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Targeting lncRNA16 by GalNAc-siRNA conjugates facilitates chemotherapeutic sensibilization via the HBB/NDUFAF5/ROS pathway

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Science China(Life Sciences) 2024年第4期67卷 663-679页

作者： Yanfang Liu Yan Wang Bing Liu Wenzhong Liu Yuanyuan Ma Yiren Cao Shi Yan Panpan Zhang Lixin Zhou Qimin Zhan Nan Wu Key laboratory of Carcinogenesis and Translational research(Ministry of education/Beijing) Department of Thoracic Surgery IIPeking University Cancer Hospital and InstituteBeijing 100142China Key laboratory of Carcinogenesis and Translational research(Ministry of education/Beijing) Laboratory of Molecular OncologyPeking University Cancer Hospital and InstituteBeijing 100142China Key laboratory of Carcinogenesis and Translational research(Ministry of education/Beijing) Department of Thoracic Oncology IIPeking University Cancer Hospital and InstituteBeijing 100142China Key laboratory of Carcinogenesis and Translational research(Ministry of education) Department of PathologyPeking University Cancer Hospital and InstituteBeijing 100142China Peking University International Cancer Institute Beijing 100191China Institute of Cancer research Shenzhen Bay LaboratoryShenzhen 518132China

Chemoresistance is a significant barrier to effective cancer treatment.Potential mechanisms for chemoresistance include reactive oxygen species(ROS)accumulation and expression of chemoresistance-promoting genes.Here,we report a novel function of lncRNA16 in the inhibition of ROS generation and the progression of chemoresistance.By analyzing the serum levels of lncRNA16 in a cohort of 35 patients with non-small cell lung cancer(NSCLC)and paired serum samples pre-and post-treatment from 10 NSCLC patients receiving neoadjuvant platinum-based chemotherapy,performing immunohistochemistry(IHC)assays on 188 NSCLC tumor samples,using comprehensive identification of RNA-binding proteins by mass spectrometry(ChIRP-MS)assays,as well as RNA immunoprecipitation(RIP)and RNA pull-down analyses,we discovered that patients with increased serum levels of lncRNA16 exhibited a poor response to platinum-based chemotherapy.The expression of hemoglobin subunit beta(HBB)and NDUFAF5 significantly increases with the development of chemoresistance.LncRNA16 binds to HBB and promotes HBB accumulation by inhibiting autophagy.LncRNA16 can also inhibit ROS generation via the HBB/NDUFAF5 axis and function as a scaffold to facilitate the colocalization of HBB and NDUFAF5 in the mitochondria.Importantly,preclinical studies in mouse models of chemo-resistant NSCLC have suggested that lncRNA16 targeting by trivalent N-acetylgalactosamine(GalNAc)-conjugated siRNA restores chemosensitivity and results in tumor growth inhibition with no detectable toxicity in vivo.Overall,lncRNA16 is a promising therapeutic target for overcoming chemoresistance,and the combination of first-line platinum-based chemotherapy with lncRNA16 intervention can substantially enhance anti-tumor efficacy.

关键词： chemoresistance lncRNARNA interference ROs chemosensitizer

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Bias distribution and regulation in photoelectrochemical overall water-splitting cells

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National Science Review 2024年第4期11卷 141-150页

作者： Kun Dang Siqin Liu Lei Wu Daojian Tang Jing Xue Jiaming Wang Hongwei Ji Chuncheng Chen Yuchao Zhang Jincai Zhao Key laboratory of Photochemistry CAS ResearchEducation Center for Excellence in Molecular Sciences Institute of Chemistry Chinese Academy of Sciences University of Chinese Academy of Sciences

The water oxidation half-reaction at anodes is always considered the rate-limiting step of overall water splitting（OWS）,but the actual bias distribution between photoanodes and cathodes of photoelectro chemical（PEC） OWS cells has not been investigated systematically.In this work,we find that,for PEC cells consisting of photoanodes（nickel-modified n-Si [Ni/n-Si] and α-Fe2O3） with low photovoltage(Vph 1V,the bias required for cathode activation can be significantly reduced,exhibiting a kinetics-controlled characteristic.Further investigations show that the bias distribution can be regulated by tuning the electrolyte pH and using alternative half-reaction couplings.Accordingly,a volcano plot is presented for the rational design of the overall reactions and unbiased PEC cells.Motivated by this,an unbiased PEC cell consisting of a simple Ni/n-Si photoanode and Pt cathode is assembled,delivering a photo current density of 5.3±0.2 mA cm-2.

