Background: Blocking the Rho A/ROCK Ⅱ/MLC 2(Ras homolog gene family member A/Rho kinase Ⅱ/myosin light chain 2) signaling pathway can initiate neuroprotective mechanisms against neurological diseases such as stroke,...Background: Blocking the Rho A/ROCK Ⅱ/MLC 2(Ras homolog gene family member A/Rho kinase Ⅱ/myosin light chain 2) signaling pathway can initiate neuroprotective mechanisms against neurological diseases such as stroke, cerebral ischemia, and subarachnoid hemorrhage. Nevertheless, it is not clear whether and how disrupting the Rho A/ROCK Ⅱ/MLC 2 signaling pathway changes the pathogenic processes of the blood–brain barrier(BBB) after intracerebral hemorrhage(ICH). The present investigation included the injection of rat caudal vein blood into the basal ganglia area to replicate the pathophysiological conditions caused by ICH. Methods: Scalp acupuncture(SA) therapy was performed on rats with ICH at the acupuncture point “Baihui”-penetrating “Qubin,” and the ROCK selective inhibitor fasudil was used as a positive control to evaluate the inhibitory effect of acupuncture on the Rho A/ROCK Ⅱ/MLC 2 signaling pathway. Post-assessments included neurological deficits, brain edema, Evans blue extravasation, Western blot, quantitative polymerase chain reaction, and transmission electron microscope imaging. Results: We found that ROCK Ⅱ acts as a promoter of the Rho A/ROCK Ⅱ/MLC 2 signaling pathway, and its expression increased at 6 h after ICH, peaked at 3 days, and then decreased at 7 days after ICH, but was still higher than the preintervention level. According to some experimental results, although 3 days is the peak, 7 days is the best time point for acupuncture treatment. Starting from 6 h after ICH, the neurovascular structure and endothelial cell morphology around the hematoma began to change. Based on the changes in the promoter ROCK Ⅱ, a 7-day time point was selected as the breakthrough point for treating ICH model rats in the main experiment. The results of this experiment showed that both SA at “Baihui”-penetrating “Qubin” and treatment with fasudil could improve the expression of endothelial-related proteins by inhibiting the Rho A/ROCK Ⅱ/MLC 2 signaling pathway and reduce neurological dysfunction, brain edema, and BBB permeability in rats. Conclusion: This study found that these experimental data indicated that SA at “Baihui”-penetrating “Qubin” could preserve BBB integrity and neurological function recovery after ICH by inhibiting Rho A/ROCK Ⅱ/MLC 2 signaling pathway activation and by regulating endothelial cell–related proteins.展开更多
Climate change has affected and will continue to affect the spatial distribution patterns of marine organisms.To understand the impact of climate change on the distribution patterns and species richness of the Sciaeni...Climate change has affected and will continue to affect the spatial distribution patterns of marine organisms.To understand the impact of climate change on the distribution patterns and species richness of the Sciaenidae in China’s coastal waters,the maximum entropy model was used to combine six environmental factors and predict the potential distribution of 12 major species of Sciaenidae by 2050s under Representative Concentration Pathways(RCPs)2.6 and 8.5.The results showed that the average area under the receiver operating characteristic curve of the model was 0.917,indicating that the model predictions were accurate and reliable.The main driving factors affecting the potential distribution of these fishes were dissolved oxygen,salinity,and sea surface temperature(SST).There was an overall northward shift in the potential habitat areas of these fishes under the two climate scenarios.The total potential habitat areas of Larimichthys polyactis,Pennahia argentata,and Pennahia pawak decreased under both climate scenarios,while the total habitat area of Johnius belengerii,Pennahia anea,Miichthys miiuy,Collichthys lucidus,and Collichthys niveatus increased,suggesting that these might be loser and winner species,respectively.The expansion rate,contraction rate,degree of centroid change,and species richness in the potential habitats were generally more significant under RCP8.5 than RCP2.6.The mean shift rates of the potential distribution were 41.50 km/(10 a) and 29.20 km/(10 a) under RCP8.5 and RCP2.6,respectively.The changes in Sciaenidae species richness under climate change were bounded by the Changjiang River Estuary waters,with obvious north-south differences.Some waters with increased species richness may become refuges for Sciaenidae fishes under climate change.The richness and habitat area change rate of some aquatic germplasm resources will decrease,meanings that these reserves are more sensitive to climate change,and more attention should be paid to the potential challenges and opportunities for fishery managers.This study may provide a scientific basis for the management and conservation of Sciaenidae in China under climate change.展开更多
