The widespread distribution of polycyclic aromatic hydrocarbons （PAHs） in groundwater has become an important environmental issue. Knowledge of microbial community changes could aid in identification of particular m...The widespread distribution of polycyclic aromatic hydrocarbons （PAHs） in groundwater has become an important environmental issue. Knowledge of microbial community changes could aid in identification of particular microorganisms that are capable of degrading PAHs in contaminated aquifers. Therefore, 16S rRNA gene clone library analysis was used to identify the archaeal and bacterial communities in an aquifer sediment microcosm used for anaerobic anthracene degradation under methanogenic conditions. A remarkable shift of the archaeal community structure occurred after anaerobic anthracene degradation, but the types of the abundant bacterial phyla did not change. However, a decrease of both archaeal and bacterial diversity was observed. Bacterial genera Bacillus, Rhodococcus and Herbaspirillum might have links with anaerobic anthracene degradation, suggesting a role of microbial consortia. This work might add some new information for understanding the mechanism of PAH degradation under methanogenic conditions.展开更多
The possibility to enhance the stability and robustness of electrohydraulic brake(EHB)systems is considered a subject of great importance in the automotive field.In such a context,the present study focuses on an actua...The possibility to enhance the stability and robustness of electrohydraulic brake(EHB)systems is considered a subject of great importance in the automotive field.In such a context,the present study focuses on an actuator with a four-way sliding valve and a hydraulic cylinder.A 4-order nonlinear mathematical model is introduced accordingly.Through the linearization of the feedback law of the high order EHB model,a sliding mode control method is proposed for the hydraulic pressure.The hydraulic pressure tracking controls are simulated and analyzed by MATLAB/Simulink soft considering separately different conditions,i.e.,a sine wave,a square wave and a square wave with superimposed sine disturbance.The results show that the proposed strategy can track the target within 0.25 s,and the mean observed error is less than 1.2 bar.Moreover,with such a strategy,faster response and less overshoot are possible,which should be regarded as significant advantages.展开更多
which highlights the necessity for developing predictive biomarkers and overcoming ICB resistance.Cancer cell-intrinsic features,especially those that can be dynamically monitored via liquid biopsy,represent a broader...which highlights the necessity for developing predictive biomarkers and overcoming ICB resistance.Cancer cell-intrinsic features,especially those that can be dynamically monitored via liquid biopsy,represent a broader scope for biomarker development.In addition,a potential mode of ICB resistance is tumor-intrinsic mechanisms leading to an immunosuppressive tumor microenvironment(TME).However,the underlying interactive network remains elusive,and the generalizable biomarkers and targeting strategies are still lacking.Here,we uncovered the potential of plasma S100 calcium-binding protein A1(S100A1)for determining ICB efficacy via liquid biopsy of patients with lung cancer.Multiomics and functional studies have suggested that tumor-intrinsic S100A1 expression correlated with an immunologically"cold"TME and resistance to ICB in multiple syngeneic murine tumors and tissue samples from patients with lung cancer.Mechanistic investigations demonstrated that interfering with the tumor-intrinsic S100A1/ubiquitin-specific protease 7/p65/granulocyte-macrophage colony-stimulating factor(GM-CSF)modulatory axis could potentiate an inflamed TME by promoting M1-like macrophage polarization and T cell function.GM-CSF priming was sufficient to enhance the ICB response in tumors with high S100A1 expression in preclinical models.These findings define S100A1 as a potential blood-based biomarker and a novel synergistic target for cancer immunotherapy.展开更多
Background To report the incidence and clinical characteristics of aqueous misdirection(AM)after glaucoma surgery in Chinese patients with primary angle-closure glaucoma.Methods Medical records of all patients diagnos...Background To report the incidence and clinical characteristics of aqueous misdirection(AM)after glaucoma surgery in Chinese patients with primary angle-closure glaucoma.Methods Medical records of all patients diagnosed with primary angle-closure glaucoma who underwent glaucoma surgery in the Eye Hospital of Wenzhou Medical University between January 2012 and December 2021 were retrospectively reviewed.Cases of AM were identified through a keyword-based search.The incidence of AM was calculated.Demographic and clinical characteristics of the AM patients were also described.Results A total of 5044 eyes with primary angle-closure glaucoma were included(mean age 65.81±9.96 years,68.11%women).Thirty-eight eyes developed AM,presenting an overall incidence of 0.75%.The