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Antitumor efficacy and potential mechanism of FAP-targeted radioligand therapy combined with immune checkpoint blockade

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Signal Transduction and Targeted Therapy 2024年第7期9卷 2936-2952页

作者： Liang Zhao Yizhen Pang yangfan Zhou Jianhao chen Hao Fu Wei Guo Weizhi Xu Xin Xue Guoqiang Su Long Sun Hua Wu jingjing Zhang Zhanxiang Wang Qin Lin Xiaoyuan chen Haojun chen Department of Nuclear Medicine and Minnan PET Center Xiamen Key Laboratory of RadiopharmaceuticalsThe First Affiliated Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamenChina Departments of Diagnostic Radiology SurgeryChemical and Biomolecular Engineeringand Biomedical EngineeringYong Loo Lin School of Medicine and College of Design and EngineeringNational University of SingaporeSingaporeSingapore Clinical Imaging Research Centre Centre for Translational MedicineYong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore Department of Radiation Oncology Xiamen Cancer CenterXiamen Key Laboratory of Radiation OncologyThe First Affiliated Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamenChina Department of Colorectal Tumor Surgery Xiamen Cancer CenterXiamen Key Laboratory of Radiation OncologyThe First Affiliated Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamenChina Department of Cardiothoracic Surgery Zhongda HospitalSchool of MedicineSoutheast UniversityNanjingChina Nanomedicine Translational Research Program NUS Center for NanomedicineYong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore Department of Neurosurgery and Department of Neuroscience Fujian Key Laboratory of Brain Tumors Diagnosis and Precision TreatmentXiamen Key Laboratory of Brain Centerthe First Affiliated Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamenChina Institute of Molecular and Cell Biology Agency for ScienceTechnology and Research(A*STAR)SingaporeSingapore Xiamen Key Laboratory of Rare Earth Photoelectric Functional Materials Xiamen Institute of Rare Earth MaterialsHaixi InstituteChinese Academy of SciencesXiamenChina

Radiotherapy combined with immune checkpoint blockade holds great promise for synergistic antitumor *** radionuclide therapy delivers radiation directly to tumor ***1004 is a fibroblast activation protein(FAP)-targeting radiopharmaceutical,conjugated with the albumin binder Evans Blue,which has demonstrated enhanced tumor uptake and retention in previous preclinical and clinical ***,we demonstrate that^(68)Ga/^(177)Lu-labeled LNC1004 exhibits increased uptake and prolonged retention in MC38/NIH3T3-FAP and CT26/NIH3T3-FAP tumor *** therapy with^(177)Lu-LNC1004 induced a transient upregulation of PD-L1 expression in tumor *** combination of^(177)Lu-LNC1004 and anti-PD-L1 immunotherapy led to complete eradication of all tumors in MC38/NIH3T3-FAP tumor-bearing mice,with mice showing 100%tumor rejection upon ***,single-cell RNA sequencing(scRNA-seq),and TCR sequencing revealed that combination therapy reprogrammed the tumor microenvironment in mice to foster antitumor immunity by suppressing malignant progression and increasing cell-to-cell communication,CD8^(+)T-cell activation and expansion,M1 macrophage counts,antitumor activity of neutrophils,and T-cell receptor diversity.A preliminary clinical study demonstrated that^(177)Lu-LNC1004 was well-tolerated and effective in patients with refractory ***,scRNA-seq of peripheral blood mononuclear cells underscored the importance of addressing immune evasion through immune checkpoint blockade *** was emphasized by the observed increase in antigen processing and presentation juxtaposed with T cell *** conclusion,our data supported the efficacy of immunotherapy combined with^(177)Lu-LNC1004 for cancer patients with FAP-positive tumors.

