Multiplex RT-PCR assays have been widely used tools for detection and differentiation of a panel of respiratory viral pathogens. In this study, we evaluated the Qiagen ResPlex lI V2.0 kit and explored factors influenc...Multiplex RT-PCR assays have been widely used tools for detection and differentiation of a panel of respiratory viral pathogens. In this study, we evaluated the Qiagen ResPlex lI V2.0 kit and explored factors influencing its sensitivity. Nasopharyngeal swab （NPS） specimens were prospectively collected from pediatric inpatients with lower respiratory tract infections at the time of admission in the Shenzhen Children＇s Hospital from May 2009 to April 2010. Total nucleic acids were extracted using the EZ1 system （Qiagen, Germany） and 17 respiratory viruses and genotypes including influenza A virus （FluA）, FluB, parainfluenza virus 1 （PIV1）, PIV2, PIV3, PIV4, respiratory syncytial virus （RSV）, human metapneumovirus （hMPV）, rhinoviruses （RhV）, enteroviruses （EnV）, human bocaviruses （hBoV）, adenoviruses （AdV）, four coronaviruses （229E, OC43, NL63 and HKU1）, and FluA 2009 pandemic H1NI（H1NI-p） were detected and identified by the ResPlex II kit. In parallel, 16 real-time TaqMan quantitative RT-PCR assays were used to quantitatively detect each virus except for RhV. Influenza and parainfluenza viral cultures were also performed. Among the total 438 NPS specimens collected during the study period, one or more viral pathogens were detected in 274 （62.6%） and 201（45.9%） specimens by monoplex TaqMan RT-PCR and multiplex ResPlex, respectively. When results from monoplex PCR or cell culture were used as the reference standard, the multiplex PCR possessed specificities of 92.9-100.0%. The sensitivity of multiplex PCR for PIV3, hMPV, PIV1 and BoV were 73.1%, 70%, 66.7% and 55.6%, respectively, while low sensitivities （11.1%-40.0%） were observed for FluA, EnV, OC43, RSV and H1N1. Among the seven viruses/genotypes detected with higher frequencies, multiplex PCR sensitivities were correlated significantly with viral loads determined by the TaqMan RT-PCR in FluA, H 1N 1-p and RSV （p=0.011-0.000） The Qiagen ResPlex II multiplex RT-PCR kit possesses excellent specificity for simultaneous detection of 17 viral pathogens in NPS specimens in pediatric inpatients at the time of admission. The sensitivity of multiplex RT-PCR was influenced by viral loads, specimen process methods, primer and probe design and amplification condition.展开更多
A new Gaussian approximation nonlinear filter called generalized cubature quadrature Kalman filter (GCQKF) is introduced for nonlinear dynamic systems. Based on standard GCQKF, two extensions are developed, namely squ...A new Gaussian approximation nonlinear filter called generalized cubature quadrature Kalman filter (GCQKF) is introduced for nonlinear dynamic systems. Based on standard GCQKF, two extensions are developed, namely square root generalized cubature quadrature Kalman filter (SR-GCQKF) and iterated generalized cubature quadrature Kalman filter (I-GCQKF). In SR-GCQKF, the QR decomposition is exploited to alter the Cholesky decomposition and both predicted and filtered error covariances have been propagated in square root format to make sure the numerical stability. In I-GCQKF, the measurement update step is executed iteratively to make full use of the latest measurement and a new terminal criterion is adopted to guarantee the increase of likelihood. Detailed numerical experiments demonstrate the superior performance on both tracking stability and estimation accuracy of I-GCQKF and SR-GCQKF compared with GCQKF.展开更多
To explore the structure-activity connections of amphiphilic permeation enhancers containing the length of the hydrophobic chains as well as the properties of the polar head,O-acylgeraniol and O-acylnerol derivatives ...To explore the structure-activity connections of amphiphilic permeation enhancers containing the length of the hydrophobic chains as well as the properties of the polar head,O-acylgeraniol and O-acylnerol derivatives were synthesized from geraniol/nerol(cis-isomer of geraniol) and pharmaceutical excipient acids in this research. Their promotion of the percutaneous absorption of three drugs as the model, flurbiprofen(FP), isosorbide dinitrate(ISDN) and donepezil(DNP), which were selected based on their physicochemical properties,was tested by in vitro skin penetration and in vivo. Molecular simulation, ATR-FTIR, CLSM and histological observation were implement to evaluate the mode of action of the enhancers.The results indicated that(E)-3,7-dimethyl-2,6-octadien-1-yl tetradecanoate(GER-C14, trans-)achieved the highest enhancement ability for the three drugs;additionally, the in vivo results obtained were in good correlation with the in vitro data. Molecular docking results suggested that enhancers loosen the hydrogen bonds between ceramides, and the results of molecular simulation indicated that GER-C14, NER-C14 could insert into the middle of the lipid bilayer to form an independent phase. According to ATR-FTIR and histological evaluation, the enhancers extracted lipids and influenced the protein region, thereby disturbing the skin array. In addition, CLSM described the dynamic effects of enhancers on lipids between stratum corneum(SC) cells. In conclusion, GER-C14 had a better penetration promotion effect, which broadened our understanding of stereoisomeric penetration enhancers.展开更多
