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Supercritical fluid technology:A game-changer for biomacromolecular nanomedicine preparation and biomedical application

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Chinese Chemical Letters 2024年第7期35卷 89-99页

作者： Yating Zheng Yulan Huang Jing Luo Xuqi Peng Xiran Gui Gang Liu Yang Zhang State Key Laboratory of Vaccines for Infectious Diseases Xiang An Biomedicine LaboratoryNational Innovation Platform for Industry-Education Integration in Vaccine ResearchState Key Laboratory of Molecular Vaccinology and Molecular DiagnosticsCenter for Molecular Imaging and Translational MedicineSchool of Public HealthXiamen UniversityXiamen 361102China Shen Zhen Research Institute of Xiamen University Shenzhen 518057China Division of Urology and Department of Surgery Brigham and Women's HospitalHarvard Medical SchoolBostonMA 02115United States Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province(IKKEM) Xiamen 361102China

Biomacromolecules are attractive in biomedical applications as therapeutic agents and potential drug carriers due to their natural active components,good biocompatibility,and high ***,their large relative molecular weight,complex structure,susceptibility to degradation,and poor stability limit their *** can address these issues by improving the therapeutic value,bioavailability,permeability,and absorption of biomacromolecules while regulating their retention time in the ***,compelling evidence has been reported that supercritical fluid(SCF)technology has emerged as an alternative that maintains the integrity of biomacromolecules and reduces environmental *** this review,we highlight a set of unique nanosizing strategies based on SCF technology for biomacromolecular nanomedicine,and extensively discuss their characteristics and *** particular,the protein-based,nucleic acid-based,and polysaccharide-based nanomedicine preparations via SCF technology and their biomedical applications are summarized,and the potential for industrial production of biomacromolecular drugs is also *** further provide perspectives on the opportunities and challenges in this excellent field of biomacromolecular drugs nanotechnology.

关键词： Biomacromolecules Supercritical fluid technology Therapeutic proteins Gene therapy Nanomedicine

The role of corneal endothelium in macular corneal dystrophy development and recurrence

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Science China(Life Sciences) 2024年第2期67卷 332-344页

作者： Bi-Ning Zhang Benxiang Qi Chunxiao Dong Bin Zhang Jun Cheng Xin Wang Suxia Li Xiaoyun Zhuang Shijiu Chen Haoyun Duan Dewei Li Sujie Zhu Guoyun Li Yihai Cao Qingjun Zhou Lixin Xie Eye Institute of Shandong First Medical University Qingdao Eye Hospital of Shandong First Medical UniversityQingdao 266071China State Key Laboratory Cultivation Base Shandong Provincial Key Laboratory of OphthalmologyQingdao 266071China School of Ophthalmology Shandong First Medical UniversityQingdao 250021China Department of medicine Qingdao UniversityQingdao 266071China Eye Institute of Shandong First Medical University Eye Hospital of Shandong First Medical University(Shandong Eye Hospital)Jinan 250021China Department of Ophthalmology School of Clinical MedicineWeifang Medical UniversityWeifang 261072China Institute of translational medicine College of MedicineQingdao UniversityQingdao 266071China Key Laboratory of Marine Drugs of Ministry of Education Shandong Provincial Key Laboratory of Glycoscience and GlycotechnologySchool of Medicine and PharmacyOcean University of ChinaQingdao 266071China Laboratory for Marine Drugs and Bioproducts Pilot National Laboratory for Marine Science and Technology(Qingdao)Qingdao 266071China Department of Microbiology Tumor and Cell BiologyBiomedicumKarolinska InstitutetStockholm 17177Sweden

