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Self-adaptive hydrogel for breast cancer therapy via accurate tumor elimination and on-demand adipose tissue regeneration

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Chinese Chemical Letters 2024年第1期35卷 371-378页

作者： Ran Tian Xinyu Qiu Wenyun Mu Bolei Cai Zhongning Liu Shiyu Liu Xin Chen School of Chemical Engineering and Technology Department of Chemical EngineeringShaanxi Key Laboratory of Energy Chemical Process IntensificationXi'an Jiao Tong UniversityXi'an 710049China School of Stomatology State Key Laboratory of Military Stomatology&National Clinical Research Center for Oral Diseases&Shaanxi Clinical Research Center for Oral DiseasesDepartment of Preventive DentistryThe Fourth Military Medical UniversityXi'an 710032China School of Stomatology State Key Laboratory of Military StomatologyDepartment of Oral and Maxillofacial SurgeryThe Fourth Military Medical UniversityXi'an 710032China Department of Prosthodontics Peking University School and Hospital of StomatologyNational Clinical Research Center for Oral DiseasesNational Engineering Laboratory for Digital and Material Technology of StomatologyBeijing Key Laboratory of Digital StomatologyBeijing 100081China School of Stomatology State Key Laboratory of Military StomatologyNational Clinical Research Center for Oral DiseasesShaanxi International Joint Research Center for Oral DiseasesCenter for Tissue EngineeringThe Fourth Military Medical UniversityXi'an 710032China

The irregular defects and residual tumor tissue after surgery are challenges for effective breast cancer ***,a smart hydrogel with self-adaptable size and dual responsive cargos release was fabricated to treat breast cancer via accurate tumor elimination,on-demand adipose tissue regeneration and effective infection *** hydrogel consisted of thiol groups ended polyethylene glycol(SH-PEG-SH)and doxorubicin encapsulated mesoporous silica nanocarriers(DOX@MSNs)double crosslinked hyaluronic acid(HA)after loading of antibacterial peptides(AP)and adipose-derived stem cells(ADSCs).A pH-cleavable unsaturated amide bond was pre-introduced between MSNs and HA frame to perform the tumor-specific acidic environment dependent DOX@MSNs release,meanwhile an esterase degradable glyceryl dimethacrylate cap was grafted on MSNs,which contributed to the selective chemotherapy in tumor cells with over-expressed *** bond cleavage between MSNs and HA would also cause the swelling of the hydrogel,which not only provide sufficient space for the growth of ADSCs,but allows the hydrogel to fully fill the irregular defects generated by surgery and residual tumor atrophy,resulting in the on-demand regeneration of adipose ***,the sustained release of AP could be simultaneously triggered along with the size change of hydrogel,which further avoided bacterial infection to promote tissue regeneration.

关键词： Smart hydrogel with self-adaptable size Breast cancer therapy Dual responsive cargoes release Selective tumor elimination On-demand adipose tissue regeneration Effective bacteria inhibition

Computer-aided molecular design and optimization of potent inhibitors disrupting APC-Asef interaction

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2631-2645页

作者： Xuefei Wang Zeqian Du Yuegui Guo Jie Zhong Kun Song Junyuan Wang Jianqiang Yu Xiuyan Yang Chen-Ying Liu Ting Shi Jian Zhang Department of Pathophysiology Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of EducationShanghai Jiao Tong UniversitySchool of MedicineShanghai 200025China Key laboratory of Protection Development and Utilization of Medicinal Resources in Liupanshan AreaMinistry of EducationPeptide&Protein Drug Research CenterSchool of PharmacyNingxia Medical UniversityYinchuan 750004China State Key laboratory of Microbial Metabolism Joint International Research Laboratory of Metabolic and Developmental SciencesSchool of Life Sciences and BiotechnologyShanghai Jiao Tong UniversityShanghai 200240China Department of Colorectal and Anal Surgery Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China Basic Science Research Center Base(Pharmaceutical Science) Yantai UniversityYantai 264005China Medicinal Chemistry and Bioinformatics Center Shanghai Jiao Tong UniversitySchool of MedicineShanghai 200025China State Key laboratory of Pharmaceutical Biotechnology Nanjing UniversityNanjing 210023China

