Profiles observed by Sea-Wing underwater gliders are widely applied in scientific research. However, the quality control(QC) of these data has received little attention. The mismatch between the temperature probe and ...Profiles observed by Sea-Wing underwater gliders are widely applied in scientific research. However, the quality control(QC) of these data has received little attention. The mismatch between the temperature probe and conductivity cell response times generates erroneous salinities, especially across a strong thermocline. A sensor drift may occur owing to biofouling and biocide leakage into the conductivity cell when a glider has operated for several months. It is therefore critical to design a mature real-time QC procedure and develop a toolbox for the QC of Sea-Wing glider data. On the basis of temperature and salinity profiles observed by several Sea-Wing gliders each installed with a Sea-Bird Glider Payload CTD sensor, a real-time QC method including a thermal lag correction, Argo-equivalent real-time QC tests, and a simple post-processing procedure is proposed. The method can also be adopted for Petrel gliders.展开更多
The international Argo program,a global observational array of nearly 4000 autonomous profiling floats initiated in the late 1990s,which measures the water temperature and salinity of the upper 2000 m of the global oc...The international Argo program,a global observational array of nearly 4000 autonomous profiling floats initiated in the late 1990s,which measures the water temperature and salinity of the upper 2000 m of the global ocean,has revolutionized oceanography.It has been recognized one of the most successful ocean observation systems in the world.Today,the proposed decade action“OneArgo”for building an integrated global,full-depth,and multidisciplinary ocean observing array for beyond 2020 has been endorsed.In the past two decades since 2002,with more than 500 Argo deployments and 80 operational floats currently,China has become an important partner of the Argo program.Two DACs have been established to process the data reported from all Chinese floats and deliver these data to the GDACs in real time,adhering to the unified quality control procedures proposed by the Argo Data Management Team.Several Argo products have been developed and released,allowing accurate estimations of global ocean warming,sea level change and the hydrological cycle,at interannual to decadal scales.In addition,Deep and BGC-Argo floats have been deployed,and time series observations from these floats have proven to be extremely useful,particularly in the analysis of synoptic-scale to decadal-scale dynamics.The future aim of China Argo is to build and maintain a regional Argo fleet comprising approximately 400 floats in the northwestern Pacific,South China Sea,and Indian Ocean,accounting for 9%of the global fleet,in addition to maintaining 300 Deep Argo floats in the global ocean(25%of the global Deep Argo fleet).A regional BGC-Argo array in the western Pacific also needs to be established and maintained.展开更多
A facial expression emotion recognition based human-robot interaction(FEER-HRI) system is proposed, for which a four-layer system framework is designed. The FEERHRI system enables the robots not only to recognize huma...A facial expression emotion recognition based human-robot interaction(FEER-HRI) system is proposed, for which a four-layer system framework is designed. The FEERHRI system enables the robots not only to recognize human emotions, but also to generate facial expression for adapting to human emotions. A facial emotion recognition method based on2D-Gabor, uniform local binary pattern(LBP) operator, and multiclass extreme learning machine(ELM) classifier is presented,which is applied to real-time facial expression recognition for robots. Facial expressions of robots are represented by simple cartoon symbols and displayed by a LED screen equipped in the robots, which can be easily understood by human. Four scenarios,i.e., guiding, entertainment, home service and scene simulation are performed in the human-robot interaction experiment, in which smooth communication is realized by facial expression recognition of humans and facial expression generation of robots within 2 seconds. As a few prospective applications, the FEERHRI system can be applied in home service, smart home, safe driving, and so on.展开更多
Objective:Several anti-programmed cell death 1(anti-PD-1)antibodies have demonstrated potential efficacy in the treatment of advanced esophageal squamous cell cancer(ESCC).However,the response to subsequent chemothera...Objective:Several anti-programmed cell death 1(anti-PD-1)antibodies have demonstrated potential efficacy in the treatment of advanced esophageal squamous cell cancer(ESCC).However,the response to subsequent chemotherapy after the failure of PD-1 blockade in ESCC patients has not been reported,and the optimal sequencing of immunotherapy and chemotherapy remains controversial.The aim of the present study was to evaluate responses to irinotecan-based subsequent chemotherapy in advanced ESCC patients who had progressed after treatment with camrelizumab(SHR-1210),a novel anti-PD-1 antibody.Methods:We retrospectively reviewed the medical records of patients with advanced ESCC treated with camrelizumab at a single institution.Consecutive patients who received subsequent irinotecan-based chemotherapy were selected for data collection and analysis.Results:Overall,a total of 28 patients were included.All patients had received at least two lines of systemic treatment prior to irinotecan salvage.The most common regimen that was administered after PD-1 blockade was irinotecan in combination with 5-fluorouracil(5-Fu)(or its derivatives),which was given to 19 patients.The objective response rate(ORR)and disease control rate(DCR)were 17.9%(5/28)and 64.3%(18/28),respectively,with 5(17.9%)patients achieving a partial response and 13(46.4%)having stable disease.The median progressionfree survival(PFS)was 3.18[95%confidence interval(95%CI),2.48-3.88]months and the median overall survival(OS)was 6.23(95%CI,4.71-7.75)months.No new safety issues,either immune-related or otherwise,were observed.Conclusions:Our results suggested that the response to irinotecan-based chemotherapy after PD-1 blockade in advanced ESCC patients appeared similar to that previously observed in patients who had not received PD-1 antibodies,and further study in larger cohorts or randomized trials is warranted to verify our observation.展开更多
