Surgery is the comm on treatme nt for early lung cancer with multiple pulm onary no dules,but it is often accompanied by the problem of significant malignancy of other nodules in non-therapeutic areas.In this study,we...Surgery is the comm on treatme nt for early lung cancer with multiple pulm onary no dules,but it is often accompanied by the problem of significant malignancy of other nodules in non-therapeutic areas.In this study,we found that a combined treatment of local rad iofreq ue ncy ablati on(RFA)and melatonin(MLT)greatly improved clinical outcomes for early lung cancer patie nts with multiple pulmonary nodules by minimizing lung function injury and reducing the probability of malignant transformation or enlargement of nodules in non-ablated areas.Mechanically,as demonstrated in an associated mouse lung tumor model,RFA not only effectively remove treated tumors but also stimulate antitumor immunity,which could inhibit tumor growth in non-ablated areas.MLT enhanced RFA-stimulated NK activity and exerted synergistic antitumor effects with RFA.Transcriptomics and proteomics analyses of residual tumor tissues revealed enhanced oxidative phosphorylation and reduced acidification as well as hypoxia in the tumor microenvironment,which suggests reprogrammed tumor metabolism after combined treatment with RFA and MLT.Analysis of residual tumor further revealed the depressed activity of MAPK,NF-kappa B,Wnt,and Hedgehog pathways and upregulated P53 pathway in tumors,which was in line with the inhibited tumor growth.Combined RFA and MLT treatment also reversed the Warburg effect and decreased tumor malignancy.These findings thus demonstrated that combined treatment of RFA and MLT effectively inhibited the malignancy of non-ablated nodules and provided an innovative non-invasive strategy for treating early lung tumors with multiple pulmonary nodules.Trial registration:www.chictr.org.cn,identifier ChiCTR2100042695,http://www.chictr.org.cn/showproj.aspx?proj=120931.展开更多
To address the increasing need for detecting and validating protein biomarkers in clinical specimens,mass spectrometry(MS)-based targeted proteomic techniques,including the selected reaction monitoring(SRM),parallel r...To address the increasing need for detecting and validating protein biomarkers in clinical specimens,mass spectrometry(MS)-based targeted proteomic techniques,including the selected reaction monitoring(SRM),parallel reaction monitoring(PRM),and massively parallel dataindependent acquisition(DIA),have been developed.For optimal performance,they require the fragment ion spectra of targeted peptides as prior knowledge.In this report,we describe a MS pipeline and spectral resource to support targeted proteomics studies for human tissue samples.To build the spectral resource,we integrated common open-source MS computational tools to assemble a freely accessible computational workflow based on Docker.We then applied the workflow to generate DPHL,a comprehensive DIA pan-human library,from 1096 data-dependent acquisition(DDA)MS raw files for 16 types of cancer samples.This extensive spectral resource was then applied to a proteomic study of 17 prostate cancer(PCa)patients.Thereafter,PRM validation was applied to a larger study of 57 PCa patients and the differential expression of three proteins in prostate tumor was validated.As a second application,the DPHL spectral resource was applied to a study consisting of plasma samples from 19 diffuse large B cell lymphoma(DLBCL)patients and 18 healthy control subjects.Differentially expressed proteins between DLBCL patients and healthy control subjects were detected by DIA-MS and confirmed by PRM.These data demonstrate that the DPHL supports DIA and PRM MS pipelines for robust protein biomarker discovery.DPHL is freely accessible at https://www.iprox.org/page/project.html?id=IPX0001400000.展开更多
The architecture and surface modifications have been regarded as effective methods to enhance the bi-ological response of biomaterials in bone tissue engineering.The porous architecture of the implanta-tion was essent...The architecture and surface modifications have been regarded as effective methods to enhance the bi-ological response of biomaterials in bone tissue engineering.The porous architecture of the implanta-tion was essential conditions for bone regeneration.Meanwhile,the design of biomimetic hydroxyap-atite(HAp)coating on porous scaffolds was demonstrated to strengthen the bioactivity and stimulate osteogenesis.However,bioactive bio-ceramics such asβ-tricalcium phosphate(β-TCP)and calcium sili-cate(CS)with superior apatite-forming ability were