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Biomimetic microchannel network with functional endothelium formed by sacrificial electrospun fibers inside 3D gelatin methacryloyl(GelMA)hydrogel models

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Journal of Zhejiang University-Science A(Applied Physics & engineering) 2024年第1期25卷 79-96页

作者： Haoyu SUN Haiyang MA Li WANG Yang LIU Tian HOU Wenjie TANG Qing YU Meiwen AN Meiling WEN Institute of biomedical engineering College of Biomedical EngineeringTaiyuan University of TechnologyTaiyuan030024China

Three-dimensional(3D)hydrogel models play a crucial role in tissue engineering for promoting tissue regeneration.A biomimetic microchannel network system in the 3D hydrogel model is necessary for optimal cellular *** report describes the preparation of a biomimetic hydrogel scaffold with an internal microchannel network,using electrospinning techniques and the sacrificial template method for 3D cell *** and cavities were created within the gelatin methacryloyl(GelMA)hydrogel by sacrificing polyvinyl alcohol(PVA)electrospun fibers(>10µm),resulting in the creation of microvessel-like *** characterizations,swelling properties,and biodegradation analysis were conducted to investigate the feasibility of a biomimetic microchannel network hydrogel scaffold for 3D cell culture *** to pure GelMA hydrogel,the hydrogel with microchannels promoted cell proliferation,adhesion,and endothelial tube ***,the results confirmed that the biomimetic microchannel network scaffold had a major impact on the distribution and arrangement of human umbilical vein endothelial cells(HUVECs)and can enable the formation of artificial microvasculature by the culture of HUVECs and cell media perfusion.

关键词： Biomimetic scaffold Photocrosslinking Microchannel network Tissue engineering Artificial microvascular

Enhanced axonal regeneration and functional recovery of the injured sciatic nerve in a rat model by lithium-loaded electrospun nanofibrous scaffolds

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Bio-Design and Manufacturing 2024年第5期7卷 701-720页

作者： Banafsheh Dolatyar Bahman Zeynali Iman Shabani Azita Parvaneh Tafreshi Reza Karimi-Soflou Developmental biology Laboratory School of BiologyCollege of ScienceUniversity of TehranTehran ***Iran Department of biomedical engineering Amirkabir University of Technology(Tehran Polytechnic)Tehran ***Iran Department of Molecular Medicine Faculty of Medical BiotechnologyNational Institute of Genetic Engineering and BiotechnologyTehran ***Iran 123

Increasing evidence indicates that engineered nerve grafts have great potential for the regeneration of peripheral nerve injuries(PNIs).While most studies have focused only on the topographical features of the grafts,we have considered both the biophysical and biochemical manipulations in our applied *** achieve this,we fabricated an electrospun nanofibrous scaffold(ENS)containing polylactide nanofibers loaded with lithium(Li)ions,a Wnt/β-catenin signaling *** addition,we seeded human adipose-derived mesenchymal stem cells(hADMSCs)onto this engineered scaffold to examine if their differentiation toward Schwann-like cells was *** further examined the efficacy of the scaffolds for nerve regeneration in vivo via grafting in a PNI rat *** results showed that Li-loaded ENSs gradually released Li within 11 d,at concentrations ranging from 0.02 to(3.64±0.10)mmol/L,and upregulated the expression of Wnt/β-catenin target genes(cyclinD1 and c-Myc)as well as those of Schwann cell markers(growth-associated protein 43(GAP43),S100 calcium binding protein B(S100B),glial fibrillary acidic protein(GFAP),and SRY-box transcription factor 10(SOX10))in differentiated *** the PNI rat model,implantation of Li-loaded ENSs with/without cells improved behavioral features such as sensory and motor functions as well as the electrophysiological characteristics of the injured *** improved function was further validated by histological analysis of sciatic nerves grafted with Li-loaded ENSs,which showed no fibrous connective tissue but enhanced organized myelinated *** potential of Li-loaded ENSs in promoting Schwann cell differentiation of hADMSCs and axonal regeneration of injured sciatic nerves suggests their potential for application in peripheral nerve tissue engineering.