Background:The etiology of pulmonary arterial hypertension associated with congenital heart disease(PAHCHD)is complicated and the phenotype is heterogeneous.Genetic defects of NOTCH3 were associated withcerebral disea...Background:The etiology of pulmonary arterial hypertension associated with congenital heart disease(PAHCHD)is complicated and the phenotype is heterogeneous.Genetic defects of NOTCH3 were associated withcerebral disease and pulmonary hypertension.However,the relationship between NOTCH3 mutations and theclinical phenotype has not been reported in CHD-PAH.Methods:We eventually enrolled 142 PAH-CHD patientsfrom Fuwai Hospital.Whole exome sequencing(WES)was performed to screen the rare deleterious variants ofNOTCH3 gene.Results:This PAH-CHD cohort included 43(30.3%)men and 99(69.7%)women with the meanage 29.8±10.9 years old.The pathogenic or likely pathogenic mutations of NOTCH3 were identified in five cases.Patients 2,5,8 and 11 carried the same NOTCH3 mutation c.1630C>T(pArg544Cys),which is the hot-spotmutation for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy(CADASIL).Patient 3 carried the NOTCH3 mutation p.Arg75Gln that has also been reported to be associatedwith the CADASIL.Patients 2,5,8,11 took the examination of the cerebral magnetic resonance imaging(MRI)and confirmed the phenotype of CADASIL.Conclusions:We first reported the NOTCH3 rare mutationsand CADASIL phenotypes in CHD-PAH patients.The NOTCH3 rare variants were with a relatively high positiverate and CADASIL phenotypes were likely enriched in PAH-CHD patients.The preoperative neurological examinationmight be recommended for PAH-CHD patients to determine the surgical contraindications and reduceintraoperative neurological complications.展开更多
In order to study the trend of climate change in the future in Weifang,and analyze the impact of climate change on the local wheat production,the air temperature and precipitation in Weifang from 2021 to 2050 were sim...In order to study the trend of climate change in the future in Weifang,and analyze the impact of climate change on the local wheat production,the air temperature and precipitation in Weifang from 2021 to 2050 were simulated by using the regional climate model PRECIS.And then put the meteorological data into the crop model to simulate the growth of wheat under climate change conditions in the future.The results showed that there would be a trend of rising temperature and increasing precipitation in Weifang in the future.Climate warming would result in growth period of wheat to be ahead of schedule and yield reduction.If taking into account the effect of CO2,the yield of wheat would increase.展开更多
Near-infrared spectroscopy coupled with kernel partial least squares-discriminant analysis was used to rapidly screen water containing malathion. In the wavenumber of 4348 cm-1 to 9091 cm-1, the overall correct classi...Near-infrared spectroscopy coupled with kernel partial least squares-discriminant analysis was used to rapidly screen water containing malathion. In the wavenumber of 4348 cm-1 to 9091 cm-1, the overall correct classification rate of kernel partial least squares-discriminant analysis was 100% for training set, and 100% for test set, with the lowest concentration detected malathion residues in water being 1 μg·ml-1. Kernel partial least squares-discriminant analysis was able to have a good performance in classifying data in nonlinear systems. It was inferred that Near-infrared spectroscopy coupled with the kernel partial least squares-discriminant analysis had a potential in rapid screening other pesticide residues in water.展开更多
Background:Effective therapeutic options are limited for patients with advanced esophageal squamous cell carcinoma(ESCC).The incorporation of an immune checkpoint inhibitor and a molecular anti-angiogenic agent into t...Background:Effective therapeutic options are limited for patients with advanced esophageal squamous cell carcinoma(ESCC).The incorporation of an immune checkpoint inhibitor and a molecular anti-angiogenic agent into the commonly adopted chemotherapy may produce synergistic effects.Therefore,we aimed to investigate the efficacy and safety of camrelizumab plus apatinib combined with chemotherapy as the first-line treatment of advanced ESCC.Methods:In this single-arm prospective phase II trial,patients with unresectable locally advanced or recurrent/metastatic ESCC received camrelizumab 200 mg,liposomal paclitaxel 150 mg/m2,and nedaplatin 50 mg/m2 on day 1,and apatinib 250 mg on days 1-14.The treatments were repeated every 14 days for up to 9 cycles,followed by maintenance therapy with camrelizumab and apatinib.The primary endpoint was objective response rate(ORR)according to the Response Evaluation Criteria in Solid Tumors(version 1.1).Secondary endpoints included disease control rate(DCR),progression-free survival(PFS),overall survival(OS),and safety.Results:We enrolled 30 patients between August 7,2018 and February 23,2019.The median follow-up was 24.98 months(95%confidence interval[CI]:23.05-26.16 months).The centrally assessed ORR was 80.0%(95%CI:61.4%-92.3%),with a median duration of response of 9.77 months(range:1.54 to 24.82+months).The DCR reached 96.7%(95%CI:82.8%-99.9%).The median PFS was 6.85 months(95%CI:4.46-14.20 months),and the median OS was 19.43 months(95%CI:9.93 months–not reached).The most common grade 3-4 treatmentrelated adverse events(AEs)were leukopenia(83.3%),neutropenia(60.0%),and increased aspartate aminotransferase level(26.7%).Treatment-related serious AEs included febrile neutropenia,leukopenia,and anorexia in one patient(3.3%),and single cases of increased blood bilirubin level(3.3%)and toxic epidermal necrolysis(3.3%).No treatment-related deaths occurred.Conclusions:Camrelizumab plus apatinib combined with liposomal paclitaxel and nedaplatin as first-line treatment demonstrated feasible anti-tumor activity and manageable safety in patients with advanced ESCC.Randomized trials to evaluate this new combination strategy are warranted.Trial registration:This trial was registered on July 27,2018,at ClinicalTrials.gov(identifier:NCT03603756).展开更多
