Imbalanced datasets are common in practical applications,and oversampling methods using fuzzy rules have been shown to enhance the classification performance of imbalanced data by taking into account the relationship ...Imbalanced datasets are common in practical applications,and oversampling methods using fuzzy rules have been shown to enhance the classification performance of imbalanced data by taking into account the relationship between data attributes.However,the creation of fuzzy rules typically depends on expert knowledge,which may not fully leverage the label information in training data and may be subjective.To address this issue,a novel fuzzy rule oversampling approach is developed based on the learning vector quantization(LVQ)algorithm.In this method,the label information of the training data is utilized to determine the antecedent part of If-Then fuzzy rules by dynamically dividing attribute intervals using LVQ.Subsequently,fuzzy rules are generated and adjusted to calculate rule weights.The number of new samples to be synthesized for each rule is then computed,and samples from the minority class are synthesized based on the newly generated fuzzy rules.This results in the establishment of a fuzzy rule oversampling method based on LVQ.To evaluate the effectiveness of this method,comparative experiments are conducted on 12 publicly available imbalance datasets with five other sampling techniques in combination with the support function machine.The experimental results demonstrate that the proposed method can significantly enhance the classification algorithm across seven performance indicators,including a boost of 2.15%to 12.34%in Accuracy,6.11%to 27.06%in G-mean,and 4.69%to 18.78%in AUC.These show that the proposed method is capable of more efficiently improving the classification performance of imbalanced data.展开更多
Dendritic cells(DCs) are professinal antigen-presenting cells with the ability to initiate primary Tcell responses. While it iswell known that inflammatory stimuli induce the functional maturation of immature DCs, whe...Dendritic cells(DCs) are professinal antigen-presenting cells with the ability to initiate primary Tcell responses. While it iswell known that inflammatory stimuli induce the functional maturation of immature DCs, whether adhesion molecule selectins regulate DCmaturation is poorly understood. Using anti-P-selectin lectin-EGF domain monoclonal antibody (PsL-EGFmAb) that blocks the adhesionof P-, E-, and L-selectin, we demonstrate herein that selectins play important role in stimulating functional maturation of immature DCs.Immature DCs are generated from human cord blood CD34+hematopoietic stem/progenitor cells that were cultured in the presence of stemcell factor, Fms-like tyrosine-kinase-3 ligand, granulocyte-macrophage colony stimulating factor, and transform growth factor-β1. Whenstimulated with tumor necrosis factor-alpha(TNF-α), immature DCs differentiated into mature DCs, producing increased levels of costim-ulatory molecules and interleukin (IL)-12 and obtaining the ability to potently activate naive Tcells. Interestingly, in contrast to matureDCs derived from TNF-α-induced immature DC cultures without PsL-EGFmAb, immature DCs treated with PsL-EGFmAb for7 days werecompletely blocked their maturation, as evidenced by decreased expression of costimulatory molecules CD80, CD86, and CD83, inhibi-ted production of IL-12, and inability to activate naive Tcellsin vitro. Thus, blockade of selectins using PsL-EGFmAb will prove to bea valuable tool for the study of the molecuar mechanisms of DC maturation, as well as for the prevention and treatment of DC-mediated au-toimmunity.展开更多
Ambient Assisted Living(AAL) is becoming an important research field. Many technologies have emerged related with pervasive computing vision, which can give support for AAL. One of the most reliable approaches is base...Ambient Assisted Living(AAL) is becoming an important research field. Many technologies have emerged related with pervasive computing vision, which can give support for AAL. One of the most reliable approaches is based on wireless sensor networks(WSNs). In this paper, we propose a coverage-aware unequal clustering protocol with load separation(CUCPLS) for data gathering of AAL applications based on WSNs. Firstly, the coverage overlap factor for nodes is introduced that accounts for the degree of target nodes covered. In addition, to balance the intra-cluster and inter-cluster energy consumptions, different competition radiuses of CHs are computed theoretically in different rings, and smaller clusters are formed near the sink. Moreover, two CHs are selected in each cluster for load separation to alleviate the substantial energy consumption difference between a single CH and its member nodes. Furthermore, a backoff waiting time is adopted during the selection of the two CHs to reduce the number of control messages employed. Simulation results demonstrate that the CUCPLS not only can achieve better coverage performance, but also balance the energy consumption of a network and prolong network lifetime.展开更多