关键词： Stem cell Schwann cell differentiation Electrospun nanofibrous scaffold Lithium ion Nerve regeneration

Mitochondria-specific near-infrared photoactivation of peroxynitrite upconversion luminescent nanogenerator for precision cancer gas therapy

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Acta Pharmaceutica Sinica B 2024年第1期14卷 378-391页

作者： Hui Yu Aliya Tiemuer Xufeng Yao Mingyuan Zuo Hai-Yan Wang Yi Liu Xiaoyuan Chen Department of biomedical engineering School of EngineeringChina Pharmaceutical UniversityNanjing 211198China School of Mechanical engineering Southeast UniversityNanjing 211189China departments of Diagnostic Radiology SurgeryChemical and Biomolecular Engineeringand Biomedical EngineeringYong Loo Lin School of Medicine and College of Design and EngineeringNational University of SingaporeSingapore 119074Singapore Clinical Imaging Research Centre Centre for Translational MedicineYong Loo Lin School of MedicineNational University of SingaporeSingapore 117599Singapore Nanomedicine Translational Research Program Yong Loo Lin School of MedicineNational University of SingaporeSingapore 117597Singapore Institute of Molecular and cell biology Agency for ScienceTechnologyand Research(A*STAR)ProteosSingapore 138673Singapore

Gas therapy is emerging as a highly promising therapeutic strategy for cancer ***,there are limitations,including the lack of targeted subcellular organelle accuracy and spatiotemporal release precision,associated with gas *** this study,we developed a series of photoactivatable nitric oxide(NO)donors NRh-R-NO(R=Me,Et,Bn,iPr,and Ph)based on an N-nitrosated upconversion luminescent rhodamine *** the irradiation of 808 nm light,only NRh-Ph-NO could effectively release NO and NRh-Ph with a significant turn-on frequency upconversion luminescence(FUCL)signal at 740 nm,ascribed to lower N-N bond dissociation *** also investigated the involved multistage near-infrared-controlled cascade release of gas therapy,including the NO released from NRh-Ph-NO along with one NRh-Ph molecule generation,the superoxide anion O_(2)^(⋅−)produced by the photodynamic therapy(PDT)effect of NRh-Ph,and highly toxic peroxynitrite anion(ONOO‒)generated from the co-existence of NO and O_(2)^(⋅−).After mild nano-modification,the nanogenerator(NRh-Ph-NO NPs)empowered with superior biocompatibility could target *** an 808 nm laser irradiation,NRh-Ph-NO NPs could induce NO/ROS to generate RNS,causing a decrease in the mitochondrial membrane potential and initiating apoptosis by caspase-3 activation,which further induced tumor immunogenic cell death(ICD).In vivo therapeutic results of NRh-Ph-NO NPs showed augmented RNS-potentiated gas therapy,demonstrating excellent biocompatibility and effective tumor inhibition guided by real-time FUCL ***,this versatile strategy defines the targeted RNS-mediated cancer therapy.

关键词： Near infrared Photo-triggered Mitochondrion Upconversion luminescent bioimaging Peroxynitrite Nanogenerator Gas therapy In vivo

Inhibition of Ehrlich ascites carcinoma growth by melatonin:Studies with micro-CT

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Oncology Research 2024年第1期32卷 175-185页

作者： SEHER YILMAZ ZÜLEYHA DOĞANYIĞIT MERT OCAK EVRIM SUNA ARIKAN SÖYLEMEZ ASLI OKAN OFLAMAZ SÜMEYYE UÇAR ŞÜKRÜATEŞ AMMAD AHMAD FAROOQI Department of anatomy Faculty of MedicineYozgat Bozok UniversityYozgatTurkey Department of Mechanical and Aerospace engineering Case Western Reserve UniversityClevelandOhioUSA Department of Histology and Embriology Faculty of MedicineYozgat Bozok UniversityYozgatTurkey Department of anatomy Faculty of DentistryAnkara UniversityAnkaraTurkey Department of Medical biology Faculty of MedicineAfyonkarahisar Health Sciences UniversityAfyonTurkey Department of anatomy Faculty of MedicineErciyes UniversityKayseriTurkey Department of Molecular Oncology Institute of Biomedical and Genetic Engineering(IBGE)IslamabadPakistan