Mushrooms in the basidiomycete family Boletaceae are ecologically and economically very important.However,due to the morphological complexity and the limited phylogenetic information on the various species and genera ...Mushrooms in the basidiomycete family Boletaceae are ecologically and economically very important.However,due to the morphological complexity and the limited phylogenetic information on the various species and genera of this fungal family,our understanding of its systematics and evolution remains rudimentary.In this study,DNA sequences of four genes(nrLSU,tef1-α,rpb1,and rpb2)were newly obtained from ca.200 representative specimens of Boletaceae.Our phylogenetic analyses revealed seven major clades at the subfamily level,namely Austroboletoideae,Boletoideae,Chalciporoideae,Leccinoideae,Xerocomoideae,Zangioideae,and the Pulveroboletus Group.In addition,59 genus-level clades were identified,of which 22 were uncovered for the first time.These 22 clades were mainly placed in Boletoideae and the Pulveroboletus Group.The results further indicated that the characters frequently used in the morphology-based taxonomy of Boletaceae,such as basidiospore ornamentation,the form of the basidioma,and the stuffed pores each had multiple origins within the family,suggesting that the use of such features for high-level classification of Boletaceae should be de-emphasized and combined with other characters.展开更多
Porcini mushrooms(Boletus sect.Boletus)have both economic and ecological importance.Recent molecular phylogenetic study has uncovered rich species diversity of this group of fungi from China.In this study,the Chinese ...Porcini mushrooms(Boletus sect.Boletus)have both economic and ecological importance.Recent molecular phylogenetic study has uncovered rich species diversity of this group of fungi from China.In this study,the Chinese porcini were characterized by both morphological andmolecular phylogenetic evidence.15 species were recognized,including nine new species,namely B.botryoides,B.fagacicola,B.griseiceps,B.monilifer,B.sinoedulis,B.subviolaceofuscus,B.tylopilopsis,B.umbrinipileus and B.viscidiceps.Three previously described species,viz.B.bainiugan,B.meiweiniuganjun and B.shiyong,were revised,and B.meiweiniuganjun is treated as a synonym of B.bainiugan.A key to the Chinese porcini mushrooms was provided.展开更多
Fungi have evolved diverse strategies to acquire nutrients as endophytes,saprobes,symbionts,or pathogens.Appressoria have been intensively studied due to their importance in attaching and breaching the host surface.Th...Fungi have evolved diverse strategies to acquire nutrients as endophytes,saprobes,symbionts,or pathogens.Appressoria have been intensively studied due to their importance in attaching and breaching the host surface.These specialized infection structures have evolved into various morpho-types:proto-appressoria,hyaline appressoria,melanized(dark)appressoria,and compound appressoria.In this review,we discuss the differences in the formation,differentiation,and function of appres-soria among fungi with diverse life strategies.Using DNA sequence information,LSU,5.8S,SSU and rpb2 gene fragments,we reconstructed the ancestral states for appressorial types in the main phyla of fungi and fungus-like organisms and found that the hyaline appressoria was the most ancestral form.Our analysis estimated proto-appressoria diversification during the Mesozoic period(92-239 million years ago),however,its origin remains inconclusive.Our data suggest that these hyaline appressoria diversified into melanized or compound appressoria,with evidence of adaptive radiation.展开更多
In plant pathology,the correct naming of a species is essential for determining the causal agents of disease.Species names not only serve the general purpose of concise communication,but also are critical for effectiv...In plant pathology,the correct naming of a species is essential for determining the causal agents of disease.Species names not only serve the general purpose of concise communication,but also are critical for effective plant quarantine,prevent-ing the introduction of new pathogens into a territory.Many phytopathogenic genera have multiple species and,in several genera,disagreements between the multiple prevailing species concept definitions result in numerous cryptic species.Some of these species were previously called by various names;forma speciales(specialised forms),subspecies,or pathotypes.However,based on new molecular evidence they are being assigned into new species.The frequent name changes and lack of consistent criteria to delineate cryptic species,species,subspecies,forms,and races create increasing confusion,often making communication among biologists arduous.Furthermore,such ambiguous information can convey misleading evo-lutionary concepts and species boundaries.The aim of this paper is to review these concepts,clarify their use,and evaluate them by referring to existing examples.We specifically address the question,“Do plant pathogens require a different ranking system?”We conclude that it is necessary to identify phytopathogens to species level based on data from multiple approaches.Furthermore,this identification must go beyond species level to clearly classify hitherto known subspecies,forms and races.In addition,when naming phytopathogenic genera,plant pathologists should provide more information about geographic locations and host ranges as well as host specificities for individual species,cryptic species,forms or races.When describing a new phytopathogen,we suggest that authors provide at least three representative strains together with pathogenicity test results.If Koch’s postulates cannot be fulfilled,it is necessary to provide complementary data such as associated disease severity on the host plant.Moreover,more sequenced collections of species causing diseases should be published in order to stabilise the boundaries of cryptic species,species,subspecies,forms,and races.展开更多