Hypoeutectic Al-Si alloys are becoming increasingly popular in automotive and aerospace engineering fields due to their excellent overall performance,and grain refinement is regarded as an important way to improve cas...Hypoeutectic Al-Si alloys are becoming increasingly popular in automotive and aerospace engineering fields due to their excellent overall performance,and grain refinement is regarded as an important way to improve casting and mechanical properties.Titanium(Ti)is a basic element for grain refinement;thus,a certain amount of Ti is often included in Al-Si alloys.In the present work,the changes in the grain re-finement,mechanical,and casting properties of Al-Si alloys with different Ti concentration levels under various grain refinement conditions were systematically investigated.The specific roles of Ti in the het-erogeneous nucleation ofα-Al grains were summarized,and the formation mechanism of Ti-rich zones in Al-Si alloys was revealed.Excess Ti concentration could not efficiently reduce the grain size of Al-Si alloys and eventually resulted in inferior mechanical and casting qualities;hence,the recommended Ti concentration level for the aluminum alloy grades of A356 and A357 is≤0.1 wt%.Furthermore,an opti-mized technique for the grain refinement of hypoeutectic Al-Si alloys was presented.A small amount of an Al-TCB master alloy was introduced to achieve the best grain refinement and mechanical properties in a trace Ti environment.The addition of 0.5 wt%of the Al-TCB master alloy at the Ti concentration level of 0.06 wt%increased the ultimate tensile strength,elongation,and quality index of the Al-7Si-0.45Mg alloy to 328.8±5.0 MPa,14.4%±0.6%,and 970.7±33.1 MPa,respectively.展开更多
A comprehensive investigation into the occur-rence of odor problem at 111 drinking water treatment plants (DWTPs) in major cities across China was undertaken using both flavor profile analysis (FPA) and gas chroma...A comprehensive investigation into the occur-rence of odor problem at 111 drinking water treatment plants (DWTPs) in major cities across China was undertaken using both flavor profile analysis (FPA) and gas chromatography-mass spectrometry (GC-MS). Eighty percent of source water samples exhibited odor problems, characterized by earthy/musty (41%) and swampy/septic (36%) odors, while the occurrence rate was lower (45%) in the finished water. Source water from rivers exhibited more pollution-origin odors, such as the swampy/septic odor, while that from lakes and reservoirs exhibited more algae- origin odors, such as earthy/musty odors. The occurrence rate of 2-methylisoborneol (2-MIB) in the surface source water samples was 75%, with 7% of samples containing 2- MIB concentrations of over 10 ng.L-1. The earthy/musty odor in the lake/reservoir water samples was mainly caused by 2-MIB (linear regression coefficient, R2= 0.69), while the correlation between 2-MIB concentration and the earthy/musty odor intensity samples was weak (R2= 0.35) in the river-source water These results will be useful for the management of odor-quality problems in drinking water of China.展开更多
Rheumatoid arthritis is an autoimmune disease that primarily affects the limbs, but the pathogenic mechanism remains unclear. 78 T cells, a T-cell subpopulation, are characterized by multiple biological functions and ...Rheumatoid arthritis is an autoimmune disease that primarily affects the limbs, but the pathogenic mechanism remains unclear. 78 T cells, a T-cell subpopulation, are characterized by multiple biological functions and associated with a variety of diseases. This study investigated the antigen-presenting effects of γδ2 cells and their relationship with rheumatoid arthritis development. We found that Vγ9Vδ2 T cells (the predominant subtype of γδ T cells in peripheral blood) were activated by isopentenyl pyrophosphate to continuously proliferate and differentiate into effector memory cells. The effector memory Vγ9Vδ2 T cells exhibited phenotypic characteristics of specific antigen-presenting cells, including high HLA-DR and CD80/86 expression. These Vγ9Vδ2 T cells could present soluble antigens and synthetic peptides to CD4+ T cells. Vγ9Vδ2 T cells with different phenotypes showed different cytokine secretion patterns. Effector memoryVγ9Vδ2 T cells simultaneously secreted not only interferon (IFN)-γbut also IL-17. The peripheral blood and joint synovial fluid from RA patients contained numerous heterogeneous γδ T cells that were predominantly effector memory Vγ9Vδ2 T cells with the ability to secrete inflammatory factors. We also found that γδ T cells had a similar antigen-presenting capability to B cells. These results suggest that during the development of rheumatoid arthritis, 78 T cells can aggravate immune dysfunction and produce abnormal immune damage by secreting cytokines and inducing inflammatory cells to participate in synergistic inflammatory responses. Furthermore, γδ T cells can behave similarly to B cells to present viral peptides and autoantigen peptides to CD4+ T cells, thus sustaining CD4+ T-cell activation.展开更多