The investigation on the aerodynamic characteristics of the high-attitude long-endurance (HALE) Diamond Joined-Wing configuration unmanned aerial vehicle ( UAV) was carried out by the theoretical analysis method and n...The investigation on the aerodynamic characteristics of the high-attitude long-endurance (HALE) Diamond Joined-Wing configuration unmanned aerial vehicle ( UAV) was carried out by the theoretical analysis method and numerical simulation. Research indicates that as the wing of the UAV is composed of the front wing and the after wing, the after wing has the ability to transmit the front wing's boundary layer to the after wing root which can inhibit the front wing's flow separation. Although the front wing was affected by the retardation of the after wing, the aerodynamic performance of the front wing was better than that of alone front wing in most cases. The after wing was also affected by the wake and downwash of the front wing, and its aerodynamic performance was greatly decreased. The characteristic curve of the pitching moment of the UAV had nonlinear characteristics. The flow field structure of the after wing changed by the front wing wake direct sweep and flow separation at the after wing root were the main reasons that non-linear ′rise′phenomenon occurred in two segments ( α = 0° and α = 8° ) of the characteristic curve of pitching moment. Moreover, coupling of the flow separation characteristic of the front wing and the after wing resulted in the pitching moment ′pitchup′ phenomenon. The lateral-directional static stability of the flat layout was weak. The HALE Diamond Joined-Wing configuration UAV ' s aerodynamic performance can be improved and the problems in engineering applications can be effectively alleviated by adjusting the overall layout parameters.展开更多
In this study we mainly focus on the attitude control problem of a quad tilt rotor aircraft with respect to unknown external disturbance. We propose a class of control methods based on a novel logarithmic fast non sin...In this study we mainly focus on the attitude control problem of a quad tilt rotor aircraft with respect to unknown external disturbance. We propose a class of control methods based on a novel logarithmic fast non singular terminal sliding surface a new fast reaching law and extended state disturbance observer. A logarithmic non singular terminal sliding surface is used owing to its convergence in finite time and significant robustness. A fast reaching law with two order characteristics of the sliding mode is designed. This reaching law can be used reduce the convergence time of traditional reaching law. In addition the extended state disturbance observer is utilized for online estimation and to compensate for system disturbance. The simulation experiment results show that the control strategy proposed in this paper outperforms the traditional non singular fast sliding mode control.展开更多
In this article,we study multivariate approximation defined over weighted anisotropic Sobolev spaces which depend on two sequences a={a j}j≥1 and b={b j}j≥1 of positive numbers.We obtain strong equivalences of the a...In this article,we study multivariate approximation defined over weighted anisotropic Sobolev spaces which depend on two sequences a={a j}j≥1 and b={b j}j≥1 of positive numbers.We obtain strong equivalences of the approximation numbers,and necessary and sufficient conditions on a,b to achieve various notions of tractability of the weighted anisotropic Sobolev embeddings.展开更多
In this paper, we study optimal recovery （reconstruction） of functions on the sphere in the average case setting. We obtain the asymptotic orders of average sampling numbers of a Sobolev space on the sphere with a G...In this paper, we study optimal recovery （reconstruction） of functions on the sphere in the average case setting. We obtain the asymptotic orders of average sampling numbers of a Sobolev space on the sphere with a Gaussian measure in the Lq （S^d-1） metric for 1 ≤ q ≤ ∞, and show that some worst-case asymptotically optimal algorithms are also asymptotically optimal in the average case setting in the Lq （S^d-1） metric for 1 ≤ q ≤ ∞.展开更多