Dear Editor,Many Cas9-derived base editors have been developed for precise C-to-T and A-to-G base editing in plants(Molla et al.,2021).They are typically based on a SpCas9 nickase or its engineered variants with alter...Dear Editor,Many Cas9-derived base editors have been developed for precise C-to-T and A-to-G base editing in plants(Molla et al.,2021).They are typically based on a SpCas9 nickase or its engineered variants with altered protospacer adjacent motif(PAM)requirements(Molla et al.,2021).CRISPR-Cas12a enables highly efficient multiplexed genome editing in plants,and its T-rich PAM preference complements the G-rich PAM requirement of SpCas9 in genome targeting(Zhang et al.,2019,2021).Because of the lack of an efficient Cas12a nickase,it has been challenging to develop efficient Cas12a base editors.Nevertheless,Cas12a cytosine base editors(CBEs)and adenine base editors(ABEs)have been developed in mammalian cells(Li et al.,2018;Kleinstiver et al.,2019)with low DNA damage(Wang et al.,2020)because deactivated Cas12a(dCas12a)was used.However,efficient dCas12a base editors are yet to be developed in plants.展开更多
Fungi are an integral part of the earth's biosphere.They are broadly distributed in all continents and ecosystems and play a diversity of roles.Here,I review our current understanding of fungal threats to humans a...Fungi are an integral part of the earth's biosphere.They are broadly distributed in all continents and ecosystems and play a diversity of roles.Here,I review our current understanding of fungal threats to humans and describe the major factors that contribute to various threats.Among the 140,000 or so known species out of the estimated six million fungal species on Earth,about 10%directly or indirectly threaten human health and welfare.Major threats include mushroom poisoning,fungal allergies,infections of crop plants,food contamination by mycotoxins,and mycoses in humans.A growing number of factors have been identified to impact various fungal threats,including human demographics,crop distributions,anthropogenic activities,pathogen dispersals,global climate change,and/or the applications of antifungal drugs and agricultural fungicides.However,while models have been developed for analyzing various processes of individual threats and threat managements,current data are primarily descriptive and incomplete,and there are significant obstacles to integration of the diverse factors into accurate quantitative assessments of fungal threats.With increasing technological advances and concerted efforts to track the spatial and temporal data on climate and environmental variables;mycotoxins in the feed and food supply chains;fungal population dynamics in crop fields,human and animal populations,and the environment;human population demographics;and the prevalence and severities of fungal allergies and diseases,our ability to accurately assess fungal threats will improve.Such improvements should help us develop holistic strategies to manage fungal threats in the future.展开更多
In this paper a label-free fluorescent sensor for probing the interaction between heparin and protein was reported.Heparin,the bioactive polyanions,formed supramolecular assemblies with cationic surfactant cetyltrimet...In this paper a label-free fluorescent sensor for probing the interaction between heparin and protein was reported.Heparin,the bioactive polyanions,formed supramolecular assemblies with cationic surfactant cetyltrimethyl ammonium bromide (CTAB).The environment-dependent dye pyrene,encapsulated in hydrophobic interiors of the supramolecular assemblies worked as the fluorescence probe.Once the heparin-binding protein was added,competing interactions of protein with heparin would weaken the interaction between CTAB and heparin.As a result,the noncovalently sequestered pyrene would be released upon disassembly and the fluorescence of the released pyrene was subsequently decreased.The binding events were exemplified by protamine and Tat peptide,these processes were also verified by DLS and TEM.Such a strategy is appealing as organic synthesis was traded off against supramolecular assembly.This label-free fluorescent system is simple,selective,convenient,and can serve as a good complement to other existing methods,also this method has the potential for preprimary drug screening.展开更多
Microbes are everywhere in the Earth's biosphere-they play crucial roles in agriculture, nutrient cycling, environmental protection, and animal and human health. However, despite the importance of microbes throughout...Microbes are everywhere in the Earth's biosphere-they play crucial roles in agriculture, nutrient cycling, environmental protection, and animal and human health. However, despite the importance of microbes throughout human history, their roles remain to be fully recognized. In China.展开更多
基金The National Natural Science Foundation under contract Nos 41621064, 41606003, U1709202 and U1811464the National Key R&D Program of China under contract No. 2016YFC0301201the China Association of Marine Affairs (“Study on the feasibility of establishing an international data sharing application platform for smart ocean”).