Melatonin is a versatile indolamine synthesized and secreted by the pineal gland in response to the photoperiodic information received by the retinohypothalamic signaling *** has many benefits,such as organizing circadian rhythms and acting as a powerful *** aimed to show the antitumor effects of melatonin in both in vivo and in vitro models through the mammalian target of rapamycin(mTOR)signaling pathway and the Argyrophilic Nucleolar Regulatory Region(AgNOR),using the Microcomputed Tomography(Micro CT).Ehrlich ascites carcinoma(EAC)cells were administered into the mice by subcutaneous *** with solid tumors were injected intraperitoneally with 50 and 100 mg/kg melatonin for 14 *** measurements for the taken tumors were made with micro-CT imaging,immunohistochemistry(IHC),real-time polymerase chain reaction(PCR)and ***,the tumor tissue volume in the Tumor+100 mg/kg melatonin group was significantly lower than that in the other groups in the data obtained from micro-CT *** the IHC analysis,the groups treated with Tumor+100 mg/kg melatonin were compared when the mTOR signaling pathway and factor 8(F8)expression were compared with the control *** was determined that there was a significant decrease(pcell apoptosis was evaluated with Annexin V in an in vitro study with different doses of melatonin;It was observed that 100µg/mL melatonin dose caused an increase in the apoptotic cell *** this study,we have reported anti-tumor effects of melatonin in cell culture studies as well as in mice *** characterization of the melatonin-mediated cancer inhibitory effects will be valuable in advanc

关键词： Signaling pathway Apoptosis Real-time PCR AgNOR

Nanomedicine-mediated immunogenic cell death and its combination with immune checkpoint blockade therapy

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Science China(Technological Sciences) 2024年第8期67卷 2350-2362页

作者： CHEN JunBin ZHANG YuXi SU Miao ZHU YueQiang YANG XianZhu School of biomedical Sciences and engineering South China University of TechnologyGuangzhou International CampusGuangzhou 511442China National engineering Research Center for Tissue Restoration and Reconstruction Guangdong Provincial Key Laboratory of Biomedical EngineeringKey Laboratory of Biomedical Materials and Engineering of the Ministry of EducationSouth China University of TechnologyGuangzhou 510006China

Cancer immunotherapies, which train the natural immune system to specifically kill tumor cells while sparing the healthy cells,have helped revolutionize cancer treatments and demonstrated promising clinical therapeutic benefits for decades. However, the therapeutic outcome of immunotherapies, even for the most successful immune checkpoint blockade(ICB) therapy, remains unsatisfactory in the clinical practice, mainly due to the low immunogenicity of solid tumors and its immunosuppressive tumor microenvironment(TME). Notably, several cancer treatment modalities, including chemotherapy, radiotherapy, and phototherapy, have been revealed to evoke tumor immunogenicity and reverse immunosuppressive TME via inducing immunogenic cell death(ICD) of tumor cells, which synergistically sensitized tumors to ICB therapy. Nanomedicines have been extensively applied to augment ICD-inducing treatment modalities and potentiate ICB therapeutic efficacy therapy due to the opportune convergence of immunotherapy and nanotechnology. Here, we discuss the recent advances in nanomedicine-mediated ICD and its combination with ICB therapy.