Colorectal cancer(CRC)is the second leading cause of cancer mortality *** initial diagnosis,approximately 20%of patients are diagnosed with metastatic CRC(mCRC).Although the APC-Asef interaction is a well-established target for mCRC therapy,the discovery and development of effective and safe drugs for mCRC patients remains an urgent and challenging *** this study,we identified a novel structural scaffold based on MAI inhibitors,the first-in-class APC-Asef inhibitors we reported *** model-driven optimizations of the N-terminal cap and experimental evaluations of inhibitory activity were performed,and 24-fold greater potency was obtained with the best inhibitor compared to the parental *** addition,the cocrystal structure validated that the two-layerπ-πstacking interactions were essential for inhibitor stabilization in the bound ***,in vitro and in vivo studies have demonstrated that novel inhibitors suppressed lung metastasis in CRC by disrupting the APC-Asef *** results provide an intrinsic structural basis to further explore drug-like molecules for APC-Asef-mediated CRC therapy.

关键词： APC-Asef Peptidomimetic Computer-aided molecular design ONIOM model π-πstacking Metastatic colorectal cancer

Thermal and exhumation history of the Songnan Low Uplift,Qiongdongnan Basin:constraints from the apatite fission-track and zircon(U-Th)/He thermochronology

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Acta Oceanologica Sinica 2024年第4期43卷 40-49页

作者： Xiaoyin Tang Kaixun Zhang Shuchun Yang Shuai Guo Xinyan Zhao Zhizhao Bai Institute of Geomechanics Chinese Academy of Geological SciencesBeijing 100081China Key laboratory of Paleomagnetism and Tectonic Reconstruction Ministry of Natural ResourcesBeijing 100081China Key laboratory of Petroleum Geomechanics China Geological SurveyBeijing 100081China China National Offshore Oil Corporation(CNOOC)Research Center Beijing 100028China

Significant advancements have been made in the study of Mesozoic granite buried hills in the Songnan Low Uplift(SNLU)of the Qiongdongnan *** findings indicate that the bedrock buried hills in this basin hold great potential for *** samples taken from the granite buried hills in the SNLU were analyzed using apatite fission track(AFT)and zircon(U-Th)/He data to unravel the thermal history of the basement *** information is crucial for understanding the processes of exhumation and alteration that occurred after its *** modeling of a sample from the western bulge of the SNLU revealed a prolonged cooling event from the late Mesozoic to the Oligocene period(~80-23.8 Ma),followed by a heating stage from the Miocene epoch until the present(~23.8 Ma to present).In contrast,the sample from the eastern bulge experienced a more complex thermal *** underwent two cooling stages during the late Mesozoic to late Eocene period(~80-36.4 Ma)and the late Oligocene period(~30-23.8 Ma),interspersed with two heating phases during the late Eocene to early Oligocene period(~36.4-30 Ma)and the Miocene epoch to recent times(~23.8-0 Ma),*** differences in exhumation histories between the western and eastern bulges during the late Eocene to Oligocene period in the SNLU can likely be attributed to differences in fault *** typical passive continental margin basins,the SNLU has experienced accelerated subsidence after the rifting phase,which began around 5.2 Ma *** possible mechanism for this abnormal post-rifting subsidence may be the decay or movement of the deep thermal source and the rapid cooling of the ***-term and multi-episodic cooling and exhumation processes play a key role in the alteration of bedrock and contribute to the formation of *** the other hand,rapid post-rifting subsidence(sedimentation)promotes the formation of cap rocks.

关键词： granite buried hills (U-Th)/He dating fission-track dating exhumation Songnan Low Uplift

Remodel the perifollicular microenvironment via Minoxidil-loaded microneedle patch and cold atmospheric plasma for treating androgenetic alopecia

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Nano Research 2024年第7期17卷 6411-6419页

作者： Hao Chen Xianzhe Tang Yueye Huang Chen Chen Yuheng Yang Chaojie Hao Wenqi Xie Tingjing Huang Xiaofeng Cheng Qingnan Xu Shicong Huang Zhi Ye Xucong Lin Zhaowei Chen Zhitong Chen MOE Key laboratory for Analytical Science of Food Safety and Biology and New Cornerstone Science LaboratoryCollege of ChemistryFuzhou UniversityFuzhou 350108China Institute of Biomedical and Health Engineering Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China Advanced Therapeutic Center National Innovation Center for Advanced Medical DevicesShenzhen 518000China Department of Chemistry University College LondonLondon WC1H 0AJUK Engineering Technology Research Center on Reagent and Instrument for Rapid Detection of Product Quality and Food Safety in Fujian Province College of ChemistryFuzhou UniversityFuzhou 350108China Key laboratory of Biomedical Imaging Science and System Chinese Academy of SciencesShenzhen 518055China