The occurrence and risks of Giardia in China have been unclear to date,which has made it difficult to properly manage source water as well as to create reasonable drinking water standards.The levels of Giardia in rive...The occurrence and risks of Giardia in China have been unclear to date,which has made it difficult to properly manage source water as well as to create reasonable drinking water standards.The levels of Giardia in river networks of several cities in Zhejiang Province,China were found to be in the range of 0-5 oocysts/10 L in the rainy season in 2008.The mortality due to Giardia infection for people in this region was calculated to be from 0 to 1.95 × 10?8 persons using a conditional probability equation.Based on multiple unboiled water intake routes,the disability-adjusted life years(DALYs) due to Giardia infection for people who consumed conventionally treated water was 0.625(95% CI:0.137-2.05) per 105 persons,with the symptom of hospitalization making the highest contribution to total DALYs(0.56 per 105 persons;95% CI:0.122-1.84).The DALYs decreased to 0.425(95% CI:0.137-2.05) per 105 persons per year for those consuming water treated with advanced technology.These values were lower than the acceptable risk(1.97 × 10?5 DALYs per year).This study revealed the risk of Giardia infection to the people in river networks of Zhejiang Province for the first time,and provides a method to evaluate the risk of Giardia infection.The results are useful for the modification of drinking water quality standards based on cost-benefit analysis.展开更多
EGFR inhibitors have revolutionized the treatment of advanced non-small-cell lung cancer(NSCLC).Mefatinib is a novel,bioavailable,second-generation,irreversible pan-EGFR inhibitor.This phase Ib/II open-label,single-ar...EGFR inhibitors have revolutionized the treatment of advanced non-small-cell lung cancer(NSCLC).Mefatinib is a novel,bioavailable,second-generation,irreversible pan-EGFR inhibitor.This phase Ib/II open-label,single-arm,multi-center study investigated the efficacy,safety,biomarker,and resistance mechanisms of mefatinib in the first-line treatment of patients with advanced EGFR-mutant NSCLC.This study included 106 patients with EGFR-mutant stage IIIB-IV NSCLC who received first-line mefatinib at a daily dose of either 60 mg(n=51)or 80 mg(n=55).The primary endpoint was progression-free survival(PFS).Secondary endpoints were overall response rate(ORR),disease control rate(DCR),overall survival(OS),and safety.The cohort achieved an ORR of 84.9%and DCR of 97.2%.The median PFS was 15.4 months and the median OS was 31.6 months.Brain metastasis was detected in 29%of patients(n=31)at diagnosis and demonstrated an ORR of 87.1%,PFS of 12.8 months,and OS of 25.2 months.Adverse events primarily involved skin and gastrointestinal toxicities,which were well-tolerated and manageable.Analyses of mutation profiles were performed using targeted sequencing of plasma samples at baseline,first follow-up 6 weeks from starting mefatinib therapy(F1),and at progression.Patients with concurrent TP53 mutations had comparable PFS as wild-type TP53(14.0 vs 15.4 months;p=0.315).Furthermore,circulating tumor DNA clearance was associated with longer PFS(p=0.040)and OS(p=0.002).EGFR T790M was the predominant molecular mechanism of mefatinib resistance(42.1%,16/38).First-line mefatinib provides durable PFS and an acceptable toxicity profile in patients with advanced EGFR-mutant NSCLC.展开更多
Membrane bioreactors(MBR) are highly efficient at intercepting particles and microbes and have become an important technology for wastewater reclamation. However, many pathogens can accumulate in activated sludge du...Membrane bioreactors(MBR) are highly efficient at intercepting particles and microbes and have become an important technology for wastewater reclamation. However, many pathogens can accumulate in activated sludge due to the long residence time usually adopted in MBR, and thus may pose health risks when membrane integrity problems occur.This study presents data from a survey on the occurrence of water-borne Giardia pathogens in reclaimed water from a full-scale wastewater treatment plant with MBR experiencing membrane integrity failure, and assessed the associated risk for green space irrigation. Due to membrane integrity failure, the MBR