mean time interval between surgery and first record of AM diagnosis was 2.57±5.24 months(range,0 day to 24 months).The incidence of AM was significantly higher in patients aged≤40 years(21.28%)and those aged 40–50 years(3.32%),compared to those>50 years(0.42%)(P<0.001).AM developed much more frequently among patients with chronic angle-closure glaucoma(1.30%),compared to those with acute angle-closure glaucoma(0.32%,P<0.001).Eleven eyes(0.37%)developed AM following non-filtering surgery compared to 24 eyes(2.27%)after filtering surgery(P<0.001).Conclusion The incidence of AM after glaucoma surgery was 0.75%in Chinese patients with primary angle closure glaucoma.Younger age,chronic angle-closure glaucoma,and undergoing filtering surgery,were identified as associated risk factors for developing AM.Phacoemulsification may have less risk of developing AM compared to filtering surgery.展开更多
With the improved understanding of driver mutations in non-small cell lung cancer (NSCLC), expanding the targeted therapeutic options improved the survival and safety. However, responses to these agents are commonly t...With the improved understanding of driver mutations in non-small cell lung cancer (NSCLC), expanding the targeted therapeutic options improved the survival and safety. However, responses to these agents are commonly temporary and incomplete. Moreover, even patients with the same oncogenic driver gene can respond diversely to the same agent. Furthermore, the therapeutic role of immune-checkpoint inhibitors (ICIs) in oncogene-driven NSCLC remains unclear. Therefore, this review aimed to classify the management of NSCLC with driver mutations based on the gene subtype, concomitant mutation, and dynamic alternation. Then, we provide an overview of the resistant mechanism of target therapy occurring in targeted alternations (“target-dependent resistance”) and in the parallel and downstream pathways (“target-independent resistance”). Thirdly, we discuss the effectiveness of ICIs for NSCLC with driver mutations and the combined therapeutic approaches that might reverse the immunosuppressive tumor immune microenvironment. Finally, we listed the emerging treatment strategies for the new oncogenic alternations, and proposed the perspective of NSCLC with driver mutations. This review will guide clinicians to design tailored treatments for NSCLC with driver mutations.展开更多
Small-cell lung cancer(SCLC)is the most aggressive and lethal subtype of lung cancer,for which,better understandings of its biology are urgently needed.Single-cell sequencing technologies provide an opportunity to pro...Small-cell lung cancer(SCLC)is the most aggressive and lethal subtype of lung cancer,for which,better understandings of its biology are urgently needed.Single-cell sequencing technologies provide an opportunity to profile individual cells within the tumor microenvironment(TME)and investigate their roles in tumorigenic processes.Here,we performed high-precision single-cell transcriptomic analysis of~5000 individual cells from primary tumors(PTs)and matched normal adjacent tissues(NATs)from 11 SCLC patients,including one patient with both PT and relapsed tumor(RT).The comparison revealed an immunosuppressive landscape of human SCLC.Malignant cells in SCLC tumors exhibited diverse states mainly related to the cell cycle,immune,and hypoxic properties.Our data also revealed the intratumor heterogeneity(ITH)of key transcription factors(TFs)in SCLC and related gene expression patterns and functions.The non-neuroendocrine(non-NE)tumors were correlated with increased inflammatory gene signatures and immune cell infiltrates in SCLC,which contributed to better responses to immune checkpoint inhibitors.These findings indicate a significant heterogeneity of human SCLC,and intensive crosstalk between cancer cells and the TME at single-cell resolution,and thus,set the stage for a better understanding of the biology of SCLC as well as for developing new therapeutics for SCLC.展开更多
In heterogeneous catalytic reactions,supported metal catalysts have attracted increasing attention for the environmental remediation and industrial manufacture due to their inherent catalytic capacity.However,leaching...In heterogeneous catalytic reactions,supported metal catalysts have attracted increasing attention for the environmental remediation and industrial manufacture due to their inherent catalytic capacity.However,leaching,agglomeration,and poisoning of active metal particles lead to catalyst deactivation,thereby limiting their applications.To avoid this,strategies to protect the active metals from such inactivating processes are major areas of research.Emerging encapsulation strategies,in which active species are coated by protective shells,have proven to be a powerful technology to enhance catalytic performance by creating a well-developed structure about the active catalytic sites.This review highlights the recent advances on preparation method and application of encapsulated catalysts since 2016.Building upon the traditional confinement effect,new categories and extended concepts of encapsulation are introduced.In parallel,effects of encapsulation structure on performance and key factors controlling the structure of encapsulated catalyst are discussed definitely in this review.Finally,future perspectives on opportunities and challenges for further research in the field are given at the end of this paper.展开更多