文摘Profiles observed by Sea-Wing underwater gliders are widely applied in scientific research. However, the quality control(QC) of these data has received little attention. The mismatch between the temperature probe and conductivity cell response times generates erroneous salinities, especially across a strong thermocline. A sensor drift may occur owing to biofouling and biocide leakage into the conductivity cell when a glider has operated for several months. It is therefore critical to design a mature real-time QC procedure and develop a toolbox for the QC of Sea-Wing glider data. On the basis of temperature and salinity profiles observed by several Sea-Wing gliders each installed with a Sea-Bird Glider Payload CTD sensor, a real-time QC method including a thermal lag correction, Argo-equivalent real-time QC tests, and a simple post-processing procedure is proposed. The method can also be adopted for Petrel gliders.
基金The National Natural Science Foundation of China under contract Nos 42122046,42076202,U1811464 and 4210060098the Project Supported by Laoshan Laboratory under contract No.LSKJ202201500the Project Supported by Southern Marine Science and Engineering Guangdong Laboratory(Zhuhai)under contract No.SML2021SP102.
文摘The international Argo program,a global observational array of nearly 4000 autonomous profiling floats initiated in the late 1990s,which measures the water temperature and salinity of the upper 2000 m of the global ocean,has revolutionized oceanography.It has been recognized one of the most successful ocean observation systems in the world.Today,the proposed decade action“OneArgo”for building an integrated global,full-depth,and multidisciplinary ocean observing array for beyond 2020 has been endorsed.In the past two decades since 2002,with more than 500 Argo deployments and 80 operational floats currently,China has become an important partner of the Argo program.Two DACs have been established to process the data reported from all Chinese floats and deliver these data to the GDACs in real time,adhering to the unified quality control procedures proposed by the Argo Data Management Team.Several Argo products have been developed and released,allowing accurate estimations of global ocean warming,sea level change and the hydrological cycle,at interannual to decadal scales.In addition,Deep and BGC-Argo floats have been deployed,and time series observations from these floats have proven to be extremely useful,particularly in the analysis of synoptic-scale to decadal-scale dynamics.The future aim of China Argo is to build and maintain a regional Argo fleet comprising approximately 400 floats in the northwestern Pacific,South China Sea,and Indian Ocean,accounting for 9%of the global fleet,in addition to maintaining 300 Deep Argo floats in the global ocean(25%of the global Deep Argo fleet).A regional BGC-Argo array in the western Pacific also needs to be established and maintained.
基金supported by the National Natural Science Foundation of China(61403422,61273102)the Hubei Provincial Natural Science Foundation of China(2015CFA010)+1 种基金the Ⅲ Project(B17040)the Fundamental Research Funds for National University,China University of Geosciences(Wuhan)
文摘A facial expression emotion recognition based human-robot interaction(FEER-HRI) system is proposed, for which a four-layer system framework is designed. The FEERHRI system enables the robots not only to recognize human emotions, but also to generate facial expression for adapting to human emotions. A facial emotion recognition method based on2D-Gabor, uniform local binary pattern(LBP) operator, and multiclass extreme learning machine(ELM) classifier is presented,which is applied to real-time facial expression recognition for robots. Facial expressions of robots are represented by simple cartoon symbols and displayed by a LED screen equipped in the robots, which can be easily understood by human. Four scenarios,i.e., guiding, entertainment, home service and scene simulation are performed in the human-robot interaction experiment, in which smooth communication is realized by facial expression recognition of humans and facial expression generation of robots within 2 seconds. As a few prospective applications, the FEERHRI system can be applied in home service, smart home, safe driving, and so on.
基金partially supported by the Capital’s Funds for Health Improvement and Research (No. CFH2018-44024)
文摘Objective:Several anti-programmed cell death 1(anti-PD-1)antibodies have demonstrated potential efficacy in the treatment of advanced esophageal squamous cell cancer(ESCC).However,the response to subsequent chemotherapy after the failure of PD-1 blockade in ESCC patients has not been reported,and the optimal sequencing of immunotherapy and chemotherapy remains controversial.The aim of the present study was to evaluate responses to irinotecan-based subsequent chemotherapy in advanced ESCC patients who had progressed after treatment with camrelizumab(SHR-1210),a novel anti-PD-1 antibody.Methods:We retrospectively reviewed the medical records of patients with advanced ESCC treated with camrelizumab at a single institution.Consecutive patients who received subsequent irinotecan-based chemotherapy were selected for data collection and analysis.Results:Overall,a total of 28 patients were included.All patients had received at least two lines of systemic treatment prior to irinotecan salvage.The most common regimen that was administered after PD-1 blockade was irinotecan in combination with 5-fluorouracil(5-Fu)(or its derivatives),which was given to 19 patients.The objective response rate(ORR)and disease control rate(DCR)were 17.9%(5/28)and 64.3%(18/28),respectively,with 5(17.9%)patients achieving a partial response and 13(46.4%)having stable disease.The median progressionfree survival(PFS)was 3.18[95%confidence interval(95%CI),2.48-3.88]months and the median overall survival(OS)was 6.23(95%CI,4.71-7.75)months.No new safety issues,either immune-related or otherwise,were observed.Conclusions:Our results suggested that the response to irinotecan-based chemotherapy after PD-1 blockade in advanced ESCC patients appeared similar to that previously observed in patients who had not received PD-1 antibodies,and further study in larger cohorts or randomized trials is warranted to verify our observation.