effluent turbidity varied between 0.23 and 1.90 NTU over a period of eight months. Though this turbidity level still met reclaimed water quality standards(≤ 5 NTU), Giardia were detected at concentrations of 0.3 to 95 cysts/10 L, with a close correlation between effluent turbidity and Giardia concentration. All β-giardin gene sequences of Giardia in the WWTP influents were genotyped as Assemblages A and B, both of which are known to infect humans. An exponential dose–response model was applied to assess the risk of infection by Giardia. The risk in the MBR effluent with chlorination was9.83 × 10-3, higher than the acceptable annual risk of 1.0 × 10^-4. This study suggested that membrane integrity is very important for keeping a low pathogen level, and multiple barriers are needed to ensure the biological safety of MBR effluent.展开更多
Coxsackievirus B1(CVB1) is a leading causative agent of severe infectious diseases in humans and has been reported to be associated with outbreaks of aseptic meningitis, myocarditis, and the development of chronic dis...Coxsackievirus B1(CVB1) is a leading causative agent of severe infectious diseases in humans and has been reported to be associated with outbreaks of aseptic meningitis, myocarditis, and the development of chronic diseases such as type 1 diabetes mellitus(T1DM). There is no approved vaccine or effective antiviral therapy to treat CBV1 infection. And animal models to assess the effects of antiviral agents and vaccine remain limited. In this study, we established a neonatal mouse model of CVB1 using a clinically isolated strain to characterize the pathological manifestations of virus infection and to promote the development of vaccines and antiviral drugs against CVB1. One-day-old BALB/c mice were susceptible to CVB1 infection by intraperitoneal injection. Mice challenged with CVB1 at a low dose [10 median tissue culture infective dose(TCID_(50))] exhibited a series of clinical symptoms, such as inactivity, emaciation, limb weakness, hair thinning,hunching and even death. Pathological examination and tissue viral load analysis showed that positive signals of CVB1 were detected in the heart, spinal cord, limb muscle and kidney without pathological damage. Particularly, CVB1 had a strong tropism towards the pancreas, causing severe cellular necrosis with inflammatory infiltration, and was spread by viraemia. Notably, the monoclonal antibody(mAb) 6H5 and antisera elicited from CVB1-vaccinated mice effectively protected the mice from CVB1 infection in the mouse model. In summary, the established neonatal mouse model is an effective tool for evaluating the efficacy of CVB1 antiviral reagents and vaccines.展开更多
Phosphine(PH3)is an important factor driving the outbreak of cyanobacterial blooms that produce toxic microcystin threating human health.To clarify the physiological and biochemical responses of cyanobacteria to PH3 u...Phosphine(PH3)is an important factor driving the outbreak of cyanobacterial blooms that produce toxic microcystin threating human health.To clarify the physiological and biochemical responses of cyanobacteria to PH3 under elevated CO2 concentration,Microcystis aeruginosa was used in the coupling treatment of 1000 ppmv CO2 and PH3 at different concentrations respectively.The chlorophyll a(Chl-a),carotenoid,net photosynthetic rate and total protein of M.aeruginosa exhibited evidently increasing tendency under the coupling treatment of 1000 ppmv CO2 and PH 3 at different concentrations(7.51×10^−3,2.48×10^−2,7.51×10^−2 mg/L).The coupling treatments resulted in the higher concentrations of Chl-a and carotenoid of M.aeruginosa,compared to those in the control and the treatment with CO2 alone,and their enhancement increased with the increase in PH 3 concentrations.The total antioxidant capacity(T-AOC)in the coupling treatment with CO2 and PH3 of 2.48×10^−2 mg/L and 7.51×10^−3 mg/L showed increasing tendency,compared to the treatment with PH 3 alone.Additionally,the coupling treatment with 1000 ppmv CO2 and PH3 also altered the pH and DO level in the culture medium.In this regard,the coupling treatment with CO2 and PH3 at an appropriate concentration can enhance the resistance of M.aeruginosa to PH3 toxicity and is beneficial to the reproduction of M.aeruginosa,presumably resulting in potential for the outbreak of cyanobacteria bloom.Given the concern about global warming and the increase in atmospheric CO2 level,our research laid a foundation for the scientific understanding of the correlation between PH3 and cyanobacteria blooms.展开更多
基金funded by the National Science Foundation of China(62006068)Hebei Natural Science Foundation(A2021402008),Natural Science Foundation of Scientific Research Project of Higher Education in Hebei Province(ZD2020185,QN2020188)333 Talent Supported Project of Hebei Province(C20221026).