关键词： cancer immunotherapy nanomedicine immunogenic cell death immune checkpoint blockade

Pseudorabies virus VHS protein abrogates interferon responses by blocking NF-κB and IRF3 nuclear translocation

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Virologica Sinica 2024年第4期39卷 587-599页

作者： Zhenfang Yan Jiayu Yue Yaxin Zhang Zhengyang Hou Dianyu Li Yanmei Yang Xiangrong Li Adi Idris Huixia Li Shasha Li Jingying Xie Ruofei Feng Key Laboratory of Biotechnology and Bioengineering of State Ethnic biomedical Research Center Northwest Minzu UniversityLanzhou730030China College of Life Science and engineering Northwest Minzu UniversityLanzhou730030China Gansu Tech Innovation Center of Animal cell Biomedical Research CenterNorthwest Minzu UniversityLanzhou730030China engineering Research Center of Key Technology and Industrialization of cell-based Vaccine Ministry of EducationBiomedical Research CenterNorthwest Minzu UniversityLanzhou730030China Centre for Immunology and Infection Control School of Biomedical SciencesQueensland University of TechnologyKelvin GroveQueensland4702Australia

Herpesviruses antagonize host antiviral responses through a myriad of molecular strategies culminating in the death of the host *** virus(PRV)is a significant veterinary pathogen in pigs,causing neurological sequalae that ultimately lead to the animal's *** is known to trigger apoptotic cell death during the late stages of *** virion host shutdown protein(VHS)encoded by UL41 plays a crucial role in the PRV infection *** this study,we demonstrate that UL41 inhibits PRV-induced activation of inflammatory cytokine and negatively regulates the cGAS-STING-mediated antiviral activity by targeting IRF3,thereby inhibiting the translocation and phosphorylation of ***,mutating the conserved amino acid sites(E192,D194,and D195)in the RNase domain of UL41 or knocking down UL41 inhibits the immune evasion of PRV,suggesting that UL41 may play a crucial role in PRV's evasion of the host immune response during *** results enhance our understanding of how PRV structural proteins assist the virus in evading the host immune response.

关键词： Pseudorabies virus(PRV) UL41 IRF3 Interferon cGAS-STING

Protein-nucleic acid hybrid nanostructures for molecular diagnostic applications

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Nano Research 2024年第10期17卷 9003-9014页

作者： Noah R.Sundah Yuxuan Seah Auginia Natalia Xiaoyan Chen Panida Cen Yu Liu Huilin Shao Institute for Health Innovation and Technology National University of SingaporeSingapore 117599Singapore Department of biomedical engineering College of Design and EngineeringNational University of SingaporeSingapore 117583Singapore Integrative Sciences and engineering Programme NUS Graduate SchoolNational University of SingaporeSingapore 119077Singapore Institute of Molecular and cell biology Agency for ScienceTechnology and ResearchSingapore 138673Singapore Department of Surgery Yong Loo Lin School of MedicineNational University of SingaporeSingapore 117597Singapore

Molecular diagnostic technologies empower new clinical opportunities in precision ***,existing approaches face limitations with respect to performance,operation and *** molecules including proteins and nucleic acids are being increasingly adopted as tools in the development of new molecular diagnostic *** particular,leveraging their complementary properties—the functional diversity of proteins and the precision programmability of nucleic acids—a wide range of protein–nucleic acid hybrid nanostructures have been *** hybrid structures take diverse forms,ranging from one-dimensional to three-dimensional hybrids,as static assemblies to dynamic machines,and possess myriad functions to recognize target biomarkers,encode vast information and execute catalytic *** by recent advances in this area of molecular nanotechnology,we review the state-of-art design and application of various types of protein–nucleic acid hybrid nanostructures for molecular diagnostics,and present an outlook on the challenges and opportunities for emerging pre-clinical and clinical applications,highlighting the promise for earlier detection,more refined diagnosis and highly tailored treatment decision that ultimately lead to improved patient outcomes.