Objective:To explore the diagnostic value of abnormal prothrombinⅡ(PIVKA-Ⅱ)and alpha-fetoprotein(AFP)in primary hepatocellular carcinoma(HCC).Methods:From 20180.01 to 2020.01,there were 158 patients with primary liv...Objective:To explore the diagnostic value of abnormal prothrombinⅡ(PIVKA-Ⅱ)and alpha-fetoprotein(AFP)in primary hepatocellular carcinoma(HCC).Methods:From 20180.01 to 2020.01,there were 158 patients with primary liver cancer caused by chronic hepatitis B(male 116,women 42)and 62 patients with chronic hepatitis B(male 34,female 28).The levels of serum PIVKA-Ⅱand AFP were measured,and the results were statistically analyzed.Results:The value of PIVKA-Ⅱin liver cancer group was distinctly higher than that in chronic viral hepatitis B group,the difference is statistically significant(P<0.05).So does the value of AFP.Draw the subject working characteristic curve(ROC curve),the area under the curve of AFP and PIVKA-Ⅱis 0.799 and 0.836,and that of the combination of AFP and PIVKA-Ⅱis 0.854,the sensitivity is 57.6%,68.4%,72.2%,respectively,the specificity is93.5%,98.4%,96.8%,respectively.After operation or interventional therapy,the value of PIVKA-Ⅱin liver cancer group was clearly lower than that before treatment,and the difference was statistically significant.Conclusion:In the diagnostic value of primary liver cancer,PIVKA-Ⅱcombined with AFP is higher than PIVKA-Ⅱ,while AFP has the lowest benefit.We also find that PIVKA-Ⅱhas higher disease monitoring value than AFP.展开更多
Introduction Cerebral venous sinus thrombosis(CVST)is a special type of cerebrovascular disease characterized by obstruction of cerebral venous reflux,disturbance of cerebrospinal fluid absorption,and intracranial hyp...Introduction Cerebral venous sinus thrombosis(CVST)is a special type of cerebrovascular disease characterized by obstruction of cerebral venous reflux,disturbance of cerebrospinal fluid absorption,and intracranial hypertension.It has many causes,and accounts for approximately 0.5%–1%of all strokes.^(1) The morbidity of CVST is approximately 1.3/100.展开更多
Based on the D-H notation, kinematics model and inverse kinematics model of 6R industrial robots are established. Using graphical method, the boundary curve equations of the 6R industrial robot workspace are obtained....Based on the D-H notation, kinematics model and inverse kinematics model of 6R industrial robots are established. Using graphical method, the boundary curve equations of the 6R industrial robot workspace are obtained. Based on the prescribed workspace, the D-H parameter optimization method of 6R industrial robots is proposed. Using the genetic algorithm to determine the structural dimensions of a 6R robot, we make sure that its workspace can exactly contain the prescribed workspace. This method can be used to reduce the overall size of the robot, save materials and reduce the power consumption of the robot during its work time.展开更多
To the Editor:Lung cancer,one of the most common types of tumor,is also the leading cause of cancer death,accounting for an estimated 1.8 million deaths worldwide.Early recognition of lung cancer is critical.It has be...To the Editor:Lung cancer,one of the most common types of tumor,is also the leading cause of cancer death,accounting for an estimated 1.8 million deaths worldwide.Early recognition of lung cancer is critical.It has been established that nitric oxide and its byproducts play a role in pathophysiological processes of lung cancer,such as tumor immunity,inflammation,and lung tumor progression.[1]Exhaled nitric oxide(eNO)concentrations can be measured by non-invasive devices.The alveolar concentration of nitric oxide(CaNO)has been proposed as a marker of distal airway inflammation,but its value in nonsmall cell lung cancer(NSCLC)is unknown.展开更多
To the Editor:Human immunodeficiency virus(HIV)epidemic poses a significant challenge to global public health.As of 2022,approximately 39.0 million people worldwide were living with HIV.[1]With the ongoing evolution o...To the Editor:Human immunodeficiency virus(HIV)epidemic poses a significant challenge to global public health.As of 2022,approximately 39.0 million people worldwide were living with HIV.[1]With the ongoing evolution of combined antiretroviral therapy(cART),HIV infection has transformed into a manageable chronic disease requiring long-term treatment.Among the various classes of antiretroviral(ARV)drugs,integrase strand transfer inhibitor(INSTI)-based regimens,known for potency and tolerability,have emerged as the predominant treatment modality worldwide.The nextgeneration of INSTI,bictegravir(BIC),received the Food and Drug Administration(FDA)approval in 2018 as a single-tablet regimen(STR)containing BIC(50 mg)/emtricitabine(FTC,200 mg)/tenofovir alafenamide(TAF,25 mg)for once daily.It has been endorsed as the preferred choice for treatment-naive patients by major guidelines,including the 2021 edition of the China Acquired Immune Deficiency Syndrome(AIDS)Diagnosis and Treatment Guidelines.[2]In China,people living with HIV(PLWH)are provided with flexible cART options,including the National Reimbursement Drug List(NRDL),self-pay drugs,and free drugs.Since being included in NRDL in 2021,BIC/FTC/TAF have gained popularity among an increasing number of patients.展开更多
