The application of deep learning is fast developing in climate prediction,in which El Ni?o–Southern Oscillation(ENSO),as the most dominant disaster-causing climate event,is a key target.Previous studies have shown th...The application of deep learning is fast developing in climate prediction,in which El Ni?o–Southern Oscillation(ENSO),as the most dominant disaster-causing climate event,is a key target.Previous studies have shown that deep learning methods possess a certain level of superiority in predicting ENSO indices.The present study develops a deep learning model for predicting the spatial pattern of sea surface temperature anomalies(SSTAs)in the equatorial Pacific by training a convolutional neural network(CNN)model with historical simulations from CMIP6 models.Compared with dynamical models,the CNN model has higher skill in predicting the SSTAs in the equatorial western-central Pacific,but not in the eastern Pacific.The CNN model can successfully capture the small-scale precursors in the initial SSTAs for the development of central Pacific ENSO to distinguish the spatial mode up to a lead time of seven months.A fusion model combining the predictions of the CNN model and the dynamical models achieves higher skill than each of them for both central and eastern Pacific ENSO.展开更多
Mangroves are crucial for protecting coastal areas against extreme disasters such as tsunamis and storm surges.An experimental study was conducted to determine how mangroves can mitigate the tsunami wave propagation.T...Mangroves are crucial for protecting coastal areas against extreme disasters such as tsunamis and storm surges.An experimental study was conducted to determine how mangroves can mitigate the tsunami wave propagation.The test was performed in a flume, where mangrove models were installed on a slope, and dam-burst waves were used to simulate tsunami waves. To study how mangrove forests reduce the impact of tsunamis, this paper measured the heights of the incoming waves under different initial conditions(tsunami wave intensity and initial water depth) and plant factors(arrangement and distribution density) and described the reduction process. The results show that, after passing through the mangrove, the tsunami bore height will decrease within a certain range as the initial water depth increases. However, there is no correlation between the increase of inundation level and the drop of water level. The bore height attenuation is more significant at higher density of mangroves,but after tsunami passing through the mangroves, the relative bore height will decrease. When the distribution density of mangroves is constant, the wave attenuation at different locations(before, on and after the slope)shows different relationships with the initial water depth and wave height for different models. The transmission coefficient(K_(i)) shows a parabolic correlation with its density. The proportion of the energy loss caused by the mangrove resistance to the total energy(E_(b)) is defined as C_(m2). The variation trend of C_(m2) corresponds to the tsunami wave energy attenuation rate(C_(a)) and K_(i).展开更多
Osteoarthritis(OA) is the most common degenerative joint disease and a major cause of pain and disability in adult individuals. The etiology of OA includes joint injury, obesity, aging, and heredity. However, the deta...Osteoarthritis(OA) is the most common degenerative joint disease and a major cause of pain and disability in adult individuals. The etiology of OA includes joint injury, obesity, aging, and heredity. However, the detailed molecular mechanisms of OA initiation and progression remain poorly understood and, currently,there are no interventions available to restore degraded cartilage or decelerate disease progression. The diathrodial joint is a complicated organ and its function is to bear weight, perform physical activity and exhibit a joint-specific range of motion during movement. During OA development, the entire joint organ is affected, including articular cartilage, subchondral bone, synovial tissue and meniscus. A full understanding of the pathological mechanism of OA development relies on the discovery of the interplaying mechanisms among different OA symptoms, including articular cartilage degradation, osteophyte formation, subchondral sclerosis and synovial hyperplasia, and the signaling pathway(s) controlling these pathological processes.展开更多
