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mRNA medicine:Recent progresses in chemical modification,design,and engineering

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Nano Research 2024年第10期17卷 9015-9030页

作者： Xiaowen Hou Jinjun shi Yuling Xiao Department of Cardiology Zhongnan Hospital of Wuhan UniversitySchool of Pharmaceutical SciencesWuhan UniversityWuhan 430071China Center for Nanomedicine and Department of Anesthesiology Perioperative and Pain MedicineBrigham and Women’s HospitalHarvard Medical SchoolBostonMA 02115USA

Messenger RNA(mRNA)is a type of RNA that carries genetic information from DNA to the ribosome,where it is translated into *** has emerged as a powerful platform for development of new types of medicine,especially after the clinical approval of COVID-19 mRNA *** modification and nanoparticle delivery have contributed to this success significantly by improving mRNA stability,reducing its immunogenicity,protecting it from enzymatic degradation,and enhancing cellular uptake and endosomal ***,substantial progresses have been made in new modification chemistries,sequence design,and structural engineering to generate more stable and efficient next-generation *** innovations could further facilitate the clinical translation of mRNA therapies and *** that numerous review articles have been published on mRNA nanoparticle delivery and biomedical applications over the last few years,we herein focus on overviewing recent advances in mRNA chemical modification,mRNA sequence optimization,and mRNA engineering(e.g.,circular RNA and multitailed mRNA),with the aim of providing new perspectives on the development of more effective and safer mRNA medicines.

关键词： mRNA self-amplifying RNA circular RNA multitailed mRNA chemical modification machine learning

Novel classification of gastric polyps:The good,the bad and the ugly

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World Journal of Gastroenterology 2024年第31期30卷 3640-3653页

作者： Deborah Costa Daryl Ramai Alberto Tringali Department of Digestive Endoscopy and Gastroenterology AULSS2Conegliano HospitalConegliano 31015Italy Department of Gastroenterology Division of Hepatology and EndoscopyBrigham and Women's HospitalBostonMA 02115United States

Gastric polyps(GPs)are increasingly *** upper endoscopy,they should be examined with white light and occasionally chromoendoscopy,and their morphology classified according to the Paris *** GPs have a typical endoscopic appearance and can be associated with diseases like Helicobacter pylori *** examination is necessary for an accurate *** most polyps are non-neoplastic and do not require treatment,some carry a risk of malignancy or are already ***,understanding the diagnosis,classification,and management of GPs is crucial for patient *** new classification categorizes GPs into"good","bad",and"ugly"based on their likelihood of becoming *** aim to provide descriptions of the endoscopic appearance,pathology,treatment,and follow-up for different GPs,as well as clinical management flowcharts.

关键词： Gastric polyps Fundic gland polyps Hyperplastic polyps Adenomas Neuroendocrine tumors Early gastric cancer

Targeting epigenetic mechanisms in amyloid-β-mediated Alzheimer’s pathophysiology:unveiling therapeutic potential

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Neural Regeneration Research 2025年第1期20卷 54-66页

作者： Jennie Z.Li Nagendran Ramalingam shaomin Li Ann Romney Center for Neurologic Diseases Brigham and Women’s Hospital and Harvard Medical SchoolBostonMAUSA

Alzheimer’s disease is a prominent chronic neurodegenerative condition characterized by a gradual decline in memory leading to *** evidence suggests that Alzheimer’s disease is associated with accumulating various amyloid-βoligomers in the brain,influenced by complex genetic and environmental *** memory and cognitive deficits observed during the prodromal and mild cognitive impairment phases of Alzheimer’s disease are believed to primarily result from synaptic *** life,environmental factors can lead to enduring changes in gene expression and the emergence of brain *** changes,known as epigenetic modifications,also play a crucial role in regulating the formation of synapses and their adaptability in response to neuronal *** this context,we highlight recent advances in understanding the roles played by key components of the epigenetic machinery,specifically DNA methylation,histone modification,and microRNAs,in the development of Alzheimer’s disease,synaptic function,and activity-dependent synaptic ***,we explore various strategies,including enriched environments,exposure to non-invasive brain stimulation,and the use of pharmacological agents,aimed at improving synaptic function and enhancing long-term potentiation,a process integral to epigenetic ***,we deliberate on the development of effective epigenetic agents and safe therapeutic approaches for managing Alzheimer’s *** suggest that addressing Alzheimer’s disease may require distinct tailored epigenetic drugs targeting different disease stages or pathways rather than relying on a single drug.