In-situ ceramics particle reinforced aluminum matrix composites are favored in the aerospace industry due to excellent properties.However,the hard ceramic particles as the reinforcement phase bring challenges to machi...In-situ ceramics particle reinforced aluminum matrix composites are favored in the aerospace industry due to excellent properties.However,the hard ceramic particles as the reinforcement phase bring challenges to machining.To study the effect of in-situ TiB_(2)particles on machinability and surface integrity of TiB_(2)/2024 composite and TiB_(2)/7075 composite,milling experiments were performed,and compared with conventional 2024 and 7075 aluminum alloys.In-situ TiB_(2)particles clustered at the grain boundaries and dispersed inside the matrix alloy grains hinder the dislocation movement of the matrix alloy.Therefore,the milling force and temperature of the composites are higher than those of the aluminum alloys due to the increase of the strength and the decrease of the plasticity.In the milling of composites,abrasive wear is the main wear form of carbide tools,due to the scratching of hard nano-TiB_(2)particles.The composites containing in-situ TiB_(2)particles have machining defects such as smearing,micro-scratches,micro-pits and tail on the machined surface.However,in-situ TiB_(2)particles impede the plastic deformation of the composites,which greatly reduces cutting edge marks on the machined surface.Therefore,under the same milling parameters,the surface roughness of TiB_(2)/2024 composite and TiB_(2)/7075 composite is much less than that of2024 and 7075 aluminum alloy respectively.Under the milling conditions of this experiment,the machined subsurface has no metamorphic layer,and the microhardness of the machined surface is almost the same as that of the material.Besides,compared with 2024 and 7075 aluminum alloy,machined surfaces of TiB_(2)/2024 composite and TiB_(2)/7075 composite both show tensile residual stress or low magnitude of compressive residual stress.展开更多
Gastric cancer imposes a considerable health burden worldwide, and its mortality ranks as the second highest for all types of cancers. The limited knowledge of the molecular mechanisms underlying gastric cancer tumori...Gastric cancer imposes a considerable health burden worldwide, and its mortality ranks as the second highest for all types of cancers. The limited knowledge of the molecular mechanisms underlying gastric cancer tumorigenesis hinders the development of therapeutic strategies. However, ongoing collaborative sequencing efforts facilitate molecular classification and unveil the genomic landscape of gastric cancer. Several new drivers and tumorigenic pathways in gastric cancer, including chromatin remodeling genes, Rho A-related pathways, TP53 dysregulation, activation of receptor tyrosine kinases, stem cell pathways and abnormal DNA methylation, have been revealed. These newly identified genomic alterations await translation into clinical diagnosis and targeted therapies. Considering that loss-of-function mutations are intractable, synthetic lethality could be employed when discussing feasible therapeutic strategies. Although many challenges remain to be tackled, we are optimistic regarding improvements in the prognosis and treatment of gastric cancer in the near future.展开更多
The role of B7-DC in T-cell responses remains controversial because both coinhibitory and costimulatory functions have been reported in various experimental systems in vitro and in vivo.In addition to interacting with...The role of B7-DC in T-cell responses remains controversial because both coinhibitory and costimulatory functions have been reported in various experimental systems in vitro and in vivo.In addition to interacting with the coinhibitory receptor PD-1,B7-DC has also been shown to bind repulsive guidance molecule b(RGMb).The functional consequences of the B7-DC/RGMb interaction,however,remain unclear.More than a decade ago,we reported that replacement of a murine B7-DC mutant lysine with serine(K113S)at positive 113 resulted in a loss of binding capacity to PD-1.Nevertheless,K113S remained costimulatory for T cells in vitro,implicating a dual functionality for B7-DC in T-cell responses.Here we show that recombinant K113S protein interacts with RGMb with a similar affinity to wild-type B7-DC.More importantly,K113S costimulates CD4^(+)T-cell responses via RGMb and promotes Th1 polarization.RGMb is expressed on the surface of naive mouse T cells,macrophages,neutrophils and dendritic cells.Finally,K113S/RGMb costimulation suppresses Th2-mediated asthma and ameliorates small airway inflammation and lung pathology in an experimental mouse model.Our findings indicate that RGMb is a costimulatory receptor for B7-DC.These findings from the K113S variant provide not only a possible explanation for the B7-DC-triggered contradictory effects on T-cell responses,but also a novel approach to investigate the B7-DC/PD-1/RGMb axis.Recombinant K113S or its derivatives could potentially be developed as an agonist for RGMb to costimulate the Th1 response without triggering PD-1-mediated T-cell inhibition.展开更多
