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Harnessing innate immune pathways for therapeutic advancement in cancer

Signal Transduction and Targeted Therapy 2024年第4期9卷 1506-1564页

作者： Ankang Hu Li Sun Hao Lin Yuheng Liao hui Yang Ying mao Department of Neurosurgery Huashan HospitalFudan UniversityShanghaiP.R.China Institute for Translational Brain Research Shanghai Medical CollegeFudan University ShanghaiPR.China National Center for Neurological Disorders Huashan HospitalShanghai Medical CollegeFudan UniversityShanghaiP.R.China Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration Shanghai Clinical Medical Center of NeurosurgeryNeurosurgical Institute of Fudan UniversityHuashan HospitalShanghai Medical CollegeFudan UniversityShanghaiP.R.China State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science and MOE Frontiers Center for Brain Science Institutes of Brain ScienceShanghai Medical CollegeFudan UniversityShanghaiP.R.China Shanghai Key Laboratory of Medical Epigenetics International Co-laboratory of Medical Epigenetics and Metabolism(Ministry of Science and Technology)and Key Laboratory of Metabolism and Molecular Medicine(Ministry of Education)and Molecular and Cell Biology LabInstitutes of Biomedical SciencesShanghai Medical College of Fudan UniversityShanghaiP.R.China

The innate immune pathway is receiving increasing attention in cancer therapy.This pathway is ubiquitous across various cell types,not only in innate immune cells but also in adaptive immune cells,tumor cells,and stromal cells.Agonists targeting the innate immune pathway have shown profound changes in the tumor microenvironment(TME)and improved tumor prognosis in preclinical studies.However,to date,the clinical success of drugs targeting the innate immune pathway remains limited.Interestingly,recent studies have shown that activation of the innate immune pathway can paradoxically promote tumor progression.The uncertainty surrounding the therapeutic effectiveness of targeted drugs for the innate immune pathway is a critical issue that needs immediate investigation.In this review,we observe that the role of the innate immune pathway demonstrates heterogeneity,linked to the tumor development stage,pathway status,and specific cell types.We propose that within the TME,the innate immune pathway exhibits multidimensional diversity.This diversity is fundamentally rooted in cellular heterogeneity and is manifested as a variety of signaling networks.The pro-tumor effect of innate immune pathway activation essentially reflects the suppression of classical pathways and the activation of potential pro-tumor alternative pathways.Refining our understanding of the tumor's innate immune pathway network and employing appropriate targeting strategies can enhance our ability to harness the anti-tumor potential of the innate immune pathway and ultimately bridge the gap from preclinical to clinicalapplication.

关键词： drugs therapeutic innate

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Multi-scale collaborative design method for macroscopic thermal optimization and mesoscopic woven structure of hypersonic vehicle's TOCMC leading edge

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Chinese Journal of Aeronautics 2024年第4期37卷 524-541页

作者： Chenwei ZHAO Zecan TU Junkui mao Jian hui Pingting CHEN College of Energy and Power Engineering Nanjing University of Aeronautics and AstronauticsNanjing 21016China Integrated Energy Institute Nanjing University of Aeronautics and AstronauticsNanjing 210016China

A new thermal protection design method for hypersonic vehicle's leading edge is proposed, which can effectively reduce temperature of the leading edge without additional cooling measures. This method reduces the leading-edge's temperature by the multi-scale collaborative design of the macroscopic thermal optimization and the mesoscopic woven structures of Three-dimensional Orthogonal Woven Ceramic Matrix Composites(TOCMC). The macroscopic thermal optimization is achieved by designing different mesoscopic woven structures in different regions to create combined heat transfer channels to dredge the heat. The combined heat transfer channel is macroscopically represented by the anisotropic thermal conductivity of TOCMC. The thermal optimization multiple linear regression model is established to optimize the heat transport channel, which predicts Theoretical Optimal Thermal Conductivity Configuration(TOTCC) in different regions to achieve the lowest leading-edge temperature. The function-oriented mesostructure design method is invented to design the corresponding mesostructure of TOCMC according to the TOTCC, which consists of universal thermal conductivity prediction formulas for TOCMC. These universal formulas are firstly derived based on the thermal resistance network method, which is verified by experiments with an error of 6.25%. The results show that the collaborative design method can effectively reduce the leading edge temperature by about 12.8% without adding cooling measures.

