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Current Medical Science 2024年第2期44卷 273-280页

作者： Lei zhang Min-ye LI Chen zhi Min ZHU Hui MA Sixth Medical Center Chinese PLA General HospitalBeijing100048China

The global incidence of infectious diseases has increased in recent years,posing a significant threat to human health.Hospitals typically serve as frontline institutions for detecting infectious diseases.However,accurately identifying warning signals of infectious diseases in a timely manner,especially emerging infectious diseases,can be challenging.Consequently,there is a pressing need to integrate treatment and disease prevention data to conduct comprehensive analyses aimed at preventing and controlling infectious diseases within hospitals.This paper examines the role of medical data in the early identification of infectious diseases,explores early warning technologies for infectious disease recognition,and assesses monitoring and early warning mechanisms for infectious diseases.We propose that hospitals adopt novel multidimensional early warning technologies to mine and analyze medical data from various systems,in compliance with national strategies to integrate clinical treatment and disease prevention.Furthermore,hospitals should establish institution-specific,clinical-based early warning models for infectious diseases to actively monitor early signals and enhance preparedness for infectious disease prevention and control.

关键词： infectious disease disease prevention and control medical data warning signals

PACS gene family-related neurological diseases: limited genotypes and diverse phenotypes

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World Journal of Pediatrics 2024年第1期20卷 82-91页

作者： Han zhang Kai Gao Shuang Wang Yue-Hua zhang zhi-Xian Yang ye Wu Yu-Wu Jiang Department of Pediatrics Peking University First Hospital.No.1 Xi'an Men StreetWest DistrictBeijing 100034China Bejing Key Laboratory of Molecular Diagnosis and Study on Pediatric Genetic Diseases BeijingChina Children Epilepsy Center Peking University First HospitalBeijingChina Key Laboratory for Neuroscience Ministry of Education/National Health and Family Planning CommissionPeking UniversityBeijingChina Center of Epilepsy Beijing Institute for Brain DisordersBeijingChina

Background The PACS gene family has been demonstrated to be related to intracellular vesicular trafficking.The phenotypic manifestations caused by the pathogenic variants of PACS include epilepsy,intellectual disability/developmental delay,and malformations,such as facial abnormalities.Methods We identified seven new cases with pathogenic or likely pathogenic PACS variants using next-generation sequencing.Detailed information obtained from these patients was analyzed along with that obtained from previously reported patients.Results With the inclusion of the newly diagnosed cases in this study,103 cases with PACS gene family-related neurological diseases were reported,of which 43 were PACS2-related cases and the remaining were PACSI-related cases.Most patients had seizures,which have been reported to be effectively controlled by several types of anti-seizure medications(ASMs).The most efficacious and frequently prescribed ASMs included sodium valproate(43.3%,13/30),oxcarbazepine/carbamazepine(26.7%,8/30),and levetiracetam(20%,6/30).Almost all patients had intellectual disability/developmental delay.The most common pathogenic missense variants were PACSI p.Arg203Trp and PACS2 p.Glu209Lys.In addition,we report a patient carrying a likely pathogenic copy number variation(CNV)(de novo heterozygous deletion of chr14:105821380-106107443,286 kilobase,destroyed part of the furin-binding region domain and the protein structure after it)with more severe and refractory late-onset epilepsy.Conclusions The clinical phenotypes of the different PACS heterozygous missense variants were similar.The pathogenic variant sites of PACSI and PACS2 were quite limited but located in different regions.A CNV destroying part of the PACS2 gene might also be pathogenic.These findings may provide an important clue for further functional studies on the pathogenic mechanism of neurological disorders related to the PACS gene family.

关键词： Developmental delay Epilepsy Intellectual disability PACSI PACS2

Gene therapy for monogenic disorders: challenges, strategies, and perspectives

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Journal of Genetics and Genomics 2024年第2期51卷 133-143页

作者： Yi zhang zhi-Ying Wu Department of Medical Genetics and Center for Rare Diseases Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310009China Department of Neurology Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310009China Key Laboratory of Medical Neurobiology of Zhejiang Province HangzhouZhejiang 310009China

Monogenic disorders refer to a group of human diseases caused by mutations in single genes. While disease-modifying therapies have offered some relief from symptoms and delayed progression for some monogenic diseases, most of these diseases still lack effective treatments. In recent decades, gene therapy has emerged as a promising therapeutic strategy for genetic disorders. Researchers have developed various gene manipulation tools and gene delivery systems to treat monogenic diseases. Despite this progress, concerns about inefficient delivery, persistent expression, immunogenicity, toxicity, capacity limitation, genomic integration, and limited tissue specificity still need to be addressed. This review gives an overview of commonly used gene therapy and delivery tools, along with the challenges they face and potential strategies to counter them.

