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Bronchoalveolar lavage fluid assessment facilitates precision medicine for lung cancer

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Cancer Biology & Medicine 2024年第3期21卷 230-251页

作者： Hantao Zhang Dan Deng Shujun Li Jing Ren Wei Huang Dan Liu Weiya Wang Department of Pathology West China HospitalSichuan UniversityChengdu 610000China west china Biobank West China HospitalSichuan UniversityChengdu 610000China Department of Respiratory and Critical Care Medicine Clinical Research Center for Respiratory DiseaseWest China HospitalSichuan UniversityChengdu 610000China

Lung cancer is the most common and fatal malignant disease worldwide and has the highest mortality rate among tumor-related causes of death.Early diagnosis and precision medicine can significantly improve the survival rate and prognosis of lung cancer patients.At present,the clinical diagnosis of lung cancer is challenging due to a lack of effective non-invasive detection methods and biomarkers,and treatment is primarily hindered by drug resistance and high tumor heterogeneity.Liquid biopsy is a method for detecting circulating biomarkers in the blood and other body fluids containing genetic information from primary tumor tissues.Bronchoalveolar lavage fluid(BALF)is a potential liquid biopsy medium that is rich in a variety of bioactive substances and cell components.BALF contains information on the key characteristics of tumors,including the tumor subtype,gene mutation type,and tumor environment,thus BALF may be used as a diagnostic supplement to lung biopsy.In this review,the current research on BALF in the diagnosis,treatment,and prognosis of lung cancer is summarized.The advantages and disadvantages of different components of BALF,including cells,cell-free DNA,extracellular vesicles,and micro RNA are introduced.In particular,the great potential of extracellular vesicles in precision diagnosis and detection of drug-resistant for lung cancer is highlighted.In addition,the performance of liquid biopsies with different body fluid sources in lung cancer detection are compared to facilitate more selective studies involving BALF,thereby promoting the application of BALF for precision medicine in lung cancer patients in the future.

关键词： Lung cancer bronchoalveolar lavage fluid extracellular vesicles liquid biopsy precision medicine

Sema3A secreted by sensory nerve induces bone formation under mechanical loads

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International Journal of Oral Science 2024年第1期16卷 62-72页

作者： Hongxiang Mei Zhengzheng Li Qinyi Lv Xingjian Li Yumeng Wu Qingchen Feng Zhishen Jiang Yimei Zhou Yule Zheng Ziqi Gao Jiawei Zhou Chen Jiang Shishu Huang Juan Li State Key Laboratory of Oral Diseases&National center for Stomatology&National Clinical research center for Oral Diseases&west china Hospital of Stomatology Sichuan UniversityChengduChina Department of Orthopedic Surgery and Orthopedic research Institute West China HospitalSichuan UniversityChengduChina

Bone formation and deposition are initiated by sensory nerve infiltration in adaptive bone remodeling. Here, we focused on the role of Semaphorin 3A(Sema3A), expressed by sensory nerves, in mechanical loads-induced bone formation and nerve withdrawal using orthodontic tooth movement(OTM) model. Firstly, bone formation was activated after the 3rd day of OTM,coinciding with a decrease in sensory nerves and an increase in pain threshold. Sema3A, rather than nerve growth factor(NGF),highly expressed in both trigeminal ganglion and the axons of periodontal ligament following the 3rd day of OTM. Moreover, in vitro mechanical loads upregulated Sema3A in neurons instead of in human periodontal ligament cells(hPDLCs) within 24 hours.Furthermore, exogenous Sema3A restored the suppressed alveolar bone formation and the osteogenic differentiation of hPDLCs induced by mechanical overload. Mechanistically, Sema3A prevented overstretching of F-actin induced by mechanical overload through ROCK2 pathway, maintaining mitochondrial dynamics as mitochondrial fusion. Therefore, Sema3A exhibits dual therapeutic effects in mechanical loads-induced bone formation, both as a pain-sensitive analgesic and a positive regulator for bone formation.

关键词： Sema3A formation overload

Intranasal boosting with RBD-HR protein vaccine elicits robust mucosal and systemic immune responses

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Genes & Diseases 2024年第4期11卷 327-339页

作者： Li Chen Wenyan Ren Hong Lei Jiayu Wang Haiying Que Dandan Wan Aqu Alu Dandan Peng Minyang Fu Weiqi Hong Yuhe Huang Xiangrong Song Guangwen Lu Xiawei Wei Laboratory of Aging research and Cancer Drug Target State Key Laboratory of Biotherapy and Cancer CenterNational Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityChengduSichuan 610041China