文摘Imbalanced datasets are common in practical applications,and oversampling methods using fuzzy rules have been shown to enhance the classification performance of imbalanced data by taking into account the relationship between data attributes.However,the creation of fuzzy rules typically depends on expert knowledge,which may not fully leverage the label information in training data and may be subjective.To address this issue,a novel fuzzy rule oversampling approach is developed based on the learning vector quantization(LVQ)algorithm.In this method,the label information of the training data is utilized to determine the antecedent part of If-Then fuzzy rules by dynamically dividing attribute intervals using LVQ.Subsequently,fuzzy rules are generated and adjusted to calculate rule weights.The number of new samples to be synthesized for each rule is then computed,and samples from the minority class are synthesized based on the newly generated fuzzy rules.This results in the establishment of a fuzzy rule oversampling method based on LVQ.To evaluate the effectiveness of this method,comparative experiments are conducted on 12 publicly available imbalance datasets with five other sampling techniques in combination with the support function machine.The experimental results demonstrate that the proposed method can significantly enhance the classification algorithm across seven performance indicators,including a boost of 2.15%to 12.34%in Accuracy,6.11%to 27.06%in G-mean,and 4.69%to 18.78%in AUC.These show that the proposed method is capable of more efficiently improving the classification performance of imbalanced data.
文摘Dendritic cells(DCs) are professinal antigen-presenting cells with the ability to initiate primary Tcell responses. While it iswell known that inflammatory stimuli induce the functional maturation of immature DCs, whether adhesion molecule selectins regulate DCmaturation is poorly understood. Using anti-P-selectin lectin-EGF domain monoclonal antibody (PsL-EGFmAb) that blocks the adhesionof P-, E-, and L-selectin, we demonstrate herein that selectins play important role in stimulating functional maturation of immature DCs.Immature DCs are generated from human cord blood CD34+hematopoietic stem/progenitor cells that were cultured in the presence of stemcell factor, Fms-like tyrosine-kinase-3 ligand, granulocyte-macrophage colony stimulating factor, and transform growth factor-β1. Whenstimulated with tumor necrosis factor-alpha(TNF-α), immature DCs differentiated into mature DCs, producing increased levels of costim-ulatory molecules and interleukin (IL)-12 and obtaining the ability to potently activate naive Tcells. Interestingly, in contrast to matureDCs derived from TNF-α-induced immature DC cultures without PsL-EGFmAb, immature DCs treated with PsL-EGFmAb for7 days werecompletely blocked their maturation, as evidenced by decreased expression of costimulatory molecules CD80, CD86, and CD83, inhibi-ted production of IL-12, and inability to activate naive Tcellsin vitro. Thus, blockade of selectins using PsL-EGFmAb will prove to bea valuable tool for the study of the molecuar mechanisms of DC maturation, as well as for the prevention and treatment of DC-mediated au-toimmunity.
基金supported by the National Nature Science Foundation of China (61170169, 61170168)
文摘Ambient Assisted Living(AAL) is becoming an important research field. Many technologies have emerged related with pervasive computing vision, which can give support for AAL. One of the most reliable approaches is based on wireless sensor networks(WSNs). In this paper, we propose a coverage-aware unequal clustering protocol with load separation(CUCPLS) for data gathering of AAL applications based on WSNs. Firstly, the coverage overlap factor for nodes is introduced that accounts for the degree of target nodes covered. In addition, to balance the intra-cluster and inter-cluster energy consumptions, different competition radiuses of CHs are computed theoretically in different rings, and smaller clusters are formed near the sink. Moreover, two CHs are selected in each cluster for load separation to alleviate the substantial energy consumption difference between a single CH and its member nodes. Furthermore, a backoff waiting time is adopted during the selection of the two CHs to reduce the number of control messages employed. Simulation results demonstrate that the CUCPLS not only can achieve better coverage performance, but also balance the energy consumption of a network and prolong network lifetime.
基金financially supported by the National Natu-ral Science Foundation of China(Nos.52071189,U2241230,and 52301167).