关键词： immunity retention holds

Clinical and genetic heterogeneity of adult polyglucosan body disease caused by GBE1 biallelic mutations in china

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Genes & Diseases 2024年第5期11卷 17-20页

作者： Yikun chen yan Shi Yuan Gao yan Hu Linying Zhou Jingmei Hong Shirui Gan Xiang Lin Wanjin chen Guorong Xu Jin He Department of Neurology and Institute of Neurology of First Affiliated Hospital Institute of Neuroscienceand Fujian Key Laboratory of Molecular NeurologyFujian Medical UniversityFuzhouFujian 350005China Fujian Key Laboratory of Molecular Neurology Institute of NeuroscienceFujian Medical UniversityFuzhouFujian 350005China Electron Microscopy Lab of Public Technology Service Center Fujian Medical UniversityFuzhouFujian 350005China

Adult polyglucosan body disease(APBD)is a rare and highly heterogeneous glycogen storage disorder due to biallelic variants in GBE1.1 Typical APBD presentations include gait abnormalities with polyneuropathy,leukodystrophy,neurogenic bladder,and mild cognitive *** diagnosis of APBD encompasses a large spectrum of conditions including axonal and demyelinating sensorimotor polyneuropathy,progressive spastic paraparesis,and leukodystrophies.

关键词： GBE bladder diagnosis

Clinical application of eight-zone laparoscopic dissection strategy for rectal cancer:Experience and discussion

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World Journal of Gastroenterology 2024年第30期30卷 3574-3583页

作者： Chang chen Xiang Zhang Xin Li yan-Lei Wang Department of General Surgery Rongchang People's HospitalChongqing 250012China Department of Colorectal Surgery Qilu HospitalShandong UniversityJinan 250012Shandong ProvinceChina Department of General Surgery Huantai Branch of Qilu Hospital of Shandong UniversityZibo 255000Shandong ProvinceChina

BACKGROUND The incidence of rectal cancer is increasing worldwide,and surgery remains the primary treatment *** the advent of total mesorectal excision(TME)technique,the probability of tumor recurrence post-surgery has significantly ***'focus has gradually shifted towards minimizing the impact of surgery on urinary and sexual *** these concerns,the optimal dissection of the rectal lateral ligaments and preservation of the pelvic floor neuro-vascular bundle have become *** explore the optimal surgical technique for TME and establish a standardized surgical protocol to minimize the impact on urinary and sexual functions,we propose the eight-zone dissection strategy for pelvic floor *** To compare the differences in surgical specimen integrity and postoperative quality of life satisfaction between the traditional pelvic floor dissection strategy and the innovative eight-zone dissection *** We analyzed the perioperative data of patients who underwent laparoscopic radical resection of rectal cancer at Qilu Hospital of Shandong university between January 1,2021 and December 1,*** study included a total of 218 patients undergoing laparoscopic radical surgery for rectal cancer,among whom 109 patients underwent traditional pelvic floor dissection strategy,and 109 patients received the eight-zone dissection *** There were no significant differences in general characteristics between the two *** in the eight-zone dissection group had higher postoperative specimen integrity(88.1%vs 78.0%,P=0.047).At the 3-month followup,patients in the eight-zone surgery group had better scores in urinary issues(6.8±3.3 vs 5.3±2.5,P=0.045)and male sexual desire(2.2±0.6 vs 2.5±0.5,P=0.047)compared to the traditional surgery strategy *** This study demonstrates that the eight-zone dissection strategy for laparoscopic lateral ligament dissection of rectal cancer is safe and ***

关键词： Eight-zone dissection strategy Rectal cancer Lateral ligament dissection Nerve injury Total mesorectal excision surgery

Asymmetrically coordinated main group atomic In-S_(1)N_(3)interface sites for promoting electrochemical CO_(2)reduction

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Nano Research 2024年第6期17卷 5011-5021页

作者： yan Gao Jinlong Ge Jingqiao Zhang Ting Cao Zhiyi Sun Wensheng yan Yu Wang Jie Lin Wenxing chen Zheng Liu Anhui Provincial Engineering Laboratory of Silicon-based Materials Bengbu UniversityBengbu 233030China State Key Laboratory of Environmental Criteria and Risk Assessment Chinese Research Academy of Environmental SciencesBeijing 100012China SEPA Key Laboratory of Eco-Industry Chinese Research Academy of Environmental SciencesBeijing 100012China Ningbo Institute of Materials Technology and Engineering Chinese Academy of ScienceNingbo 315201China Energy&Catalysis Center School of Materials Science and EngineeringBeijing Institute of TechnologyBeijing 100081China National Synchrotron Radiation Laboratory University of Science and Technology of ChinaHefei 230029China Shanghai Synchrotron Radiation Facilities Shanghai Institute of Applied PhysicsChinese Academy of ScienceShanghai 201204China