The early diagnosis of Parkinson’s disease(PD)provides opportunities for early intervention to slow the progression of neurological degeneration in patients,particularly as the aging population increases in our socie...The early diagnosis of Parkinson’s disease(PD)provides opportunities for early intervention to slow the progression of neurological degeneration in patients,particularly as the aging population increases in our society.Among a series of pathological features of PD,mitochondria abnormalities have been identified as central event that occurs at the early stage of PD.However,the method for detecting mitochondrial abnormalities-associated early PD has not been fully developed.We herein report a specifically mitochondrial targeting probe(named TPA-BT-SCP)that is able to characterize mitochondria abnormalities for early diagnosis of PD and monitor PD neurodegenerative progress.The probe is an aggregation-induced emission(AIE)probe with a strong positive charge,a 3D distorted molecular structure,and a separated HOMO-LUMO distribution,designed with unique molecular design guidelines.Our research demonstrated that TPA-BT-SCP could emit stable and strong fluorescence,and rapidly accumulate in mitochondria due to the negative charge.After intranasal administration of 1-methy-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced PD mice,TPA-BT-SCP successfully bypassed the blood−brain barrier to light up the brain,allowing the grading of PD severity based on its high sensitivity.Taken together,this work develops a novel AIE probe that exhibits dramatically high sensitivity to mitochondrial changes and enables noninvasive diagnosis of early PD in the brain.展开更多
Background and Aims:Alagille syndrome(AGS)is an autosomal dominant multisystem disorder caused by mutations in the JAG1 and NOTCH2 genes.AGS has been rarely reported in adult patients,mainly because its characteristic...Background and Aims:Alagille syndrome(AGS)is an autosomal dominant multisystem disorder caused by mutations in the JAG1 and NOTCH2 genes.AGS has been rarely reported in adult patients,mainly because its characteristics in adults are subtle.The study aimed to improve the understanding of adult AGS by a descriptive case series.Methods:Eight adults diagnosed with AGS at our hospital between June 2016 and June 2019 were included in the study.Clinical data,biochemical results,imaging results,liver histopathology,and genetic testing were analyzed.Results:Three female and five male patients with a median age of 24.5 years at the time of diagnosis were included in the analysis.The clinical manifestations were adult-onset(62.5%,5/8),cholestasis(50%,4/8),butterfly vertebrae(62.5%,5/8),systolic murmurs(12.5%,1/8),typical facies(12.5%,1/8),posterior embryotoxon,and renal abnormalities(0/8).Genetic sequencing showed that all patients had mutations,with four occurring in the JAG1 gene and four in the NOTCH2 gene.Six were substitution mutations,one was a deletion mutation,and one was a splicing mutation.Five had been previously reported;but the others,one JAG1 mutation and two NOTCH2 mutations were unique and are reported here for the first time.Conclusions:The clinical manifestations highlighted by the current diagnostic criteria for most adults with AGS are atypical.Those who do not meet the criteria but are highly suspicious of having AGS need further evaluation,especially genetic testing.展开更多
Dear Editor,Human adenoviruses (HAd Vs) are associated with respiratory,gastrointestinal,ophthalmological,genitourinary,and neurological infections.To date,more than 100genotypes of HAd Vs have been identified.They ar...Dear Editor,Human adenoviruses (HAd Vs) are associated with respiratory,gastrointestinal,ophthalmological,genitourinary,and neurological infections.To date,more than 100genotypes of HAd Vs have been identified.They are classified into seven species,A to G (HAd V Working Group,http://hadvwg.gmu.edu/).展开更多
Fungal infections cause~1.5 million deaths each year worldwide,and the mortality rate of disseminated candidiasis currently exceeds that of breast cancer and malaria.The major reasons for the high mortality of candidi...Fungal infections cause~1.5 million deaths each year worldwide,and the mortality rate of disseminated candidiasis currently exceeds that of breast cancer and malaria.The major reasons for the high mortality of candidiasis are the limited number of antifungal drugs and the emergence of drug-resistant species.Therefore,a better understanding of antifungal host defense mechanisms is crucial for the development of effective preventive and therapeutic strategies.Here,we report that DOCK2(dedicator of cytokinesis 2)promotes indispensable antifungal innate immune signaling and proinflammatory gene expression in macrophages.DOCK2-deficient macrophages exhibit decreased RAC GTPase(Rac family small GTPase)activation and ROS(reactive oxygen species)production,which in turn attenuates the killing of intracellular fungi and the activation of downstream signaling pathways.Mechanistically,after fungal stimulation,activated SYK(spleen-associated tyrosine kinase)phosphorylates DOCK2 at tyrosine 985 and 1405,which promotes the recruitment and activation of RAC GTPases and then increases ROS production and downstream signaling activation.Importantly,nanoparticle-mediated delivery of in vitro transcribed(IVT)Rac1 mRNA promotes the activity of Rac1 and helps to eliminate fungal infection in vivo.Taken together,this study not only identifies a critical role of DOCK2 in antifungal immunity via regulation of RAC GTPase activity but also provides proof of concept for the treatment of invasive fungal infections by using IVT mRNA.展开更多