The emergence of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)variants has decreased the efficacy of SARs-CoV-2 vaccines in containing coronavirus disease 2019(CoVID-19)over time,and booster vaccination strategies are urgently necessitated to achieve sufficient protection.Intranasal immunization can improvemucosal immunity,offer-ing protection against the infection and sustaining the spread of SARS-CoV-2.In this study,an intranasal booster of the RBD-HR vaccine after two doses of the mRNA vaccine significantly increased the levels of specific binding antibodies in serum,nasal lavage fluid,and bronchoal-veolar lavage fluid compared with only two doses of mRNA vaccine.After intranasal boosting with the RBD-HR vaccine,the levels of serum neutralizing antibodies against prototype and variant strains of SARS-Cov-2 pseudoviruses weremarkedly higher than those in mice receiving mRNA vaccine alone,and intranasal boosting with the RBD-HR vaccine also inhibited the bind-ing of RBD to hACE2 receptors.Furthermore,the heterologous intranasal immunization regimen promoted extensive memory T cell responses and activated CD103+dendritic cells in the respiratory mucosa,and potently enhanced the formation of T follicular helper cells and germinal center B cells in vital immune organs,including mediastinal lymph nodes,inguinal lymph nodes,and spleen.Collectively,these data infer that heterologous intranasal boosting with the RBD-HR vaccine elicited broad protective immunity against SARS-CoV-2 both locallyandsystemically.

关键词： Heterologous immunization Intranasal immunization mRNA vaccine SARS-CoV-2 Subunitprotein vaccine

Safety, immunogenicity and protective effectiveness of heterologous boost with a recombinant COVID-19 vaccine (Sf9 cells) in adult recipients of inactivated vaccines

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1165-1173页

作者： Wenxin Luo Jiadi Gan Zhu Luo Shuangqing Li Zhoufeng Wang Jiaxuan Wu Huohuo Zhang Jinghong Xian Ruixin Cheng Xiumei Tang Yi Liu Ling Yang Qianqian Mou Xue Zhang Yi Chen Weiwen Wang Yantong Wang Lin Bai Xuan Wei Rui Zhang Lan Yang Yaxin Chen Li Yang Yalun Li Dan Liu Weimin Li Lei Chen Department of Pulmonary and Critical Care Medicine West China HospitalSichuan UniversityChengduChina Institute of Respiratory Health Frontiers Science Center for Disease-related Molecular NetworkWest China HospitalSichuan UniversityChengduChina Precision Medicine center Precision Medicine Key Laboratory of Sichuan ProvinceWest China HospitalSichuan UniversityChengduChina State Key Laboratory of Respiratory Health and Multimorbidity West China HospitalChengduChina Institute of Respiratory Health and Multimorbidity West China HospitalSichuan UniversityChengduChina Clinical Trial center West China HospitalSichuan UniversityChengduChina General Practice Medical center West China HospitalSichuan UniversityChengduChina Fangcao Community Health Service center of Chengdu High-tech Zone ChengduChina The research Units of west china Chinese Academy of Medical SciencesWest China HospitalChengduChina west china School of Nursing Sichuan UniversityChengduChina Department of Infection Control West China HospitalSichuan UniversityChengduChina Department of Pathology West China HospitalSichuan UniversityChengduChina Department of Respiratory and Critical Care Medicine the First Affiliated Hospital of Chongqing Medical UniversityChongqingChina Department of Neurology West China HospitalSichuan UniversityChengduChina

Vaccines have proven effective in protecting populations against COVID-19,including the recombinant COVID-19 vaccine(Sf9 cells),the first approved recombinant protein vaccine in china.In this positive-controlled trial with 85 adult participants(Sf9 cells group:n=44;CoronaVac group:n=41),we evaluated the safety,immunogenicity,and protective effectiveness of a heterologous boost with the Sf9 cells vaccine in adults who had been vaccinated with the inactivated vaccine,and found a post-booster adverse events rate of 20.45%in the Sf9 cells group and 31.71%in the CoronaVac group(p=0.279),within 28 days after booster injection.Neither group reported any severe adverse events.Following the Sf9 cells vaccine booster,the geometric mean titer(GMT)of binding antibodies to the receptor-binding domain of prototype SARS-CoV-2 on day 28 post-booster was significantly higher than that induced by the CoronaVac vaccine booster(100,683.37 vs.9,451.69,p<0.001).In the Sf9 cells group,GMTs of neutralizing antibodies against pseudo SARS-CoV-2 viruses(prototype and diverse variants of concern[VOCs])increased by 22.23–75.93 folds from baseline to day 28 post-booster,while the CoronaVac group showed increases of only 3.29–10.70 folds.Similarly,neutralizing antibodies against live SARS-CoV-2 viruses(prototype and diverse VOCs)increased by 68.18–192.67 folds on day 14 post-booster compared with the baseline level,significantly greater than the CoronaVac group(19.67–37.67 folds).A more robust Th1 cellular response was observed with the Sf9 cells booster on day 14 post-booster(mean IFN-γ+spot-forming cells per 2×105 peripheral blood mononuclear cells:26.66 vs.13.59).Protective effectiveness against symptomatic COVID-19 was approximately twice as high in the Sf9 cells group compared to the CoronaVac group(68.18%vs.36.59%,p=0.004).Our study findings support the high protective effectiveness of heterologous boosting with the recombinant COVID-19 vaccine(Sf9 cells)against symptomatic COVID-19 of diverse SARS-CoV-2 variants of concern,while causing