COVID-19 patients can recover with a median SARS-CoV-2 clearance of 20 days post initial symptoms(PIS).However,we observed some COVID-19 patients with existing SARS-CoV-2 for more than 50 days PIS.This study aimed to ...COVID-19 patients can recover with a median SARS-CoV-2 clearance of 20 days post initial symptoms(PIS).However,we observed some COVID-19 patients with existing SARS-CoV-2 for more than 50 days PIS.This study aimed to investigate the cause of viral clearance delay and the infectivity in these patients.Demographic data and clinical characteristics of 22 long-term COVID-19 patients were collected.The median age of the studied cohort was59.83±12.94 years.All patients were clinically cured after long-term SARS-CoV-2 infection ranging from 53 to112 days PIS.Peripheral lymphocytes counts were normal.The ratios of interferon gamma(IFN-c)-secreting cells to total CD4^(+)and CD8^(+)cells were normal as 24.68%±9.60%and 66.41%±14.87%respectively.However,the number of IFNc-secreting NK cells diminished(58.03%±11.78%).All patients presented detectable IgG,which positively correlated with mild neutralizing activity(Mean value neutralisation antibodies titers=157.2,P=0.05).No SARS-CoV-2 virus was isolated in Vero E6 cells inoculated with nasopharyngeal swab samples from all patients 50 days PIS,and the cytopathic effect was lacking.But one sample was positive for SARS-CoV-2 nucleic acid test in cell supernatants after two passages.Genome sequencing revealed that only three synonymous variants were identified in spike protein coding regions.In conclusion,decreased IFN-c production by NK cells and low neutralizing antibodies might favor SARS-CoV-2 long-term existence.Further,low viral load and weak viral pathogenicity were observed in COVID-19 patients with long-term SARSCoV-2 infection.展开更多
The specification of theαβ/γδlineage and the maturation of medullary thymic epithelial cells(mTECs)coordinate central tolerance to self-antigens.However,the mechanisms underlying this biological process remain poo...The specification of theαβ/γδlineage and the maturation of medullary thymic epithelial cells(mTECs)coordinate central tolerance to self-antigens.However,the mechanisms underlying this biological process remain poorly clarified.Here,we report that dual-stage loss of TOX in thymocytes hierarchically impaired mTEC maturation,promoted thymic IL-17A-producingγδT-cell(Tγδ17)lineage commitment,and led to the development of fatal autoimmune hepatitis(AIH)via different mechanisms.Transfer ofγδT cells from TOX-deficient mice reproduced AIH.TOX interacted with and stabilized the TCF1 protein to maintain the balance ofγδT-cell development in thymic progenitors,and overexpression of TCF1 normalizedαβ/γδlineage specification and activation.In addition,TOX expression was downregulated inγδT cells from AIH patients and was inversely correlated with the AIH diagnostic score.Our findings suggest multifaceted roles of TOX in autoimmune control involving mTEC and Tγδ17 development and provide a potential diagnostic marker for AIH.展开更多
Tests under mechanical strain control were performed to investigate the TMF behavior of Z2CND18.12N within the temperature range between 150–550 ？ C. Different strain amplitudes and phase-angles were applied. Total ...Tests under mechanical strain control were performed to investigate the TMF behavior of Z2CND18.12N within the temperature range between 150–550 ？ C. Different strain amplitudes and phase-angles were applied. Total strain controlled low cycle fatigue test was also performed at the peak temperature of TMF cycling. The results show that the cyclic stress response of the material displayed an initial hardening regime followed by a saturation period and then cyclic softening till failure. The TMF cycling leads to the development of significant amounts of mean stress. Some life prediction models were employed to predict the TMF life of Z2CND18.12N, and the results indicate that the energy-based models provide good prediction on the thermal-mechanical fatigue behaviors of this material. An optical microscopic observation shows that the surface crack initiations and crack propagations are typically transgranular mode.展开更多
The importance of tunable subwavelength optical devices in modern electromagnetic and photonic systems is indisputable.Herein,a lithography-free,wide-angle,and reconfigurable subwavelength optical device with high tun...The importance of tunable subwavelength optical devices in modern electromagnetic and photonic systems is indisputable.Herein,a lithography-free,wide-angle,and reconfigurable subwavelength optical device with high tunability operating in the near-infrared regions is proposed and experimentally demonstrated,based on a reversible nanochemistry approach.The reconfigurable subwavelength optical device basically comprises an ultrathin copper oxide(CuO)thin film on an optical thick gold substrate by utilizing the reversible chemical conversion of CuO to sulfides upon exposure to hydrogen sulfide gas.Proof-of-concept experimental results show that the maximal modulation depth of reflectance can be as high as 90%at the wavelength of 1.79μm with the initial thickness of CuO taken as 150 nm.Partially reflected wave calculations combined with the transfer matrix method are employed to analytically investigate the optical properties of the structure,which show good agreement with experimental results.We believe that the proposed versatile approaches can be implemented for dynamic control management,allowing applications in tunable photonics,active displays,optical encryption,and gas sensing.展开更多
Developing an efficientmethod to improve the photocatalytic efficiency of graphitic carbon nitride(g-C3 N4)is of great significance for solar H2 production.Electronic structure modulation has been considered one of th...Developing an efficientmethod to improve the photocatalytic efficiency of graphitic carbon nitride(g-C3 N4)is of great significance for solar H2 production.Electronic structure modulation has been considered one of the most crucial strategies to improving the photocatalytic efficiency of g-C_(3)N_(4),but how to efficiently modulate its electronic structure remains a huge challenge.Herein,we,for the first time,report a facile and highly-efficient approach to modulating the electronic structure of g-C_(3)N_(4)through single Ag atom implantation with a Ag_(1)-N_(3)coordination configuration into the g-C_(3)N_(4)framework.展开更多