Objective:This study aims to evaluate the natural history of patients with chronic lymphocytic leukemia(CLL)and a 17p deletion(17p-)and identify the predictive factors within this subgroup.Methods:The sample of patien...Objective:This study aims to evaluate the natural history of patients with chronic lymphocytic leukemia(CLL)and a 17p deletion(17p-)and identify the predictive factors within this subgroup.Methods:The sample of patients with CLL were analyzed by fluorescence in situ hybridization for deletions in chromosome bands 11q22,13q14 and 17p13;trisomy of bands 12q13;and translocation involving band 14q32.The data from 456 patients with or without a 17p-were retrospectively collected and analyzed.Results:The overall response rate(ORR)in patients with a 17p-was 56.9%,and patients with a high percentage of 17p-(defined as more than 25%of cells harbouring a 17p-)had a lower ORR.The median overall survival(OS)in patients with a 17p-was 78.0 months,which was significantly shorter than the OS in patients without this genetic abnormality(median 162.0 months,P<0.001).Within the subgroup with a 17p-,the progression-free survival was significantly shorter in patients at Binet stage B-C and patients with elevated lactate dehydrogenase(LDH),B symptoms,unmutated IGHV and a high percentage of 17p-.Conclusions:These results indicated that patients with a 17p-CLL have a variable prognosis that might be predicted using simple clinical and laboratory characteristics.展开更多
β-Catenin plays a critical role in cartilage formation and development. To further understand the role of β-catenin in osteoarthritis(OA) development in temporomandibular joint(TMJ), we have generated β-catenin con...β-Catenin plays a critical role in cartilage formation and development. To further understand the role of β-catenin in osteoarthritis(OA) development in temporomandibular joint(TMJ), we have generated β-catenin conditional activation mice(β-cat(ex3)^(Agc1CreER))by breeding Agc1-CreER mice with β-catenin^(flox(ex3)/+)mice. Results of histologic analysis showed the progressive TMJ defects in 3-and 6-month-old β-cat(ex3)^(Agc1CreER)mice(tamoxifen induction was performed at 2 weeks of age), including decreased chondrocyte numbers in the superficial layer associated with less Alcian blue staining, increased numbers of hypertrophic chondrocytes in deep layers, and rough articular surface. Compared to the TMJ phenotype of β-cat(ex3)^(Col2CreER)mice, β-cat(ex3)^(Agc1CreER)mice showed much severe morphological defects in the superficial layer of TMJ. This may reflect that Agc1-CreER mice could efficiently target cells in the superficial layer of TMJ. Results of immunostaining showed significantly increased expression of MMP13, Col-X, Adamts4,and Adamts5 in TMJ of β-cat(ex3)^(Agc1CreER)mice. Results of proliferating cell nuclear antigen(PCNA), Ki67, and terminal deoxinucleotidyl transferase-mediated d UTP-fluorescein nick end labeling(TUNEL) staining further demonstrated that cell proliferation was decreased and cell apoptosis was increased in condylar cartilage of β-cat(ex3)^(Agc1CreER)mice. Our findings indicate that abnormal upregulation of β-catenin in TMJ leads to defects assembling to OA-like phenotype, further demonstrating that β-catenin plays a critical role in TMJ pathogenesis.展开更多
Carboxyl terminus of Hsp70-interacting protein(CHIP or STUB1) is an E3 ligase and regulates the stability of several proteins which are involved in different cellular functions. Our previous studies demonstrated that ...Carboxyl terminus of Hsp70-interacting protein(CHIP or STUB1) is an E3 ligase and regulates the stability of several proteins which are involved in different cellular functions. Our previous studies demonstrated that Chip deficient mice display bone loss phenotype due to increased osteoclast formation through enhancing TRAF6 activity in osteoclasts. In this study we provide novel evidence about the function of CHIP. We found that osteoblast differentiation and bone formation were also decreased in Chip KO mice. In bone marrow stromal(BMS) cells derived from Chip^(-/-) mice, expression of a panel of osteoblast marker genes was significantly decreased. ALP activity and mineralized bone matrix formation were also reduced in Chip-deficient BMS cells. We also found that in addition to the regulation of TRAF6, CHIP also inhibits TNFα-induced NF-κB signaling through promoting TRAF2 and TRAF5 degradation. Specific deletion of Chip in BMS cells downregulated expression of osteoblast marker genes which could be reversed by the addition of NF-κB inhibitor. These results demonstrate that the osteopenic phenotype observed in Chip^(-/-) mice was due to the combination of increased osteoclast formation and decreased osteoblast differentiation. Taken together, our findings indicate a significant role of CHIP in bone remodeling.展开更多