Androgenetic alopecia(AGA)is a chronic and progressive form of hair loss characterized by vascular degeneration in the perifollicular microenvironment,leading to cell apoptosis and eventual loss of hair follicles(HFs).Traditional therapeutic formulations,such as Minoxidil(MXD)tincture,have limitations in reshaping the perifollicular microenvironment and exhibit limited ***,we report a multi-synergistic therapeutic platform for high-performance hair regeneration *** platform combines microneedle(MN)patches loaded with MXD-encapsulated nanostructured lipid carriers(MXD-NLC-MNs)and cold atmospheric plasma(cap).The MNs’mechanical strength enables efficient transdermal delivery of MXD to the targeted dermal papilla cells,promoting cell ***,in collaboration with MXD,the mechanical stimulation exerted by MN application synergistically upregulates the expression of vascular endothelial growth factor,leading to ***,the transient microchannels in the skin created by MNs facilitate the transdermal delivery of capgenerated nitric oxide(NO)to the sites of HF lesions,whereby the synergistic interaction between MXD and NO boosts perifollicular ***,the perifollicular microenvironment can be effectively reshaped to accelerate hair regeneration in AGA murine *** multi-synergistic combination therapy strategy would hold great promise for effectively treating AGA and promoting hair regrowth.

关键词： nanomedicine androgenetic alopecia microneedle cold atmospheric plasma drug delivery

Simultaneous Degradation, Dehalogenation, and Detoxification of Halogenated Antibiotics by Carbon Dioxide Radical Anions

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Engineering 2024年第6期37卷 78-86页

作者： Yanzhou Ding Xia Yu Shuguang Lyu Huajun Zhen Wentao Zhao Cheng Peng Jiaxi Wang Yiwen Zhu Chengfei Zhu Lei Zhou Qian Sui State Environmental Protection Key laboratory of Environmental Risk Assessment and Control on Chemical Process School of Resources and Environmental EngineeringEast China University of Science and TechnologyShanghai 200237China Shanghai Institute of Pollution Control and Ecological Security Shanghai 200092China State Key laboratory of Pollution Control and Resource Reuse College of Environmental Science and EngineeringTongji UniversityShanghai 200092China Shanghai Academy of Environmental Sciences Shanghai 200233China

Despite the extensive application of advanced oxidation processes(AOPs)in water treatment,the efficiency of AOPs in eliminating various emerging contaminants such as halogenated antibiotics is constrained by a number of *** moieties exhibit strong resistance to oxidative radicals,affecting the dehalogenation and detoxification *** address these limitations of AOPs,advanced reduction processes(ARPs)have been ***,a novel nucleophilic reductant—namely,the carbon dioxide radical anion(CO_(2)^(·-))—is introduced for the simultaneous degradation,dehalogenation,and detoxification of florfenicol(FF),a typical halogenated *** results demonstrate that FF is completely eliminated by CO_(2)^(·-),with approximately 100%of Cland 46%of Freleased after 120 min of *** detoxification is observed,which exhibits a linear response to the release of free inorganic halogen ions(R2=0.97,p75%)in degrading a series of halogenated antibiotics,including chloramphenicol(cap),thiamphenicol(THA),diclofenac(DLF),triclosan(TCS),and ciprofloxacin(CIP).The system shows high tolerance to the pH of the solution and the presence of natural water constituents,and demonstrates an excellent degradation performance in actual groundwater,indicating the strong application potential of CO_(2)^(·-)-based ARPs in real ***,this study elucidates the feasibility of CO_(2)^(·-)for the simultaneous degradation,dehalogenation,and detoxification of halogena

关键词： Carbon dioxide radical anions Advanced reduction processes Halogenated antibiotics Dehalogenation Detoxification

Long-term Variation of the Solar Polar Magnetic Fields at Different Latitudes

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Research in Astronomy and Astrophysics 2024年第7期24卷 193-200页