关键词： molecular nanotechnology DNA-protein hybrid molecular diagnostics precision medicine

Bioactive compounds in Hericium erinaceus and their biological properties:a review

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Food Science and Human Wellness 2024年第4期13卷 1825-1844页

作者： Yue Qiu Genglan Lin Weiming Liu Fuming Zhang Robert J.Linhardt Xingli Wang Anqiang Zhang College of Food Science and engineering Zhejiang University of TechnologyHangzhou 310014China Zhejiang Biosan Biotech Co. Ltd.Hangzhou 310052China Department of Chemical and Biological engineering Center for Biotechnology and Interdisciplinary StudiesRensselaer Polytechnic InstituteTroyNY 12180USA departments of Chemistry and Chemical biology and biomedical engineering Biological ScienceCenter for Biotechnology and Interdisciplinary StudiesRensselaer Polytechnic InstituteTroyNY 12180USA

Hericium erinaceus is a nutritious edible and medicinal fungi,rich in a variety of functional active ingredients,with various physiological functions such as antioxidation,anticancer,and enhancing *** is also effective in protecting the digestive system and preventing neurodegenerative *** this review paper,we summarize the sources,structures and efficacies of the main active components in *** fruiting body,mycelium,and culture media,and update the latest research progress on their biological activities and the related molecular *** on this information,we provide detailed challenges in current research,industrialization and information on the active ingredients of *** for future studies and new applications of *** are proposed.

关键词： Hericium erinaceus Bioactive compounds Biological activities Antioxidation Neuroprotection Immunoregulation

Gene-knockout by iSTOP enables rapid reproductive disease modeling and phenotyping in germ cells of the founder generation

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Science China(Life Sciences) 2024年第5期67卷 1035-1050页

作者： Yaling Wang Jingwen Chen Xueying Huang Bangguo Wu Peng Dai Feng Zhang Jinsong Li Lingbo Wang State Key Laboratory of Genetic engineering Shanghai Key Laboratory of Metabolic Remodeling and HealthInstitute of Metabolism and Integrative BiologyFudan UniversityShanghai 200438China Institute of Reproduction and Development Obstetrics and Gynecology HospitalFudan UniversityShanghai 200011China NHC Key Lab of Reproduction Regulation(Shanghai Institute for biomedical and Pharmaceutical Technologies) School of PharmacyFudan UniversityShanghai 200433China Shanghai Key Laboratoryof Maternal and Fetal Medicine Clinical and Translational Research Center of Shanghai First Maternity and Infant HospitalFrontier Science Center for Stem Cell ResearchSchoolof Life Sciences and TechnologyTongji UniversityShanghai 200092China State Key Laboratory of cell biology CAS Center for Excellence in Molecular Cell ScienceShanghai Institute of Biochemistry and Cell BiologyChinese Academy of SciencesShanghai 200031China

Cytosine base editing achieves C·G-to-T·A substitutions and can convert four codons(CAA/CAG/CGA/TGG)into STOP-codons(induction of STOP-codons,iSTOP)to knock out genes with reduced *** enables direct phenotyping in founders’somatic cells,but it remains unknown whether this works in founders’germ cells so as to rapidly reveal novel genes for ***,we initially establish that iSTOP in mouse zygotes enables functional characterization of known genes in founders’germ cells:Cfap43-iSTOP male founders manifest expected sperm features resembling human“multiple morphological abnormalities of the flagella”syndrome(i.e.,MMAF-like features),while oocytes of Zp3-iSTOP female founders have no zona *** further illustrate iSTOP’s utility for dissecting the functions of unknown genes with Ccdc183,observing MMAF-like features and male infertility in Ccdc183-iSTOP founders,phenotypes concordant with those of Ccdc183-KO *** ultimately establish that CCDC183 is essential for sperm morphogenesis through regulating the assembly of outer dynein arms and participating in the intra-flagellar *** study demonstrates iSTOP as an efficient tool for direct reproductive disease modeling and phenotyping in germ cells of the founder generation,and rapidly reveals the essentiality of Ccdc183 in fertility,thus providing a time-saving approach for validating genetic defects(like nonsense mutations)for human infertility.

关键词： disease modeling infertility multiple morphological abnormalities of the flagella(MMAF) induction of STOP-codons(iSTOP CRISPR-STOP) sperm motility