关键词： protective vaccine boost

Ginsenoside modified lipid-coated perfluorocarbon nanodroplets: A novel approach to reduce complement protein adsorption and prolong in vivo circulation

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1845-1863页

作者： Jie Zhou Binyang Gao Huan Zhang Rui Yang Jianbo Huang Xin Li Yi Zhong Yan Wang Xiaoxia Zhu Yan Luo Feng Yan Ultrasound Department of west china Hospital Sichuan UniversityChengdu 610041China Laboratory of Ultrasound Imaging of west china Hospital Sichuan UniversityChengdu 610041China west china Washington Mitochondria and Metabolism research center West China HospitalSichuan UniversityChengdu 610041China research Core Facilities of west china Hospital Sichuan UniversityChengdu 610041China

Lipid-coated perfluorocarbon nanodroplets(lp-NDs)hold great promise in bio-medicine as vehicles for drug delivery,molecular imaging and vaccine agents.However,their clinical utility is restricted by limited targeted accumulation,attributed to the innate immune system(IIS),which acts as the initial defense mechanism in humans.This study aimed to optimize lp-ND formulations to mini-mize non-specific clearance by the IIS.Ginsenosides(Gs),the principal components of Panax ginseng,possessing complement inhibition ability,structural similarity to cholesterol,and comparable fat solubi-lity to phospholipids,were used as promising candidate IIS inhibitors.Two different types of ginsenoside-based Ip-NDs(Gs Ip-NDs)were created,and their efficacy in reducing IS recognition was examined.The Gs p-NDs were observed to inhibit the adsorption of C3 in the protein corona(PC)and the generation of SC5b-9.Adding Gs to Ip-NDs reduced complement adsorption and phagocytosis,resulting in a longer blood circulation time in vivo compared to lp-NDs that did not contain Gs.These results suggest that Gs can act as anti-complement and anti-phagocytosis adjuvants,potentially reducing non-specific clear-ance by the IS and improving lifespan.

关键词： Lipid-coated perfluorocarbon nanodroplets Protein corona Complement C3 Phagocytosis Ginsenosidelipid-coated perfluorocarbon nanodroplets Innate immune system Complement system Mononuclear phagocytic system

Biomaterials and tissue engineering in traumatic brain injury:novel perspectives on promoting neural regeneration

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Neural Regeneration research 2024年第10期19卷 2157-2174页

作者： Shihong Zhu Xiaoyin Liu Xiyue Lu Qiang Liao Huiyang Luo Yuan Tian Xu Cheng Yaxin Jiang Guangdi Liu Jing Chen Department of Neurosurgery West China HospitalWest China Medical SchoolSichuan UniversityChengduSichuan ProvinceChina National Engineering research center for Biomaterials College of Biomedical EngineeringSichuan UniversityChengduSichuan ProvinceChina Department of Anesthesiology West China HospitalWest China Medical SchoolSichuan UniversityChengduSichuan ProvinceChina Department of Pharmacy West China HospitalWest China Medical SchoolSichuan UniversityChengduSichuan ProvinceChina Out-patient Department West China HospitalWest China Medical SchoolSichuan UniversityChengduSichuan ProvinceChina Department of Respiratory and Critical Care Medicine West China HospitalWest China Medical SchoolSichuan UniversityChengduSichuan ProvinceChina

Traumatic brain injury is a serious medical condition that can be attributed to falls, motor vehicle accidents, sports injuries and acts of violence, causing a series of neural injuries and neuropsychiatric symptoms. However, limited accessibility to the injury sites, complicated histological and anatomical structure, intricate cellular and extracellular milieu, lack of regenerative capacity in the native cells, vast variety of damage routes, and the insufficient time available for treatment have restricted the widespread application of several therapeutic methods in cases of central nervous system injury. Tissue engineering and regenerative medicine have emerged as innovative approaches in the field of nerve regeneration. By combining biomaterials, stem cells, and growth factors, these approaches have provided a platform for developing effective treatments for neural injuries, which can offer the potential to restore neural function, improve patient outcomes, and reduce the need for drugs and invasive surgical procedures. Biomaterials have shown advantages in promoting neural development, inhibiting glial scar formation, and providing a suitable biomimetic neural microenvironment, which makes their application promising in the field of neural regeneration. For instance, bioactive scaffolds loaded with stem cells can provide a biocompatible and biodegradable milieu. Furthermore, stem cells-derived exosomes combine the advantages of stem cells, avoid the risk of immune rejection, cooperate with biomaterials to enhance their biological functions, and exert stable functions, thereby inducing angiogenesis and neural regeneration in patients with traumatic brain injury and promoting the recovery of brain function. Unfortunately, biomaterials have shown positive effects in the laboratory, but when similar materials are used in clinical studies of human central nervous system regeneration, their efficacy is unsatisfactory. Here, we review the characteristics and properties of various bioactive materials, followed by the