基金supported by the National Natural Science Foundation of China(numbers:81774416 and 81473764)。
文摘Background: Blocking the Rho A/ROCK Ⅱ/MLC 2(Ras homolog gene family member A/Rho kinase Ⅱ/myosin light chain 2) signaling pathway can initiate neuroprotective mechanisms against neurological diseases such as stroke, cerebral ischemia, and subarachnoid hemorrhage. Nevertheless, it is not clear whether and how disrupting the Rho A/ROCK Ⅱ/MLC 2 signaling pathway changes the pathogenic processes of the blood–brain barrier(BBB) after intracerebral hemorrhage(ICH). The present investigation included the injection of rat caudal vein blood into the basal ganglia area to replicate the pathophysiological conditions caused by ICH. Methods: Scalp acupuncture(SA) therapy was performed on rats with ICH at the acupuncture point “Baihui”-penetrating “Qubin,” and the ROCK selective inhibitor fasudil was used as a positive control to evaluate the inhibitory effect of acupuncture on the Rho A/ROCK Ⅱ/MLC 2 signaling pathway. Post-assessments included neurological deficits, brain edema, Evans blue extravasation, Western blot, quantitative polymerase chain reaction, and transmission electron microscope imaging. Results: We found that ROCK Ⅱ acts as a promoter of the Rho A/ROCK Ⅱ/MLC 2 signaling pathway, and its expression increased at 6 h after ICH, peaked at 3 days, and then decreased at 7 days after ICH, but was still higher than the preintervention level. According to some experimental results, although 3 days is the peak, 7 days is the best time point for acupuncture treatment. Starting from 6 h after ICH, the neurovascular structure and endothelial cell morphology around the hematoma began to change. Based on the changes in the promoter ROCK Ⅱ, a 7-day time point was selected as the breakthrough point for treating ICH model rats in the main experiment. The results of this experiment showed that both SA at “Baihui”-penetrating “Qubin” and treatment with fasudil could improve the expression of endothelial-related proteins by inhibiting the Rho A/ROCK Ⅱ/MLC 2 signaling pathway and reduce neurological dysfunction, brain edema, and BBB permeability in rats. Conclusion: This study found that these experimental data indicated that SA at “Baihui”-penetrating “Qubin” could preserve BBB integrity and neurological function recovery after ICH by inhibiting Rho A/ROCK Ⅱ/MLC 2 signaling pathway activation and by regulating endothelial cell–related proteins.
基金The Xiamen Youth Innovation Fund under contract No.3502Z20206096the National Key Research and Development Program of China under contract No.2019YFE0124700+1 种基金the National Natural Science Foundation of China under contract Nos 42176153,41906127,and 42076163the National Program on Global Change and Air-Sea Interaction under contract No.HR01-200701.
文摘Climate change has affected and will continue to affect the spatial distribution patterns of marine organisms.To understand the impact of climate change on the distribution patterns and species richness of the Sciaenidae in China’s coastal waters,the maximum entropy model was used to combine six environmental factors and predict the potential distribution of 12 major species of Sciaenidae by 2050s under Representative Concentration Pathways(RCPs)2.6 and 8.5.The results showed that the average area under the receiver operating characteristic curve of the model was 0.917,indicating that the model predictions were accurate and reliable.The main driving factors affecting the potential distribution of these fishes were dissolved oxygen,salinity,and sea surface temperature(SST).There was an overall northward shift in the potential habitat areas of these fishes under the two climate scenarios.The total potential habitat areas of Larimichthys polyactis,Pennahia argentata,and Pennahia pawak decreased under both climate scenarios,while the total habitat area of Johnius belengerii,Pennahia anea,Miichthys miiuy,Collichthys lucidus,and Collichthys niveatus increased,suggesting that these might be loser and winner species,respectively.The expansion rate,contraction rate,degree of centroid change,and species richness in the potential habitats were generally more significant under RCP8.5 than RCP2.6.The mean shift rates of the potential distribution were 41.50 km/(10 a) and 29.20 km/(10 a) under RCP8.5 and RCP2.6,respectively.The changes in Sciaenidae species richness under climate change were bounded by the Changjiang River Estuary waters,with obvious north-south differences.Some waters with increased species richness may become refuges for Sciaenidae fishes under climate change.The richness and habitat area change rate of some aquatic germplasm resources will decrease,meanings that these reserves are more sensitive to climate change,and more attention should be paid to the potential challenges and opportunities for fishery managers.This study may provide a scientific basis for the management and conservation of Sciaenidae in China under climate change.