To the Editor:Glaucoma is a leading cause of irreversible blindness worldwide.[1]Trabeculectomy with mitomycin C(MMC)has been the standard surgical intervention for reducing intraocular pressure(IOP)and slow down the ...To the Editor:Glaucoma is a leading cause of irreversible blindness worldwide.[1]Trabeculectomy with mitomycin C(MMC)has been the standard surgical intervention for reducing intraocular pressure(IOP)and slow down the progression of glaucoma.[2]However,some serious complications with devastating consequences can occur after trabeculectomy,such as bleb-related infections,suprachoroidal hemorrhage,vitreous hemorrhage,and malignant glaucoma.Over the last decade,many novel ophthalmic surgical devices have been used in glaucoma.The XEN45 microstent(Allergan,Dublin,CA,USA)is a hydrophilic cross-linked porcine gelatin stent.It is implanted ab-interno.展开更多
The publisher regrets that some of the authors’affiliations were mistakenly annotated in the manuscript.Hence,the authors of the below article were contacted after publication to request a correction of the author af...The publisher regrets that some of the authors’affiliations were mistakenly annotated in the manuscript.Hence,the authors of the below article were contacted after publication to request a correction of the author affliction and responded with the correct by the time this erratum is being published.展开更多
Background:Small cell lung cancer(SCLC)transformation had previously been reported mainly in epidermal growth factor receptor(EGFR)mutant adenocarcinoma.However,the underlying genomic profile remains un-clear.Our stud...Background:Small cell lung cancer(SCLC)transformation had previously been reported mainly in epidermal growth factor receptor(EGFR)mutant adenocarcinoma.However,the underlying genomic profile remains un-clear.Our study aimed to find the evolution and genotypic characteristic of SCLC transformation.Methods:Thirty-one SCLC transformation patients who were initially diagnosed as non-small cell lung cancer(NSCLC)patients were included.Whole exome sequencing(WES)of both primary and transformed re-biopsy lesions was conducted on 12 patients.Clinical characteristics were analyzed using R software(v.3.6.1).Results:Our study included 31 patients,of whom,three had lung squamous cell carcinoma,6 patients did not carry EGFR mutations,and 30 patients received chemotherapy for SCLCs.The disease control rate(DCR)was 96.7%,and the median progression-free survival(PFS)was 4.03 months.The median time to transformation was 33.07 months,and the median overall survival(OS)was 62.08 months.Somatic mutation analysis showed that besides TP53,RB1,and EGFR,there was a high occurrence of mutations to CSMD3 and ADAMTS19,espe-cially in the EGFR-wild type(EGFR-wt)group.Concerning mutational signature,the EGFR-mutant(EGFR-mut)transformed group favored an apolipoprotein B(APOBEC)mRNA editing catalytic polypeptide-like-associated mutation pattern(P=0.16).DNA damage repair(DDR)-related signatures were significantly enriched in the EGFR-wt transformed group(P=0.034).Additionally,clonal evolution analysis revealed that all patients had the same main trunk genes in the phylogenetic tree.Transformed SCLCs are not sensitive to immunotherapy,possibly due to increased tumor heterogeneity.Conclusions:Our results indicate that the EGFR-wt patients could also transform to SCLCs,but they have different genetic features with EGFR-mut patients.SCLC-transformed patients respond to classical chemotherapy and have a better prognosis than those with classical SCLCs.展开更多
基金supported by the National Natural Science Foundation of China (No. 50979002)the State Key Laboratory of Ecohydraulic Engineering in Shaanxi
文摘The widespread distribution of polycyclic aromatic hydrocarbons （PAHs） in groundwater has become an important environmental issue. Knowledge of microbial community changes could aid in identification of particular microorganisms that are capable of degrading PAHs in contaminated aquifers. Therefore, 16S rRNA gene clone library analysis was used to identify the archaeal and bacterial communities in an aquifer sediment microcosm used for anaerobic anthracene degradation under methanogenic conditions. A remarkable shift of the archaeal community structure occurred after anaerobic anthracene degradation, but the types of the abundant bacterial phyla did not change. However, a decrease of both archaeal and bacterial diversity was observed. Bacterial genera Bacillus, Rhodococcus and Herbaspirillum might have links with anaerobic anthracene degradation, suggesting a role of microbial consortia. This work might add some new information for understanding the mechanism of PAH degradation under methanogenic conditions.