基金Grant 81425002 from the National Science Fund for Distinguished Young ScholarsGrants 81670052,and 81870050 from the National Natural Science Foundation of ChinaGrant 2018ZX09711001-003-012 from the Drug Innovation Major Project,CAMS Fund for Key Laboratory of Pulmonary Vascular Medicine(2017PT32016).
文摘Background:The etiology of pulmonary arterial hypertension associated with congenital heart disease(PAHCHD)is complicated and the phenotype is heterogeneous.Genetic defects of NOTCH3 were associated withcerebral disease and pulmonary hypertension.However,the relationship between NOTCH3 mutations and theclinical phenotype has not been reported in CHD-PAH.Methods:We eventually enrolled 142 PAH-CHD patientsfrom Fuwai Hospital.Whole exome sequencing(WES)was performed to screen the rare deleterious variants ofNOTCH3 gene.Results:This PAH-CHD cohort included 43(30.3%)men and 99(69.7%)women with the meanage 29.8±10.9 years old.The pathogenic or likely pathogenic mutations of NOTCH3 were identified in five cases.Patients 2,5,8 and 11 carried the same NOTCH3 mutation c.1630C>T(pArg544Cys),which is the hot-spotmutation for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy(CADASIL).Patient 3 carried the NOTCH3 mutation p.Arg75Gln that has also been reported to be associatedwith the CADASIL.Patients 2,5,8,11 took the examination of the cerebral magnetic resonance imaging(MRI)and confirmed the phenotype of CADASIL.Conclusions:We first reported the NOTCH3 rare mutationsand CADASIL phenotypes in CHD-PAH patients.The NOTCH3 rare variants were with a relatively high positiverate and CADASIL phenotypes were likely enriched in PAH-CHD patients.The preoperative neurological examinationmight be recommended for PAH-CHD patients to determine the surgical contraindications and reduceintraoperative neurological complications.
基金Supported by Project of Study on the Impact of Climate Change on Wheat Production in Weifang City(2011wfqxkt05)
文摘In order to study the trend of climate change in the future in Weifang,and analyze the impact of climate change on the local wheat production,the air temperature and precipitation in Weifang from 2021 to 2050 were simulated by using the regional climate model PRECIS.And then put the meteorological data into the crop model to simulate the growth of wheat under climate change conditions in the future.The results showed that there would be a trend of rising temperature and increasing precipitation in Weifang in the future.Climate warming would result in growth period of wheat to be ahead of schedule and yield reduction.If taking into account the effect of CO2,the yield of wheat would increase.
文摘Near-infrared spectroscopy coupled with kernel partial least squares-discriminant analysis was used to rapidly screen water containing malathion. In the wavenumber of 4348 cm-1 to 9091 cm-1, the overall correct classification rate of kernel partial least squares-discriminant analysis was 100% for training set, and 100% for test set, with the lowest concentration detected malathion residues in water being 1 μg·ml-1. Kernel partial least squares-discriminant analysis was able to have a good performance in classifying data in nonlinear systems. It was inferred that Near-infrared spectroscopy coupled with the kernel partial least squares-discriminant analysis had a potential in rapid screening other pesticide residues in water.
基金This study was supported by the Chinese Society of Clinical Oncology(CSCO)-Hengrui Oncology Research Fund(No.Y-HR2018-364)。
文摘Background:Effective therapeutic options are limited for patients with advanced esophageal squamous cell carcinoma(ESCC).The incorporation of an immune checkpoint inhibitor and a molecular anti-angiogenic agent into the commonly adopted chemotherapy may produce synergistic effects.Therefore,we aimed to investigate the efficacy and safety of camrelizumab plus apatinib combined with chemotherapy as the first-line treatment of advanced ESCC.Methods:In this single-arm prospective phase II trial,patients with unresectable locally advanced or recurrent/metastatic ESCC received camrelizumab 200 mg,liposomal paclitaxel 150 mg/m2,and nedaplatin 50 mg/m2 on day 1,and apatinib 250 mg on days 1-14.The treatments were repeated every 14 days for up to 9 cycles,followed by maintenance therapy with camrelizumab and apatinib.The primary endpoint was objective response rate(ORR)according to the Response Evaluation Criteria in Solid Tumors(version 1.1).Secondary endpoints included disease control rate(DCR),progression-free survival(PFS),overall survival(OS),and safety.Results:We enrolled 30 patients between August 7,2018 and February 23,2019.The median follow-up was 24.98 months(95%confidence interval[CI]:23.05-26.16 months).The centrally assessed ORR was 80.0%(95%CI:61.4%-92.3%),with a median duration of response of 9.77 months(range:1.54 to 24.82+months).The DCR reached 96.7%(95%CI:82.8%-99.9%).The median PFS was 6.85 months(95%CI:4.46-14.20 months),and the median OS was 19.43 months(95%CI:9.93 months–not reached).The most common grade 3-4 treatmentrelated adverse events(AEs)were leukopenia(83.3%),neutropenia(60.0%),and increased aspartate aminotransferase level(26.7%).Treatment-related serious AEs included febrile neutropenia,leukopenia,and anorexia in one patient(3.3%),and single cases of increased blood bilirubin level(3.3%)and toxic epidermal necrolysis(3.3%).No treatment-related deaths occurred.Conclusions:Camrelizumab plus apatinib combined with liposomal paclitaxel and nedaplatin as first-line treatment demonstrated feasible anti-tumor activity and manageable safety in patients with advanced ESCC.Randomized trials to evaluate this new combination strategy are warranted.Trial registration:This trial was registered on July 27,2018,at ClinicalTrials.gov(identifier:NCT03603756).