Designing catalysts with highly active,selectivity,and stability for electrocatalytic CO_(2)to formate is currently a severe ***,we developed an electronic structure engineering on carbon nano frameworks embedded with nitrogen and sulfur asymmetrically dual-coordinated indium active sites toward the efficient electrocatalytic CO_(2)reduction *** expected,atomically dispersed In-based catalysts with In-S_(1)N_(3)atomic interface with asymmetrically coordinated exhibited high efficiency for CO_(2)reduction reaction(CO_(2)RR)to *** achieved a maximum Faradaic efficiency(FE)of 94.3%towards formate generation at−0.8 V *** hydrogen electrode(RHE),outperforming that of catalysts with In-S2N2 and In-N4 atomic *** at a potential of−1.10 V ***,In-S_(1)N_(3)achieves an impressive Faradaic efficiency of 93.7%in flow *** catalytic performance of In-S_(1)N_(3)sites was confirmed to be enhanced through in-situ X-ray absorption near-edge structure(XANES)measurements under electrochemical *** discovery provides the guidance for performance regulation of main group metal catalysts toward CO_(2)RR at atomic scale.

关键词： indium single-site catalyst main group metal asymmetrical coordination CO_(2)reduction reaction structure-activity relationship

Exploring the taste presentation and receptor perception mechanism of salty peptides from Stropharia rugosoannulata based on molecular dynamics and thermodynamics simulation

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Food Science and Human Wellness 2024年第4期13卷 2277-2288页

作者： Wen Li Shuai Sun Wanchao chen Haile Ma Tingzhao Li Zhong Zhang Di Wu Mengqiu yan yan yang Institute of Edible Fungi Shanghai Academy of Agricultural SciencesNational Engineering Research Center of Edible FungiKey Laboratory of Edible Fungi Resources and Utilization(South)Ministry of Agriculture and Rural AffairsShanghai 201403China school of Food&Biological Engineering Institute of Food Physical ProcessingJiangsu UniversityZhenjiang 212013China Amway(Shanghai)Innovation&Science Co. Ltd.Shanghai 201203China Amway(china)Botanical R&D Center Wuxi 214115China

The taste presentation and receptor perception mechanism of the salty peptide of Stropharia rugosoannulata were predicted and verified using peptide omics and molecular interaction *** combination of aspartic acid(D)and glutamic acid(E),or peptide fragments composed of arginine(R),constitute the characteristic taste structural basis of salty peptides of *** taste intensity of the salty peptide positively correlates with its concentration within a specific concentration range(0.25–1.0 mg/mL).The receptor more easily recognizes the first amino acid residue at the N-terminal of salty peptides and the aspartic acid residue in the ***513,ASP707,and VAL508 are the critical amino acid residues for the receptor to recognize salty ***1 is specifically the receptor for recognizing salty *** bonds and electrostatic interactions are the main driving forces for the interactions between salty peptides and TRPV1 *** has the most potent binding capacity with the receptor and has tremendous potential for application in sodium salt *** study confirmed the taste receptor that specifically recognizes salty peptides,analyzed the receptor-peptide binding interaction,and provided a new idea for understanding the taste receptor perception of salty peptides.