文摘Hypoeutectic Al-Si alloys are becoming increasingly popular in automotive and aerospace engineering fields due to their excellent overall performance,and grain refinement is regarded as an important way to improve casting and mechanical properties.Titanium(Ti)is a basic element for grain refinement;thus,a certain amount of Ti is often included in Al-Si alloys.In the present work,the changes in the grain re-finement,mechanical,and casting properties of Al-Si alloys with different Ti concentration levels under various grain refinement conditions were systematically investigated.The specific roles of Ti in the het-erogeneous nucleation ofα-Al grains were summarized,and the formation mechanism of Ti-rich zones in Al-Si alloys was revealed.Excess Ti concentration could not efficiently reduce the grain size of Al-Si alloys and eventually resulted in inferior mechanical and casting qualities;hence,the recommended Ti concentration level for the aluminum alloy grades of A356 and A357 is≤0.1 wt%.Furthermore,an opti-mized technique for the grain refinement of hypoeutectic Al-Si alloys was presented.A small amount of an Al-TCB master alloy was introduced to achieve the best grain refinement and mechanical properties in a trace Ti environment.The addition of 0.5 wt%of the Al-TCB master alloy at the Ti concentration level of 0.06 wt%increased the ultimate tensile strength,elongation,and quality index of the Al-7Si-0.45Mg alloy to 328.8±5.0 MPa,14.4%±0.6%,and 970.7±33.1 MPa,respectively.
基金This work was financially supported by the National Natural Science Foundation of China (Grant No. 50938007), the Funds for Major Science and Technology Program for Water Pollution Control and Treatment (No. 2009ZX07419-001) and the Key Scientific and Technological Projects of Science and Technology Commission of Shanghai Municipality (No. 12231201600). The authors would like to express their gratitude toward members from the water treatment plants for their assistance during sampling.
文摘A comprehensive investigation into the occur-rence of odor problem at 111 drinking water treatment plants (DWTPs) in major cities across China was undertaken using both flavor profile analysis (FPA) and gas chromatography-mass spectrometry (GC-MS). Eighty percent of source water samples exhibited odor problems, characterized by earthy/musty (41%) and swampy/septic (36%) odors, while the occurrence rate was lower (45%) in the finished water. Source water from rivers exhibited more pollution-origin odors, such as the swampy/septic odor, while that from lakes and reservoirs exhibited more algae- origin odors, such as earthy/musty odors. The occurrence rate of 2-methylisoborneol (2-MIB) in the surface source water samples was 75%, with 7% of samples containing 2- MIB concentrations of over 10 ng.L-1. The earthy/musty odor in the lake/reservoir water samples was mainly caused by 2-MIB (linear regression coefficient, R2= 0.69), while the correlation between 2-MIB concentration and the earthy/musty odor intensity samples was weak (R2= 0.35) in the river-source water These results will be useful for the management of odor-quality problems in drinking water of China.
基金ACKNOWLEGEMENTS This work was supported by the grants from the following: National Natural Science Foundation of China (no. 30471593, 30872304 and 81072470), Shanghai Commission of Science and Technology (no. 10IC14 08500 and 10ZR1426100), Shanghai Leading Academic Discipline-Surgery (no. $30204- K01), Shanghai Municipal education Commission (no. 150207 and 09YZ102), Shanghai Institute of Immunology (no. 08-A04), Clinical Medicine Technology Development Foundation of Jiangsu University (no. ILY2010091) and Foundation of Shanghai Xuhui Central Hospital (no. 2011XHCH07).
文摘Rheumatoid arthritis is an autoimmune disease that primarily affects the limbs, but the pathogenic mechanism remains unclear. 78 T cells, a T-cell subpopulation, are characterized by multiple biological functions and associated with a variety of diseases. This study investigated the antigen-presenting effects of γδ2 cells and their relationship with rheumatoid arthritis development. We found that Vγ9Vδ2 T cells (the predominant subtype of γδ T cells in peripheral blood) were activated by isopentenyl pyrophosphate to continuously proliferate and differentiate into effector memory cells. The effector memory Vγ9Vδ2 T cells exhibited phenotypic characteristics of specific antigen-presenting cells, including high HLA-DR and CD80/86 expression. These Vγ9Vδ2 T cells could present soluble antigens and synthetic peptides to CD4+ T cells. Vγ9Vδ2 T cells with different phenotypes showed different cytokine secretion patterns. Effector memoryVγ9Vδ2 T cells simultaneously secreted not only interferon (IFN)-γbut also IL-17. The peripheral blood and joint synovial fluid from RA patients contained numerous heterogeneous γδ T cells that were predominantly effector memory Vγ9Vδ2 T cells with the ability to secrete inflammatory factors. We also found that γδ T cells had a similar antigen-presenting capability to B cells. These results suggest that during the development of rheumatoid arthritis, 78 T cells can aggravate immune dysfunction and produce abnormal immune damage by secreting cytokines and inducing inflammatory cells to participate in synergistic inflammatory responses. Furthermore, γδ T cells can behave similarly to B cells to present viral peptides and autoantigen peptides to CD4+ T cells, thus sustaining CD4+ T-cell activation.