作者： Shuhong Yang Jie Jiang Zifan Wang Yijun Hou Chunlan Jin Qiao Song Yukun Luo Ting Li Jun Zhang Yuzong Zhang Guiping Zhou Yuanyong Deng Jingxiu Wang National Astronomical Observatories Chinese Academy of Sciences School of Astronomy and Space Science University of Chinese Academy of Sciences State Key laboratory of Solar Activity and Space Weather National Space Science CenterChinese Academy of Sciences School of Space and Environment Beihang University Key laboratory of Space Weather National Satellite Meteorological Center (National Center for Space Weather) Innovation Center for FengYun Meteorological Satellite (FYSIC) School of Physics and Materials Science Anhui University

The polar magnetic fields of the Sun play an important role in governing solar activity and powering fast solar wind. However, because our view of the Sun is limited in the ecliptic plane, the polar regions remain largely uncharted. Using the high spatial resolution and polarimetric precision vector magnetograms observed by Hinode from 2012 to 2021, we investigate the long-term variation of the magnetic fields in polar caps at different *** Hinode magnetic measurements show that the polarity reversal processes in the north and south polar caps are non-simultaneous. The variation of the averaged radial magnetic flux density reveals that, in each polar cap, the polarity reversal is completed successively from the 70° latitude to the pole, reflecting a poleward magnetic flux migration therein. These results clarify the polar magnetic polarity reversal process at different latitudes.

关键词： dynamo Sun: magnetic fields Sun: photosphere

Stratigraphic framework and sedimentary evolution during the Cryogenian-Ediacaran transition in northeastern Sichuan Basin,South China

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Petroleum Science 2024年第2期21卷 823-835页

作者： Yi Zhang Hong-Wei Kuang Yong-Qing Liu Qiang Shi Dong-Ge Wang Ke-Ning Qi Yu-Chong Wang Da-Wei Qiao Xiao-Shuai Chen Li-Zhi Wu Meng Tian Long Chen Yi Wei Liao-Yuan Song Jian Li Zi-Gang Wu Yun-Qian Liu Xuan-Chun Liu An-Qing Chen Zhi-Wei Liao Institute of Geology Chinese Academy of Geological SciencesBeijing100037China State Key laboratory of Coal Mine Disaster Dynamics and Control School of Resources and Safety EngineeringChongqing UniversityChongqing400044China No.205 Geological Team Chongqing Bureau of Geology and Minerals ExplorationChongqing401121China Chongqing Institute of Geological Survey Chongqing401122China Key laboratory of Deep-time Geography and Environment Reconstruction and Applications of Ministry of Natural Resources Chengdu University of TechnologyChengdu610059SichuanChina

The northeastern Sichuan area in the northern Yangtze margin has unique Ediacaran geological records,especially the Doushantuo Formation(DST),and become a hot research area in recent ***,the Cryogenian-Ediacaran(C-E)boundary has not been precisely identified,which restricts the in-depth study of geological information during this crucial transitional period and is unfavorable for a systematic and complete understanding of the Yangtze Block and even the global paleogeographic *** study conducted stratigraphy,sedimentology,and chronostratigraphy to establish the stratigraphic framework and sedimentary evolution of the C-E transition strata in northeastern *** results showed that the Ediacaran sediments,without the cap dolomite,unconformably overlaid the Cryogenian sediments in the studied *** Member II of the DST,characterized by 50-160 m of red-green sandstone(approximately equivalent to the original Chengkou“Guanyinya Formation”),directly overlaid the Cryogenian sediments and displayed a 623±2.3 Ma maximum depositional age from the detrital zircon U-Pb *** stratigraphic correlations indicate that the C-E transition strata in northeastern Sichuan had a consistent lithological association and sedimentary sequence characteristics but differed from the Three ***,the upper Nantuo massive glacial diamictites transition to the icebergs rafted lonestone-bearing mudstones at the top,then change upward to DST barrier coast *** proposed DST of the northeastern Sichuan Basin was divided into three lithostratigraphic members without the regional Member I cap dolomite:(i)Member II purple-red,gray-green sandstone strata,(ii)MemberⅢblack mudstone strata,and(iii)Member IV P-Mn bearing *** the C-E transition,the study area experienced(i)the global deglaciation stage in the terminal Marinoan glaciation and(ii)the filling-leveling up stage with clastic rocks in the early ***,the early Ediacaran

关键词： Marinoan glaciation Doushantuo formation cap dolomite Deglacial and coastal deposits Detrital zircon U-Pb dating

Coiled-coil domain-containing 38 is required for acrosome biogenesis and fibrous sheath assembly in mice

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Journal of Genetics and Genomics 2024年第4期51卷 407-418页