基金Zhejiang Medical and Health Science and Technology Plan Project(2019KY663)Wenzhou Science and Technology Plan Project of Zhejiang Province(Y20180182)Science and Technology Plan Project of Ruian City,Zhejiang Province(Y2014017)。
文摘Objective:To explore the diagnostic value of abnormal prothrombinⅡ(PIVKA-Ⅱ)and alpha-fetoprotein(AFP)in primary hepatocellular carcinoma(HCC).Methods:From 20180.01 to 2020.01,there were 158 patients with primary liver cancer caused by chronic hepatitis B(male 116,women 42)and 62 patients with chronic hepatitis B(male 34,female 28).The levels of serum PIVKA-Ⅱand AFP were measured,and the results were statistically analyzed.Results:The value of PIVKA-Ⅱin liver cancer group was distinctly higher than that in chronic viral hepatitis B group,the difference is statistically significant(P<0.05).So does the value of AFP.Draw the subject working characteristic curve(ROC curve),the area under the curve of AFP and PIVKA-Ⅱis 0.799 and 0.836,and that of the combination of AFP and PIVKA-Ⅱis 0.854,the sensitivity is 57.6%,68.4%,72.2%,respectively,the specificity is93.5%,98.4%,96.8%,respectively.After operation or interventional therapy,the value of PIVKA-Ⅱin liver cancer group was clearly lower than that before treatment,and the difference was statistically significant.Conclusion:In the diagnostic value of primary liver cancer,PIVKA-Ⅱcombined with AFP is higher than PIVKA-Ⅱ,while AFP has the lowest benefit.We also find that PIVKA-Ⅱhas higher disease monitoring value than AFP.
基金Zhejiang Medical and Health Science and Technology Plan Project(2019KY663)Wenzhou Science and Technology Plan Project of Zhejiang Province(Y20180182)Science and Technology Plan Project of Ruian City,Zhejiang Province(Y2014017)。
文摘Introduction Cerebral venous sinus thrombosis(CVST)is a special type of cerebrovascular disease characterized by obstruction of cerebral venous reflux,disturbance of cerebrospinal fluid absorption,and intracranial hypertension.It has many causes,and accounts for approximately 0.5%–1%of all strokes.^(1) The morbidity of CVST is approximately 1.3/100.
文摘Based on the D-H notation, kinematics model and inverse kinematics model of 6R industrial robots are established. Using graphical method, the boundary curve equations of the 6R industrial robot workspace are obtained. Based on the prescribed workspace, the D-H parameter optimization method of 6R industrial robots is proposed. Using the genetic algorithm to determine the structural dimensions of a 6R robot, we make sure that its workspace can exactly contain the prescribed workspace. This method can be used to reduce the overall size of the robot, save materials and reduce the power consumption of the robot during its work time.
基金National Natural Science Foundation of China(Nos.82170032 and 81970032)
文摘To the Editor:Lung cancer,one of the most common types of tumor,is also the leading cause of cancer death,accounting for an estimated 1.8 million deaths worldwide.Early recognition of lung cancer is critical.It has been established that nitric oxide and its byproducts play a role in pathophysiological processes of lung cancer,such as tumor immunity,inflammation,and lung tumor progression.[1]Exhaled nitric oxide(eNO)concentrations can be measured by non-invasive devices.The alveolar concentration of nitric oxide(CaNO)has been proposed as a marker of distal airway inflammation,but its value in nonsmall cell lung cancer(NSCLC)is unknown.
基金supported by the Research project of Hunan Provincial Department of Science and Technology(No.2020SK21361)
文摘To the Editor:Human immunodeficiency virus(HIV)epidemic poses a significant challenge to global public health.As of 2022,approximately 39.0 million people worldwide were living with HIV.[1]With the ongoing evolution of combined antiretroviral therapy(cART),HIV infection has transformed into a manageable chronic disease requiring long-term treatment.Among the various classes of antiretroviral(ARV)drugs,integrase strand transfer inhibitor(INSTI)-based regimens,known for potency and tolerability,have emerged as the predominant treatment modality worldwide.The nextgeneration of INSTI,bictegravir(BIC),received the Food and Drug Administration(FDA)approval in 2018 as a single-tablet regimen(STR)containing BIC(50 mg)/emtricitabine(FTC,200 mg)/tenofovir alafenamide(TAF,25 mg)for once daily.It has been endorsed as the preferred choice for treatment-naive patients by major guidelines,including the 2021 edition of the China Acquired Immune Deficiency Syndrome(AIDS)Diagnosis and Treatment Guidelines.[2]In China,people living with HIV(PLWH)are provided with flexible cART options,including the National Reimbursement Drug List(NRDL),self-pay drugs,and free drugs.Since being included in NRDL in 2021,BIC/FTC/TAF have gained popularity among an increasing number of patients.