关键词： Alzheimer’s disease DNA methylation enriched environments histone modification microRNAs non-invasive brain stimulation synaptic plasticity

Acoustofluidics-enhanced biosensing with simultaneously high sensitivity and speed

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Microsystems & Nanoengineering 2024年第3期10卷 335-346页

作者： Yuang Li Yang Zhao Yang Yang Wenchang Zhang Yun Zhang sheng sun Lingqian Zhang Mingxiao Li Hang Gao Chengjun Huang Institute of Microelectronics of the Chinese Academy of sciences Beijing 100029P.R.China University of Chinese Academy of sciences Beijing 101408P.R.China Department of Medicine Brigham and Women’s HospitalHarvard Medical SchoolBostonMA 02115USA

simultaneously achieving high sensitivity and detection speed with traditional solid-state biosensors is usually limited since the target molecules must passively diffuse to the sensor surface before they can be *** techniques have been applied to shorten the diffusion time by continuously moving molecules through the biosensing ***,the binding efficiencies of the biomolecules are still limited by the inherent laminar flow inside microscale *** this study,focused traveling surface acoustic waves were directed into an acoustic microfluidic chip,which could continuously enrich the target molecules into a constriction zone for immediate detection of the immune reactions,thus significantly improving the detection sensitivity and *** demonstrate the enhancement of biosensing,we first developed an acoustic microfluidic chip integrated with a focused interdigital transducer;this transducer had the ability to capture more than 91%of passed ***,polystyrene microbeads were pre-captured with human IgG molecules at different concentrations and loaded for detection on the *** representative results,~0.63,2.62,11.78,and 19.75 seconds were needed to accumulate significant numbers of microbeads pre-captured with human IgG molecules at concentrations of 100,10,1,and 0.1 ng/mL(~0.7 pM),respectively;this process was faster than the other methods at the hour level and more sensitive than the other methods at the nanomolar *** results indicated that the proposed method could significantly improve both the sensitivity and speed,revealing the importance of selective enrichment strategies for rapid biosensing of rare molecules.

关键词： fluid continuously simultaneous

Engineering nanomedicines for immunogenic eradication of cancer cells:Recent trends and synergistic approaches

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Acta Pharmaceutica sinica B 2024年第6期14卷 2475-2504页

作者： Ahmed O.Elzoghby Omar samir Hagar E.Emam Ahmed soliman Riham M.Abdelgalil Yomna M.Elmorshedy Kadria A.Elkhodairy Mahmoud L.Nasr Division of Engineering in Medicine and Division of Renal Medicine Department of MedicineBrigham and Women's HospitalHarvard Medical SchoolBoston 02115MAUSA Cancer Nanotechnology Research Laboratory(CNRL) Faculty of PharmacyAlexandria UniversityAlexandria 21521Egypt

Resistance to cancer immunotherapy is mainly attributed to poor tumor immunogenicity as well as the immunosuppressive tumor microenvironment(TME)leading to failure of immune *** therapeutic strategies including chemotherapy,radiotherapy,photodynamic,photothermal,magnetic,chemodynamic,sonodynamic and oncolytic therapy,have been developed to induce immunogenic cell death(ICD)of cancer cells and thereby elicit immunogenicity and boost the antitumor immune ***,many challenges hamper the clinical application of ICD inducers resulting in modest immunogenic ***,we outline the current state of using nanomedicines for boosting ICD of cancer ***,synergistic approaches used in combination with ICD inducing nanomedicines for remodeling the TME via targeting immune checkpoints,phagocytosis,macrophage polarization,tumor hypoxia,autophagy and stromal modulation to enhance immunogenicity of dying cancer cells were *** further highlight the emerging trends of using nanomaterials for triggering amplified ICD-mediated antitumor immune *** reticulum localized ICD,focused ultrasound hyperthermia,cell membrane camouflaged nanomedicines,amplified reactive oxygen species(ROs)generation,metallo-immunotherapy,ion modulators and engineered bacteria are among the most innovative *** challenges,merits and demerits of ICD inducer nanomedicines were also discussed with shedding light on the future role of this technology in improving the outcomes of cancer immunotherapy.