We optimized the extraction process of Lysurus mokusin(L.)Fr.insecticidal compound(LMIC)using response surface methodology with ultrasonic extraction(UE).The surface morphologies of maceration extract(ME)and UE residu...We optimized the extraction process of Lysurus mokusin(L.)Fr.insecticidal compound(LMIC)using response surface methodology with ultrasonic extraction(UE).The surface morphologies of maceration extract(ME)and UE residues were compared by scanning electron microscopy,and then the activity of LMIC on Lymantria dispar(Asian gypsy moths)larvae was determined.Results showed that the optimal condition of UE was followed by 80 min of extraction time,60%of ethanol concentration and 80 mL g^-1 of liquid–solid ratio.The surface morphologies of UE residue were looser and rougher than ME residue.The corrected mortalities of LMIC on L.dispar larvae was 59.77%.This result indicated that L.mokusin was a good candidate as pesticide for pest management.展开更多
As extremely important physiological indicators,respiratory signals can often reflect or predict the depth and urgency of various diseases.However,designing a wearable respiratory monitoring system with convenience,ex...As extremely important physiological indicators,respiratory signals can often reflect or predict the depth and urgency of various diseases.However,designing a wearable respiratory monitoring system with convenience,excellent durability,and high precision is still an urgent challenge.Here,we designed an easy-fabricate,lightweight,and badge reel-like retractable selfpowered sensor(RSPS)with high precision,sensitivity,and durability for continuous detection of important indicators such as respiratory rate,apnea,and respiratory ventilation.By using three groups of interdigital electrode structures with phase differences,combined with flexible printed circuit boards(FPCBs)processing technology,a miniature rotating thin-film triboelectric nanogenerator(RTF-TENG)was developed.Based on discrete sensing technology,the RSPS has a sensing resolution of 0.13 mm,sensitivity of 7 P·mm^(−1),and durability more than 1 million stretching cycles,with low hysteresis and excellent anti-environmental interference ability.Additionally,to demonstrate its wearability,real-time,and convenience of respiratory monitoring,a multifunctional wearable respiratory monitoring system(MWRMS)was designed.The MWRMS demonstrated in this study is expected to provide a new and practical strategy and technology for daily human respiratory monitoring and clinical diagnosis.展开更多
Osteoarthritis(OA)is a painful degenerative joint disease and is the leading cause of chronic disability among elderly individuals.To improve the quality of life for patients with OA,the primary goal for OA treatment ...Osteoarthritis(OA)is a painful degenerative joint disease and is the leading cause of chronic disability among elderly individuals.To improve the quality of life for patients with OA,the primary goal for OA treatment is to relieve the pain.During OA progression,nerve ingrowth was observed in synovial tissue and articular cartilage.These abnormal neonatal nerves act as nociceptors to detect OA pain signals.The molecular mechanisms for transmitting OA pain in the joint tissues to the central nerve system(CNS)is currently unknown.MicroRNA miR-204 has been demonstrated to maintain the homeostasis of joint tissues and have chondro-protective effect on OA pathogenesis.However,the role of miR-204 in OA pain has not been determined.In this study,we investigated interactions between chondrocytes and neural cells and evaluated the effect and mechanism of miR-204 delivered by exosome in the treatment of OA pain in an experimental OA mouse model.Our findings demonstrated that miR-204 could protect OA pain by inhibition of SP1-LDL Receptor Related Protein 1(LRP1)signaling and blocking neuro-cartilage interaction in the joint.Our studies defined novel molecular targets for the treatment of OA pain.展开更多
Rituximab maintenance(RM)prolongs the progression-free survival(PFS)of responding patients with follicular lymphoma(FL),but the maintenance efficacy in different Follicular Lymphoma International Prognostic Index(FLIP...Rituximab maintenance(RM)prolongs the progression-free survival(PFS)of responding patients with follicular lymphoma(FL),but the maintenance efficacy in different Follicular Lymphoma International Prognostic Index(FLIPI)risk group is still confusing.We performed a retrospective analysis of the effect of RM treatments in patients with FL responding to induction therapy based on their FLIPI risk assessment carried out prior to treatment.We identified 93 patients between 2013 and 2019 who received RM every 3 months for≥4 doses(RM group),and 60 patients who did not accept RM or received rituximab