基金supported by the National Natural Science Foundation of China[grant number 51565011]the Foundation of Educational Department of Jiangxi Province[grant number GJJ180302].
文摘The possibility to enhance the stability and robustness of electrohydraulic brake(EHB)systems is considered a subject of great importance in the automotive field.In such a context,the present study focuses on an actuator with a four-way sliding valve and a hydraulic cylinder.A 4-order nonlinear mathematical model is introduced accordingly.Through the linearization of the feedback law of the high order EHB model,a sliding mode control method is proposed for the hydraulic pressure.The hydraulic pressure tracking controls are simulated and analyzed by MATLAB/Simulink soft considering separately different conditions,i.e.,a sine wave,a square wave and a square wave with superimposed sine disturbance.The results show that the proposed strategy can track the target within 0.25 s,and the mean observed error is less than 1.2 bar.Moreover,with such a strategy,faster response and less overshoot are possible,which should be regarded as significant advantages.
基金the following funding sources:National Key R&D Program of China(2022YFC2505000)NSFC general program(82272796)+3 种基金NSFC general program(8197112364)NSFC special program(82241229)CAMS Innovation Fund for Medical Sciences(CIFMS 2022-12M-1-009)Heilongjiang Province"Unveiling the Leader"Science and Technology Research Project(2022ZXJ03CO).
文摘which highlights the necessity for developing predictive biomarkers and overcoming ICB resistance.Cancer cell-intrinsic features,especially those that can be dynamically monitored via liquid biopsy,represent a broader scope for biomarker development.In addition,a potential mode of ICB resistance is tumor-intrinsic mechanisms leading to an immunosuppressive tumor microenvironment(TME).However,the underlying interactive network remains elusive,and the generalizable biomarkers and targeting strategies are still lacking.Here,we uncovered the potential of plasma S100 calcium-binding protein A1(S100A1)for determining ICB efficacy via liquid biopsy of patients with lung cancer.Multiomics and functional studies have suggested that tumor-intrinsic S100A1 expression correlated with an immunologically"cold"TME and resistance to ICB in multiple syngeneic murine tumors and tissue samples from patients with lung cancer.Mechanistic investigations demonstrated that interfering with the tumor-intrinsic S100A1/ubiquitin-specific protease 7/p65/granulocyte-macrophage colony-stimulating factor(GM-CSF)modulatory axis could potentiate an inflamed TME by promoting M1-like macrophage polarization and T cell function.GM-CSF priming was sufficient to enhance the ICB response in tumors with high S100A1 expression in preclinical models.These findings define S100A1 as a potential blood-based biomarker and a novel synergistic target for cancer immunotherapy.
基金supported by the Program for Zhejiang Leading Talent of S&T Innovation(Grant No.2021R52012)the National Key Research and Development Project of China(Grant No.2020YFC2008200)+2 种基金Key Research and Development Projects of Zhejiang Province(Grant No.2022C03112)the Basic Scientific Research Program of Wenzhou(Grant No.Y2020365)Key Innovation and Guidance Program of the Eye Hospital,School of Ophthalmology and Optometry,Wenzhou Medical University(Grant No.YNZD2201903).