Importance:A cluster of influenza-associated deaths occurred among children during pandemic 2009 influenza A(H 1N1)in China,but the risk factors and causes for death have not been clarified.Objective:We describe the c...Importance:A cluster of influenza-associated deaths occurred among children during pandemic 2009 influenza A(H 1N1)in China,but the risk factors and causes for death have not been clarified.Objective:We describe the clinical findings regarding 2009 influenza A(H1N1)-associated pediatric deaths in China,including the risk factors for death.Methods:The definition of 2009 influenza A(H1N1)-associated pediatric death is death in a child who is younger than 14 years and has laboratory-confirmed influenza.We collected data of total 810 hospitalized patients with 2009 influenza A(H 1N 1)infection from September 2009 to February 2010 in 17 hospitals across China.The clinical characteristics,laboratory abnormalities,and treatment course were retrospectively studied.Results:Of the 810 patients hospitalized with 2009 influenza A(H1N1)infection,19(2.3%)died.Ten patients died from severe pneumonia and acute respiratory distress syndrome;eight died from encephalopathy/encephalitis;one died from secondary fungal meningitis.Patients who died were more likely than patients who survived to have neutrophilia,lymphopenia,elevated C-reactive protein,and elevations of lactate dehydrogenase,creatine kinase,creatine kinase-MB,aspartate aminotransferase and alanine aminotransferase.There were no significant differences in the median age,median time from onset of illness to admission,underlying chronic disease,and initiation of antiviral therapy within 48 hours of illness onset,between patients who died and those who survived.Interpretation:The risk factors for pediatric death associated with 2009 influenza A(H 1N 1)infection are different from those of seasonal influenza.The most common causes of death are viral pneumonia,acute respiratory distress syndrome,and encephalopathy/encephalitis.展开更多
Background The prevalence of zinc deficiency is high in patients with chronic liver disease,but few studies have hitherto explored the relationship between the serum zinc level and hepatitis B virus(HBV)-related acute...Background The prevalence of zinc deficiency is high in patients with chronic liver disease,but few studies have hitherto explored the relationship between the serum zinc level and hepatitis B virus(HBV)-related acute-on-chronic liver failure(ACLF).This study aimed to assess the association between zinc deficiency and infectious complications,and model for end-stage liver disease(MELD)score in patients with HBV-related ACLF.Methods Patients with HBV-related ACLF from the Department of Infectious Diseases of the Third Affiliated Hospital of Sun Yat-sen University(Guangzhou,China)between January 2019 and December 2019 were retrospectively analysed in this study.Their demographic,clinical,and laboratory data were retrieved from the hospital information system and analysed.The Student’s t-test was used for normally distributed continuous variables between two groups and the Chi-square test was used for categorical data.Univariate and multivariate logistic regression analyses were applied to identify independent parameters.Results A total of 284 patients were included in this study,including 205 liver cirrhosis and 79 non-cirrhosis patients.The proportion of patients with zinc deficiency was the highest(84.5%),followed by subclinical zinc deficiency(14.1%)and normal zinc level(1.4%).Patients in the zinc deficiency group had a higher MELD score than the subclinical zinc deficiency or normal zinc group(P=0.021).Age,total bilirubin,and serum zinc level were independent factors for infection(P_(s)<0.05).The serum zinc level in patients without complications at admission was significantly higher than that in patients with complications(P=0.004).Moreover,the serum zinc level in patients with prothrombin time activity(PTA)of<20%was significantly lower than that in patients with 20%≤PTA<30%(P=0.007)and that in patients with 30%≤PTA<40%(P<0.001).Conclusions Zinc deficiency is common in patients with HBV-related ACLF.Zinc deficiency is closely associated with infectious complications and MELD score in patients with HBV-related ACLF.展开更多
基金supported in part by Grant Name awarded to the State Key Lab of Respiratory Diseases,Guangzhou Medical College (2007DA780154F0910)