关键词： Salty peptide Molecular docking Biolayer interferometry Isothermal titration calorimetry

Unraveling the mechanism of potassium metal capacitor for highly efficient charge storage

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Science china Chemistry 2024年第5期67卷 1578-1588页

作者： Qianqian Yao Pei Tang Kunyao Peng Zhenyuan Miao Yuecong chen Qingyun Dou Xingbin yan Department of Materials Science and Engineering Sun Yat-sen UniversityGuangzhou 510275China South china Academy of Advanced Optoelectronics South China Normal UniversityGuangzhou 510006China

Although hybrid metal ion capacitors(MICs) are highly desired to achieve both high power density of supercapacitors and high energy density of rechargeable batteries, the mismatch problem of electrochemical kinetics of negative and positive electrodes in MICs hampers the realization of this goal. Here, a new hybrid capacitor concept-potassium metal capacitor(PMC) is proposed for the first time, where potassium metal and commercial activated carbon(AC) without any modification are applied as negative and positive electrodes, respectively, and the electrolyte is the same as that of non-aqueous potassium ion batteries. The simplest PMC prototype exhibits a good combination of high energy density(184.9 Wh kg^(-1)) and power density(12.4 kW kg^(-1)), which benefits from the synergistic effect of potassium metal and AC electrode. The former experiences fast potassium plating/striping during charging and discharging, and the later possesses complex multiple charge behaviors driven by low potential of potassium metal. Specifically, below open-circuit voltage, transportation of solvated cations in AC pores plays an important role;beyond this voltage, synergy actions of cations and anions, including adsorption/desorption of solvated cations and anions, and ions exchange between them, dominate the capacitance contribution. This work enriches the types of MICs, and deepens the understanding of the energy storage mechanism of non-aqueous hybrid metal capacitors.

关键词： hybrid capacitor potassium metal activated carbon charge storage mechanism

Nonlinear proinflammatory effect of short-term PM_(2.5)exposure:A potential role of lipopolysaccharide

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Journal of Environmental Sciences 2024年第2期136卷 292-300页

作者： Fangxia Shen Mutong Niu Haoxuan chen Ting Zhang Jing Li Haijie Tong yan Wu school of Space and Environment Beihang UniversityBeijing 100191China College of Environmental Sciences and Engineering Peking UniversityBeijing 100871China Institute of Surface Science Helmholtz-Zentrum HereonGeesthacht 21502Germany school of Environmental Science and Engineering Shandong UniversityJinan 250100China

The association between PM_(2.5)(particulate matter≤2.5μm)short-term exposure and its health effect is non-linear from the epidemiological *** this nonlinearity is suggested to be related with the PM_(2.5)heterogeneity,however,the underlying biological mechanism is still ***,a total of 38 PM_(2.5)filters were collected continuously for three weeks in winter Beijing,with the ambient PM_(2.5)varying between 10 and 270μg/m^(3).Human monocytes-derived macrophages(THP-1)were treated with PM_(2.5)water-soluble elutes at10μg/mL to investigate the PM_(2.5)short-term exposure effect from a proinflammatory *** proinflammatory cytokine tumor necrosis factor(TNF)induced by the PM_(2.5)elutes at equal concentrations were unequal,showing the heterogeneity of PM_(2.5)proinflammatory *** the various chemical and biological components,lipopolysaccharide(LPS)showed a strong positive association with the TNF ***,some outliers were observed among the TNF-LPS ***,for PM_(2.5)from relatively clean air episodes,the higher LPS amount corresponded to relatively low TNF *** this phenomenon was also observed in the promotion tests by treating macrophages with PM_(2.5)elutes dosed with additional trace *** expression analysis indicated the involvement of oxidative-stress related genes in the LPS signaling ***,a potential oxidative-stress-mediated suppression on the PM_(2.5)-borne LPS proinflammatory effect was proposed to be accounted for the ***,the results showed the differential role of LPS in the heterogeneity of PM_(2.5)proinflammatory effects from a component-based *** experimental studies are needed to elucidate the signaling pathway of LPS attached on PM_(2.5)from different air quality episodes.