reported to present better osteogenic activity than that of HAp.Hence in this study,3D-printed interconnected porous bioactive ceramicsβ-TCP/CS scaf-fold was fabricated and the biomimetic HAp apatite coating were constructed in situ via hydrothermal reaction,and the effects of HAp apatite layer on the fate of mouse bone mesenchymal stem cells(mBM-SCs)and the potential mechanisms were explored.The results indicated that HAp apatite coating en-hanced cell proliferation,alkaline phosphatase(ALP)activity,and osteogenic gene expression.Further-more,PI3K/AKT/mTOR signaling pathway is proved to have an important impact on cellular functions.The present results demonstrated that the key molecules of phosphatidylinositol 3-kinase(PI3K),protein kinase B(AKT)and mammalian target of rapamycin(mTOR)were activated after the biomimetic hydrox-yapatite coating were constructed on the 3D-printed ceramic scaffolds.Besides,the activated influence on the protein expression of Runx2 and BMP2 could be suppressed after the treatment of inhibitor HY-10358.In vivo studies showed that the constructed HAp coating promoted bone formation and strengthen the bone quality.These results suggest that biomimetic HAp coating constructed on the 3D-printed bioac-tive composite scaffolds could strengthen the bioactivity and the obtained biomimetic multi-structured scaffolds might be a potential alternative bone graft for bone regeneration.展开更多
Dear Editor,Kras and p53 mutation are among the most common gene mutations in lung cancer,which has both the highest incidence and mortality rate among cancers.1 Kras/p53 mutation also causes mitochondrial dysfunction...Dear Editor,Kras and p53 mutation are among the most common gene mutations in lung cancer,which has both the highest incidence and mortality rate among cancers.1 Kras/p53 mutation also causes mitochondrial dysfunction,which has been implicated to promote the inflammation-to-cancer transition.2 We established a lung adenocarcinoma model by using conditional alleles of KrasLSLG12D/p53flox/flox in mice3 to evaluate the effect of Baicalein(5,6,7-trihydroxyflavone),a principal component of Scutellaria baicalensis in traditional Chinese medicine,4 on the initiation and progression of lung cancer.Cre-mediated expression of KrasG12D and deletion of p53 caused obvious tumor lesions in the lung,which were strongly inhibited by the administration of Baicalein(Fig.1a,b and Supplementary Fig.1a,b),indicating that Baicalein is highly potent in inhibiting the progression of primary lung cancer.展开更多
The potential application of gold nanoparticles(GNPs)in biomedicine has been extensively reported.However,there is still too much puzzle about their real face and potential health risks in comparison with the commerci...The potential application of gold nanoparticles(GNPs)in biomedicine has been extensively reported.However,there is still too much puzzle about their real face and potential health risks in comparison with the commercial drug molecules.The emergence of atomically precise gold nanoclusters(APGNCs)provides the opportunity to address the puzzle due to their ultrasmall size,defined molecular formula,editable surface engineering,available structures and unique physicochemical properties including excellent biocompatibility,strong luminescence,enzyme-like activity and efficient renal clearance,et al.Recently,these advantages of APGNCs also endow them promising performances in healthcare such as bioimaging,drug delivery,antibacterial and cancer therapy.Especially,their clear composition and structures like the commercial drug molecules facilitate the study of their functions and the structure-activity relationship in healthcare,which is essential for the guided design of APGNC nanomedicine.Therefore,this review will focus the advantages and recent progress of APGNCs in health care and envision their prospects for the future.展开更多
Tissue engineering aims to offer large-scale replacement of damaged organs using implants with the com-bination of cells,growth factors and scaffolds.However,the intra/peri-implant region is exposed to se-vere hypoxic...Tissue engineering aims to offer large-scale replacement of damaged organs using implants with the com-bination of cells,growth factors and scaffolds.However,the intra/peri-implant region is exposed to se-vere hypoxic stress and oxidative stress during the early stage of implantation with bone graft materials,which endangers the survival,proliferation and differentiation of seed cells within the implants as well as the host cells surrounding the implants.If the bone graft material could spontaneously and