基金the National Natural Science Foundation of China(No.51875356)。
文摘In-situ ceramics particle reinforced aluminum matrix composites are favored in the aerospace industry due to excellent properties.However,the hard ceramic particles as the reinforcement phase bring challenges to machining.To study the effect of in-situ TiB_(2)particles on machinability and surface integrity of TiB_(2)/2024 composite and TiB_(2)/7075 composite,milling experiments were performed,and compared with conventional 2024 and 7075 aluminum alloys.In-situ TiB_(2)particles clustered at the grain boundaries and dispersed inside the matrix alloy grains hinder the dislocation movement of the matrix alloy.Therefore,the milling force and temperature of the composites are higher than those of the aluminum alloys due to the increase of the strength and the decrease of the plasticity.In the milling of composites,abrasive wear is the main wear form of carbide tools,due to the scratching of hard nano-TiB_(2)particles.The composites containing in-situ TiB_(2)particles have machining defects such as smearing,micro-scratches,micro-pits and tail on the machined surface.However,in-situ TiB_(2)particles impede the plastic deformation of the composites,which greatly reduces cutting edge marks on the machined surface.Therefore,under the same milling parameters,the surface roughness of TiB_(2)/2024 composite and TiB_(2)/7075 composite is much less than that of2024 and 7075 aluminum alloy respectively.Under the milling conditions of this experiment,the machined subsurface has no metamorphic layer,and the microhardness of the machined surface is almost the same as that of the material.Besides,compared with 2024 and 7075 aluminum alloy,machined surfaces of TiB_(2)/2024 composite and TiB_(2)/7075 composite both show tensile residual stress or low magnitude of compressive residual stress.
基金supported by the Science and Technology Commission of Shanghai Municipality (16ZR1410400, 14DZ2270100)the State Scholarship Council (201506145040)
文摘Gastric cancer imposes a considerable health burden worldwide, and its mortality ranks as the second highest for all types of cancers. The limited knowledge of the molecular mechanisms underlying gastric cancer tumorigenesis hinders the development of therapeutic strategies. However, ongoing collaborative sequencing efforts facilitate molecular classification and unveil the genomic landscape of gastric cancer. Several new drivers and tumorigenic pathways in gastric cancer, including chromatin remodeling genes, Rho A-related pathways, TP53 dysregulation, activation of receptor tyrosine kinases, stem cell pathways and abnormal DNA methylation, have been revealed. These newly identified genomic alterations await translation into clinical diagnosis and targeted therapies. Considering that loss-of-function mutations are intractable, synthetic lethality could be employed when discussing feasible therapeutic strategies. Although many challenges remain to be tackled, we are optimistic regarding improvements in the prognosis and treatment of gastric cancer in the near future.
基金supported by grants from Guangdong Province Innovative Research Program Project(No.2011Y035)863 Project grants to Sun Yat-sen University and the United Technologies Corporation endowed chair from Yale University.
文摘The role of B7-DC in T-cell responses remains controversial because both coinhibitory and costimulatory functions have been reported in various experimental systems in vitro and in vivo.In addition to interacting with the coinhibitory receptor PD-1,B7-DC has also been shown to bind repulsive guidance molecule b(RGMb).The functional consequences of the B7-DC/RGMb interaction,however,remain unclear.More than a decade ago,we reported that replacement of a murine B7-DC mutant lysine with serine(K113S)at positive 113 resulted in a loss of binding capacity to PD-1.Nevertheless,K113S remained costimulatory for T cells in vitro,implicating a dual functionality for B7-DC in T-cell responses.Here we show that recombinant K113S protein interacts with RGMb with a similar affinity to wild-type B7-DC.More importantly,K113S costimulates CD4^(+)T-cell responses via RGMb and promotes Th1 polarization.RGMb is expressed on the surface of naive mouse T cells,macrophages,neutrophils and dendritic cells.Finally,K113S/RGMb costimulation suppresses Th2-mediated asthma and ameliorates small airway inflammation and lung pathology in an experimental mouse model.Our findings indicate that RGMb is a costimulatory receptor for B7-DC.These findings from the K113S variant provide not only a possible explanation for the B7-DC-triggered contradictory effects on T-cell responses,but also a novel approach to investigate the B7-DC/PD-1/RGMb axis.Recombinant K113S or its derivatives could potentially be developed as an agonist for RGMb to costimulate the Th1 response without triggering PD-1-mediated T-cell inhibition.
基金support by National Natural Science Foundation of China under Grant(81800095)Key Scientific and Technological Project of Hubei province(2020FCA004)。
文摘COVID-19 patients can recover with a median SARS-CoV-2 clearance of 20 days post initial symptoms(PIS).However,we observed some COVID-19 patients with existing SARS-CoV-2 for more than 50 days PIS.This study aimed to investigate the cause of viral clearance delay and the infectivity in these patients.Demographic data and clinical characteristics of 22 long-term COVID-19 patients were collected.The median age of the studied cohort was59.83±12.94 years.All patients were clinically cured after long-term SARS-CoV-2 infection ranging from 53 to112 days PIS.Peripheral lymphocytes counts were normal.The ratios of interferon gamma(IFN-c)-secreting cells to total CD4^(+)and CD8^(+)cells were normal as 24.68%±9.60%and 66.41%±14.87%respectively.However,the number of IFNc-secreting NK cells diminished(58.03%±11.78%).All patients presented detectable IgG,which positively correlated with mild neutralizing activity(Mean value neutralisation antibodies titers=157.2,P=0.05).No SARS-CoV-2 virus was isolated in Vero E6 cells inoculated with nasopharyngeal swab samples from all patients 50 days PIS,and the cytopathic effect was lacking.But one sample was positive for SARS-CoV-2 nucleic acid test in cell supernatants after two passages.Genome sequencing revealed that only three synonymous variants were identified in spike protein coding regions.In conclusion,decreased IFN-c production by NK cells and low neutralizing antibodies might favor SARS-CoV-2 long-term existence.Further,low viral load and weak viral pathogenicity were observed in COVID-19 patients with long-term SARSCoV-2 infection.