文摘Background To report the incidence and clinical characteristics of aqueous misdirection(AM)after glaucoma surgery in Chinese patients with primary angle-closure glaucoma.Methods Medical records of all patients diagnosed with primary angle-closure glaucoma who underwent glaucoma surgery in the Eye Hospital of Wenzhou Medical University between January 2012 and December 2021 were retrospectively reviewed.Cases of AM were identified through a keyword-based search.The incidence of AM was calculated.Demographic and clinical characteristics of the AM patients were also described.Results A total of 5044 eyes with primary angle-closure glaucoma were included(mean age 65.81±9.96 years,68.11%women).Thirty-eight eyes developed AM,presenting an overall incidence of 0.75%.The mean time interval between surgery and first record of AM diagnosis was 2.57±5.24 months(range,0 day to 24 months).The incidence of AM was significantly higher in patients aged≤40 years(21.28%)and those aged 40–50 years(3.32%),compared to those>50 years(0.42%)(P<0.001).AM developed much more frequently among patients with chronic angle-closure glaucoma(1.30%),compared to those with acute angle-closure glaucoma(0.32%,P<0.001).Eleven eyes(0.37%)developed AM following non-filtering surgery compared to 24 eyes(2.27%)after filtering surgery(P<0.001).Conclusion The incidence of AM after glaucoma surgery was 0.75%in Chinese patients with primary angle closure glaucoma.Younger age,chronic angle-closure glaucoma,and undergoing filtering surgery,were identified as associated risk factors for developing AM.Phacoemulsification may have less risk of developing AM compared to filtering surgery.
基金Beijing Natural Science Foundation(No.7222144)National Key Research and Development Project(No.2019YFC1315700)CAMS Key Laboratory of Translational Research on Lung Cancer(No.2018PT31035).
文摘With the improved understanding of driver mutations in non-small cell lung cancer (NSCLC), expanding the targeted therapeutic options improved the survival and safety. However, responses to these agents are commonly temporary and incomplete. Moreover, even patients with the same oncogenic driver gene can respond diversely to the same agent. Furthermore, the therapeutic role of immune-checkpoint inhibitors (ICIs) in oncogene-driven NSCLC remains unclear. Therefore, this review aimed to classify the management of NSCLC with driver mutations based on the gene subtype, concomitant mutation, and dynamic alternation. Then, we provide an overview of the resistant mechanism of target therapy occurring in targeted alternations (“target-dependent resistance”) and in the parallel and downstream pathways (“target-independent resistance”). Thirdly, we discuss the effectiveness of ICIs for NSCLC with driver mutations and the combined therapeutic approaches that might reverse the immunosuppressive tumor immune microenvironment. Finally, we listed the emerging treatment strategies for the new oncogenic alternations, and proposed the perspective of NSCLC with driver mutations. This review will guide clinicians to design tailored treatments for NSCLC with driver mutations.
基金Beijing Advanced Innovation Center for Genomics,the National Natural Sciences Foundation Key Program(8163007)Ministry of Education Innovation Team Development Project(IRT-17R10)+1 种基金Qingqing Li was supported in part by the Postdoctoral Fellowship of Peking-Tsinghua Center for Life SciencesSome of the bioinformatics analysis were carried out on High Performance Computing Platform of the Center for Life Science.
文摘Small-cell lung cancer(SCLC)is the most aggressive and lethal subtype of lung cancer,for which,better understandings of its biology are urgently needed.Single-cell sequencing technologies provide an opportunity to profile individual cells within the tumor microenvironment(TME)and investigate their roles in tumorigenic processes.Here,we performed high-precision single-cell transcriptomic analysis of~5000 individual cells from primary tumors(PTs)and matched normal adjacent tissues(NATs)from 11 SCLC patients,including one patient with both PT and relapsed tumor(RT).The comparison revealed an immunosuppressive landscape of human SCLC.Malignant cells in SCLC tumors exhibited diverse states mainly related to the cell cycle,immune,and hypoxic properties.Our data also revealed the intratumor heterogeneity(ITH)of key transcription factors(TFs)in SCLC and related gene expression patterns and functions.The non-neuroendocrine(non-NE)tumors were correlated with increased inflammatory gene signatures and immune cell infiltrates in SCLC,which contributed to better responses to immune checkpoint inhibitors.These findings indicate a significant heterogeneity of human SCLC,and intensive crosstalk between cancer cells and the TME at single-cell resolution,and thus,set the stage for a better understanding of the biology of SCLC as well as for developing new therapeutics for SCLC.
基金supported by the National Natural Science Foundation of China(Nos.21971002 and 42077361)the Natural Science Foundation of Anhui Province(No.1908085QB45)+1 种基金Open Fund of State Key Lab of Pollution Control and Resource Reuse Research,China(No.PCRRF20002)the University Natural Science Research Project of Anhui Province(No.KJ2020A0064).