intelligently regulate the hypoxic stress and oxidative stress to a moderate level,it will facilitate the vascularization of the implants and the rapid regeneration of the bone tissue.In this review,we will first introduce the signaling pathways of cellular response under hypoxic stress and oxidative stress,then present the clas-sical material designs and examples in response to hypoxic stress and oxidative stress.And finally,we will address the important role of epigenetic mechanisms in the regulation of hypoxic stress and oxida-tive stress and describe the potential applications and prospective smart bone graft materials based on novel epigenetic factors against hypoxic stress and oxidative stress in bone repair.The main content of this review is summarized in the following graphical abstract.展开更多
Dear editors,Colorectal cancer(CRC)is the second leading cause of cancer deaths in developed countries[1].The malignant transformation from small clumps to cancer takes about 10 years[2].This study aimed to characteri...Dear editors,Colorectal cancer(CRC)is the second leading cause of cancer deaths in developed countries[1].The malignant transformation from small clumps to cancer takes about 10 years[2].This study aimed to characterize proteomic dynamics associated with CRC development and progres-sion,and identify novel therapeutic targets for intercepting the underlying oncogenic processes.We have optimized pressure cycling technology(PCT)coupled with data-independent acquisition mass spectrometry(DIA-MS)for robust and reproducible proteomic analysis of biopsy-level formalin-fixed paraffin-embedded(FFPE)tissues[3].展开更多
College of Electrical Engineering, Yanshan University, Qinhuangdao hebei 066004)Qi, hanhong Tian,Yongjun, Wei,Yanjun Wang, Tiansheng(State Key Laboratory for Superconductor, Institute of Physics, Chinese Academy of Sc...College of Electrical Engineering, Yanshan University, Qinhuangdao hebei 066004)Qi, hanhong Tian,Yongjun, Wei,Yanjun Wang, Tiansheng(State Key Laboratory for Superconductor, Institute of Physics, Chinese Academy of Science, Beijing 100080)Zheng,DongningAbatract : A set of virtual instrument system based on Labview for measuring the R^T curve of the high temperature superconductor is designed in this paper. The control for the Current Source and nanovoltage meter is realized by the IEEE488 bus. The superconductivity is measured based on the zero resistance characteristics of the superconductor. The measurement is of high precision and of high speed. The man-machine interface is direct and friendly.展开更多
基金supported by the National Natural Science Foundation of China(Nos.31770131,81473469)International Cooperation Project of the Belt and Road(No.20400750600)+1 种基金Shanghai Shen Kang Hospital Development Center Plan(SHDC12018119)Shanghai Municipal Commission of Health and Family Plan(201840056).
文摘Surgery is the comm on treatme nt for early lung cancer with multiple pulm onary no dules,but it is often accompanied by the problem of significant malignancy of other nodules in non-therapeutic areas.In this study,we found that a combined treatment of local rad iofreq ue ncy ablati on(RFA)and melatonin(MLT)greatly improved clinical outcomes for early lung cancer patie nts with multiple pulmonary nodules by minimizing lung function injury and reducing the probability of malignant transformation or enlargement of nodules in non-ablated areas.Mechanically,as demonstrated in an associated mouse lung tumor model,RFA not only effectively remove treated tumors but also stimulate antitumor immunity,which could inhibit tumor growth in non-ablated areas.MLT enhanced RFA-stimulated NK activity and exerted synergistic antitumor effects with RFA.Transcriptomics and proteomics analyses of residual tumor tissues revealed enhanced oxidative phosphorylation and reduced acidification as well as hypoxia in the tumor microenvironment,which suggests reprogrammed tumor metabolism after combined treatment with RFA and MLT.Analysis of residual tumor further revealed the depressed activity of MAPK,NF-kappa B,Wnt,and Hedgehog pathways and upregulated P53 pathway in tumors,which was in line with the inhibited tumor growth.Combined RFA and MLT treatment also reversed the Warburg effect and decreased tumor malignancy.These findings thus demonstrated that combined treatment of RFA and MLT effectively inhibited the malignancy of non-ablated nodules and provided an innovative non-invasive strategy for treating early lung tumors with multiple pulmonary nodules.Trial registration:www.chictr.org.cn,identifier ChiCTR2100042695,http://www.chictr.org.cn/showproj.aspx?proj=120931.