关键词： Multi-scale collaborative design Thermal optimization Ceramic matrix composite Hypersonic vehicle Thermal protection Intelligent optimization

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Clinical relevance of distolingual roots and periodontal status in mandibular first molars: a cross-sectional study employing CBCT analysis

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第3期25卷 244-253页

作者： Feifei mao Meng WANG Shuai ZHOU Yan ZHAO Jiaping HUANG Fengying YIN Haiping YANG Pei-hui DING Stomatology Hospital School of StomatologyZhejiang University School of MedicineZhejiang Provincial Clinical Research Center for Oral DiseasesKey Laboratory of Oral Biomedical Research of Zhejiang ProvinceCancer Center of Zhejiang UniversityHangzhou 310016China

Objectives:Distolingual root of the permanent mandibular first molar(PMFM-DLR)has been frequently reported,which may complicate the treatment of periodontitis.This study aimed to assess the morphological features of PMFM-DLR and investigate the correlation between the morphological features of PMFM-DLR and periodontal status in patients with Eastern Chinese ethnic background.Materials and methods:A total of 836 cone beam computed tomography(CBCT)images with 1497 mandibular first molars were analyzed to observe the prevalence of PMFM-DLR at the patients and tooth levels in Eastern China.Among them,complete periodontal charts were available for 69 Chinese patients with 103 teeth.Correlation and regression analyses were used to evaluate the correlation between the morphological features of DLR,bone loss,and periodontal clinical parameters,including clinical attachment loss(CAL),probing pocket depth(PPD),gingival recession(GR),and furcation involvement(FI).Results:The patient-level prevalence and tooth-level prevalence of DLR in mandibular first molars were 29.4%and 26.3%,respectively.Multiple linear regression analysis suggested that bone loss at the lingual site and CAL were negatively affected by the angle of separation between distolingual and mesial roots in the transverse section,while they were significantly influenced by age and the angle of separation between distobuccal and mesial roots in the coronal section.Conclusions:The prevalence of PMFM-DLR in Eastern China was relatively high in our cohort.The morphological features of DLR were correlated with the periodontal status of mandibular first molars.This study provides critical information on the morphological features of DLR for improved diagnosis and treatment options of mandibular molars with DLR.

关键词： Distolingual root Mandibular first molar Periodontal clinical parameter Clinical attachment loss Cone beam computed tomography(CBCT)

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3D printing in space:from mechanical structures to living tissues

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International Journal of Extreme Manufacturing 2024年第2期6卷 378-387页

作者： mao mao Zijie Meng Xinxin Huang hui Zhu Lei Wang Xiaoyong Tian Jiankang He Dichen Li Bingheng Lu State Key Laboratory for Manufacturing Systems Engineering Xi’an Jiaotong UniversityXi’an 710049People’s Republic of China National Medical Products Administration(NMPA)Key Laboratory for Research and Evaluation of Additive Manufacturing Medical Devices Xi’an Jiaotong UniversityXi’an 710049People’s Republic of China National Innovation Platform(Center)for Industry-Education Integration of Medical Technology Xi’an Jiaotong UniversityXi’an 710049People’s Republic of China Frontier Institute of Science and Technology Xi’an Jiaotong UniversityXi’an 710049People’s Republic of China National Innovation Institute of Additive Manufacturing Xi’an 710000People’s Republic of China

3D printing stands at the forefront of transforming space exploration,offering unprecedented on-demand and rapid manufacturing capabilities.It adeptly addresses challenges such as mass reduction,intricate component fabrication,and resource constraints.Despite the obstacles posed by microgravity and extreme environments,continual advancements underscore the pivotal role of 3D printing in aerospace science.Beyond its primary function of producing space structures,3D printing contributes significantly to progress in electronics,biomedicine,and resource optimization.This perspective delves into the technological advantages,environmental challenges,development status,and opportunities of 3D printing in space.Envisioning its crucial impact,we anticipate that 3D printing will unlock innovative solutions,reshape manufacturing practices,and foster self-sufficiency in future space endeavors.