文摘Multiplex RT-PCR assays have been widely used tools for detection and differentiation of a panel of respiratory viral pathogens. In this study, we evaluated the Qiagen ResPlex lI V2.0 kit and explored factors influencing its sensitivity. Nasopharyngeal swab （NPS） specimens were prospectively collected from pediatric inpatients with lower respiratory tract infections at the time of admission in the Shenzhen Children＇s Hospital from May 2009 to April 2010. Total nucleic acids were extracted using the EZ1 system （Qiagen, Germany） and 17 respiratory viruses and genotypes including influenza A virus （FluA）, FluB, parainfluenza virus 1 （PIV1）, PIV2, PIV3, PIV4, respiratory syncytial virus （RSV）, human metapneumovirus （hMPV）, rhinoviruses （RhV）, enteroviruses （EnV）, human bocaviruses （hBoV）, adenoviruses （AdV）, four coronaviruses （229E, OC43, NL63 and HKU1）, and FluA 2009 pandemic H1NI（H1NI-p） were detected and identified by the ResPlex II kit. In parallel, 16 real-time TaqMan quantitative RT-PCR assays were used to quantitatively detect each virus except for RhV. Influenza and parainfluenza viral cultures were also performed. Among the total 438 NPS specimens collected during the study period, one or more viral pathogens were detected in 274 （62.6%） and 201（45.9%） specimens by monoplex TaqMan RT-PCR and multiplex ResPlex, respectively. When results from monoplex PCR or cell culture were used as the reference standard, the multiplex PCR possessed specificities of 92.9-100.0%. The sensitivity of multiplex PCR for PIV3, hMPV, PIV1 and BoV were 73.1%, 70%, 66.7% and 55.6%, respectively, while low sensitivities （11.1%-40.0%） were observed for FluA, EnV, OC43, RSV and H1N1. Among the seven viruses/genotypes detected with higher frequencies, multiplex PCR sensitivities were correlated significantly with viral loads determined by the TaqMan RT-PCR in FluA, H 1N 1-p and RSV （p=0.011-0.000） The Qiagen ResPlex II multiplex RT-PCR kit possesses excellent specificity for simultaneous detection of 17 viral pathogens in NPS specimens in pediatric inpatients at the time of admission. The sensitivity of multiplex RT-PCR was influenced by viral loads, specimen process methods, primer and probe design and amplification condition.
基金supported by the National Natural Science Foundation of China(6147322711472222)+2 种基金the Aerospace Technology Support Fund of China(2014-HT-XGD)the Natural Science Foundation of Shaanxi Province(2015JM6304)the Aeronautical Science Foundation of China(20151353018)
文摘A new Gaussian approximation nonlinear filter called generalized cubature quadrature Kalman filter (GCQKF) is introduced for nonlinear dynamic systems. Based on standard GCQKF, two extensions are developed, namely square root generalized cubature quadrature Kalman filter (SR-GCQKF) and iterated generalized cubature quadrature Kalman filter (I-GCQKF). In SR-GCQKF, the QR decomposition is exploited to alter the Cholesky decomposition and both predicted and filtered error covariances have been propagated in square root format to make sure the numerical stability. In I-GCQKF, the measurement update step is executed iteratively to make full use of the latest measurement and a new terminal criterion is adopted to guarantee the increase of likelihood. Detailed numerical experiments demonstrate the superior performance on both tracking stability and estimation accuracy of I-GCQKF and SR-GCQKF compared with GCQKF.
基金The Natural Science Foundation of Hebei Province [grant numbers H2019209254]North China University of Science and Technology Foundation for Distinguished Young Scholars[grant numbers JQ201713]Distinguished Young Scholars of Hebei Province。
文摘To explore the structure-activity connections of amphiphilic permeation enhancers containing the length of the hydrophobic chains as well as the properties of the polar head,O-acylgeraniol and O-acylnerol derivatives were synthesized from geraniol/nerol(cis-isomer of geraniol) and pharmaceutical excipient acids in this research. Their promotion of the percutaneous absorption of three drugs as the model, flurbiprofen(FP), isosorbide dinitrate(ISDN) and donepezil(DNP), which were selected based on their physicochemical properties,was tested by in vitro skin penetration and in vivo. Molecular simulation, ATR-FTIR, CLSM and histological observation were implement to evaluate the mode of action of the enhancers.The results indicated that(E)-3,7-dimethyl-2,6-octadien-1-yl tetradecanoate(GER-C14, trans-)achieved the highest enhancement ability for the three drugs;additionally, the in vivo results obtained were in good correlation with the in vitro data. Molecular docking results suggested that enhancers loosen the hydrogen bonds between ceramides, and the results of molecular simulation indicated that GER-C14, NER-C14 could insert into the middle of the lipid bilayer to form an independent phase. According to ATR-FTIR and histological evaluation, the enhancers extracted lipids and influenced the protein region, thereby disturbing the skin array. In addition, CLSM described the dynamic effects of enhancers on lipids between stratum corneum(SC) cells. In conclusion, GER-C14 had a better penetration promotion effect, which broadened our understanding of stereoisomeric penetration enhancers.
