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Biomimetic“Gemini nanoimmunoregulators”orchestrated for boosted photoimmunotherapy by spatiotemporally modulating PD-L1 and tumor-associated macrophages

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1345-1361页

作者： honglin Huang Ningxi li Xiaodan Wei Qingzhi li Junhan Guo geng Yang hong Yang Lulu Cai Yiyao liu Chunhui Wu Department of Pharmacy Personalized Drug Therapy Key Laboratory of Sichuan ProvinceSichuan Provincial People’s Hospitaland School of Life Science and TechnologyUniversity of Electronic Science and Technology of ChinaChengdu 610054China TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province Hospital of Chengdu University of Traditional Chinese MedicineChengdu 610072China

A novel strategy of not only stimulating the immune cycle but also modulating the immunosuppressive tumor microenvironment is of vital importance to efficient cancer immunotherapy.Here,a new type of spatiotemporal biomimetic“Gemini nanoimmunoregulators”was engineered to activate robust systemic photoimmunotherapy by integrating the triple-punch of amplified immunogenic cell death(ICD),tumor-associated macrophages(TAMs)phenotype reprogramming and programmed cell death ligand 1(PD-L1)degradation.The“Gemini nanoimmunoregulators”PM@RM-T7 and PR@RM-M2 were constructed by taking the biocompatible mesoporous polydopamine(mPDA)as nanovectors to deliver metformin(Met)and toll-like receptor 7/8 agonist resiquimod(R848)to cancer cells and TAMs by specific biorecognition via wrapping of red blood cell membrane(RM)inlaid with T7or M2 peptides.mPDA/Met@RM-T7(abbreviated as PM@RM-T7)was constructed to elicit an amplified in situ ICD effect through the targeted PTT and effectively stimulated the anticancer immunity.Meanwhile,PD-L1 on the remaining cancer cells was degraded by the burst metformin to prevent immune evasion.Subsequently,mPDA/R848@RM-M2(abbreviated as PR@RM-M2)specifically recognized TAMs and reset the phenotype from M2 to M1 state,thus disrupting the immunosuppressive microenvironment and further boosting the function of cytotoxic T lymphocytes.This pair of sister nanoimmunoregulators cooperatively orchestrated the comprehensive anticancer activity,which remarkably inhibited the growth of primary and distant 4T1 tumors and prevented malignant metastasis.This study highlights the spatiotemporal cooperative modalities using multiple nanomedicines and provides a new paradigm for efficient cancer immunotherapy against metastatic-prone tumors.

关键词： Biomimetic immunoregulator Spatiotemporal delivery Targeted photothermal therapy Amplified immunogenic cell death Immunosuppressive tumor microenvironment PD-L1 degradation TAMs phenotype reversion Metastasis inhibition

Structural engineered living materials

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Nano Research 2024年第2期17卷 715-733页

作者： Yang geng Zian Jia ling li 635 Prices Fork Road Department of Mechanical EngineeringVirginia Polytechnic Institute and State UniversityBlacksburg VA24061USA

Biological structural materials not only exhibit remarkable mechanical properties but also often embody dynamic characteristics such as environmental responsiveness,autonomy,and self-healing,which are difficult to achieve in conventional engineering materials.By merging materials science,synthetic biology,and other disciplines,engineered living materials(ELMs)provide a promising solution to combine living organisms with abiotic components,thus facilitating the construction of functional“living”materials.like natural materials,ELMs possess vitality and hold immense application potential in areas such as medicine,electronics,and construction,captivating increasing research attention recently.As an emerging branch of ELMs,structural ELMs aim to mimic living biological structural materials by achieving desired mechanical performance while maintaining important“living”characteristics.Here we summarize the recent progress and provide our perspectives for this emerging research area.We first summarize the superiority of structural ELMs by reviewing biological structural materials and biomimetic material design strategies.Subsequently,we provide a systematic discussion on the definition and classifications of structural ELMs,their mechanical performance,and physiological behaviors.Finally,we summarize some critical challenges faced by structural ELMs and highlight directions of future development.We hope this review article can provide a timely summary of the state of the art and relevant perspectives for future development of structural ELMs.