关键词： photoelectrochemistry overall reaction cell bias distribution photoanode water splitting

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Twisted Integration of Complex Oxide Magnetoelectric Heterostructures via Water‑Etching and Transfer Process

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Nano-Micro Letters 2024年第1期16卷 360-369页

作者： Guannan Yang Guohua Dong Butong Zhang Xu Xu Yanan Zhao Zhongqiang Hu Ming Liu State Key laboratory for Manufacturing Systems Engineering Electronic Materials Research LaboratoryKey Laboratory of the Ministry of EducationEngineering Research Center of Spin Quantum Sensor ChipsUniversities of Shaanxi ProvinceSchool of Electronic Science and EngineeringXi’an Jiaotong UniversityXi’an 710049People’s Republic of China

Manipulating strain mode and degree that can be applied to epitaxial complex oxide thin films have been a cornerstone of strain engineering.In recent years,lift-off and transfer technology of the epitaxial oxide thin films have been developed that enabled the integration of heterostructures without the limitation of material types and crystal orientations.Moreover,twisted integration would provide a more interesting strategy in artificial magnetoelectric heterostructures.A specific twist angle between the ferroelectric and ferromagnetic oxide layers corresponds to the distinct strain regulation modes in the magnetoelectric coupling process,which could provide some insight in to the physical phenomena.In this work,the La_(0.67)Sr_(0.33)MnO_(3)(001)/0.7Pb(Mg_(1/3)Nb_(2/3))O_(3)-0.3PbTiO_(3)(011)(LSMO/PMN-PT)heterostructures with 45.and 0.twist angles were assembled via water-etching and transfer process.The transferred LSMO films exhibit a fourfold magnetic anisotropy with easy axis along LSMO.A coexistence of uniaxial and fourfold magnetic anisotropy with LSMO[110]easy axis is observed for the 45°Sample by applying a 7.2 kV cm^(−1)electrical field,significantly different from a uniaxial anisotropy with LSMO[100]easy axis for the 0°Sample.The fitting of the ferromagnetic resonance field reveals that the strain coupling generated by the 45°twist angle causes different lattice distortion of LSMO,thereby enhancing both the fourfold and uniaxial anisotropy.This work confirms the twisting degrees of freedom for magnetoelectric coupling and opens opportunities for fabricating artificial magnetoelectric heterostructures.

关键词： Magnetoelectric heterostructures Twist angle Epitaxial lift-off Magnetic anisotropy Ferromagnetic resonance

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Value of multiple models of diffusion-weighted imaging to predict hepatic lymph node metastases in colorectal liver metastases patients

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World Journal of Gastroenterology 2024年第4期30卷 308-317页

作者： Hai-Bin Zhu Bo Zhao Xiao-Ting Li Xiao-Yan Zhang Qian Yao Ying-Shi Sun Key laboratory of Carcinogenesis and Translational research(Ministry of education/Beijing) Department of RadiologyPeking University Cancer Hospital and InstituteBeijing 100142China Key laboratory of Carcinogenesis and Translational research(Ministry of education/Beijing) Department of PathologyPeking University Cancer Hospital and InstituteBeijing 100142China