基金supported by the Funds for International Cooperation and Exchange of the National Natural Science Foundation of China(31210103919)the National Basic Research Program of China(2014CB138305)the CAS/SAFEA International Partnership Program for Creative Research Teams.
文摘Mushrooms in the basidiomycete family Boletaceae are ecologically and economically very important.However,due to the morphological complexity and the limited phylogenetic information on the various species and genera of this fungal family,our understanding of its systematics and evolution remains rudimentary.In this study,DNA sequences of four genes(nrLSU,tef1-α,rpb1,and rpb2)were newly obtained from ca.200 representative specimens of Boletaceae.Our phylogenetic analyses revealed seven major clades at the subfamily level,namely Austroboletoideae,Boletoideae,Chalciporoideae,Leccinoideae,Xerocomoideae,Zangioideae,and the Pulveroboletus Group.In addition,59 genus-level clades were identified,of which 22 were uncovered for the first time.These 22 clades were mainly placed in Boletoideae and the Pulveroboletus Group.The results further indicated that the characters frequently used in the morphology-based taxonomy of Boletaceae,such as basidiospore ornamentation,the form of the basidioma,and the stuffed pores each had multiple origins within the family,suggesting that the use of such features for high-level classification of Boletaceae should be de-emphasized and combined with other characters.
基金supported by the Funds for International Cooperation and Exchange of the National Natural Science Foundation of China(31210103919)the National Basic Research Program of China(2014CB138305)the CAS/SAFEA International Partnership Program for Creative Research Teams.
文摘Porcini mushrooms(Boletus sect.Boletus)have both economic and ecological importance.Recent molecular phylogenetic study has uncovered rich species diversity of this group of fungi from China.In this study,the Chinese porcini were characterized by both morphological andmolecular phylogenetic evidence.15 species were recognized,including nine new species,namely B.botryoides,B.fagacicola,B.griseiceps,B.monilifer,B.sinoedulis,B.subviolaceofuscus,B.tylopilopsis,B.umbrinipileus and B.viscidiceps.Three previously described species,viz.B.bainiugan,B.meiweiniuganjun and B.shiyong,were revised,and B.meiweiniuganjun is treated as a synonym of B.bainiugan.A key to the Chinese porcini mushrooms was provided.
文摘Fungi have evolved diverse strategies to acquire nutrients as endophytes,saprobes,symbionts,or pathogens.Appressoria have been intensively studied due to their importance in attaching and breaching the host surface.These specialized infection structures have evolved into various morpho-types:proto-appressoria,hyaline appressoria,melanized(dark)appressoria,and compound appressoria.In this review,we discuss the differences in the formation,differentiation,and function of appres-soria among fungi with diverse life strategies.Using DNA sequence information,LSU,5.8S,SSU and rpb2 gene fragments,we reconstructed the ancestral states for appressorial types in the main phyla of fungi and fungus-like organisms and found that the hyaline appressoria was the most ancestral form.Our analysis estimated proto-appressoria diversification during the Mesozoic period(92-239 million years ago),however,its origin remains inconclusive.Our data suggest that these hyaline appressoria diversified into melanized or compound appressoria,with evidence of adaptive radiation.
基金We would like to thank the Thailand Research Fund,Grant RDG6130001 entitled“Impact of climate change on fungal diversity and biogeography in the Greater Mekong Subregion”.Kevin D Hyde thanks Chiang Mai University for the award of a Visiting Professor.Ishara S Manawasinghe thank Prof Marco Thines for guiding the development of this paper by providing valuable ideas and comments.Alan JL Phillips acknowledges the support from UIDB/04046/2020 and UIDP/04046/2020 Centre grants from FCT,Portugal(to BioISI).
