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World Journal of Gastroenterology 2024年第9期30卷 1224-1236页

作者： Hai-Yang Li Lin-Lin Zheng Nan Hu zhi-hao wang Chang-Cheng Tao Ya-Ru wang Yue Liu Zulihumaer Aizimuaji Hong-Wei wang Rui-Qi Zheng Ting Xiao Wei-Qi Rong Department of Hepatobiliary Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of Hepatobiliary Hernia Surgery Liaocheng Dongcangfu People’s HospitalLiaocheng 252000Shandong ProvinceChina State Key Laboratory of Molecular Oncology Department of Etiology and CarcinogenesisNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

BACKGROUND As a critical early event in hepatocellular carcinogenesis,telomerase activation might be a promising and critical biomarker for hepatocellular carcinoma(HCC)patients,and its function in the genesis and treatment of HCC has gained much attention over the past two decades.AIM To perform a bibliometric analysis to systematically assess the current state of research on HCC-related telomerase.METHODS The Web of Science Core Collection and PubMed were systematically searched to retrieve publications pertaining to HCC/telomerase limited to“articles”and“reviews”published in English.A total of 873 relevant publications related to HCC and telomerase were identified.We employed the Bibliometrix package in R to extract and analyze the fundamental information of the publications,such as the trends in the publications,citation counts,most prolific or influential writers,and most popular journals;to screen for keywords occurring at high frequency;and to draw collaboration and cluster analysis charts on the basis of coauthorship and co-occurrences.VOSviewer was utilized to compile and visualize the bibliometric data.RESULTS A surge of 51 publications on HCC/telomerase research occurred in 2016,the most productive year from 1996 to 2023,accompanied by the peak citation count recorded in 2016.Up to December 2023,35226 citations were made to all publications,an average of 46.6 citations to each paper.The United States received the most citations(n=13531),followed by China(n=7427)and Japan(n=5754).In terms of national cooperation,China presented the highest centrality,its strongest bonds being to the United States and Japan.Among the 20 academic institutions with the most publications,ten came from China and the rest of Asia,though the University of Paris Cité,Public Assistance-Hospitals of Paris,and the National Institute of Health and Medical Research(INSERM)were the most prolific.As for individual contributions,Hisatomi H,Kaneko S,and Ide T were the three most prolific authors.Kaneko S ranked first by H-index,G-index,

关键词： Telomerase Bibliometric analysis Telomerase reverse transcriptase Prognosis Treatment Hepatocellular carcinoma

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Learnware:small models do big

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Science China(Information Sciences) 2024年第1期67卷 39-50页

作者： zhi-Hua ZHOU zhi-hao TAN National Key Laboratory for Novel Software Technology Nanjing University

There are complaints about current machine learning techniques such as the requirement of a huge amount of training data and proficient training skills,the difficulty of continual learning,the risk of catastrophic forgetting,and the leaking of data privacy/proprietary.Most research efforts have been focusing on one of those concerned issues separately,paying less attention to the fact that most issues are entangled in practice.The prevailing big model paradigm,which has achieved impressive results in natural language processing and computer vision applications,has not yet addressed those issues,whereas becoming a serious source of carbon emissions.This article offers an overview of the learnware paradigm,which attempts to enable users not to need to build machine learning models from scratch,with the hope of reusing small models to do things even beyond their original purposes,where the key ingredient is the specification which enables a trained model to be adequately identified to reuse according to the requirement of future users who know nothing about the model in advance.

关键词： artificial intelligence machine learning learnware

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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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Intermittent Theta Burst Stimulation Attenuates Cognitive Deficits and Alzheimer’s Disease-Type Pathologies via ISCA1-Mediated Mitochondrial Modulation in APP/PS1 Mice

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Neuroscience Bulletin 2024年第2期40卷 182-200页

作者： Yang Zhu hao Huang zhi Chen Yong Tao Ling-Yi Liao Shi-hao Gao Yan-Jiang wang Chang-Yue Gao Department of Rehabilitation Medicine Daping HospitalArmy Medical UniversityChongqing 400042China Department of Neurology and Center for Clinical Neuroscience Daping HospitalArmy Medical UniversityChongqing 400042China Department of Special Medicine Daping HospitalArmy Medical UniversityChongqing 400042China