BACKGROUND About 10%-31% of colorectal liver metastases(CRLM)patients would concomitantly show hepatic lymph node metastases(LNM),which was considered as sign of poor biological behavior and a relative contraindication for liver resection.Up to now,there’s still lack of reliable preoperative methods to assess the status of hepatic lymph nodes in patients with CRLM,except for pathology examination of lymph node after resection.AIM To compare the ability of mono-exponential,bi-exponential,and stretchedexponential diffusion-weighted imaging(DWI)models in distinguishing between benign and malignant hepatic lymph nodes in patients with CRLM who received neoadjuvant chemotherapy prior to surgery.METHODS In this retrospective study,97 CRLM patients with pathologically confirmed hepatic lymph node status underwent magnetic resonance imaging,including DWI with ten b values before and after chemotherapy.Various parameters,such as the apparent diffusion coefficient from the mono-exponential model,and the true diffusion coefficient,the pseudo-diffusion coefficient,and the perfusion fraction derived from the intravoxel incoherent motion model,along with distributed diffusion coefficient(DDC)andαfrom the stretched-exponential model(SEM),were measured.The parameters before and after chemotherapy were compared between positive and negative hepatic lymph node groups.A nomogram was constructed to predict the hepatic lymph node status.The reliability and agreement of the measurements were assessed using the coefficient of variation and intraclass correlation coefficient.RESULTS Multivariate analysis revealed that the pre-treatment DDC value and the short diameter of the largest lymph node after treatment were independent predictors of metastatic hepatic lymph nodes.A nomogram combining these two factors demonstrated excellent performance in distinguishing between benign and malignant lymph nodes in CRLM patients,with an area under the curve of 0.873.Furthermore,parameters from SEM showed substantial repeatability.CONCLUSION The dev

关键词： Colorectal cancer Individualized treatment Diffusion magnetic resonance imaging Intravoxel incoherent motion Liver

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Exceptional points enhance sensing in silicon micromechanical resonators

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Microsystems & Nanoengineering 2024年第1期10卷 17-25页

作者： Man-Na Zhang Lei Dong Li-Feng Wang Qing-An Huang Key laboratory of MEMS of the Ministry of education Southeast UniversityNanjing 210096China

Exceptional points(EPs)have recently emerged as a new method for engineering the response of open physical systems,that is,systems that interact with the environment.The systems at the EPs exhibit a strong response to a small perturbation.Here,we show a method by which the sensitivity of silicon resonant sensors can be enhanced when operated at EPs.In our experiments,we use a pair of mechanically coupled silicon micromechanical resonators constituting a parity-time(PT)-symmetric dimer.Small perturbations introduced on the mechanically coupled spring cause the frequency to split from the EPs into the PT-symmetric regime without broadening the two spectrum linewidths,and this frequency splitting scales with the square root of the perturbation strength.The overall signal-tonoise ratio is still greatly enhanced,although the measured noise spectral density of the EP sensing scheme has a slight increase comparable to the traditional counterpart.Our results pave the way for resonant sensors with ultrahigh sensitivity.

关键词： resonant symmetric points

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PDK1 promotes breast cancer progression by enhancing the stability and transcriptional activity of HIF-1α

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Genes & Diseases 2024年第4期11卷 353-367页

作者： Yu Wei Dian Zhang He Shi Husun Qian Hongling Chen Qian Zeng Fangfang Jin Yan Ye Zuli Ou Minkang Guo Bianqin Guo Tingmei Chen Key laboratory of Clinical laboratory Diagnostics(Ministry of education) College of Laboratory MedicineChongqing Medical UniversityChongqing 400016China Chongqing Key laboratory of Translational research for Cancer Metastasis and Individualized Treatment Chongqing University Cancer HospitalChongqing 400030China

Pyruvate dehydrogenase kinase 1(PDK1)phosphorylates the pyruvate dehydroge-nase complex,which inhibits its activity.Inhibiting pyruvate dehydrogenase complex inhibits the tricarboxylic acid cycle and the reprogramming of tumor cell metabolism to glycolysis,which plays an important role in tumor progression.This study aims to elucidate how PDK1 pro-motes breast cancer progression.We found that PDK1 was highly expressed in breast cancer tissues,and PDK1 knockdown reduced the proliferation,migration,and tumorigenicity of breast cancer cells and inhibited the HIF-1α(hypoxia-inducible factor 1a)pathway.Further investigation showed that PDK1 promoted the protein stability of HIF-1αby reducing the level of ubiquitination of HIF-1a.The HIF-1αprotein levels were dependent on PDK1 kinase activity.Furthermore,HIF-1a phosphorylation at serine 451 was detected in wild-type breast cancer cells but not in PDK1 knockout breast cancer cells.The phosphorylation of HIF-1αat Ser 451 stabilized its protein levels by inhibiting the interaction of HIF-1a with von Hippel-Lindau and prolyl hydroxylase domain.We also found that PDK1 enhanced HIF-1αtranscriptional ac-tivity.In summary,PDK1 enhances HIF-1αprotein stability by phosphorylating HIF-1a at Ser451 and promotes HIF-1αtranscriptional activity by enhancing the binding of HIF-1αto P300.PDK1 and HIF-1a form a positive feedback loop to promote breast cancer progression.