关键词： 3D printing in space space manufacturing microgravity

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Effect of La on the Corrosion Behavior and Mechanism of 3Ni Weathering Steel in a Simulated Marine Atmospheric Environment

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Acta Metallurgica Sinica(English Letters) 2024年第2期37卷 308-324页

作者： Gang Niu Rui Yuan R.D.K.Misra Na Gong Zhi-hui Zhang Hao-Xiu Chen hui-Bin Wu Cheng-Jia Shang Xin-Ping mao Collaborative Innovation Center of Steel Technology University of Science and Technology BeijingBeijing100083China Laboratory for Excellence in Advanced Steel Research Department of MetallurgicalMaterials and Biomedical EngineeringUniversity of Texas at El PasoEl PasoTX79968USA Institute of Materials Research and Engineering Agency for ScienceTechnologyand ResearchSingapore138634Singapore Department of Materials Science and Engineering University of TorontoTorontoONM5S 3E4Canada

The corrosion behavior and mechanism of 3Ni weathering steel in a simulated oceanic atmospheric environment are investigated in order to comprehend the impacts of La,as determined through electrochemical analysis and rust layer characterization.The results of this study demonstrate that the addition of La enhances the corrosion resistance of 3Ni weathering steel in the marine atmospheric environment,thereby reducing the corrosion rate and improving the protection of the rust layer.The influence of La on corrosion resistance can be attributed to two primary factors.Firstly,La functions as a grain refiner,minimizing the potential difference of the micro-regions on the substrate surface,thereby significantly reducing the corrosion of bare steel in the marine environment.Secondly,La inhibits the process of Fe_(3)O_(4) oxidation back toγ-FeOOH during corrosion at the local site,thus decreasing the formation ofγ-FeOOH and enhancing the charge transfer resistance.This research work may serve as a reference for expanding the application of rare earth elements in the field of weathering steel.

关键词： Weathering steel Rare earth Rust layer Corrosion behavior Corrosion resistance

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Delineating asthma according to inflammation phenotypes with a focus on paucigranulocytic asthma

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Chinese Medical Journal 2023年第13期136卷 1513-1522页

作者： Yinhe Feng Xiaoyin Liu Yubin Wang Rao Du hui mao Department of Respiratory and Critical Care Medicine West China HospitalSichuan UniversityChengduSichuan 610041China West China Hospital West China Medical SchoolSichuan UniversityChengduSichuan 610041China

Asthma is characterized by chronic airway inflammation and airway hyper-responsiveness.However,the differences in pathophysiology and phenotypic symptomology make a diagnosis of"asthma"too broad hindering individualized treatment.Four asthmatic inflammatory phenotypes have been identified based on inflammatory cell profiles in sputum:eosinophilic,neutrophilic,paucigranulocytic,and mixed-granulocytic.Paucigranulocytic asthma may be one of the most common phenotypes in stable asthmatic patients,yet it remains much less studied than the other inflammatory phenotypes.Understanding of paucigranulocytic asthma in terms of phenotypic discrimination,distribution,stability,surrogate biomarkers,underlying pathophysiology,clinical characteristics,and current therapies is fragmented,which impedes clinical management of patients.This review brings together existing knowledge and ongoing research about asthma phenotypes,with a focus on paucigranulocytic asthma,in order to present a comprehensive picture that may clarify specific inflammatory phenotypes and thus improve clinical diagnoses and disease management.

关键词： Asthma Inflammatory phenotype Paucigranulocytic asthma

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Anticoagulation therapy for pulmonary embolism involving a myxoma mimicking, giant type C thrombus: A case report

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The Journal of Biomedical Research 2023年第2期37卷 148-152页

作者： Yinhe Feng Yubin Wang Xiaolong Li hui mao Department of Respiratory and Critical Care Medicine People's Hospital of Deyang CityAffiliated Hospital of Chengdu College of MedicineDeyangSichuan 618000China Department of Respiratory and Critical Care Medicine West China HospitalSichuan UniversityChengduSichuan 610041China

Right heart thrombus(RHTh) with concurrent acute pulmonary embolism(PE) is rare and can seriously destabilize hemodynamics, leading to an emergency situation with high mortality. Diagnosis and treatment of RHTh with acute PE are not yet standardized. There are few reports of acute PE concurrent with RHTh and even less is known about patients with a right heart mural thrombus. For physicians, the diagnostic choice and treatment of these patients are particularly difficult due to the lack of knowledge. Here, we report a rare case of partial mural RHTh(type C RHTh) with acute PE. The mural mass in the right heart was initially diagnosed as atrial myxoma according to transthoracic echocardiography(TTE), and both pulmonary embolus and the mural mass were completely absorbed after administering Rivaroxiban. This case suggests that TTE alone is insufficient to identify and diagnoses a right heart mural mass such as this. However, novel oral anticoagulants may be effective at alleviating PE with type C RHTh.