less than 4 doses(control group).After a median follow-up of 39 months,neither median overall survival(OS)nor PFS was reached for the entire population.The PFS was significantly prolonged in the RM group compared to the control group(median PFS NA vs 83.1 months,P=.00027).When the population was divided into the 3 FLIPI risk groups,the PFS differed significantly(4-year PFS rates,97.5%vs 88.8%vs 72.3%,P=.01)according to group.There was no significant difference in PFS for FLIPI low-risk patients with RM compared to the control group(4-year PFS rates,100%vs 93.8%,P=.23).However,the PFS of the RM group was significantly prolonged for FLIPI intermediate-risk(4-year PFS rates,100%vs 70.3%,P=.00077)and high-risk patients(4-year PFS rates,86.7%vs 57.1%,P=.023).These data suggest that standard RM significantly prolongs the PFS of patients assigned to intermediate-and high-risk FLIPI groups but not to low-risk FLIPI group,and pending larger-scale studies to validate.展开更多
To the Editor:As a rare indolent B cell non-Hodgkin lymphoma,lymphoplasmacytic lymphoma/Waldenström’s macroglobulinemia(LPL/WM)has unique clinical and biological characteristics.[1]However,due to the difficulties in...To the Editor:As a rare indolent B cell non-Hodgkin lymphoma,lymphoplasmacytic lymphoma/Waldenström’s macroglobulinemia(LPL/WM)has unique clinical and biological characteristics.[1]However,due to the difficulties in obtaining tumor metaphase for karyotyping and slow cell proliferation,only very few studies have detected the cytogenetic aberration of LPL/WM.[2,3]In addition,6q deletion is the most common cytogenetic aberration in WM,with an incidence rate of about 50%.[2]Nevertheless,other cytogenetic aberrations remain largely unclear,and the prognostic role of cytogenetic aberrations needs to be further explored.In the present study,we systematically analyzed 305 LPL/WM cases in China,focusing on the characteristics and cytogenetic aberrations in Chinese patients.展开更多
MicroRNAs(MiRNAs)carried by exosomes play pivotal roles in the crosstalk between cell components in the tumor microenvironment.Our study aimed at identifying the expression profile of exosomal miRNAs(exo-miRNAs)in the...MicroRNAs(MiRNAs)carried by exosomes play pivotal roles in the crosstalk between cell components in the tumor microenvironment.Our study aimed at identifying the expression profile of exosomal miRNAs(exo-miRNAs)in the serum of multiple myeloma(MM)patients and investigating the regulation networks and their potential functions by integrated bioinformatics analysis.Exosomes in serum from 19 newly diagnosed MM patients and 9 healthy donors were isolated and the miRNA profile was investigated by small RNA sequencing.Differential expression of exo-miRNAs was calculated and target genes of miRNAs were predicted.CytoHubba was applied to identify the hub miRNAs and core target genes.The LASSO Cox regression model was used to develop the prognostic model,and the ESTIMATE immune score was calculated to investigate the correlation between the model and immune status in MM patients.The top six hub differentially expressed serum exo-miRNAs were identified.513 target genes of the six hub exo-miRNAs were confirmed to be differentially expressed in MM cells in the Zhan Myeloma microarray dataset.Functional enrichment analysis indicated that these target genes were mainly involved in mRNA splicing,cellular response to stress,and deubiquitination.13 core exo-miRNA target genes were applied to create a novel prognostic signature to provide risk stratification for MM patients,which is associated with the immune microenvironment of MM patients.Our study comprehensively investigated the exo-miRNA profiles in MM patients.A novel prognostic signature was constructed to facilitate the risk stratification of MM patients with distinct outcomes.展开更多
Multi-core processor is widely used as the running platform for safety-critical real-time systems such as spacecraft,and various types of real-time tasks are dynamically added at runtime.In order to improve the utiliz...Multi-core processor is widely used as the running platform for safety-critical real-time systems such as spacecraft,and various types of real-time tasks are dynamically added at runtime.In order to improve the utilization of multi-core processors and ensure the real-time performance of the system,it is necessary to adopt a reasonable real-time task allocation method,but the existing methods are only for single-core processors or the performance is too low to be applicable.Aiming at the task allocation problem when mixed real-time tasks are dynamically added,we propose a heuristic mixed real-time task allocation algorithm