Macular corneal dystrophy(MCD)is a progressive,bilateral stromal dystrophic disease that arises from mutations in carbohydrate sulfotransferase 6(CHST6).Corneal transplantation is the ultimate therapeutic solution for MCD ***,postoperative recurrence remains a significant *** conducted a retrospective review of a clinical cohort comprising 102 MCD patients with 124 eyes that underwent either penetrating keratoplasty(PKP)or deep anterior lamellar keratoplasty(DALK).Our results revealed that the recurrence rate was nearly three times higher in the DALK group(39.13%,9/23 eyes)compared with the PKP group(10.89%,11/101 eyes),suggesting that surgical replacement of the corneal endothelium for treating MCD is advisable to prevent postoperative *** experimental data confirmed the robust m RNA and protein expression of CHST6 in human corneal endothelium and the rodent homolog CHST5 in mouse *** knockdown of wild-type Chst5 in mouse corneal endothelium(AC^(siChst5)),but not in the corneal stroma,induced experimental MCD with similar extracellular matrix synthesis impairments and corneal thinning as observed in MCD *** carrying Chst5 point mutation also recapitulated clinical phenotypes of MCD,along with corneal endothelial *** injection of wild-type Chst5 rescued the corneal impairments in AC^(siChst5)mice and retarded the disease progression in Chst5 mutant ***,our study provides new mechanistic insights and therapeutic approaches for MCD treatment by highlighting the role of corneal endothelium in MCD development.

关键词： macular corneal dystrophy recurrence corneal endothelium keratan sulfate penetrating keratoplasty

The neutrophil–osteogenic cell axis promotes bone destruction in periodontitis

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International Journal of Oral Science 2024年第1期16卷 154-162页

作者： Yutaro Ando Masayuki Tsukasaki Nam Cong-Nhat Huynh Shizao Zang Minglu Yan Ryunosuke Muro Kazutaka Nakamura Masatsugu Komagamine Noriko Komatsu Kazuo Okamoto Kenta Nakano Tadashi Okamura Akira Yamaguchi Kazuyuki Ishihara Hiroshi Takayanagi Department of Immunology Graduate School of Medicine and Faculty of MedicineThe University of Tokyo7-3-1HongoBunkyo-kuTokyoJapan Department of Microbiology Tokyo Dental College2-1-14 Kanda-Misaki-choChiyoda-kuTokyoJapan Oral Health Science Center Tokyo Dental College2-9-18Kanda-Misaki-choChiyodakuTokyoJapan Department of Osteoimmunology Graduate School of Medicine and Faculty of MedicineThe University of Tokyo7-3-1HongoBunkyo-kuTokyoJapan Unit of Prosthodontics Laboratory of Oral-Maxillofacial Biology Faculty of Odonto-StomatologyUniversity of Medicine and Pharmacy at Ho Chi Minh CityHo Chi Minh CityVietnam Department of Oral and Maxillofacial Surgery Department of Sensory and Motor System MedicineGraduate School of MedicineThe University of TokyoTokyoJapan Division of Rheumatology Department of Internal MedicineKeio University School of MedicineTokyoJapan Department of Laboratory Animal medicine Research InstituteNational Center for Global Health and MedicineTokyoJapan

The immune-stromal cell interactions play a key role in health and diseases. In periodontitis, the most prevalent infectious disease in humans, immune cells accumulate in the oral mucosa and promote bone destruction by inducing receptor activator of nuclear factor-κB ligand (RANKL) expression in osteogenic cells such as osteoblasts and periodontal ligament cells. However, the detailed mechanism underlying immune–bone cell interactions in periodontitis is not fully understood. Here, we performed single-cell RNAsequencing analysis on mouse periodontal lesions and showed that neutrophil–osteogenic cell crosstalk is involved in periodontitis-induced bone loss. The periodontal lesions displayed marked infiltration of neutrophils, and in silico analyses suggested that the neutrophils interacted with osteogenic cells through cytokine production. Among the cytokines expressed in the periodontal neutrophils, oncostatin M (OSM) potently induced RANKL expression in the primary osteoblasts, and deletion of the OSM receptor in osteogenic cells significantly ameliorated periodontitis-induced bone loss. Epigenomic data analyses identified the OSM-regulated RANKL enhancer region in osteogenic cells, and mice lacking this enhancer showed decreased periodontal bone loss while maintaining physiological bone metabolism. These findings shed light on the role of neutrophils in bone regulation during bacterial infection, highlighting the novel mechanism underlying osteoimmune crosstalk.