关键词： Breast cancer HIF-1α PDK1 Protein phosphorylation Transcriptional activity

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Homogenous coating of Li+ conductive Li5AlO4 on single-crystalline nonstoichiometric Li1.04Ni0.92Al0.04O2 for rechargeable lithium-ion batteries

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Journal of Energy Chemistry 2024年第8期95卷 651-659页

作者： Guoyu Ding Shizhou Wang Jinhan Li Ziyan Wu Jiayu Chen Jiayong Du Xinhui Huang Kuiming Liu Yudong Zhang Zhonghan Wu Yiyang Peng Qiancheng Zhao Meng Yu Fangyi Cheng Key laboratory of Advanced Energy Materials Chemistry(Ministry of education) Engineering Research Center of High-efficiency Energy Storage(Ministry of Education) College of Chemistry Nankai University State Key laboratory of Advanced Chemical Power Sources Nankai University Haihe laboratory of Sustainable Chemical Transformations

Cobalt-free,nickel-rich LiNi1-xAlxO2（x ≤ 0.1） is an attractive cathode material because of high energy density and low cost but suffers from severe structural degradation and poor rate performance.In this study,we propose a molten salt-assisted synthesis in combination with a Li-refeeding induced aluminum segregation strategy to prepare Li5AlO4-coated single-crystalline slightly Li-rich Li1.04Ni0.92Al0.04O2.The symbiotic formation of Li5AlO4from reaction between molten lithium hydroxide and doped aluminum in the bulk ensures a high lattice matching between the Ni-rich oxide and the homogenous conductive Li5AlO4that permits high Li+conductivity.Benefiting from mitigated undesirable side reactions and phase evolution,the Li5AlO4-coated single-crystalline Li1.04Ni0.92Al0.04O2delivers a high specific capacity of220.2 mA h g-1at 0.1 C and considerable rate capability(182.5 mA h g-1at 10 C).Besides,superior capacity retention of 90.8% is obtained at 1/3 C after 100 cycles in a 498.1 mA h pouch full cell.Furthermore,the particulate morphology of Li1.04Ni0.92Al0.04O2remains intact after cycling at a cutoff voltage of 4.3 V,whereas slightly Li-deficient Li0.98Ni0.97Al0.05O2features intragranular cracks and irreversible lattice distortion.The results highlight the value of molten salt-assisted synthesis and Li-refeeding induced elemental segregation strategy to upgrade Ni-based layered oxide cathode materials for advanced Li-ion batteries.

关键词： Aluminum segregation Cathode materials Molten synthesis Nonstoichiometric oxides Surface coating

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Ultrafast micro/nano-manufacturing of metastable materials for energy

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National Science Review 2024年第4期11卷 283-298页

作者： Xiaoya Cui Yanchang Liu Yanan Chen School of Materials Science and Engineering Key Laboratory of Advanced Ceramics and Machining Technology(Ministry of Education) and Tianjin Key Laboratory of Composite and Functional MaterialsTianjin University Ministry of education Key laboratory of Protein Sciences School of Life SciencesTsinghua University

The structural engineering of metastable nanomaterials with abundant defects has attracted much attention in energy-related fields. The high-temperature shock(HTS) technique, as a rapidly developing and advanced synthesis strategy, offers significant potential for the rational design and fabrication of high-quality nanocatalysts in an ultrafast, scalable, controllable and eco-friendly way. In this review, we provide an overview of various metastable micro-and nanomaterials synthesized via HTS, including single metallic and bimetallic nanostructures, high entropy alloys, metal compounds(e.g. metal oxides) and carbon nanomaterials. Note that HTS provides a new research dimension for nanostructures, i.e. kinetic modulation. Furthermore, we summarize the application of HTS—as supporting films for transmission electron microscopy grids—in the structural engineering of 2D materials, which is vital for the direct imaging of metastable materials. Finally, we discuss the potential future applications of high-throughput and liquid-phase HTS strategies for non-equilibrium micro/nano-manufacturing beyond energy-related fields.It is believed that this emerging research field will bring new opportunities to the development of nanoscience and nanotechnology in both fundamental and practical aspects.