Intermittent theta burst stimulation(iTBS),a time-saving and cost-effective repetitive transcranial magnetic stimulation regime,has been shown to improve cognition in patients with Alzheimer’s disease(AD).However,the specific mechanism underlying iTBS-induced cognitive enhancement remains unknown.Previous studies suggested that mitochondrial functions are modulated by magnetic stimulation.Here,we showed that iTBS upregulates the expression of iron-sulfur cluster assembly 1(ISCA1,an essential regulatory factor for mitochondrial respiration)in the brain of APP/PS1 mice.In vivo and in vitro studies revealed that iTBS modulates mitochondrial iron-sulfur cluster assembly to facilitate mitochondrial respiration and function,which is required for ISCA1.Moreover,iTBS rescues cognitive decline and attenuates AD-type pathologies in APP/PS1 mice.The present study uncovers a novel mechanism by which iTBS modulates mitochondrial respiration and function via ISCA1-mediated iron-sulfur cluster assembly to alleviate cognitive impairments and pathologies in AD.We provide the mechanistic target of iTBS that warrants its therapeutic potential for AD patients.

关键词： Intermittent theta burst stimulation Alzheimer’s disease Iron-sulfur cluster assembly 1 Mitochondrial dysfunction Neurodegeneration

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Bioengineered skin organoids:from development to applications

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Military Medical Research 2024年第3期11卷 449-466页

作者： Zi-Xuan Hong Shun-Tian Zhu hao Li Jing-zhi Luo Yu Yang Yang An Xi wang Kai wang Department of Physiology and Pathophysiology School of Basic Medical SciencesState Key Laboratory of Vascular Homeostasis and RemodelingPeking UniversityBeijing 100191China Department of Hepatopancreatobiliary Surgery the Third Affiliated Hospital of Soochow UniversityChangzhou 213000JiangsuChina Department of Plastic Surgery Peking University Third HospitalBeijing 100191China Clinical Stem Cell Research Center Peking University Third HospitalBeijing 100191China State Key Laboratory of Cardiovascular Disease Fuwai HospitalBeijing 100037China Beijing Key Laboratory of Metabolic Disorder Related Cardiovascular Disease Capital Medical UniversityBeijing 100050China

Signifcant advancements have been made in recent years in the development of highly sophisticated skin organoids.Serving as three-dimensional(3D)models that mimic human skin,these organoids have evolved into complex structures and are increasingly recognized as efective alternatives to traditional culture models and human skin due to their ability to overcome the limitations of two-dimensional(2D)systems and ethical concerns.The inherent plasticity of skin organoids allows for their construction into physiological and pathological models,enabling the study of skin development and dynamic changes.This review provides an overview of the pivotal work in the progression from 3D layered epidermis to cyst-like skin organoids with appendages.Furthermore,it highlights the latest advancements in organoid construction facilitated by state-of-the-art engineering techniques,such as 3D printing and microfuidic devices.The review also summarizes and discusses the diverse applications of skin organoids in developmental biology,disease modelling,regenerative medicine,and personalized medicine,while considering their prospects and limitations.

关键词： Skin organoid Organoid generation Skin appendage Tissue engineering Disease modelling Regenerative medicine

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A novel alternative for pyrogen detection based on a transgenic cell line

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1221-1229页

作者： Qing He Chuan-Fei Yu Gang Wu Kai-Qin wang Yong-Bo Ni Xiao Guo zhi-hao Fu Lan wang De-Jiang Tan Hua Gao Can wang Gang Chen Xu-Hong Chen Bo Chen Jun-zhi wang National Institutes for Food and Drug Control BeijingChina School of Life Science and Biopharmaceutics Shenyang Pharmaceutical UniversityShenyangChina Shanghai Institute for Food and Drug Control ShanghaiChina KeyMed Biosciences Inc. ChengduChina

Pyrogen,often as a contaminant,is a key indicator affecting the safety of almost all parenteral drugs(including biologicals,chemicals,traditional Chinese medicines and medical devices).It has become a goal to completely replace the in vivo rabbit pyrogen test by using the in vitro pyrogen test based on the promoted‘reduction,replacement and refinement’principle,which has been highly considered by regulatory agencies from different countries.We used NF-κB,a central signalling molecule mediating inflammatory responses,as a pyrogenic marker and the monocyte line THP-1 transfected with a luciferase reporter gene regulated by NF-κB as an in vitro model to detect pyrogens by measuring the intensity of a fluorescence signal.Here,we show that this test can quantitatively and sensitively detect endotoxin(lipopolysaccharide from different strains)and nonendotoxin(lipoteichoic acid,zymosan,peptidoglycan,lectin and glucan),has good stability in terms of NF-κB activity and cell phenotypes at 39 cell passages and can be applied to detect pyrogens in biologicals(group A&C meningococcal polysaccharide vaccine;basiliximab;rabies vaccine(Vero cells)for human use,freeze-dried;Japanese encephalitis vaccine(Vero cells),inactivated;insulin aspart injection;human albumin;recombinant human erythropoietin injection(CHO Cell)).The within-laboratory reproducibility of the test in three independent laboratories was 85%,80%and 80%and the interlaboratory reproducibility among laboratories was 83.3%,95.6%and 86.7%.The sensitivity(true positive rate)and specificity(true negative rate)of the test were 89.9%and 90.9%,respectively.In summary,the test provides a novel alternative for pyrogen detection.