关键词： structural materials engineered living materials(ELMs) structural ELMs composites mechanical properties

Enhancing Relational Triple Extraction in Specific Domains:Semantic Enhancement and Synergy of Large Language Models and Small Pre-Trained Language Models

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Computers, Materials & Continua 2024年第5期79卷 2481-2503页

作者： Jiakai li Jianpeng Hu geng Zhang School of Electronic and Electrical Engineering Shanghai University of Engineering ScienceShanghai201620China

In the process of constructing domain-specific knowledge graphs,the task of relational triple extraction plays a critical role in transforming unstructured text into structured information.Existing relational triple extraction models facemultiple challenges when processing domain-specific data,including insufficient utilization of semantic interaction information between entities and relations,difficulties in handling challenging samples,and the scarcity of domain-specific datasets.To address these issues,our study introduces three innovative components:Relation semantic enhancement,data augmentation,and a voting strategy,all designed to significantly improve the model’s performance in tackling domain-specific relational triple extraction tasks.We first propose an innovative attention interaction module.This method significantly enhances the semantic interaction capabilities between entities and relations by integrating semantic information fromrelation labels.Second,we propose a voting strategy that effectively combines the strengths of large languagemodels(LLMs)and fine-tuned small pre-trained language models(SLMs)to reevaluate challenging samples,thereby improving the model’s adaptability in specific domains.Additionally,we explore the use of LLMs for data augmentation,aiming to generate domain-specific datasets to alleviate the scarcity of domain data.Experiments conducted on three domain-specific datasets demonstrate that our model outperforms existing comparative models in several aspects,with F1 scores exceeding the State of the Art models by 2%,1.6%,and 0.6%,respectively,validating the effectiveness and generalizability of our approach.

关键词： Relational triple extraction semantic interaction large language models data augmentation specific domains

Rare esophageal carcinoma-primary adenoid cystic carcinoma of the esophagus: A case report

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World Journal of Clinical Cases 2024年第3期12卷 630-636页

作者： li-Dan geng Jie li li Yuan Xiao-Bo Du Department of Oncology Mianyang Central HospitalMianyang 621000Sichuan ProvinceChina

BACKGROUND Esophageal adenoid cystic carcinoma(EACC)is an exceedingly rare malignant tumor of the esophagus,posing significant challenges in the clinic.CASE SUMMARY This report detailed the case of a 72-year-old male whose diagnosis of EACC was confirmed through postoperative histopathological examination.The patient underwent thoracoscopy-assisted radical resection of the esophageal tumor,coupled with lymph node dissection.Pathological findings revealed an adenoid cystic carcinoma infiltrating the entire layer of the muscularis propria,locally extending into the outer membrane of the esophageal fiber,involving the cardia and exhibiting no lymph node metastasis.The patient’s condition was classified as primary EACC,T3N0M0,per the American Joint Committee on Cancer(2017;8th edition).One month after surgery,the patient received postoperative adjuvant radiation therapy.CONCLUSION In addressing the rarity and high potential for biopsy misdiagnosis of EACC,this study delved into its diagnostic methods and treatment.

关键词： Esophageal adenoid cystic carcinoma Malignant tumor Lymph node dissection Adjuvant radiation therapy Misdiagnosis Case report

Microfluidic-oriented synthesis of enriched iridium nanodots/carbon architecture for robust electrocatalytic nitrogen fixation

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Green Energy & Environment 2024年第3期9卷 544-555页

作者： Hengyuan liu Xingjiang Wu Yuhao geng Xin li Jianhong Xu The State Key Laboratory of Chemical Engineering Department of Chemical EngineeringTsinghua UniversityBeijing100084China

Electrocatalytic nitrogen reduction reaction(NRR)is considered as a promising candidate to achieve ammonia synthesis because of clean electric energy,moderate reaction condition,safe operating process and harmless by-products.However,the chemical inertness of nitrogen and poor activated capacity on catalyst surface usually produce low ammonia yield and faradic efficiency.Herein,the microfluidic technology is proposed to efficiently fabricate enriched iridium nanodots/carbon architecture.Owing to in-situ co-precipitation reaction and microfluidic manipulation,the iridium nanodots/carbon nanomaterials possess small average size,uniform dispersion,high conductivity and abundant active sites,producing good proton activation and rapid electrons transmission and moderate adsorption/desorption capacity.As a result,the as-prepared iridium nanodots/carbon nanomaterials realize large ammonia yield of 28.73 μg h^(-1) cm^(-2) and faradic efficiency of 9.14%in KOH solution.Moreover,the high ammonia yield of 11.21 μg h^(-1) cm^(-2) and faradic efficiency of 24.30%are also achieved in H_(2)SO_(4) solution.The microfluidic method provides a reference for large-scale fabrication of nano-sized catalyst materials,which may accelerate the progress of electrocatalytic NRR in industrialization field.