关键词： high-temperature shock technique defect engineering metastable phase kinetic modulation non-equilibrium micro/nano-manufacturing

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Polysaccharides from Chinese herbal medicine:a review on the hepatoprotective and molecular mechanism

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Chinese Journal of Natural Medicines 2024年第1期22卷 4-14页

作者： LI Jifeng GUO Haolin DONG Ying YUAN Shuo WEI Xiaotong ZHANG Yuxin DONG Lu WANG Fei BAI Ting YANG Yong Dalian Key laboratory of Chronic Disease research Center Dalian UniversityDalian 116622China Key laboratory of Natural Medicines of the Changbai Mountain Ministry of EducationCollege of PharmacyYanbian UniversityYanji 133002China

Polysaccharides,predominantly extracted from traditional Chinese medicinal herbs such as Lycium barbarum,Angelica sinensis,Astragalus membranaceus,Dendrobium officinale,Ganoderma lucidum,and Poria cocos,represent principal bioactive constituents extensively utilized in Chinese medicine.These compounds have demonstrated significant anti-inflammatory capabilities,especially anti-liver injury activities,while exhibiting minimal adverse effects.This review summarized recent studies to elucidate the hepatoprotective efficacy and underlying molecular mechanisms of these herbal polysaccharides.It underscored the role of these polysaccharides in regulating hepatic function,enhancing immunological responses,and improving antioxidant capacities,thus contributing to the attenuation of hepatocyte apoptosis and liver protection.Analyses of molecular pathways in these studies revealed the intricate and indispensable functions of traditional Chinese herbal polysaccharides in liver injury management.Therefore,this review provides a thorough examination of the hepatoprotective attributes and molecular mechanisms of these medicinal polysaccharides,thereby offering valuable insights for the advancement of polysaccharide-based therapeutic research and their potential clinical applications in liver disease treatment.

关键词： Polysaccharides Hepatoprotective Chinese herbal medicine Mechanism

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Gut-targeted therapies for type 2 diabetes mellitus: A review

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World Journal of Clinical Cases 2024年第1期12卷 1-8页

作者： Tian-Cheng Xu Yun Liu Zhi Yu Bin Xu Key laboratory of Acupuncture and Medicine research of Ministry of education Nanjing University of Chinese MedicineNanjing 210023Jiangsu ProvinceChina

Type 2 diabetes mellitus(T2DM)is a chronic metabolic disorder characterized by hyperglycemia and insulin resistance.The global prevalence of T2DM has reached epidemic proportions,affecting approximately 463 million adults worldwide in 2019.Current treatments for T2DM include lifestyle modifications,oral antidiabetic agents,and insulin therapy.However,these therapies may carry side effects and fail to achieve optimal glycemic control in some patients.Therefore,there is a growing interest in the role of gut microbiota and more gut-targeted therapies in the management of T2DM.The gut microbiota,which refers to the community of microorganisms that inhabit the human gut,has been shown to play a crucial role in the regulation of glucose metabolism and insulin sensitivity.Alterations in gut microbiota composition and diversity have been observed in T2DM patients,with a reduction in beneficial bacteria and an increase in pathogenic bacteria.This dysbiosis may contribute to the pathogenesis of the disease by promoting inflammation and impairing gut barrier function.Several gut-targeted therapies have been developed to modulate the gut microbiota and improve glycemic control in T2DM.One potential approach is the use of probio-tics,which are live microorganisms that confer health benefits to the host when administered in adequate amounts.Several randomized controlled trials have demonstrated that certain probiotics,such as Lactobacillus and Bifidobacterium species,can improve glycemic control and insulin sensitivity in T2DM patients.Mechanisms may include the production of short-chain fatty acids,the improvement of gut barrier function,and the reduction of inflammation.Another gut-targeted therapy is fecal microbiota transplantation(FMT),which involves the transfer of fecal material from a healthy donor to a recipient.FMT has been used successfully in the treatment of Clostridioides difficile infection and is now being investigated as a potential therapy for T2DM.A recent randomized controlled trial showed that FMT from lea

关键词： Type 2 diabetes mellitus Gastroenterology Bacteria Implanted device

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