关键词： Gene therapy Monogenic diseases Geneediting Genedelivery Challenges

Deciphering and integrating invariants for neural operator learning with various physical mechanisms

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National Science Review 2024年第4期11卷 111-122页

作者： Rui zhang Qi Meng zhi-Ming Ma Academy of Mathematics and Systems Science Chinese Academy of Sciences(CAS) Microsoft Research

Neural operators have been explored as surrogate models for simulating physical systems to overcome the limitations of traditional partial differential equation(PDE) solvers. However, most existing operator learning methods assume that the data originate from a single physical mechanism, limiting their applicability and performance in more realistic scenarios. To this end, we propose the physical invariant attention neural operator(PIANO) to decipher and integrate the physical invariants for operator learning from the PDE series with various physical mechanisms. PIANO employs self-supervised learning to extract physical knowledge and attention mechanisms to integrate them into dynamic convolutional layers.Compared to existing techniques, PIANO can reduce the relative error by 13.6%–82.2% on PDE forecasting tasks across varying coefficients, forces or boundary conditions. Additionally, varied downstream tasks reveal that the PI embeddings deciphered by PIANO align well with the underlying invariants in the PDE systems, verifying the physical significance of PIANO.

关键词： neural operator PDE solver contrastive learning physical invariants

P-symmetric Subharmonic Solutions for Nonlinear Hamiltonian Systems

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Acta Mathematica Sinica,English Series 2024年第6期40卷 1388-1408页

作者： Duan zhi zhang zhi Hao ZHAO School of Mathematical Sciences Nankai UniversityTianjin 300071P.R.China

In this paper,we prove that for each positive k≡1 mod m there exists a P-symmetric kmτ-periodic solution xk for asymptotically linear mτ-periodic Hamiltonian systems,which are nonautonomous and endowed with a P-symmetry.If the P-symmetric Hamiltonian function is semi-positive,one can prove,under a new iteration inequality of the Maslov-type P-index,that xk_(1) and xk_(2) are geometrically distinct for k_(1)/k_(2)≥(2n+1)m+1;and xk_(1),xk_(2) are geometrically distinct for k_(1)/k_(2)≥m+1 provided xk_(1) is non-degenerate.

关键词： P-symmetric subharmonic Hamiltonian systems Maslov-type index theory iteration inequality asymptotically linear

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Enhanced memristor performance via coupling effect of oxygen vacancy and ferroelectric polarization

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Journal of Materials Science & Technology 2024年第4期171卷 139-146页

作者： zhi Yun Yue zhi Dong zhang Zhan Jie Wang Shenyang National Laboratory for Materials Science Institute of Metal ResearchChinese Academy of SciencesShenyang 110016China School of Materials Science and Engineering University of Science and Technology of ChinaShenyang 110016China School of Materials Science and Engineering Shenyang University of TechnologyShenyang 110870China

As a new type of nonvolatile memory,the resistive memristor has broad application prospects in in-formation storage and neural computing based on its excellent resistive switching(RS)performance.At present,it is still a great challenge to improve both ferroelectric polarization and leakage current to achieve a high RS on/offratio of ferroelectric memristors.Herein,epitaxial Pb(Zr_(0.40)Ti_(0.60))O_(3)(PZT)thin films with low content Ca doping were deposited on the Nb:SrTiO_(3)substrate to prepare PCZT/NSTO het-erostructures and their RS behaviors were studied.The research findings show that compared with pure PZT film,the ferroelectric polarization of 1-mol%-Ca-doped PZT film is slightly improved,while the leak-age current is increased by three orders of magnitude.Therefore,the RS on/offratio reaches 2.5×10^(5),about three orders of magnitude higher than pure PZT films.The theoretical analysis reveals that the RS behavior of PCZT/NSTO heterostructures is controlled by the PCZT/NSTO interfacial barrier and the space charge-limited current mechanism.Our results demonstrate that the ferroelectricity and electricity of ferroelectric thin films can be improved simultaneously by doping low-content Ca ions to increase the RS performance,which provides a good reference for the development of high-performance ferroelectric memristor devices.