基金supported by the National Natural Science Foundation of China(Grant No.81972492)National Science Fund for Young Scholars(Grant No.21904107)+7 种基金Zhejiang Provincial Natural Science Foundation for Distinguished Young Scholars(Grant No.LR19C050001)Hangzhou Agriculture and Society Advancement Program(Grant No.20190101A04)Westlake Startup Grantresearch funds from the National Cancer Centre Singapore and Singapore General Hospital,Singaporethe National Key R&D Program of China(Grant No.2016YFC0901704)Zhejiang Innovation Discipline Project of Laboratory Animal Genetic Engineering(Grant No.201510)the Netherlands Cancer Society(Grant No.NKI 2014-6651)The Netherlands Organization for Scientific Research(NWO)-Middelgroot(Grant No.91116017)
文摘To address the increasing need for detecting and validating protein biomarkers in clinical specimens,mass spectrometry(MS)-based targeted proteomic techniques,including the selected reaction monitoring(SRM),parallel reaction monitoring(PRM),and massively parallel dataindependent acquisition(DIA),have been developed.For optimal performance,they require the fragment ion spectra of targeted peptides as prior knowledge.In this report,we describe a MS pipeline and spectral resource to support targeted proteomics studies for human tissue samples.To build the spectral resource,we integrated common open-source MS computational tools to assemble a freely accessible computational workflow based on Docker.We then applied the workflow to generate DPHL,a comprehensive DIA pan-human library,from 1096 data-dependent acquisition(DDA)MS raw files for 16 types of cancer samples.This extensive spectral resource was then applied to a proteomic study of 17 prostate cancer(PCa)patients.Thereafter,PRM validation was applied to a larger study of 57 PCa patients and the differential expression of three proteins in prostate tumor was validated.As a second application,the DPHL spectral resource was applied to a study consisting of plasma samples from 19 diffuse large B cell lymphoma(DLBCL)patients and 18 healthy control subjects.Differentially expressed proteins between DLBCL patients and healthy control subjects were detected by DIA-MS and confirmed by PRM.These data demonstrate that the DPHL supports DIA and PRM MS pipelines for robust protein biomarker discovery.DPHL is freely accessible at https://www.iprox.org/page/project.html?id=IPX0001400000.
基金This work was sponsored by the National Science Foundation of China(Nos.32071341,52202358,52003302)The Natural Science Foundation of Guangdong Province(No.2017A030308004)+1 种基金the Guangdong Basic and Applied Basic Research Foundation(No.2021A1515110824)the Science and Technology Project of Guangdong province(No.2018A050506021).
文摘The architecture and surface modifications have been regarded as effective methods to enhance the bi-ological response of biomaterials in bone tissue engineering.The porous architecture of the implanta-tion was essential conditions for bone regeneration.Meanwhile,the design of biomimetic hydroxyap-atite(HAp)coating on porous scaffolds was demonstrated to strengthen the bioactivity and stimulate osteogenesis.However,bioactive bio-ceramics such asβ-tricalcium phosphate(β-TCP)and calcium sili-cate(CS)with superior apatite-forming ability were reported to present better osteogenic activity than that of HAp.Hence in this study,3D-printed interconnected porous bioactive ceramicsβ-TCP/CS scaf-fold was fabricated and the biomimetic HAp apatite coating were constructed in situ via hydrothermal reaction,and the effects of HAp apatite layer on the fate of mouse bone mesenchymal stem cells(mBM-SCs)and the potential mechanisms were explored.The results indicated that HAp apatite coating en-hanced cell proliferation,alkaline phosphatase(ALP)activity,and osteogenic gene expression.Further-more,PI3K/AKT/mTOR signaling pathway is proved to have an important impact on cellular functions.The present results demonstrated that the key molecules of phosphatidylinositol 3-kinase(PI3K),protein kinase B(AKT)and mammalian target of rapamycin(mTOR)were activated after the biomimetic hydrox-yapatite coating were constructed on the 3D-printed ceramic scaffolds.Besides,the activated influence on the protein expression of Runx2 and BMP2 could be suppressed after the treatment of inhibitor HY-10358.In vivo studies showed that the constructed HAp coating promoted bone formation and strengthen the bone quality.These results suggest that biomimetic HAp coating constructed on the 3D-printed bioac-tive composite scaffolds could strengthen the bioactivity and the obtained biomimetic multi-structured scaffolds might be a potential alternative bone graft for bone regeneration.
基金the National Natural Science Foundation of China(Nos.31770131,81473469 to L.F.and 81922030 to H.L.)International Cooperation Project of the Belt and Road(No.20400750600)+2 种基金Construction project of Shanghai TCM-intigrated innovative flagship hospital(ZY(2021-2023)-0205-05,ZXXT-202203)Shanghai Municipal Commission of Health and Family Plan(201840056)H.L.was sponsored by Shanghai Shuguang Program(20SG19).
文摘Dear Editor,Kras and p53 mutation are among the most common gene mutations in lung cancer,which has both the highest incidence and mortality rate among cancers.1 Kras/p53 mutation also causes mitochondrial dysfunction,which has been implicated to promote the inflammation-to-cancer transition.2 We established a lung adenocarcinoma model by using conditional alleles of KrasLSLG12D/p53flox/flox in mice3 to evaluate the effect of Baicalein(5,6,7-trihydroxyflavone),a principal component of Scutellaria baicalensis in traditional Chinese medicine,4 on the initiation and progression of lung cancer.Cre-mediated expression of KrasG12D and deletion of p53 caused obvious tumor lesions in the lung,which were strongly inhibited by the administration of Baicalein(Fig.1a,b and Supplementary Fig.1a,b),indicating that Baicalein is highly potent in inhibiting the progression of primary lung cancer.