关键词： period neutrophil destruction

Nanomedicine targeting ferroptosis to overcome anticancer therapeutic resistance

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Science China(Life Sciences) 2024年第1期67卷 19-40页

作者： Jing Cai Xiaoding Xu Phei Er Saw Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Guangdong-Hong Kong Joint Laboratory for RNA MedicineMedical Research CenterSun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China Nanhai translational Innovation Center of Precision Immunology Sun Yat-sen Memorial HospitalSun Yat-sen UniversityFoshan 528200China

A potential reason for the failure of tumor therapies is treatment *** to chemotherapy,radiotherapy,and immunotherapy continues to be a major obstacle in clinic,resulting in tumor recurrence and *** major mechanisms of therapy resistance are inhibitions of cell deaths,like apoptosis and necrosis,through drug inactivation and excretion,repair of DNA damage,tumor heterogeneity,or changes in tumor microenvironment,*** studies have shown that ferroptosis play a major role in therapies resistance by inducing phospholipid peroxidation and iron-dependent cell *** ferroptosis inducers in combination with clinical treatment techniques have been used to enhance the effect in tumor ***,versatile ferroptosis nanoinducers exhibit an extensive range of functions in reversing therapy resistance,including directly triggering ferroptosis and feedback ***,we provide a detailed description of the design,mechanism,and therapeutic application of ferroptosis-mediated synergistic tumor *** also discuss the prospect and challenge of nanomedicine in tumor therapy resistance by regulating ferroptosis and combination therapy.

关键词： ferroptosis cancer therapy therapy resistance nanoinducers

DNA damage response-related immune activation signature predicts the response to immune checkpoint inhibitors: from gastrointestinal cancer analysis to pan-cancer validation

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Cancer Biology & medicine 2024年第3期21卷 252-266页

作者： Junya Yan Shibo Wang Jing Zhang Qiangqiang Yuan Xianchun Gao Nannan Zhang Yan Pan Haohao Zhang Kun Liu Jun Yu Linbin Lu Hui Liu Xiaoliang Gao Sheng Zhao Wenyao Zhang Abudurousuli Reyila Yu Qi Qiujin Zhang Shundong Cang Yuanyuan Lu Yanglin Pan Yan Kong Yongzhan Nie State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and national Clinical Research Center for Digestive Diseases Xijing Hospital of Air Force Military Medical UniversityXi'an 710032China Department of Oncology Henan Provincial People's HospitalZhengzhou University People's HospitalZhengzhou 450o03China Faculty of Life Science Northwest UniversityXi'an 710069China Unit 73211 of the People's Liberation Army Nanjing 211800China Key Laboratory of Resource Biology and Biotechnology in Western China(Ministry of Education) School of MedicineNorthwest UniversityXi'an 710069China Shaanxi University of Chinese medicine Second Clinical Medicine FacultyXi'an 712046China Key Laboratory of Carcinogenesis and translational Research(Ministry of Education) Department of Renal Cancer and MelanomaPeking University Cancer Hospital and InstituteBeijing 100142China

Objective: DNA damage response(DDR) deficiency has emerged as a prominent determinant of tumor immunogenicity. This study aimed to construct a DDR-related immune activation(DRIA) signature and evaluate the predictive accuracy of the DRIA signature for response to immune checkpoint inhibitor(ICI) therapy in gastrointestinal(GI) ***: A DRIA signature was established based on two previously reported DNA damage immune response assays. Clinical and gene expression data from two published GI cancer cohorts were used to assess and validate the association between the DRIA score and response to ICI therapy. The predictive accuracy of the DRIA score was validated based on one ICI-treated melanoma and three pan-cancer published ***: The DRIA signature includes three genes(CXCL10, IDO1, and IFI44L). In the discovery cancer cohort, DRIA-high patients with gastric cancer achieved a higher response rate to ICI therapy than DRIA-low patients(81.8% vs. 8.8%;P < 0.001), and the predictive accuracy of the DRIA score [area under the receiver operating characteristic curve(AUC) = 0.845] was superior to the predictive accuracy of PD-L1 expression, tumor mutational burden, microsatellite instability, and Epstein–Barr virus status. The validation cohort demonstrated that the DRIA score identified responders with microsatellite-stable colorectal and pancreatic adenocarcinoma who received dual PD-1 and CTLA-4 blockade with radiation therapy. Furthermore, the predictive performance of the DRIA score was shown to be robust through an extended validation in melanoma, urothelial cancer, and ***: The DRIA signature has superior and robust predictive accuracy for the efficacy of ICI therapy in GI cancer and pancancer, indicating that the DRIA signature may serve as a powerful biomarker for guiding ICI therapy decisions.