基金This work was supported by grants from the State Key Program of the National Natural Science Foundation(81930086 and 82120108012 to BS,82073157 and 81600487 to WT)the Science and Technology Project of Jiangsu Province(BE2018603 to BS)the Postgraduate Innovative Research Program of Jiangsu Province(KYCX20_0047 to QH).
文摘The specification of theαβ/γδlineage and the maturation of medullary thymic epithelial cells(mTECs)coordinate central tolerance to self-antigens.However,the mechanisms underlying this biological process remain poorly clarified.Here,we report that dual-stage loss of TOX in thymocytes hierarchically impaired mTEC maturation,promoted thymic IL-17A-producingγδT-cell(Tγδ17)lineage commitment,and led to the development of fatal autoimmune hepatitis(AIH)via different mechanisms.Transfer ofγδT cells from TOX-deficient mice reproduced AIH.TOX interacted with and stabilized the TCF1 protein to maintain the balance ofγδT-cell development in thymic progenitors,and overexpression of TCF1 normalizedαβ/γδlineage specification and activation.In addition,TOX expression was downregulated inγδT cells from AIH patients and was inversely correlated with the AIH diagnostic score.Our findings suggest multifaceted roles of TOX in autoimmune control involving mTEC and Tγδ17 development and provide a potential diagnostic marker for AIH.
基金supported by the National High Technical Research and Development Program of China (No.2009AA04Z403)PhD Programs Foundation of Ministry of Education of China (No.20090032110016)support (No.2010NGQ003) from Key Laboratory of Efficient & Clean Energy Utilization, College of Hunan Province
文摘Tests under mechanical strain control were performed to investigate the TMF behavior of Z2CND18.12N within the temperature range between 150–550 ？ C. Different strain amplitudes and phase-angles were applied. Total strain controlled low cycle fatigue test was also performed at the peak temperature of TMF cycling. The results show that the cyclic stress response of the material displayed an initial hardening regime followed by a saturation period and then cyclic softening till failure. The TMF cycling leads to the development of significant amounts of mean stress. Some life prediction models were employed to predict the TMF life of Z2CND18.12N, and the results indicate that the energy-based models provide good prediction on the thermal-mechanical fatigue behaviors of this material. An optical microscopic observation shows that the surface crack initiations and crack propagations are typically transgranular mode.
基金National Key Research and Development Program of China(2017YFA0205800)National Natural Science Foundation of China(61471345,62075231)+3 种基金Science and Technology Commission of Shanghai Municipality(20JC1414603)Shanghai Municipal Science and Technology Major Project(2019SHZDZX01)Shanghai Innovation Project(2021-cyxt1-kj04)Fundamental Research Funds for the Central Universities.
文摘The importance of tunable subwavelength optical devices in modern electromagnetic and photonic systems is indisputable.Herein,a lithography-free,wide-angle,and reconfigurable subwavelength optical device with high tunability operating in the near-infrared regions is proposed and experimentally demonstrated,based on a reversible nanochemistry approach.The reconfigurable subwavelength optical device basically comprises an ultrathin copper oxide(CuO)thin film on an optical thick gold substrate by utilizing the reversible chemical conversion of CuO to sulfides upon exposure to hydrogen sulfide gas.Proof-of-concept experimental results show that the maximal modulation depth of reflectance can be as high as 90%at the wavelength of 1.79μm with the initial thickness of CuO taken as 150 nm.Partially reflected wave calculations combined with the transfer matrix method are employed to analytically investigate the optical properties of the structure,which show good agreement with experimental results.We believe that the proposed versatile approaches can be implemented for dynamic control management,allowing applications in tunable photonics,active displays,optical encryption,and gas sensing.
基金supported by National Natural Science Foundation of China(no.21978030),and also sponsored by the Chinese Ministry of Education via the Program for New Century Excellent Talents in University(no.NCET-12-0079).
文摘Developing an efficientmethod to improve the photocatalytic efficiency of graphitic carbon nitride(g-C3 N4)is of great significance for solar H2 production.Electronic structure modulation has been considered one of the most crucial strategies to improving the photocatalytic efficiency of g-C_(3)N_(4),but how to efficiently modulate its electronic structure remains a huge challenge.Herein,we,for the first time,report a facile and highly-efficient approach to modulating the electronic structure of g-C_(3)N_(4)through single Ag atom implantation with a Ag_(1)-N_(3)coordination configuration into the g-C_(3)N_(4)framework.