基金supported by the National Natural Science Foundation of China(21971246,22371108,22075122)Taishan Scholar Foundation of Shandong Province(tsqn202211242)the Chunhui Program of the Ministry of Education of China(HZKY20220463).
文摘The potential application of gold nanoparticles(GNPs)in biomedicine has been extensively reported.However,there is still too much puzzle about their real face and potential health risks in comparison with the commercial drug molecules.The emergence of atomically precise gold nanoclusters(APGNCs)provides the opportunity to address the puzzle due to their ultrasmall size,defined molecular formula,editable surface engineering,available structures and unique physicochemical properties including excellent biocompatibility,strong luminescence,enzyme-like activity and efficient renal clearance,et al.Recently,these advantages of APGNCs also endow them promising performances in healthcare such as bioimaging,drug delivery,antibacterial and cancer therapy.Especially,their clear composition and structures like the commercial drug molecules facilitate the study of their functions and the structure-activity relationship in healthcare,which is essential for the guided design of APGNC nanomedicine.Therefore,this review will focus the advantages and recent progress of APGNCs in health care and envision their prospects for the future.
基金financially supported by the National Nat-ural Science Foundation of China(Nos.32071341,82202741,52003302,31430030,51973021,32201111,and 52202358)the Chinese Postdoctoral Science Foundation(Nos.2021M703710 and 2021M691464)+1 种基金the Guangdong Basic and Applied Basic Re-search Foundation(Nos.2021A1515111040,2019A1515110841 and 2019A1515011935)the Beijing Municipal Health Commis-sion(Nos.BMHC-20216 and PXM 2020_026275_000002)。
文摘Tissue engineering aims to offer large-scale replacement of damaged organs using implants with the com-bination of cells,growth factors and scaffolds.However,the intra/peri-implant region is exposed to se-vere hypoxic stress and oxidative stress during the early stage of implantation with bone graft materials,which endangers the survival,proliferation and differentiation of seed cells within the implants as well as the host cells surrounding the implants.If the bone graft material could spontaneously and intelligently regulate the hypoxic stress and oxidative stress to a moderate level,it will facilitate the vascularization of the implants and the rapid regeneration of the bone tissue.In this review,we will first introduce the signaling pathways of cellular response under hypoxic stress and oxidative stress,then present the clas-sical material designs and examples in response to hypoxic stress and oxidative stress.And finally,we will address the important role of epigenetic mechanisms in the regulation of hypoxic stress and oxida-tive stress and describe the potential applications and prospective smart bone graft materials based on novel epigenetic factors against hypoxic stress and oxidative stress in bone repair.The main content of this review is summarized in the following graphical abstract.
基金supported by the National Key Research and Development Program of China(Grant No.2017YFC0908200),National Natural Science Founda-tion of China(Grant No.81972270,81972492,32027801,21904107),the Zhejiang Provincial Science Foundation for Distinguished Young Scholars(Grant No.LR19C050001),Hangzhou Agriculture and Society Advancement Program(Grant No.20190101A04)and 2019 Zhejiang University Academic Award for Outstanding Doctoral Candidates to YK.S(Grant No.2019071).
文摘Dear editors,Colorectal cancer(CRC)is the second leading cause of cancer deaths in developed countries[1].The malignant transformation from small clumps to cancer takes about 10 years[2].This study aimed to characterize proteomic dynamics associated with CRC development and progres-sion,and identify novel therapeutic targets for intercepting the underlying oncogenic processes.We have optimized pressure cycling technology(PCT)coupled with data-independent acquisition mass spectrometry(DIA-MS)for robust and reproducible proteomic analysis of biopsy-level formalin-fixed paraffin-embedded(FFPE)tissues[3].
文摘College of Electrical Engineering, Yanshan University, Qinhuangdao hebei 066004)Qi, hanhong Tian,Yongjun, Wei,Yanjun Wang, Tiansheng(State Key Laboratory for Superconductor, Institute of Physics, Chinese Academy of Science, Beijing 100080)Zheng,DongningAbatract : A set of virtual instrument system based on Labview for measuring the R^T curve of the high temperature superconductor is designed in this paper. The control for the Current Source and nanovoltage meter is realized by the IEEE488 bus. The superconductivity is measured based on the zero resistance characteristics of the superconductor. The measurement is of high precision and of high speed. The man-machine interface is direct and friendly.