关键词： DNA damage response-related immune activation immune checkpoint inhibitors biomarker gastrointestinal cancer pan-cancer

Trends in Incidence of HIV and Syphilis Among Men Who Have Sex with Men—Tianjin Municipality,China,2013-2022

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China CDC weekly 2024年第27期6卷 651-657页

作者： Yan Guo Fangfang Chen Hui Gong Ziming Wu Xinying Zhang Tielin Ning Zhongquan Liu Jianyun Bai Long Li Jie Yang Fangning Zhao Jinyu Hou Maohe Yu Houlin Tang STD&AIDS Control and Prevention Section Tianjin Center for Disease Control and PreventionTianjinChina national Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases National Center for AIDS/STD Control and PreventionChinese Center for Disease Control and PreventionBeijingChina STD&AIDS Control and Prevention department Tianjin Hongqiao District Center for Disease Control and PreventionTianjinChina Tianjin Shenlan Public Health Counseling Service Center TianjinChina Tianjin Key Laboratory of Pathogenic Microbiology of Infectious Disease Tianjin Centers for Disease Control and PreventionTianjinChina

Summary What is already known about this topic?Given the common modes of transmission,outbreaks of both human immunodeficiency virus(HIV)and syphilis are primarily observed in men who have sex with men(MSM).However,minimal research has been conducted to concurrently evaluate the rates and trends of HIV and syphilis incidence within this community in *** is added by this report?

关键词： Incidence primarily immunodeficiency

Mechanical regulation of lipid and sugar absorption by Piezo1 in enterocytes

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3576-3590页

作者： Tian Tao Qing Shu Yawen Zhao Wenying Guo Jinting Wang Yuhao Shi Shiqi Jia Hening Zhai Hui Chen Cunchuan Wang Geyang Xu Department of Physiology School of MedicineJinan UniversityGuangzhou 510632China Department of Metabolic and Bariatric Surgery the First Affiliated Hospital of Jinan UniversityGuangzhou 510630China Endoscopy Center the First Affiliated Hospital of Jinan UniversityGuangzhou 510630China Biotherapy Center Cell-gene Therapy Translational Medicine Research Centerthe Third Affiliated HospitalSun Yat-sen UniversityGuangzhou 510630China Key Laboratory of Viral Pathogenesis&Infection Prevention and Control(Jinan University) Ministry of EducationGuangzhou 510632China

Obesity is primarily caused by excessive intake as well as absorption of sugar and *** surge in distention pressure and intestinal motility accelerates the absorption of *** response of intestinal epithelial cells to mechanical stimulation is not fully ***1,a mechanosensitive ion channel,is widely expressed throughout the digestive ***,its function in intestinal nutrient absorption is not yet *** our study,excessive lipid deposition was observed in the duodenum of obese patients,while duodenal Piezo1-CaMKK2-AMPKa was decreased when compared to normal-weight *** high-fat diet condition,the Piezo1iKO mice exhibited abnormally elevated sugar and lipid absorption as well as severe lipid deposition in the duodenum and *** phenotypes were mainly caused by the inhibition of duodenal CaMKK2-AMPKa and the upregulation of SGLT1 and *** contrast,Yoda1,a Piezo1 agonist,was found to reduce intestinal lipid absorption in diet induced obese *** of Piezo1,stretch and Yoda1 inhibited lipid accumulation and the expression of DGAT2 and SGLT1,whereas knockdown of Piezo1 stimulated lipid accumulation and DGAT2 in Caco-2 *** study reveals a previously unexplored mechanical regulation of nutrient absorption in intestinal epithelial cells,which may shed new light on the therapy of obesity.