关键词： Iridium nanodots Carbon Microfluidic technology Efficient synthesis Electrocatalytic nitrogen fixation

Polymer: Non-fullerene acceptor heterojunction-based phototransistor for short-wave infrared photodetection

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Nano Research 2024年第4期17卷 3087-3095页

作者： Jing li Weigang Zhu Yang Han Yanhou geng Wenping Hu Key Laboratory of Organic Integrated Circuits of Ministry of Education&Key Laboratory of Molecular Optoelectronic Sciences School of Science&Collaborative Innovation Center of Chemical Science and Engineering(Tianjin)Tianjin UniversityTianjin 300072China Key Laboratory of Organic Integrated Circuits of Ministry of Education&Key Laboratory of Molecular Optoelectronic Sciences School of Materials Science and EngineeringTianjin UniversityTianjin 300072China

It remains full of challenge for extending short-wave infrared(SWIR)spectral response and weak-light detection in the context of broad spectral responses for phototransistor.In this work,a novel poly(2,5-bis(4-hexyldodecyl)-2,5-dihydro-3,6-di-2-thienyl-pyrrolo[3,4-c]pyrrole-1,4-dione-alt-thiophene)(PDPPT3-HDO):COTIC-4F organic bulk-heterojunction is prepared as active layer for bulk heterojunction phototransistors.PDPPT3-HDO serves as a hole transport material,while COTIC-4F enhances the absorption of SWIR light to 1020 nm.As a result,smooth and connected PDPPT3-HDO film is fabricated by blade coating method and exhibits high hole mobility up to 2.34 cm^(2)·V^(-1)·s^(-1) with a current on/off ratio of 4.72×10^(5) in organic thin film transistors.PDPPT3-HDO:COTIC-4F heterojunction phototransistors exhibit high responsivity of 2680 A·W^(-1) to 900 nm and 815 A·W^(-1) to 1020 nm,with fast response time(rise time~20 ms and fall time~100 ms).The photosensitivity of the heterojunction phototransistor improves as the mass ratio of non-fullerene acceptors increases,resulting in an approximately two orders of magnitude enhancement compared to the bare polymer phototransistor.Importantly,the phototransistor exhibits decent responsivity even under ultra-weak light power of 43μW·cm^(-2) to 1020 nm.This work represents a highly effective and general strategy for fabricating efficient and sensitive SWIR light photodetectors.

关键词： photodetection phototransistor organic semiconductor heterojunction non-fullerene acceptor

Endoscopic features and treatments of gastric cystica profunda

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World Journal of Gastroenterology 2024年第7期30卷 673-684页

作者： Zi-Han geng Yan Zhu Pei-Yao Fu Yi-Fan Qu Wei-Feng Chen Xia Yang Ping-hong Zhou Quan-lin li Endoscopy Center and Endoscopy Research Institute Zhongshan HospitalFudan UniversityShanghai 200032China

BACKGROUND Gastric cystica profunda(GCP)represents a rare condition characterized by cystic dilation of gastric glands within the mucosal and/or submucosal layers.GCP is often linked to,or may progress into,early gastric cancer(EGC).AIM To provide a comprehensive evaluation of the endoscopic features of GCP while assessing the efficacy of endoscopic treatment,thereby offering guidance for diagnosis and treatment.METHODS This retrospective study involved 104 patients with GCP who underwent endoscopic resection.Alongside demographic and clinical data,regular patient followups were conducted to assess local recurrence.RESULTS Among the 104 patients diagnosed with GCP who underwent endoscopic resection,12.5%had a history of previous gastric procedures.The primary site predominantly affected was the cardia(38.5%,n=40).GCP commonly exhibited intraluminal growth(99%),regular presentation(74.0%),and ulcerative mucosa(61.5%).The leading endoscopic feature was the mucosal lesion type(59.6%,n=62).The average maximum diameter was 20.9±15.3 mm,with mucosal involvement in 60.6%(n=63).Procedures lasted 73.9±57.5 min,achieving complete resection in 91.3%(n=95).Recurrence(4.8%)was managed via either surgical intervention(n=1)or through endoscopic resection(n=4).Final pathology confirmed that 59.6%of GCP cases were associated with EGC.Univariate analysis indicated that elderly males were more susceptible to GCP associated with EGC.Conversely,multivariate analysis identified lesion morphology and endoscopic features as significant risk factors.Survival analysis demonstrated no statistically significant difference in recurrence between GCP with and without EGC(P=0.72).CONCLUSION The findings suggested that endoscopic resection might serve as an effective and minimally invasive treatment for GCP with or without EGC.