基金Sponsored by the Civil Aircraft Project(Grant No.MIE-2015-F-009)the Shaanxi Province Science and Technology Project(Grant No.2015KTCQ01-78)
文摘The investigation on the aerodynamic characteristics of the high-attitude long-endurance (HALE) Diamond Joined-Wing configuration unmanned aerial vehicle ( UAV) was carried out by the theoretical analysis method and numerical simulation. Research indicates that as the wing of the UAV is composed of the front wing and the after wing, the after wing has the ability to transmit the front wing's boundary layer to the after wing root which can inhibit the front wing's flow separation. Although the front wing was affected by the retardation of the after wing, the aerodynamic performance of the front wing was better than that of alone front wing in most cases. The after wing was also affected by the wake and downwash of the front wing, and its aerodynamic performance was greatly decreased. The characteristic curve of the pitching moment of the UAV had nonlinear characteristics. The flow field structure of the after wing changed by the front wing wake direct sweep and flow separation at the after wing root were the main reasons that non-linear ′rise′phenomenon occurred in two segments ( α = 0° and α = 8° ) of the characteristic curve of pitching moment. Moreover, coupling of the flow separation characteristic of the front wing and the after wing resulted in the pitching moment ′pitchup′ phenomenon. The lateral-directional static stability of the flat layout was weak. The HALE Diamond Joined-Wing configuration UAV ' s aerodynamic performance can be improved and the problems in engineering applications can be effectively alleviated by adjusting the overall layout parameters.
文摘In this study we mainly focus on the attitude control problem of a quad tilt rotor aircraft with respect to unknown external disturbance. We propose a class of control methods based on a novel logarithmic fast non singular terminal sliding surface a new fast reaching law and extended state disturbance observer. A logarithmic non singular terminal sliding surface is used owing to its convergence in finite time and significant robustness. A fast reaching law with two order characteristics of the sliding mode is designed. This reaching law can be used reduce the convergence time of traditional reaching law. In addition the extended state disturbance observer is utilized for online estimation and to compensate for system disturbance. The simulation experiment results show that the control strategy proposed in this paper outperforms the traditional non singular fast sliding mode control.
基金the National Natural Science Foundation of China(11671271)the Natural Science Foundation of Beijing Municipality(1172004).
文摘In this article,we study multivariate approximation defined over weighted anisotropic Sobolev spaces which depend on two sequences a={a j}j≥1 and b={b j}j≥1 of positive numbers.We obtain strong equivalences of the approximation numbers,and necessary and sufficient conditions on a,b to achieve various notions of tractability of the weighted anisotropic Sobolev embeddings.
基金supported by the National Natural Science Foundation of China(No.11426179)the National Natural Science Foundation of China(Nos.10871132,11271263)+4 种基金the Key Scientific Research Fund of Xihua University(No.z1312624)the Foundation of Sichuan Educational Committee(No.14ZA0112)the Preeminent Youth Fund for School of Science in Xihua Universitythe Beijing Natural Science Foundation(No.1132001)BCMIIS
文摘In this paper, we study optimal recovery （reconstruction） of functions on the sphere in the average case setting. We obtain the asymptotic orders of average sampling numbers of a Sobolev space on the sphere with a Gaussian measure in the Lq （S^d-1） metric for 1 ≤ q ≤ ∞, and show that some worst-case asymptotically optimal algorithms are also asymptotically optimal in the average case setting in the Lq （S^d-1） metric for 1 ≤ q ≤ ∞.