文摘In plant pathology,the correct naming of a species is essential for determining the causal agents of disease.Species names not only serve the general purpose of concise communication,but also are critical for effective plant quarantine,prevent-ing the introduction of new pathogens into a territory.Many phytopathogenic genera have multiple species and,in several genera,disagreements between the multiple prevailing species concept definitions result in numerous cryptic species.Some of these species were previously called by various names;forma speciales(specialised forms),subspecies,or pathotypes.However,based on new molecular evidence they are being assigned into new species.The frequent name changes and lack of consistent criteria to delineate cryptic species,species,subspecies,forms,and races create increasing confusion,often making communication among biologists arduous.Furthermore,such ambiguous information can convey misleading evo-lutionary concepts and species boundaries.The aim of this paper is to review these concepts,clarify their use,and evaluate them by referring to existing examples.We specifically address the question,“Do plant pathogens require a different ranking system?”We conclude that it is necessary to identify phytopathogens to species level based on data from multiple approaches.Furthermore,this identification must go beyond species level to clearly classify hitherto known subspecies,forms and races.In addition,when naming phytopathogenic genera,plant pathologists should provide more information about geographic locations and host ranges as well as host specificities for individual species,cryptic species,forms or races.When describing a new phytopathogen,we suggest that authors provide at least three representative strains together with pathogenicity test results.If Koch’s postulates cannot be fulfilled,it is necessary to provide complementary data such as associated disease severity on the host plant.Moreover,more sequenced collections of species causing diseases should be published in order to stabilise the boundaries of cryptic species,species,subspecies,forms,and races.
基金Some linkers used in this study were disclosed in a Syngenta patent application(WO2021061507).No conflict of interest is declared.
文摘Dear Editor,Many Cas9-derived base editors have been developed for precise C-to-T and A-to-G base editing in plants(Molla et al.,2021).They are typically based on a SpCas9 nickase or its engineered variants with altered protospacer adjacent motif(PAM)requirements(Molla et al.,2021).CRISPR-Cas12a enables highly efficient multiplexed genome editing in plants,and its T-rich PAM preference complements the G-rich PAM requirement of SpCas9 in genome targeting(Zhang et al.,2019,2021).Because of the lack of an efficient Cas12a nickase,it has been challenging to develop efficient Cas12a base editors.Nevertheless,Cas12a cytosine base editors(CBEs)and adenine base editors(ABEs)have been developed in mammalian cells(Li et al.,2018;Kleinstiver et al.,2019)with low DNA damage(Wang et al.,2020)because deactivated Cas12a(dCas12a)was used.However,efficient dCas12a base editors are yet to be developed in plants.
文摘Fungi are an integral part of the earth's biosphere.They are broadly distributed in all continents and ecosystems and play a diversity of roles.Here,I review our current understanding of fungal threats to humans and describe the major factors that contribute to various threats.Among the 140,000 or so known species out of the estimated six million fungal species on Earth,about 10%directly or indirectly threaten human health and welfare.Major threats include mushroom poisoning,fungal allergies,infections of crop plants,food contamination by mycotoxins,and mycoses in humans.A growing number of factors have been identified to impact various fungal threats,including human demographics,crop distributions,anthropogenic activities,pathogen dispersals,global climate change,and/or the applications of antifungal drugs and agricultural fungicides.However,while models have been developed for analyzing various processes of individual threats and threat managements,current data are primarily descriptive and incomplete,and there are significant obstacles to integration of the diverse factors into accurate quantitative assessments of fungal threats.With increasing technological advances and concerted efforts to track the spatial and temporal data on climate and environmental variables;mycotoxins in the feed and food supply chains;fungal population dynamics in crop fields,human and animal populations,and the environment;human population demographics;and the prevalence and severities of fungal allergies and diseases,our ability to accurately assess fungal threats will improve.Such improvements should help us develop holistic strategies to manage fungal threats in the future.
基金Financial support from the Natural Science Foundation of China (Nos.50830106,21174126),the China National Funds for Distinguished Young Scientists (No.51025312) and the Open Project of State Key Laboratory of Supramolecular Structure and Materials (No.sklssm201316) is gratefully acknowledged.
文摘In this paper a label-free fluorescent sensor for probing the interaction between heparin and protein was reported.Heparin,the bioactive polyanions,formed supramolecular assemblies with cationic surfactant cetyltrimethyl ammonium bromide (CTAB).The environment-dependent dye pyrene,encapsulated in hydrophobic interiors of the supramolecular assemblies worked as the fluorescence probe.Once the heparin-binding protein was added,competing interactions of protein with heparin would weaken the interaction between CTAB and heparin.As a result,the noncovalently sequestered pyrene would be released upon disassembly and the fluorescence of the released pyrene was subsequently decreased.The binding events were exemplified by protamine and Tat peptide,these processes were also verified by DLS and TEM.Such a strategy is appealing as organic synthesis was traded off against supramolecular assembly.This label-free fluorescent system is simple,selective,convenient,and can serve as a good complement to other existing methods,also this method has the potential for preprimary drug screening.
文摘Microbes are everywhere in the Earth's biosphere-they play crucial roles in agriculture, nutrient cycling, environmental protection, and animal and human health. However, despite the importance of microbes throughout human history, their roles remain to be fully recognized. In China.