关键词： pulmonary embolism intracardiac thrombus atrial myxoma anticoagulant

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Postoperative encapsulated hemoperitoneum in a patient with gastric stromal tumor treated by exposed endoscopic full-thickness resection: A case report

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World Journal of Gastrointestinal Surgery 2024年第2期16卷 601-608页

作者： hui-Fei Lu Jing-Jing Li De-Bin Zhu Li-Qi mao Li-Fen Xu Jing Yu Lin-Hua Yao Department of Gastroenterology the First People’s Hospital of HuzhouHuzhou 313000Zhejiang ProvinceChina

BACKGROUND Gastric stromal tumors,originating from mesenchymal tissues,are one of the most common tumors of the digestive tract.For stromal tumors originating from the muscularis propria,compared with conventional endoscopic submucosal dissection(ESD),endoscopic full-thickness resection(EFTR)can remove deep lesions and digestive tract wall tumors completely.However,this technique has major limitations such as perforation,postoperative bleeding,and post-polypectomy syndrome.Herein,we report a case of postoperative serous surface bleeding which formed an encapsulated hemoperitoneum in a patient with gastric stromal tumor that was treated with exposed EFTR.Feasible treatment options to address this complication are described.CASE SUMMARY A 47-year-old male patient had a hemispherical protrusion found during gastric endoscopic ultrasonography,located at the upper gastric curvature adjacent to the stomach fundus,with a smooth surface mucosa and poor mobility.The lesion was 19.3 mm×16.1 mm in size and originated from the fourth ultrasound layer.Computed tomography(CT)revealed no significant evidence of lymph node enlargement or distant metastasis.Using conventional ESD technology for mucosal pre-resection,exposed EFTR was performed to resect the intact tumor in order to achieve a definitive histopathological diagnosis.Based on its morphology and immunohistochemical expression of CD117 and DOG-1,the lesion was proven to be consistent with a gastric stromal tumor.Six days after exposed EFTR,CT showed a large amount of encapsulated fluid and gas accumulation around the stomach.In addition,gastroscopy suggested intracavitary bleeding and abdominal puncture drainage indicated serosal bleeding.Based on these findings,the patient was diagnosed with serosal bleeding resulting in encapsulated abdominal hemorrhage after exposed EFTR for a gastric stromal tumor.The patient received combined treatments,such as hemostasis under gastroscopy,gastrointestinal decompression,and abdominal drainage.All examinations were normal within six

关键词： Exposed endoscopic full-thickness resection Gastric stromal tumors Hemoperitoneum Abdominal infection Complication Postoperative bleeding Case report

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Frequency and associated factors of accommodation and non-strabismic binocular vision dysfunction among medical university students

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International Journal of Ophthalmology(English edition) 2024年第2期17卷 374-379页

作者： Jie Cai Wen-Wen Fan Yun-hui Zhong Cai-Lan Wen Xiao-Dan Wei Wan-Chen Wei Wan-Yan Xiang Jin-mao Chen Department of Ophthalmology First Affiliated Hospital of Guangxi Medical UniversityNanning 530021Guangxi Zhuang Autonomous RegionChina Digital and Intelligent Technology Transformation and Application Research Institute of Visual Function Tianjin 300000China Guangxi Medical University Nanning 530021Guangxi Zhuang Autonomous RegionChina