关键词： Piezo1 DGAT2 SGLT1 Lipid metabolism Obesity Mechanical sensing Intestinal lipid absorption Intestinal glucose absorption

A nanoagent for concurrent therapy of breast cancer bone metastasis and cancer-induced bone pain through SLC7A11 interruption and photodynamic therapy

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Chinese Chemical Letters 2024年第2期35卷 295-299页

作者： Qi Fu Zhongming Lian Mengya Niu Yaru Huang Yanqiu Ai Long He Dandan Zhang Cuixia Zheng Jian-Jun Yang Lei Wang Dandan Tian Department of Anesthesiology Pain and Perioperative MedicineThe First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450001China School of Pharmaceutical Sciences Zhengzhou UniversityZhengzhou 450001China translational Medical Center of Huaihe Hospital Henan UniversityKaifeng 475004China Key Laboratory of Advanced Drug Preparation Technologies Ministry of EducationSchool of Pharmaceutical SciencesZhengzhou UniversityZhengzhou 450001China

Bone metastasis,a life-threatening complication of advanced breast cancer,is often accompanied by debilitating pain(cancer-induced bone pain,CIBP)that severely impairs life quality and *** concurrent treatment of bone metastases and CIBP remains a clinical challenge because the therapeutic options are *** this study,we construct a near-infrared light-activated nano-therapeutic system to meet this *** detail,sorafenib(SRF)and photosensitizer(chlorin e6,Ce6)are encapsulated into mesoporous hydroxyapatite nanoparticles(HANPs),which are further functionalized with hyaluronic acid(HA)to obtain HA-SRF/Ce6@HANPs *** designed nanoplatform destroys tumor cells in vitro and in vivo via the synergism of SRF(interrupting the exchange of cystine/glutamate by inhibiting SLC7A11)and photodynamic therapy(PDT,inducing reactive oxygen species generation).The decrease in tumor burden and reduction of extracellular glutamate significantly attenuate CIBP in mice model with developing bone ***,the combination of HA-SRF/Ce6@HANPs and PDT inhibit osteoclasts activation,promote osteoblast differentiation and accelerate bone ***,the nanoagent with good biocompatibility may provide an effective therapy method for the concurrent treatment of breast cancer bone metastasis and CIBP.

关键词： Breast cancer bone metastasis Cancer-induced bone pain Cystine/glutamate antiporter Sorafenib Photodynamic therapy

Dual-objective two-photon microscope for volumetric imaging of dense scattering biological samples by bidirectional excitation and collection

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Photonics Research 2024年第6期12卷 1351-1361页

作者： MUYUE ZHAI JING YU YANHUI HU HANG YU BEICHEN XIE YI YU DAWEI LI AIMIN WANG HEPING CHENG national Biomedical Imaging Center College of Future TechnologyPeking UniversityBeijing 100871China Research Unit of Mitochondria in Brain Diseases Chinese Academy of Medical SciencesPKU-Nanjing Institute of Translational MedicineNanjing 211500China Beijing Transcend Vivoscope Biotech Beijing 100085China College of Engineering Peking UniversityBeijing 100871China Academy for Advanced Interdisciplinary Studies Peking UniversityBeijing 100871China Center for Quantitative Biology Peking UniversityBeijing 100871China School of Electronics Peking UniversityBeijing 100871China State Key Laboratory of Advanced Optical Communication System and Networks Peking UniversityBeijing 100871China

Full view observation throughout entire specimens over a prolonged period is crucial when exploring the physiological functions and system-level ***-photon microscopy(MPM)has been widely employed for such purposes owing to its deep penetration ***,the current MPM struggles with balancing the imaging depth and quality while avoiding photodamage for the exponential increasement of excitation power with the imaging ***,we present a dual-objective two-photon microscope(Duo-2P),characterized by bidirectional two-photon excitation and fluorescence collection,for long-duration volumetric imaging of dense scattering ***-2P effectively doubles the imaging depth,reduces the total excitation energy by an order of magnitude for samples with a thickness five times the scattering length,and enhances the signal-to-noise ratio up to 1.4 *** these advantages,we acquired volumetric images of a 380-μm suprachiasmatic nucleus slice for continuous 4-h recording at a rate of 1.67 s/volume,visualized the calcium activities over 4000 neurons,and uncovered their state-switching *** conclude that Duo-2P provides an elegant and powerful means to overcome the fundamental depth limit while mitigating photodamages for deep tissue volumetric imaging.

关键词： excitation overcome exponential