基金National Natural Science Foundation of China,Grant/Award Numbers:82241058,31922045,31771031Natural Science Foundation of Tianjin Province of China,Grant/Award Number:21JCZDJC00290+2 种基金State Key Laboratory of Medicinal Chemical Biology in Nankai University,Grant/Award Number:2020017State Key Laboratory of Biochemical EngineeringOpen Funding Project of State Key Laboratory of Biochemical Engineering,Grant/Award Number:2021KF-01。
文摘The early diagnosis of Parkinson’s disease(PD)provides opportunities for early intervention to slow the progression of neurological degeneration in patients,particularly as the aging population increases in our society.Among a series of pathological features of PD,mitochondria abnormalities have been identified as central event that occurs at the early stage of PD.However,the method for detecting mitochondrial abnormalities-associated early PD has not been fully developed.We herein report a specifically mitochondrial targeting probe(named TPA-BT-SCP)that is able to characterize mitochondria abnormalities for early diagnosis of PD and monitor PD neurodegenerative progress.The probe is an aggregation-induced emission(AIE)probe with a strong positive charge,a 3D distorted molecular structure,and a separated HOMO-LUMO distribution,designed with unique molecular design guidelines.Our research demonstrated that TPA-BT-SCP could emit stable and strong fluorescence,and rapidly accumulate in mitochondria due to the negative charge.After intranasal administration of 1-methy-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced PD mice,TPA-BT-SCP successfully bypassed the blood−brain barrier to light up the brain,allowing the grading of PD severity based on its high sensitivity.Taken together,this work develops a novel AIE probe that exhibits dramatically high sensitivity to mitochondrial changes and enables noninvasive diagnosis of early PD in the brain.
基金5010 Cultivation Program of Clinical Research of Sun Yatsen University (2018024)Startup Fund for scientific research of Fujian Medical University (2017XQ1205).
文摘Background and Aims:Alagille syndrome(AGS)is an autosomal dominant multisystem disorder caused by mutations in the JAG1 and NOTCH2 genes.AGS has been rarely reported in adult patients,mainly because its characteristics in adults are subtle.The study aimed to improve the understanding of adult AGS by a descriptive case series.Methods:Eight adults diagnosed with AGS at our hospital between June 2016 and June 2019 were included in the study.Clinical data,biochemical results,imaging results,liver histopathology,and genetic testing were analyzed.Results:Three female and five male patients with a median age of 24.5 years at the time of diagnosis were included in the analysis.The clinical manifestations were adult-onset(62.5%,5/8),cholestasis(50%,4/8),butterfly vertebrae(62.5%,5/8),systolic murmurs(12.5%,1/8),typical facies(12.5%,1/8),posterior embryotoxon,and renal abnormalities(0/8).Genetic sequencing showed that all patients had mutations,with four occurring in the JAG1 gene and four in the NOTCH2 gene.Six were substitution mutations,one was a deletion mutation,and one was a splicing mutation.Five had been previously reported;but the others,one JAG1 mutation and two NOTCH2 mutations were unique and are reported here for the first time.Conclusions:The clinical manifestations highlighted by the current diagnostic criteria for most adults with AGS are atypical.Those who do not meet the criteria but are highly suspicious of having AGS need further evaluation,especially genetic testing.
基金supported by Sanming Project of Medicine in Shenzhen (SZSM201512030)Shenzhen Key Medical Discipline Construction Fund (SZXK032)Shenzhen Fund for Guangdong Provincial High-level Clinical Key Specialties (No. SZGSP012)。
文摘Dear Editor,Human adenoviruses (HAd Vs) are associated with respiratory,gastrointestinal,ophthalmological,genitourinary,and neurological infections.To date,more than 100genotypes of HAd Vs have been identified.They are classified into seven species,A to G (HAd V Working Group,http://hadvwg.gmu.edu/).
基金supported by a grant from the National Key Research and Development Program of China (2020YFA0710700 to CHW)the National Natural Science Foundation of China (Grant No.82101859 to WWS)+4 种基金the Original Exploration Program of National Natural Science Foundation of China (82150102,to CHW)the Key Research and Development Program of Sichuan Province (22ZDYF3738,to CHW)the Fundamental Research Funds for the Central Universities,HUST (2021GCRC031 to CHW)the National Natural Science Foundation of China (31870165 to BZ)the Shenzhen Science and Technology Innovation Fund (JCYJ20210324115811032 to BZ).
文摘Fungal infections cause~1.5 million deaths each year worldwide,and the mortality rate of disseminated candidiasis currently exceeds that of breast cancer and malaria.The major reasons for the high mortality of candidiasis are the limited number of antifungal drugs and the emergence of drug-resistant species.Therefore,a better understanding of antifungal host defense mechanisms is crucial for the development of effective preventive and therapeutic strategies.Here,we report that DOCK2(dedicator of cytokinesis 2)promotes indispensable antifungal innate immune signaling and proinflammatory gene expression in macrophages.DOCK2-deficient macrophages exhibit decreased RAC GTPase(Rac family small GTPase)activation and ROS(reactive oxygen species)production,which in turn attenuates the killing of intracellular fungi and the activation of downstream signaling pathways.Mechanistically,after fungal stimulation,activated SYK(spleen-associated tyrosine kinase)phosphorylates DOCK2 at tyrosine 985 and 1405,which promotes the recruitment and activation of RAC GTPases and then increases ROS production and downstream signaling activation.Importantly,nanoparticle-mediated delivery of in vitro transcribed(IVT)Rac1 mRNA promotes the activity of Rac1 and helps to eliminate fungal infection in vivo.Taken together,this study not only identifies a critical role of DOCK2 in antifungal immunity via regulation of RAC GTPase activity but also provides proof of concept for the treatment of invasive fungal infections by using IVT mRNA.