AIM:To investigate the frequency and associated factors of accommodation and non-strabismic binocular vision dysfunction among medical university students.METHODS:Totally 158 student volunteers underwent routine vision examination in the optometry clinic of Guangxi Medical University.Their data were used to identify the different types of accommodation and nonstrabismic binocular vision dysfunction and to determine their frequency.Correlation analysis and logistic regression were used to examine the factors associated with these abnormalities.RESULTS:The results showed that 36.71%of the subjects had accommodation and non-strabismic binocular vision issues,with 8.86%being attributed to accommodation dysfunction and 27.85%to binocular abnormalities.Convergence insufficiency(CI)was the most common abnormality,accounting for 13.29%.Those with these abnormalities experienced higher levels of eyestrain(χ2=69.518,P<0.001).The linear correlations were observed between the difference of binocular spherical equivalent(SE)and the index of horizontal esotropia at a distance(r=0.231,P=0.004)and the asthenopia survey scale(ASS)score(r=0.346,P<0.001).Furthermore,the right eye's SE was inversely correlated with the convergence of positive and negative fusion images at close range(r=-0.321,P<0.001),the convergence of negative fusion images at close range(r=-0.294,P<0.001),the vergence facility(VF;r=-0.234,P=0.003),and the set of negative fusion images at far range(r=-0.237,P=0.003).Logistic regression analysis indicated that gender,age,and the difference in right and binocular SE did not influence the emergence of these abnormalities.CONCLUSION:Binocular vision abnormalities are more prevalent than accommodation dysfunction,with CI being the most frequent type.Greater binocular refractive disparity leads to more severe eyestrain symptoms.

关键词： optometry clinic non-strabismic binocular vision dysfunction college students convergence insufficiency

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All-trans retinoic acid alleviates transmissible gastroenteritis virus-induced intestinal inflammation and barrier dysfunction in weaned piglets

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Journal of Animal Science and Biotechnology 2024年第3期15卷 1131-1144页

作者： Junning Pu Daiwen Chen Gang Tian Jun He Ping Zheng Zhiqing Huang Xiangbing mao Jie Yu Yuheng Luo Junqiu Luo hui Yan Aimin Wu Bing Yu Institute of Animal Nutrition Sichuan Agricultural UniversityChengdu 611130SichuanPeople’s Republic of China Key Laboratory of Animal Disease-Resistance Nutrition Ministry of EducationMinistry of Agriculture and Rural AffairsKey Laboratory of Sichuan Province611130 ChengduSichuanPeople’s Republic of China

Background Transmissible gastroenteritis virus(TGEV)is one of the main pathogens causing severe diarrhea of pig-lets.The pathogenesis of TGEV is closely related to intestinal inflammation.All-trans retinoic acid(ATRA)is the main active metabolite of vitamin A,which has immunomodulatory and anti-inflammatory properties.However,it is unclear whether ATRA can alleviate TGEV-induced intestinal inflammation and barrier dysfunction in piglets.This study aimed to investigate the effects of ATRA on growth performance,diarrhea,intestinal inflammation and intesti-nal barrier integrity of TGEV-challenged piglets.Methods In a 19-d study,32 weaned piglets were randomly divided into 4 treatments:Control group(basal diet),TGEV group(basal diet+TGEV challenge),TGEV+ATRA5 group(basal diet+5 mg/d ATRA+TGEV challenge)and TGEV+ATRA15 group(basal diet+15 mg/d ATRA+TGEV challenge).On d 14,piglets were orally administered TGEV or the sterile medium.Results Feeding piglets with 5 and 15 mg/d ATRA alleviated the growth inhibition and diarrhea induced by TGEV(P<0.05).Feeding piglets with 5 and 15 mg/d ATRA also inhibited the increase of serum diamine oxidase(DAO)activ-ity and the decrease of occludin and claudin-1 protein levels in jejunal mucosa induced by TGEV,and maintained intestinal barrier integrity(P<0.05).Meanwhile,5 mg/d ATRA feeding increased the sucrase activity and the expres-sions of nutrient transporter related genes(GLUT2 and SLC7A1)in jejunal mucosa of TGEV-challenged piglets(P<0.05).Furthermore,5 mg/d ATRA feeding attenuated TGEV-induced intestinal inflammatory response by inhibit-ing the release of interleukin(IL)-1β,IL-8 and tumor necrosis factor-α(TNF-α),and promoting the secretion of IL-10 and secretory immunoglobulin A(sIgA)(P<0.05).Feeding 5 mg/d ATRA also down-regulated the expressions of Toll-like receptors and RIG-I like receptors signaling pathway related genes(TLR3,TLR4,RIG-I,MyD88,TRIF and MAVS)and the phosphorylation level of nuclear factor-κB-p65(NF-κB p65),and up-regulated the inhibitor kappa B alpha(IκBα)p

关键词： All-trans retinoic acid Inflammation Intestinal barrier Piglets Transmissible gastroenteritis virus

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