关键词： Gastric cystica profunda Early gastric cancer Endoscopic features Endoscopic resection Endoscopy

Universal transfer of full-class metal electrodes for barrier-free two-dimensional semiconductor contacts

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InfoMat 2024年第1期6卷 96-107页

作者： Mengyu hong Xiankun Zhang Yu geng Yunan Wang Xiaofu Wei li Gao Huihui Yu Zhihong Cao Zheng Zhang Yue Zhang Academy for Advanced Interdisciplinary Science and Technology School of Materials Science and EngineeringUniversity of Science and Technology BeijingBeijingthe People's Republic of China Key Laboratory of Advanced Materials and Devices for Post-Moore Chips Ministry of EducationUniversity of Science and Technology BeijingBeijingthe People's Republic of China

Metal–semiconductor contacts are crucial components in semiconductor devices.Ultrathin two-dimensional transition-metal dichalcogenide semiconductors can sustain transistor scaling for next-generation integrated circuits.However,their performance is often degraded by conventional metal deposition,which results in a high barrier due to chemical disorder and Fermi-level pinning(FLP).Although,transferring electrodes can address these issues,they are limited in achieving universal transfer of full-class metals due to strong adhesion between pre-deposited metals and substrates.Here,we propose a nanobelt-assisted transfer strategy that can avoid the adhesion limitation and enables the universal transfer of over 20 different types of electrodes.Our contacts obey the Schottky–Mott rule and exhibit a FLP of S=0.99.Both the electron and hole contacts show record-low Schottky barriers of 4.2 and 11.2 meV,respectively.As a demonstration,we construct a doping-free WSe_(2) inverter with these high-performance contacts,which exhibits a static power consumption of only 58 pW.This strategy provides a universal method of electrode preparation for building high-performance post-Moore electronic devices.

关键词： metal electrode transfer metal–semiconductor contacts Schottky barrier two-dimensional semiconductors

Sinomenine increases osteogenesis in mice with ovariectomyinduced bone loss by modulating autophagy

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World Journal of Stem Cells 2024年第5期16卷 486-498页

作者： Hai-Xiang Xiao Lei Yu Yu Xia Kai Chen Wen-Ming li Gao-Ran Ge Wei Zhang Qing Zhang hong-Tao Zhang De-Chun geng Department of Orthopedics The Fourth Affiliated Hospital of Soochow UniversitySuzhou Dushu Lake HospitalMedical Centre of Soochow UniversitySuzhou 215006Jiangsu ProvinceChina Department of Orthopedics Jingjiang People’s Hospital Affiliated to Yangzhou UniversityJingjiang 214500Jiangsu ProvinceChina Department of Orthopedics The First Affiliated Hospital of Soochow UniversitySuzhou 215006Jiangsu ProvinceChina Department of Orthopedics Hai’an People’s HospitalHai’an 226600Jiangsu ProvinceChina Department of Orthopedics The Affiliated Huai’an Hospital of Xuzhou Medical UniversityHuai’an Second People’s HospitalXuzhou 223002Jiangsu ProvinceChina Department of Orthopaedics The First Affiliated Hospital of Soochow UniversitySuzhou 215006Jiangsu ProvinceChina

BACKGROUND A decreased autophagic capacity of bone marrow mesenchymal stromal cells(BMSCs)has been suggested to be an important cause of decreased osteogenic differentiation.A pharmacological increase in autophagy of BMSCs is a potential therapeutic option to increase osteoblast viability and ameliorate osteoporosis.AIM To explore the effects of sinomenine(SIN)on the osteogenic differentiation of BMSCs and the underlying mechanisms.METHODS For in vitro experiments,BMSCs were extracted from sham-treated mice and ovariectomized mice,and the levels of autophagy markers and osteogenic differentiation were examined after treatment with the appropriate concen-trations of SIN and the autophagy inhibitor 3-methyladenine.In vivo,the therapeutic effect of SIN was verified by establishing an ovariectomy-induced mouse model and by morphological and histological assays of the mouse femur.RESULTS SIN reduced the levels of AKT and mammalian target of the rapamycin(mTOR)phosphorylation in the phosphatidylinositol 3-kinase(PI3K)/AKT/mTOR signaling pathway,inhibited mTOR activity,and increased autophagy ability of BMSCs,thereby promoting the osteogenic differentiation of BMSCs and effectively alleviating bone loss in ovariectomized mice in vivo.CONCLUSION The Chinese medicine SIN has potential for the treatment of various types of osteoporosis,bone homeostasis disorders,and autophagy-related diseases.

关键词： Sinomenine Osteogenesis Autophagy Ovariectomy Osteoporosis