关键词： pyrogen rabbit replace

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METTL14 downregulation drives S100A4^(+)monocyte-derived macrophages via MyD88/NF-κB pathway to promote MAFLD progression

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2176-2192页

作者： Yue-fan wang Wen-li Zhang zhi-xuan Li Yue Liu Jian Tan hao-zan Yin zhi-chao Zhang Xian-jie Piao Min-hao Ruan zhi-hui Dai Si-jie wang Chen-yang Mu Ji-hang Yuan Shu-han Sun Hui Liu Fu Yang The Third Department of Hepatic Surgery Eastern Hepatobiliary Surgery Hospital Affiliated to Naval Medical University200438 ShanghaiChina The Department of Medical Genetics Naval Medical University200433 ShanghaiChina Translational Medicine Research Center Medical Innovation Research Division and Fourth Medical Center of the Chinese PLA General Hospital100048 BeijingChina The Department of Pharmaceutical Analysis School of PharmacyNaval Medical University200433 ShanghaiChina Key Laboratory of Biosafety Defense Ministry of Education200433 ShanghaiChina Shanghai Key Laboratory of Medical Biodefense 200433 ShanghaiChina

Without intervention,a considerable proportion of patients with metabolism‐associated fatty liver disease(MAFLD)will progress from simple steatosis to metabolism‐associated steatohepatitis(MASH),liver fibrosis,and even hepatocellular carcinoma.However,the molecular mechanisms that control progressive MAFLD have yet to be fully determined.Here,we unraveled that the expression of the N6-methyladenosine(m6A)methyltransferase METTL14 is remarkably downregulated in the livers of both patients and several murine models of MAFLD,whereas hepatocyte-specific depletion of this methyltransferase aggravated lipid accumulation,liver injury,and fibrosis.Conversely,hepatic Mettl14 overexpression alleviated the above pathophysiological changes in mice fed on a high-fat diet(HFD).Notably,in vivo and in vitro mechanistic studies indicated that METTL14 downregulation decreased the level of GLS2 by affecting the translation efficiency mediated by YTHDF1 in an m6A-depedent manner,which might help to form an oxidative stress microenvironment and accordingly recruit Cx3cr1^(+)Ccr2^(+)monocyte-derived macrophages(Mo-macs).In detail,Cx3cr1^(+)Ccr2^(+)Mo-macs can be categorized into M1-like macrophages and S100A4-positive macrophages and then further activate hepatic stellate cells(HSCs)to promote liver fibrosis.Further experiments revealed that CX3CR1 can activate the transcription of S100A4 via CX3CR1/MyD88/NF-κB signaling pathway in Cx3cr1^(+)Ccr2^(+)Mo-macs.Restoration of METTL14 or GLS2,or interfering with this signal transduction pathway such as inhibiting MyD88 could ameliorate liver injuries and fibrosis.Taken together,these findings indicate potential therapies for the treatment of MAFLD progression.

关键词： S100A4 MyD88 metabolism

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Sigmatropic rearrangements of B(MIDA)-propargylic alcohols towards the diverse synthesis of α-functionalized organoborons

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Science China Chemistry 2024年第2期67卷 568-575页

作者： Jiasheng Qian Li-Cai Liu zhi-hao Chen Yuan Liu Yin Li Qingjiang Li Honggen wang Guangdong Key Laboratory of Chiral Molecule and Drug Discovery School of Pharmaceutical SciencesSun Yat-Sen UniversityGuangzhou510006China

α-Functionalized organoborons are useful building blocks and key structural elements in functional molecules.Their previous synthesis relied on the famous Matteson reaction or the late-stage borylative modification of alkynes or alkenes.Recently,the synthetic transformation of borylated building blocks offers another useful strategy and is currently actively explored.We report herein that B(MIDA)-propargylic alcohols(BPAs) are a useful type of borylated building blocks.Bearing two complementary functional group handles(alkyne and hydroxyl) in close proximity,the redox-neutral [3,3] and [2,3] sigmatropic rearrangements of BPAs allow the efficient synthesis of several types of α-functionalized boronates,including α,β-unsaturated acylborons,α-S/P-substituted allenylborons,boryl-substituted thiazoles and a borylated α,β-unsaturated hydrazine,some of which are otherwise challenging targets using other synthetic methods.