关键词： Fine PM PM_(2.5)pro-inflammatory effects Aerosol health effect Endotoxin Oxidative stress

Jellyfish-inspired alginate composite hydrogel filter prepared by macro-micro double bionic strategy for efficient water purification

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Frontiers of Environmental Science & Engineering 2024年第4期18卷 141-157页

作者： Huiting Peng yan chen Jiaopan Lin Chelsea Benally Mohamed Gamal El-Din Junkai Gao school of Naval Architecture and Marinetime Zhejiang Ocean UniversityZhoushan 316022China Department of Civil and Environmental Engineering University of AlbertaEdmontonAB T6G 1H9Canada

Recently,research on hydrogel materials with a porous structure and superior water absorption capabilities significantly ***,the hydrogel under gravity-driven separation conditions often exhibit an unstable pore structure,poor mechanical properties,and limited *** this end,this work presents a novel approach that combines a macro-micro double bionic strategy with a triple crosslinking method to develop a multifunctional alginate composite hydrogel filter(2%-SA-κCG-PVA-Ca^(2+),2%-SKP-Ca^(2+)for short)with a stable pore structure and superior mechanical properties,which possessed an umbrella-shaped structure resembling that of *** 2%-SKPCa^(2+)filter was synthesized using polyvinyl alcohol(PVA)as a stable structure-directing agent,and sodium alginate(SA)andκ-carrageenan(κ-CG)as polymer *** distinctive umbrellashaped hydrogel of 2%-SKP-Ca^(2+)filter,formed through the triple crosslinking method,overcomes the limitations of unstable pore structure and poor durability seen in hydrogels prepared by traditional crosslinking ***,the utilization of the 2%-SKP-Ca^(2+)filter in water treatment demonstrates its good selective permeability,excellent resistance to fouling,and extended longevity,which enables it to simultaneously achieve the multifunctional water purification and the coating of multi-substrate anti-fouling ***,not only does this research provide an efficient,multifunctional,highly pollution-resistant preparation method for designing a new filter,but it also confirms the application prospect of the macro-micro dual bionic strategy developed in this study in complex water treatment.

关键词： Triple crosslinking method Alginate Umbrella-shaped Jellyfish Water purification

Retrieval of Antarctic sea ice freeboard and thickness from HY-2B satellite altimeter data

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Acta Oceanologica Sinica 2024年第3期43卷 87-101页

作者： Yizhuo chen Xiaoping Pang Qing Ji Zhongnan yan Zeyu Liang chenlei Zhang Chinese Antarctic Center of Surveying and Mapping Wuhan UniversityWuhan 430079China Key Laboratory of Polar Surveying and Mapping Science Ministry of Natural ResourcesWuhan 430079China Key Laboratory of Polar Environment Monitoring and Public Governance Ministry of EducationWuhan 430079China 4 school of Geography and Tourism Anhui Normal UniversityWuhu 241002China

Antarctic sea ice is an important part of the Earth’s atmospheric system,and satellite remote sensing is an important technology for observing Antarctic sea *** Chinese Haiyang-2B(HY-2B)satellite altimeter data could be used to estimate sea ice freeboard and provide alternative Antarctic sea ice thickness information with a high precision and long time series,as other radar altimetry satellites can,needs further *** paper proposed an algorithm to discriminate leads and then retrieve sea ice freeboard and thickness from HY-2B radar altimeter *** first collected the Moderate-resolution Imaging Spectroradiometer ice surface temperature(IST)product from the National Aeronautics and Space Administration to extract leads from the Antarctic waters and verified their accuracy through Sentinel-1 Synthetic Aperture Radar ***,a surface classification decision tree was generated for HY-2B satellite altimeter measurements of the Antarctic waters to extract leads and calculate local sea surface *** then estimated the Antarctic sea ice freeboard and thickness based on local sea surface heights and the static equilibrium ***,the retrieved HY-2B Antarctic sea ice thickness was compared with the CryoSat-2 sea ice thickness and the Antarctic Sea Ice Processes and Climate(ASPeCt)ship-based observed sea ice *** results indicate that our classification decision tree constructed for HY-2B satellite altimeter measurements was reasonable,and the root mean square error of the obtained sea ice thickness compared to the ship measurements was 0.62 *** proposed sea ice thickness algorithm for the HY-2B radar satellite fills a gap in this application domain for the HY-series satellites and can be a complement to existing Antarctic sea ice thickness products;this algorithm could provide long-time-series and large-scale sea ice thickness data that contribute to research on global climate change.

关键词： HY-2B satellite altimeter classification decision tree sea ice freeboard and thickness Antarctic waters