作者： Yaling Wang Xueying Huang Guoying Sun Jingwen Chen Bangguo Wu Jiahui Luo Shuyan Tang Peng Dai Feng Zhang Jinsong Li Lingbo Wang Shanghai Key laboratory of Metabolic Remodeling and Health Institute of Metabolism and Integrative BiologyFudan UniversityShanghai 200438China Institute of Reproduction and Development Obstetrics and Gynecology HospitalFudan UniversityShanghai 200011China Shanghai Key laboratory of Maternal and Fetal Medicine Clinical and Translational Research Center of Shanghai First Maternity and Infant HospitalFrontier Science Center for Stem Cell ResearchSchool of 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

During spermiogenesis,haploid spermatids undergo dramatic morphological changes to form slender sperm flagella and cap-like acrosomes,which are required for successful *** deformities in flagella cause a male infertility syndrome,multiple morphological abnormalities of the flagella(MMAF),while acrosomal hypoplasia in some cases leads to sub-optimal embryonic developmental ***,evidence regarding the occurrence of acrosomal hypoplasia in MMAF is ***,we report the generation of base-edited mice knocked out for coiled-coil domain-containing 38(Ccdc38)via inducing a nonsense mutation and find that the males are *** Ccdc38-KO sperm display acrosomal hypoplasia and typical MMAF *** find that the acrosomal membrane is loosely anchored to the nucleus and fibrous sheaths are disorganized in Ccdc38-KO *** analyses reveal that Ccdc38 knockout causes a decreased level of TEKT3,a protein associated with acrosome biogenesis,in testes and an aberrant distribution of TEKT3 in *** finally show that intracytoplasmic sperm injection overcomes Ccdc38-related *** study thus reveals a previously unknown role for CCDC38 in acrosome biogenesis and provides additional evidence for the occurrence of acrosomal hypoplasia in MMAF.

关键词： Acrosomal hypoplasia Multiple morphological abnormalities of the flagella(MMAF) Infertility Sperm motility Asthenoteratozoospermia Disease modeling

Heparin-binding protein as a predictor of mortality in patients with diabetes mellitus and community-acquired pneumonia in intensive care unit:a propensity score matched study

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World Journal of Emergency Medicine 2024年第4期15卷 263-272页

作者： Yuhan Sun Baoqing Sun Zhigang Ren Mingshan Xue Changju Zhu Qi Liu Translational Medicine Center Department of Emergency Medicinethe First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China State Key laboratory of Respiratory Disease National Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory Healththe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510230China Department of Infectious Disease the First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Henan Medical Key laboratory of Emergency and Trauma Research Department of Emergency Medicinethe First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China

BACKGROUND:Patients with diabetes mellitus(DM)are vulnerable to community-acquired pneumonia(cap),which have a high mortality *** aimed to investigate the value of heparin-binding protein(HBP)as a prognostic marker of mortality in patients with DM and ***:This retrospective study included cap patients who were tested for HBP at intensive care unit(ICU)admission from January 2019 to April *** were allocated to the DM or non-DM group and paired with propensity score *** characteristics and clinical outcomes up to 90 days were *** primary outcome was the 10-day *** operating characteristic(ROC)curves,Kaplan-Meier analysis,and Cox regression were used for statistical ***:Among 152 enrolled patients,60 pairs were successfully *** was no significant difference in 10-day mortality,while more patients in the DM group died within 28 d(P=0.024)and 90 d(P=0.008).In the DM group,HBP levels at ICU admission were higher in 10-day non-survivors than in 10-day survivors(median 182.21[IQR:55.43-300]ng/ml *** 66.40[IQR:34.13-107.85]ng/mL,P=0.019),and HBP levels could predict the 10-day mortality with an area under the ROC curve of *** cut-off value,sensitivity,and specificity were 160.6 ng/mL,66.7%,and 90.2%,*** Cox regression analysis indicated that HBP was an independent prognostic factor for 10-day(HR 7.196,95%CI:1.596-32.455,P=0.01),28-day(HR 4.381,95%CI:1.449-13.245,P=0.009),and 90-day mortality(HR 4.581,95%CI:1.637-12.819,P=0.004)in patients with ***:Plasma HBP at ICU admission was associated with the 10-day,28-day,and 90-day mortality,and might be a prognostic factor in patients with DM and cap.

关键词： Community-acquired pneumonia Diabetes mellitus Heparin-binding protein Propensity score match