关键词： bioactive materials biomaterials exosomes neural regeneration scaffolds stem cells tissue engineering traumatic brain injury

Synthesis of granulated Li_(1.33)Mn_(1.67)O_(4) via two antisolvent methods for lithium adsorption from gas-produced water

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Chinese Journal of Chemical Engineering 2024年第5期69卷 34-46页

作者： Jun Qiu Lu-Ri Bao Wei Guo Ying Yang Shu-Ying Sun National Engineering research center for Integrated Utilization of Salt Lake Resource East China University of Science and TechnologyShanghai 200237China

Gas-produced water is an accompanying wastewater in the natural gas extraction process,and it is a potential liquid lithium resource that contains a considerable amount of lithium.This study investigated the feasibility of using manganese-based ion sieves to adsorb and extract lithium from gas-produced water.And we focused on the applicability of two different granulation methods,extrusion and droplet,in gas-produced water systems.Two types of H_(1.33)Mn_(1.67)O_(4) particles were prepared by the extrusion method(EHMO)and the droplet method(DHMO).The porosity of DHMO was much higher than that of EHMO,and the adsorption performance of DHMO increased with the decrease of binder concentration.DHMO prepared with a binder concentration of 0.14 g·ml^(-1)exhibited the best adsorption performance in gas-produced water,and the Li^(+)adsorption capacity could reach 25.14 mg·g^(-1).In gas-produced water,the adsorption equilibrium of DHMO only took 9 h,and the adsorption process conformed to the Langmuir model and pseudo-second-order kinetic model.The pore diffusion model(PDM)could well describe its adsorption process.Besides,DHMO showed a great selectivity to Li^(+),and the selectivity order of DHMO in gas-produced water was Li^(+)>Ba^(2+)>>Mg^(2+),Ca^(2+),Sr^(2+)>>Na^(+)>>K^(+).After 20 cycles,the Li^(+)adsorption capacity was still higher than 17.30 mg·g^(-1),and the rate of manganese dissolution was less than 1%.

关键词： Gas-produced water Granulation Li_(1.33)Mn_(1.67)O_(4)

Emerging roles of exosomes in oral diseases progression

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International Journal of Oral Science 2024年第1期16卷 36-51页

作者： Jiayi Wang Junjun Jing Chenchen Zhou Yi Fan State Key Laboratory of Oral Diseases&National center for Stomatology&National Clinical research center for Oral Diseases&Department of Cariology and Endodontics West China Hospital of StomatologySichuan UniversityChengduChina State Key Laboratory of Oral Diseases&National center for Stomatology&National Clinical research center for Oral Diseases&west china Hospital of Stomatology Sichuan UniversityChengduChina State Key Laboratory of Oral Diseases&National center for Stomatology&National Clinical research center for Oral Diseases&Department of Pediatric Dentistry West China Hospital of StomatologySichuan UniversityChengduChina

Oral diseases, such as periodontitis, salivary gland diseases, and oral cancers, significantly challenge health conditions due to their detrimental effects on patient's digestive functions, pronunciation, and esthetic demands. Delayed diagnosis and non-targeted treatment profoundly influence patients' prognosis and quality of life. The exploration of innovative approaches for early detection and precise treatment represents a promising frontier in oral medicine.

关键词： diseases diagnosis salivary

Structural analysis of conformational changes in the mpox virus A7 protein

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Virologica Sinica 2024年第2期39卷 331-334页

作者： Xincheng Ni Kai Wang Yinze Han Jian Lei National Clinical research center for Geriatrics and State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan UniversityChengdu610041China

Dear Editor,The mpox(formerly known as monkeypox)disease caused by the mpox virus(MPXV)has infected more than 89,700 people and is linked to 157 deaths in 114 countries worldwide as of September 2023(www.***.int).Mpox is a zoonotic disease,the first human case of which was reported in 1970(Breman et al.,1980).Common symptoms in mpox-infected individuals include fever,myalgia,fatigue,headache,and a characteristic rash(Isidro et al.,2022).Current treatments for mpox remain limited,and an in-depth investigation of essential viral protein(s)will help to explore novel drug targets.

关键词： infected headache