文摘Importance:A cluster of influenza-associated deaths occurred among children during pandemic 2009 influenza A(H 1N1)in China,but the risk factors and causes for death have not been clarified.Objective:We describe the clinical findings regarding 2009 influenza A(H1N1)-associated pediatric deaths in China,including the risk factors for death.Methods:The definition of 2009 influenza A(H1N1)-associated pediatric death is death in a child who is younger than 14 years and has laboratory-confirmed influenza.We collected data of total 810 hospitalized patients with 2009 influenza A(H 1N 1)infection from September 2009 to February 2010 in 17 hospitals across China.The clinical characteristics,laboratory abnormalities,and treatment course were retrospectively studied.Results:Of the 810 patients hospitalized with 2009 influenza A(H1N1)infection,19(2.3%)died.Ten patients died from severe pneumonia and acute respiratory distress syndrome;eight died from encephalopathy/encephalitis;one died from secondary fungal meningitis.Patients who died were more likely than patients who survived to have neutrophilia,lymphopenia,elevated C-reactive protein,and elevations of lactate dehydrogenase,creatine kinase,creatine kinase-MB,aspartate aminotransferase and alanine aminotransferase.There were no significant differences in the median age,median time from onset of illness to admission,underlying chronic disease,and initiation of antiviral therapy within 48 hours of illness onset,between patients who died and those who survived.Interpretation:The risk factors for pediatric death associated with 2009 influenza A(H 1N 1)infection are different from those of seasonal influenza.The most common causes of death are viral pneumonia,acute respiratory distress syndrome,and encephalopathy/encephalitis.
基金supported by grants from the National Major Science and Technology Project for the Prevention and Treatment of AIDS and Viral Hepatitis[no.2018ZX10302204-002–002 to L.P.]the Five-Year Plan of the Third Affiliated Hospital of Sun Yat-sen University[no.K00006 to L.P.]+1 种基金the Clinical Research Program of the Third Affiliated Hospital of Sun Yat-Sen University[no.QHJH201808 to W.X.]the Guangzhou Science and Technology Project[no.202102080064 to W.X.].
文摘Background The prevalence of zinc deficiency is high in patients with chronic liver disease,but few studies have hitherto explored the relationship between the serum zinc level and hepatitis B virus(HBV)-related acute-on-chronic liver failure(ACLF).This study aimed to assess the association between zinc deficiency and infectious complications,and model for end-stage liver disease(MELD)score in patients with HBV-related ACLF.Methods Patients with HBV-related ACLF from the Department of Infectious Diseases of the Third Affiliated Hospital of Sun Yat-sen University(Guangzhou,China)between January 2019 and December 2019 were retrospectively analysed in this study.Their demographic,clinical,and laboratory data were retrieved from the hospital information system and analysed.The Student’s t-test was used for normally distributed continuous variables between two groups and the Chi-square test was used for categorical data.Univariate and multivariate logistic regression analyses were applied to identify independent parameters.Results A total of 284 patients were included in this study,including 205 liver cirrhosis and 79 non-cirrhosis patients.The proportion of patients with zinc deficiency was the highest(84.5%),followed by subclinical zinc deficiency(14.1%)and normal zinc level(1.4%).Patients in the zinc deficiency group had a higher MELD score than the subclinical zinc deficiency or normal zinc group(P=0.021).Age,total bilirubin,and serum zinc level were independent factors for infection(P_(s)<0.05).The serum zinc level in patients without complications at admission was significantly higher than that in patients with complications(P=0.004).Moreover,the serum zinc level in patients with prothrombin time activity(PTA)of<20%was significantly lower than that in patients with 20%≤PTA<30%(P=0.007)and that in patients with 30%≤PTA<40%(P<0.001).Conclusions Zinc deficiency is common in patients with HBV-related ACLF.Zinc deficiency is closely associated with infectious complications and MELD score in patients with HBV-related ACLF.