关键词： Ferroelectric memristor Ca-doped PZT Ferroelectric polarization Oxygen vacancies Resistive switching

Advances in MET tyrosine kinase inhibitors in gastric cancer

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Cancer Biology & Medicine 2024年第6期21卷 484-498页

作者： Yifan zhang Lin Shen zhi Peng Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Department of Gastrointestinal Oncology Peking University Cancer Hospital & Institute State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers Beijing Key Laboratory of Carcinogenesis and Translational Research Department of Gastrointestinal Oncology Peking University Cancer Hospital & Institute

Gastric cancer is among the most frequently occurring cancers and a leading cause of cancer-related deaths globally. Because gastric cancer is highly heterogenous and comprised of different subtypes with distinct molecular and clinical characteristics, the management of gastric cancer calls for better-defined, biomarker-guided, molecular-based treatment strategies. MET is a receptor tyrosine kinase mediating important physiologic processes, such as embryogenesis, tissue regeneration, and wound healing. However, mounting evidence suggests that aberrant MET pathway activation contributes to tumour proliferation and metastasis in multiple cancer types, including gastric cancer, and is associated with poor patient outcomes. As such, MET-targeting therapies are being actively developed and promising progress has been demonstrated, especially with MET tyrosine kinase inhibitors. This review aims to briefly introduce the role of MET alterations in gastric cancer and summarize in detail the current progress of MET tyrosine kinase inhibitors in this disease area with a focus on savolitinib, tepotinib, capmatinib, and crizotinib. Building on current knowledge, this review further discusses existing challenges in MET alterations testing, possible resistance mechanisms to MET inhibitors, and future directions of MET-targeting therapies.

关键词： Gastric cancer MET alterations MET testing MET tyrosine kinase inhibitors savolitinib

Combination of diketone and PAO to achieve macroscale oil-based superlubricity at relative high contact pressures

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Friction 2024年第5期12卷 869-883页

作者： Shaonan DU Chenhui zhang zhi LUO State Key Laboratory of Tribology in Advanced Equipment Tsinghua UniversityBeijing100084China Beijing National Laboratory of Molecular Sciences CAS Key Laboratory of Engineering PlasticsInstitute of ChemistryChinese Academy of SciencesBeijing100190China

1-(4-ethylphenyl)-nonane-1,3-dione(0206)is an oil-soluble liquid molecule with rod-like structure.In this study,the chelate(0206-Fe)with octahedral structure was prepared by the reaction of ferric chloride and 1,3-diketone.The experimental results show that when using 0206 and a mixed solution containing 60%0206-Fe and 40%0206(0206-Fe(60%))as lubricants of the steel friction pairs,superlubricity can be achieved(0.007,0.006).But their wear scar diameters(WSD)were very large(532µm,370µm),which resulted in the pressure of only 44.3 and 61.8 MPa in the contact areas of the friction pairs.When 0206-Fe(60%)was mixed with PAO6,it was found that the friction coefficient(COF)decreased with increase of 0206-Fe(60%)in the solution.When the ratio of 0206-Fe(60%)to PAO6 was 8:2(PAO6(20%)),it exhibited better comprehensive tribological properties(232.3 MPa).Subsequent studies have shown that reducing the viscosity of the base oil in the mixed solution helped to reduce COF and increased WSD.Considering the COF,contact pressure,and running-in time,it was found that the mixed lubricant(Oil3(20%))prepared by the base oil with a viscosity of 19.7 mPa·s(Oil3)and 0206-Fe(60%)exhibited the best tribological properties(0.007,161.4 MPa,3,100 s).