关键词： organoboron diverse synthesis sigmatropic rearrangement heteroarene amide

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Verteporfin fluorescence in antineoplastic-treated pancreatic cancer cells found concentrated in mitochondria

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 968-978页

作者： Ying-Qiao Zhang Qing-hao Liu Lu Liu Peng-Yu Guo Run-Ze wang zhi-Chang Ba Department of Radiology Harbin Medical University Cancer HospitalHarbin 150010Heilongjiang ProvinceChina Department of Digestive Internal Medicine Harbin Medical University Cancer HospitalHarbin 150010Heilongjiang ProvinceChina

BACKGROUND Traditional treatments for pancreatic cancer(PC)are inadequate.Photodynamic therapy(PDT)is non-invasive,and proven safe to kill cancer cells,including PC.However,the mitochondrial concentration of the photosensitizer,such as verteporfin,is key.AIM To investigate the distribution of fluorescence of verteporfin in PC cells treated with antitumor drugs,post-PDT.METHODS Workable survival rates of PC cells(AsPC-1,BxPC-3)were determined with chemotherapy[doxorubicin(DOX)and gemcitabine(GEM)]and non-chemotherapy[sirolimus(SRL)and cetuximab(CTX)]drugs in vitro,with or without verteporfin,as measured via MTT,flow cytometry,and laser confocal microscopy.Reduced cell proliferation was associated with GEM that was more enduring compared with DOX.Confocal laser microscopy allowed observation of GEM-and verteporfin-treated PC cells co-stained with 4’,6-diamidino-2-phenylindole and MitoTracker Green to differentiate living and dead cells and subcellular localization of verteporfin,respectively.RESULTS Cell survival significantly dropped upon exposure to either chemotherapy drug,but not to SRL or CTX.Both cell lines responded similarly to GEM.The intensity of fluorescence was associated with the concentration of verteporfin.Additional experiments using GEM showed that survival rates of the PC cells treated with 10μmol/L verteporfin(but not less)were significantly lower relative to nil verte-porfin.Living and dead stained cells treated with GEM were distinguishable.After GEM treatment,verteporfin was observed primarily in the mitochondria.CONCLUSION Verteporfin was observed in living cells.In GEM-treated human PC cells,verteporfin was particularly prevalent in the mitochondria.This study supports further study of PDT for the treatment of PC after neoadjuvant chemotherapy.

关键词： Photodynamic therapy Pancreatic cancer Verteporfin Mitochondria Chemotherapy Gemcitabine

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Insight into structural degradation of NCMs under extreme fast charging process

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Rare Metals 2024年第1期43卷 41-50页

作者： Yu Tang Xing-Yu wang Jin-Can Ren Bo-Wen Chen zhi-Yong Huang Wei wang Ya-Lan Huang Bing-hao Zhang Si Lan Zhang-Long He Qi Liu hao He Department of Physics City University of Hong KongHong Kong 999077China Shenzhen Research Institute City University of Hong KongShenzhen 518057China College of Materials Science and Engineering Changsha University of Science&TechnologyChangsha 410114China

Lithium-ion batteries(LIBs)with extreme fast charging(XFC)capability are considered an effective way to alleviate range anxiety for electric vehicle(EV)buyers.Owing to the high ionic and electronic conductivity of LiNi_(x)Co_(y)Mn_zO_(2)(x+y+z=1,NCM)cathodes,the inevitable Li plating of graphite in NCM|graphite cell is usually identified as a key bottleneck for XFC LIBs.However,the capacity decay mechanism of cathode materials under XFC has not been fully investigated.In this work,three typical NCM cathode materials with different Ni fractions were chosen and their electrochemical performances under XFC associated with structural evolution were investigated.A faster capacity decay of NCMs under XFC conditions is observed,especially for Ni-rich NCMs.In-situ X-ray diffraction(XRD)reveals that the multiple caxis parameters appear at the high-voltage regions in Nirich NCMs,which is probably triggered by the larger obstruction of Li(de)intercalation.Particularly,NCMs with moderate Ni fraction also present a similar trend under XFC conditions.This phenomenon is more detrimental to the structural and morphological stability,resulting in a faster capacity decay than that under low current charging.This work provides new insight into the degradation mechanism of NCMs under XFC conditions,which can promote the development of NCM cathode materials with XFC capability.

关键词： Lithium-ion batteries Ni fraction Extreme fast charging Structural evolution

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