关键词： Immunogenic cell death Immunogenic eradication Nanomedicines Drug delivery Cancer immunotherapy Antitumor immunity T cells Tumor associated antigens synergistic immune response

Dual‑Atom Nanozyme Eye Drops Attenuate Inflammation and Break the Vicious Cycle in Dry Eye Disease

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Nano-Micro Letters 2024年第6期16卷 439-457页

作者： Dandan Chu Mengyang Zhao shisong Rong Wonho Jhe Xiaolu Cai Yi Xiao Wei Zhang Xingchen Geng Zhanrong Li Xingcai Zhang Jingguo Li Henan Eye hospital Henan Provincial People’s HospitalPeople’s Hospital of Zhengzhou UniversityZhengzhou 450003People’s Republic of China Department of Ophthalmology Mass Eye and EarMass General BrighamHarvard Medical SchoolBostonMA 02114USA school of Engineering and Applied sciences Harvard UniversityCambridgeMA 02138USA College of Chemistry Zhengzhou UniversityZhengzhou 450001People’s Republic of China

Dry eye disease(DED)is a major ocular pathology worldwide,causing serious ocular discomfort and even visual *** incidence of DED is gradually increasing with the highfrequency use of electronic *** inflammation is core cause of the DED vicious cycle,reactive oxygen species(ROs)play a pivotal role in the vicious cycle by regulating inflammation from ***,current therapies merely targeting inflammation show the failure of DED ***,a novel dual-atom nanozymes(DAN)-based eye drops are *** antioxidative DAN is successfully prepared by embedding Fe and Mn bimetallic single-atoms in N-doped carbon material and modifying it with a hydrophilic *** in vitro and in vivo results demonstrate the DAN is endowed with superior biological activity in scavenging excessive ROs,inhibiting NLRP3 inflammasome activation,decreasing proinflammatory cytokines expression,and suppressing cell ***,the DAN effectively alleviate ocular inflammation,promote corneal epithelial repair,recover goblet cell density and tear secretion,thus breaking the DED vicious *** findings open an avenue to make the DAN as an intervention form to DED and ROsmediated inflammatory diseases.

关键词： Dry eye disease DAN Dual-atom nanozyme Vicious cycle NLRP3 inflammasome Nanomedicine

Microfluidic bubble-generator enables digital light processing 3D printing of porous structures

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Aggregate 2024年第1期5卷 280-291页

作者： Philipp Weber Ling Cai Francisco Javier Aguilar Rojas Carlos Ezio Garciamendez-Mijares Maria Celeste Tirelli Francesco Nalin Jakub Jaroszewicz Wojciech swi eszkowski Marco Costantini Yu shrike Zhang Division of Engineering in Medicine Department of MedicineBrigham and Women’s HospitalHarvard Medical SchoolCambridgeMassachusettsUSA Institute of Physical Chemistry—Polish Academy of sciences KasprzakaPoland Biomaterials Group Materials Design DivisionFaculty of Materials Science and EngineeringWarsaw University of TechnologyWoloskaPoland

Three-dimensional(3D)printing is an emerging technique that has shown promising success in engineering human tissues in recent *** development of vatphotopolymerization printing modalities has significantly enhanced the complexity level for 3D printing of various functional structures and ***,the development of microfluidic chip systems is an emerging research sector with promising medical *** work demonstrates the coupling of a digital light processing(DLP)printing procedure with a microfluidic chip system to produce size-tunable,3D-printable porosities with narrow pore size distributions within a gelatin methacryloyl(GelMA)hydrogel *** is found that the generation of size-tunable gas bubbles trapped within an aqueous GelMA hydrogel-precursor can be controlled with high ***,the porosities are printed in two-dimensional(2D)as well as in 3D using the DLP *** addition,the cytocompatibility of the printed porous scaffolds is investigated using fibroblasts,where high cell viabilities as well as cell proliferation,spreading,and migration are *** is anticipated that the strategy is widely applicable in a range of application areas such as tissue engineering and regenerative medicine,among others.

关键词： 3D printing biofabrication bubble digital light processing microfluidics porous

The efficacy of vitamin E in preventing arthrofibrosis after joint replacement

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Animal Models and Experimental Medicine 2024年第2期7卷 145-155页

作者： Yingfang Fan Jean Yuh sashank Lekkala Mehmet D.Asik Andrew Thomson Madeline McCanne Mark A.Randolph Antonia F.Chen Ebru Oral Harris Orthopaedic Laboratory Department of Orthopaedic SurgeryMassachusetts General HospitalBostonMassachusettsUSA Department of Orthopaedic surgery Harvard Medical SchoolBostonMassachusettsUSA Department of surgery Harvard Medical SchoolBostonMassachusettsUSA Department of Orthopaedic surgery Brigham and Women's HospitalBostonMassachusettsUSA