基金supported by the Foundation of Major Science and Technology Program for Water Pollution Control and Treatment (No. 2009ZX07419-002)the National Natural Science Foundation of China (No. 50778171,50809066, 20807013)
文摘The occurrence and risks of Giardia in China have been unclear to date,which has made it difficult to properly manage source water as well as to create reasonable drinking water standards.The levels of Giardia in river networks of several cities in Zhejiang Province,China were found to be in the range of 0-5 oocysts/10 L in the rainy season in 2008.The mortality due to Giardia infection for people in this region was calculated to be from 0 to 1.95 × 10?8 persons using a conditional probability equation.Based on multiple unboiled water intake routes,the disability-adjusted life years(DALYs) due to Giardia infection for people who consumed conventionally treated water was 0.625(95% CI:0.137-2.05) per 105 persons,with the symptom of hospitalization making the highest contribution to total DALYs(0.56 per 105 persons;95% CI:0.122-1.84).The DALYs decreased to 0.425(95% CI:0.137-2.05) per 105 persons per year for those consuming water treated with advanced technology.These values were lower than the acceptable risk(1.97 × 10?5 DALYs per year).This study revealed the risk of Giardia infection to the people in river networks of Zhejiang Province for the first time,and provides a method to evaluate the risk of Giardia infection.The results are useful for the modification of drinking water quality standards based on cost-benefit analysis.
基金This work was sponsored by Hangzhou Zhongmei Huadong Pharmaceutical Co.Ltd.and supported by a grant from the Key R&D Program of Zhejiang Province(2020C03027).
文摘EGFR inhibitors have revolutionized the treatment of advanced non-small-cell lung cancer(NSCLC).Mefatinib is a novel,bioavailable,second-generation,irreversible pan-EGFR inhibitor.This phase Ib/II open-label,single-arm,multi-center study investigated the efficacy,safety,biomarker,and resistance mechanisms of mefatinib in the first-line treatment of patients with advanced EGFR-mutant NSCLC.This study included 106 patients with EGFR-mutant stage IIIB-IV NSCLC who received first-line mefatinib at a daily dose of either 60 mg(n=51)or 80 mg(n=55).The primary endpoint was progression-free survival(PFS).Secondary endpoints were overall response rate(ORR),disease control rate(DCR),overall survival(OS),and safety.The cohort achieved an ORR of 84.9%and DCR of 97.2%.The median PFS was 15.4 months and the median OS was 31.6 months.Brain metastasis was detected in 29%of patients(n=31)at diagnosis and demonstrated an ORR of 87.1%,PFS of 12.8 months,and OS of 25.2 months.Adverse events primarily involved skin and gastrointestinal toxicities,which were well-tolerated and manageable.Analyses of mutation profiles were performed using targeted sequencing of plasma samples at baseline,first follow-up 6 weeks from starting mefatinib therapy(F1),and at progression.Patients with concurrent TP53 mutations had comparable PFS as wild-type TP53(14.0 vs 15.4 months;p=0.315).Furthermore,circulating tumor DNA clearance was associated with longer PFS(p=0.040)and OS(p=0.002).EGFR T790M was the predominant molecular mechanism of mefatinib resistance(42.1%,16/38).First-line mefatinib provides durable PFS and an acceptable toxicity profile in patients with advanced EGFR-mutant NSCLC.
基金supported by the Creative Research Groups of China (No. 51221892, 21277169)
文摘Membrane bioreactors(MBR) are highly efficient at intercepting particles and microbes and have become an important technology for wastewater reclamation. However, many pathogens can accumulate in activated sludge due to the long residence time usually adopted in MBR, and thus may pose health risks when membrane integrity problems occur.This study presents data from a survey on the occurrence of water-borne Giardia pathogens in reclaimed water from a full-scale wastewater treatment plant with MBR experiencing membrane integrity failure, and assessed the associated risk for green space irrigation. Due to membrane integrity failure, the MBR effluent turbidity varied between 0.23 and 1.90 NTU over a period of eight months. Though this turbidity level still met reclaimed water quality standards(≤ 5 NTU), Giardia were detected at concentrations of 0.3 to 95 cysts/10 L, with a close correlation between effluent turbidity and Giardia concentration. All β-giardin gene sequences of Giardia in the WWTP influents were genotyped as Assemblages A and B, both of which are known to infect humans. An exponential dose–response model was applied to assess the risk of infection by Giardia. The risk in the MBR effluent with chlorination was9.83 × 10-3, higher than the acceptable annual risk of 1.0 × 10^-4. This study suggested that membrane integrity is very important for keeping a low pathogen level, and multiple barriers are needed to ensure the biological safety of MBR effluent.