文摘In heterogeneous catalytic reactions,supported metal catalysts have attracted increasing attention for the environmental remediation and industrial manufacture due to their inherent catalytic capacity.However,leaching,agglomeration,and poisoning of active metal particles lead to catalyst deactivation,thereby limiting their applications.To avoid this,strategies to protect the active metals from such inactivating processes are major areas of research.Emerging encapsulation strategies,in which active species are coated by protective shells,have proven to be a powerful technology to enhance catalytic performance by creating a well-developed structure about the active catalytic sites.This review highlights the recent advances on preparation method and application of encapsulated catalysts since 2016.Building upon the traditional confinement effect,new categories and extended concepts of encapsulation are introduced.In parallel,effects of encapsulation structure on performance and key factors controlling the structure of encapsulated catalyst are discussed definitely in this review.Finally,future perspectives on opportunities and challenges for further research in the field are given at the end of this paper.
基金supported by grants from the Program for Zhejiang Leading Talent of S&T Innovation(No.2021R52012)the Key Research and Development Projects of Zhejiang Province(No.2022C03112)the Wenzhou Innovation Team.
文摘To the Editor:Glaucoma is a leading cause of irreversible blindness worldwide.[1]Trabeculectomy with mitomycin C(MMC)has been the standard surgical intervention for reducing intraocular pressure(IOP)and slow down the progression of glaucoma.[2]However,some serious complications with devastating consequences can occur after trabeculectomy,such as bleb-related infections,suprachoroidal hemorrhage,vitreous hemorrhage,and malignant glaucoma.Over the last decade,many novel ophthalmic surgical devices have been used in glaucoma.The XEN45 microstent(Allergan,Dublin,CA,USA)is a hydrophilic cross-linked porcine gelatin stent.It is implanted ab-interno.
文摘The publisher regrets that some of the authors’affiliations were mistakenly annotated in the manuscript.Hence,the authors of the below article were contacted after publication to request a correction of the author affliction and responded with the correct by the time this erratum is being published.
基金supported by the Beijing Municipal Administration of Hospitals Incubating Program(PX2019038,PX2020044)Beijing Youth Program for Outstanding Talents(2018000021469G262)+3 种基金National Key Research and Development Project(2019YFC1315700)NSFC Key Program(81630071)NSFC General Program(81871889,81972905)CAMS Key Lab of Translational Research on Lung Cancer(2018PT31035)and Aiyou Foundation(KY201701).
文摘Background:Small cell lung cancer(SCLC)transformation had previously been reported mainly in epidermal growth factor receptor(EGFR)mutant adenocarcinoma.However,the underlying genomic profile remains un-clear.Our study aimed to find the evolution and genotypic characteristic of SCLC transformation.Methods:Thirty-one SCLC transformation patients who were initially diagnosed as non-small cell lung cancer(NSCLC)patients were included.Whole exome sequencing(WES)of both primary and transformed re-biopsy lesions was conducted on 12 patients.Clinical characteristics were analyzed using R software(v.3.6.1).Results:Our study included 31 patients,of whom,three had lung squamous cell carcinoma,6 patients did not carry EGFR mutations,and 30 patients received chemotherapy for SCLCs.The disease control rate(DCR)was 96.7%,and the median progression-free survival(PFS)was 4.03 months.The median time to transformation was 33.07 months,and the median overall survival(OS)was 62.08 months.Somatic mutation analysis showed that besides TP53,RB1,and EGFR,there was a high occurrence of mutations to CSMD3 and ADAMTS19,espe-cially in the EGFR-wild type(EGFR-wt)group.Concerning mutational signature,the EGFR-mutant(EGFR-mut)transformed group favored an apolipoprotein B(APOBEC)mRNA editing catalytic polypeptide-like-associated mutation pattern(P=0.16).DNA damage repair(DDR)-related signatures were significantly enriched in the EGFR-wt transformed group(P=0.034).Additionally,clonal evolution analysis revealed that all patients had the same main trunk genes in the phylogenetic tree.Transformed SCLCs are not sensitive to immunotherapy,possibly due to increased tumor heterogeneity.Conclusions:Our results indicate that the EGFR-wt patients could also transform to SCLCs,but they have different genetic features with EGFR-mut patients.SCLC-transformed patients respond to classical chemotherapy and have a better prognosis than those with classical SCLCs.