关键词： diketone oil-based lubricants chelate superlubricity

Polaron interfacial entropy as a route to high thermoelectric performance in DAE-doped PEDOT:PSS films

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National Science Review 2024年第3期11卷 259-270页

作者： Jiajia zhang Caichao ye Genwang Wei Liang Guo Yuhang Cai zhi Li Xinzhi Wu Fangyi Sun Qikai Li Yupeng Wang Huan Li Yuchen Li Shuaihua Wang Wei Xu Xuefeng Guo Wenqing zhang Weishu Liu Department of Materials Science and Engineering Southern University of Science and Technology Academy for Advanced Interdisciplinary Studies and Guangdong Provincial Key Laboratory of Computational Science and Material Design Southern University of Science and Technology Department of Mechanical and Energy Engineering Southern University of Science and Technology Beijing National Laboratory for Molecular Sciences Key Laboratory of Organic Solids Institute of Chemistry Chinese Academy of Sciences College of Chemistry and Molecular Engineering National Biomedical Imaging Centre Peking University Guangdong Provincial Key Laboratory of Functional Oxide Materials and Devices Southern University of Science and Technology

Enhancing the thermoelectric transport properties of conductive polymer materials has been a long-term challenge, in spite of the success seen with molecular doping strategies. However, the strong coupling between the thermopower and the electrical conductivity limits thermoelectric performance. Here, we use polaron interfacial occupied entropy engineering to break through this intercoupling for a PEDOT:PSS(poly（3,4-ethylenedioxythiophene）-poly（4-styrenesulfonate）) thin film by using photochromic diarylethene（DAE） dopants coupled with UV-light modulation. With a 10-fold enhancement of the thermopower from 13.5 μV K-1to 135.4 μV K-1and almost unchanged electrical conductivity, the DAE-doped PEDOT:PSS thin film achieved an extremely high power factor of 521.28 μW m-1K-2from an original value of 6.78 μW m-1K-2. The thermopower was positively correlated with the UV-light intensity but decreased with increasing temperature, indicating resonant coupling between the planar closed DAE molecule and PEDOT. Both the experiments and theoretical calculations consistently confirmed the formation of an interface state due to this resonant coupling. Interfacial entropy engineering of polarons could play a critical role in enhancing the thermoelectric performance of the organic film.

关键词： thermoelectric PEDOT: PSS interfacial occupied entropy resonant coupling UV-light modulation

Elevated peripheral levels of receptor-interacting protein kinase 1(RIPK1)and IL-8 as biomarkers of human amyotrophic lateral sclerosis

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Signal Transduction and Targeted Therapy 2024年第1期9卷 271-278页

作者： Jun Wei Min Li zhi ye Xinqian Hu Xiaoyan He Jia Wang Gaofeng Chen Chengyu Zou Daichao Xu Hongbing zhang Junying Yuan Yunhong Zha Institute of Neural Regeneration and Repair and Department of Neurology The First College of Clinical Medical ScienceYichang Central HospitalCollege of Basic Medical ScienceChina Three Gorges UniversityHubei Province Clinical Medical Research Center for Rare Diseases of Nervous SystemYichang 443000China Interdisciplinary Research Center on Biology and Chemistry Shanghai Institute of Organic ChemistryChinese Academy of SciencesShanghai Key Laboratory of Aging StudiesShanghai 201210China State Key Laboratory of Common Mechanism Research for Major Diseases Haihe Laboratory of Cell EcosystemDepartment of PhysiologyInstitute of Basic Medical Sciences and School of Basic MedicineChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

Amyotrophic lateral sclerosis(ALS)is a devastating fatal neurodegenerative disease with no cure.Receptor-interacting protein kinase 1(RIPK1)has been proposed to mediate pathogenesis of ALS.Primidone has been identified as an old drug that can also inhibit RIPK1 kinase.We conducted a drug-repurposing biomarker study of primidone as a RIPK1 inhibitor using SOD1G93A mice and ALS patients.SOD1G93A mice treated with primidone showed significant delay of symptomatic onset and improved motor performance.One-hundred-sixty-two ALS participants dosed daily with primidone(62.5 mg)completed 24-week follow-up.A significant reduction was showed in serum levels of RIPK1 and IL-8,which were significantly higher in ALS patients than that of healthy controls(P<0.0001).Serum RIPK1 levels were correlated positively with the severity of bulbar symptoms(P<0.05).Our study suggests that serum levels of RIPK1 and IL-8 in peripheral can be used as clinical biomarkers for the activation of RIPK1 in central nervous system in human ALS patients.Repurposing primidone may provide a promising therapeutic strategy for ALS.The effect of primidone for the treatment of other inflammatory diseases may also be considered,since the activation of RIPK1 has been implicated in mediating a variety of inflammatory diseases including COVID-19-associated cytokine release syndrome(CRS).(ChiCTR2200060149).

关键词： RIPK1 diseases Serum