基金This research was supported by grants from the National Natural Science Foundation of China(No.82072282 and 81801646)the National Science and Technology Major Project of Infectious Diseases(No.2017ZX10304402-002-003)the National Science and Technology Major Projects for Major New Drugs Innovation and Development(No.2018ZX09711003-005003)。
文摘Coxsackievirus B1(CVB1) is a leading causative agent of severe infectious diseases in humans and has been reported to be associated with outbreaks of aseptic meningitis, myocarditis, and the development of chronic diseases such as type 1 diabetes mellitus(T1DM). There is no approved vaccine or effective antiviral therapy to treat CBV1 infection. And animal models to assess the effects of antiviral agents and vaccine remain limited. In this study, we established a neonatal mouse model of CVB1 using a clinically isolated strain to characterize the pathological manifestations of virus infection and to promote the development of vaccines and antiviral drugs against CVB1. One-day-old BALB/c mice were susceptible to CVB1 infection by intraperitoneal injection. Mice challenged with CVB1 at a low dose [10 median tissue culture infective dose(TCID_(50))] exhibited a series of clinical symptoms, such as inactivity, emaciation, limb weakness, hair thinning,hunching and even death. Pathological examination and tissue viral load analysis showed that positive signals of CVB1 were detected in the heart, spinal cord, limb muscle and kidney without pathological damage. Particularly, CVB1 had a strong tropism towards the pancreas, causing severe cellular necrosis with inflammatory infiltration, and was spread by viraemia. Notably, the monoclonal antibody(mAb) 6H5 and antisera elicited from CVB1-vaccinated mice effectively protected the mice from CVB1 infection in the mouse model. In summary, the established neonatal mouse model is an effective tool for evaluating the efficacy of CVB1 antiviral reagents and vaccines.
基金This work was supported by the Natural Science Foundation of Guangdong Province(No.2017A030313239)Research Project of Sino-Singapore International Joint Research Institute(No.202-A018001)+4 种基金the Jiangsu Natural Science Foundation(Nos.BK20180109,BK)the State Key Laboratory of Lake Science and Environment,Nanjing Institute of Geography and Limnology,Chinese Academy of Sciences(No.2016SKL011)the Ministry of Science and Technology of China for State Key Research and Development Project(No.2016YFC04007082)the Student Research Project of South China University of Technology(No.7387)and the State Key Laboratory of Pollution Control and Resource Reuse(No.PCRRF14006,PCRRF17018).
文摘Phosphine(PH3)is an important factor driving the outbreak of cyanobacterial blooms that produce toxic microcystin threating human health.To clarify the physiological and biochemical responses of cyanobacteria to PH3 under elevated CO2 concentration,Microcystis aeruginosa was used in the coupling treatment of 1000 ppmv CO2 and PH3 at different concentrations respectively.The chlorophyll a(Chl-a),carotenoid,net photosynthetic rate and total protein of M.aeruginosa exhibited evidently increasing tendency under the coupling treatment of 1000 ppmv CO2 and PH 3 at different concentrations(7.51×10^−3,2.48×10^−2,7.51×10^−2 mg/L).The coupling treatments resulted in the higher concentrations of Chl-a and carotenoid of M.aeruginosa,compared to those in the control and the treatment with CO2 alone,and their enhancement increased with the increase in PH 3 concentrations.The total antioxidant capacity(T-AOC)in the coupling treatment with CO2 and PH3 of 2.48×10^−2 mg/L and 7.51×10^−3 mg/L showed increasing tendency,compared to the treatment with PH 3 alone.Additionally,the coupling treatment with 1000 ppmv CO2 and PH3 also altered the pH and DO level in the culture medium.In this regard,the coupling treatment with CO2 and PH3 at an appropriate concentration can enhance the resistance of M.aeruginosa to PH3 toxicity and is beneficial to the reproduction of M.aeruginosa,presumably resulting in potential for the outbreak of cyanobacteria bloom.Given the concern about global warming and the increase in atmospheric CO2 level,our research laid a foundation for the scientific understanding of the correlation between PH3 and cyanobacteria blooms.