Background:Arthrofibrosis is a joint disorder characterized by excessive scar formation in the joint *** E is an antioxidant with potential anti-fibroblastic *** aim of this study was to establish an arthrofibrosis rat model after joint replacement and assess the effects of vitamin E supplementation on joint ***:We simulated knee replacement in 16 male sprague–Dawley *** immobilized the surgical leg with a suture in full *** control groups were killed at 2 and 12 weeks(n=5 per group),and the test group was supplemented daily with vitamin E(0.2 mg/mL)in their drinking water for 12 weeks(n=6).We performed histological staining to investigate the presence and severity of *** staining andα2-macroglobulin(α2M)enzyme-linked immunosorbent assay(ELIsA)were used to assess local and systemic *** weight bearing(total internal reflection)and range of motion(ROM)were collected for functional ***:The ROM and weight-bearing symmetry decreased after the procedure and recovered slowly with still significant deficit at the end of the study for both *** analysis confirmed fibrosis in both lateral and posterior periarticular *** E supplementation showed a moderate anti-inflammatory effect on the local and systemic *** vitamin E group exhibited significant improvement in ROM and weight-bearing symmetry at day 84 compared to the control ***:This model is viable for simulating arthrofibrosis after joint *** E may benefit postsurgical arthrofibrosis,and further studies are needed for dosing requirements.

关键词： arthrofibrosis range of motion total knee arthroplasty vitamin E

N-acetylserotonin alleviates retinal ischemia-reperfusion injury via HMGB1/RAGE/NF-κB pathway in rats

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International Journal of Ophthalmology(English edition) 2024年第2期17卷 228-238页

作者： Yu-Ze Zhao Xue-Ning Zhang Yi Yin Pei-Lun Xiao Meng Gao Lu-Ming Zhang shuan-Hu Zhou shu-Na Yu Xiao-Li Wang Yan-song Zhao Department of Ophthalmology Affiliated Hospital of Weifang Medical UniversityWeifang 261031Shandong ProvinceChina school of Medical Imaging Weifang Medical UniversityWeifang 261053Shandong ProvinceChina Department of Anatomy Weifang Medical UniversityWeifang 261053Shandong ProvinceChina Departments of Orthopedic surgery Brigham and Women’s HospitalHarvard Medical SchoolBostonMA 02115USA

AIM:To observe the effects of N-acetylserotonin(NAs)administration on retinal ischemia-reperfusion(RIR)injury in rats and explore the underlying mechanisms involving the high mobility group box 1(HMGB1)/receptor for advanced glycation end-products(RAGE)/nuclear factor-kappa B(NF-κB)signaling ***:A rat model of RIR was developed by increasing the pressure of the anterior chamber of the *** male sprague Dawley were randomly divided into five groups:sham group(n=8),RIR group(n=28),RIR+NAs group(n=28),RIR+FPs-ZM1 group(n=8)and RIR+NAs+FPs-ZM1 group(n=8).The therapeutic effects of NAs were examined by hematoxylin-eosin(H&E)staining,and retinal ganglion cells(RGCs)*** expression of interleukin 1 beta(IL-1β),HMGB1,RAGE,and nod-like receptor 3(NLRP3)proteins and the phosphorylation of nuclear factorkappa B(p-NF-κB)were analyzed by immunohistochemistry staining and Western blot *** expression of HMGB1 protein was also detected by enzyme-linked immunosorbent assay(ELIsA).REsULTs:H&E staining results showed that NAs significantly reduced retinal edema and increased the number of RGCs in RIR *** NAs therapy,the HMGB1 and RAGE expression decreased significantly,and the activation of the NF-κB/NLRP3 pathway was antagonized along with the inhibition of p-NF-κB and NLRP3 protein ***,NAs exhibited an anti-inflammatory effect by reducing IL-1β*** inhibitory of RAGE binding to HMGB1 by RAGE inhibitor FPs-ZM1 led to a significant decrease of p-NF-κB and NLRP3 expression,so as to the IL-1βexpression and retinal edema,accompanied by an increase of RGCs in RIR ***:NAs may exhibit a neuroprotective effect against RIR via the HMGB1/RAGE/NF-κB signaling pathway,which may be a useful therapeutic target for retinal disease.

关键词： retinal diseases retinal ischemia—reperfusion injury N-acetylserotonin high mobility group box 1 receptor for advanced glycation end-products nuclear factor-κB rats