, not organic polysulfides. Studies on the mechanism of action（MoA） show that H2S_nspecifically inactivates H. pylori glucose-6-phosphate dehydrogenase（G6PDH） by interfering with electron transfer from glucose-6-phosphate（G6P） to nicotinamide adenine dinucleotide phosphate（NADP+）. However, low H2S_nyield makes garlic derivatives hard to be a reliable donor of H2S_nto treat H. pylori infection. To address this challenge, we established a polysulfide transformation process from garlic organosulfur compounds into Fe3S4that generates H2S_nwith a 25–58 times increase in *** chitosan encapsulation, we designed a gastric-adaptive H2S_nmicroreactor（GAPSR） that eradicates H. pylori with 250 times higher efficiency under gastric conditions. A single GAPSR achieves more rapid H. pylori eradication than combined antibiotics therapy without disturbing the gut microbiota. These findings indicate a distinct MoA transformation mediated by polysulfide as an alternative candidate to treat H. pylori infection.

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