of virtual utilization VU-WF(Virtual Utilization Worst Fit)in multi-core processor.First,a 4-tuple task model is established to describe the fixedpoint task and the sporadic task in a unified manner.Then,a VDS(Virtual Deferral Server)for serving execution requests of fixed-point task is constructed and a schedulability test of the mixed task set is derived.Finally,combined with the analysis of VDS's capacity,VU-WF is proposed,which selects cores in ascending order of virtual utilization for the schedulability test.Experiments show that the overall performance of VU-WF is better than available algorithms,not only has a good schedulable ratio and load balancing but also has the lowest runtime overhead.In a 4-core processor,compared with available algorithms of the same schedulability ratio,the load balancing is improved by 73.9%,and the runtime overhead is reduced by 38.3%.In addition,we also develop a visual multi-core mixed task scheduling simulator RT-MCSS(open source)to facilitate the design and verification of multi-core scheduling for users.As the high performance,VU-WF can be widely used in resource-constrained and safety-critical real-time systems,such as spacecraft,self-driving cars,industrial robots,etc.展开更多
A novel 2D/2D Bi_(2)MoO_(6)/g-C_(3)N_(4) step-scheme(S-scheme)composite by loading Au as cocatalyst was successfully fabricated using a photoreduction and hydrothermal route.The obtained Bi_(2)MoO_(6)/g-C_(3)N_(4)/Au ...A novel 2D/2D Bi_(2)MoO_(6)/g-C_(3)N_(4) step-scheme(S-scheme)composite by loading Au as cocatalyst was successfully fabricated using a photoreduction and hydrothermal route.The obtained Bi_(2)MoO_(6)/g-C_(3)N_(4)/Au photocatalysts were characterized by X-ray diffraction(XRD),transmission electron microscope(TEM),X-ray photo-electron spectroscopy(XPS),UV–vis diffuse reflectance spectra(UV–vis),Fourier transform infrared spectroscopy(FTIR),photoluminescence(PL),photocurrent response(I-t),and electrochemical impedance spectroscopy(EIS).The HRTEM images revealed that an intimate interface in composites were formed.The optimum photocatalytic activity of Rhodamine B degradation over Bi_(2)MoO_(6)/g-C_(3)N_(4)/Au was about 9.7 times and 13.1 times as high as those of Bi_(2)MoO_(6) and g-C_(3)N_(4),respectively.The notably improved photocatalytic activity of Bi_(2)MoO_(6)/g-C_(3)N_(4)/Au could be mainly ascribed to the abundant active sites and the enhanced separation efficiency of photogenerated carriers in Bi_(2)MoO_(6)/g-C_(3)N_(4) S-scheme system.Notably,Au nanoparticles could act as a co-catalyst to further promote electron transfer and separation from the conduction band of g-C_(3)N_(4).Additionally,a possible step-scheme photocatalytic reaction mechanism of Rh B degradation over Bi_(2)MoO_(6)/g-C_(3)N_(4)/Au was tentatively proposed.PL and transient photocurrent analysis implied that Bi_(2)MoO_(6)/g-C_(3)N_(4)/Au photocatalysts possessed the lower recombination rate of photogenerated carriers compared with pure Bi_(2) MoO_(6) and g-C_(3)N_(4),respectively.The present work is expected to provide useful information in designing 2D/2D S-scheme heterojunction photocatalysts.展开更多
To the Editor:Creatine kinase(CK),also called creatine phosphokinase,is primarily located in the cytoplasm and mitochondria.It can be used to diagnose cardiac diseases such as myocardial infarction,viral myocarditis,a...To the Editor:Creatine kinase(CK),also called creatine phosphokinase,is primarily located in the cytoplasm and mitochondria.It can be used to diagnose cardiac diseases such as myocardial infarction,viral myocarditis,and pericarditis because it is a vital kinase directly related to intracellular energy operation,muscle contraction,and adenosine triphosphate(ATP)regeneration.Several studies have confirmed in recent years that serum biomarkers such as elevated CK are associated with Alzheimer’s disease(AD)and its related pathological protein.[1]Previous research indicated that systemic conditions,particularly cardiovascular and cerebrovascular diseases,are significant risk factors for cognitive impairment,and dysfunction of peripheral organs may also contribute to cognitive decline and AD.[2]However,the connection between CK and AD remains unknown.Therefore,to investigate the association between CK and cerebrospinal fluid(CSF)AD pathology biomarkers,we analyzed data from the Alzheimer’s Disease Neuroimaging Initiative(ADNI),a global multi-centered database.展开更多
基金supported by the National Key R&D Program of China(Grant No.2019YFA0606703)the National Natural Science Foundation of China(Grant No.41975116)the Youth Innovation Promotion Association of the Chinese Academy of Sciences(Grant No.Y202025)。
文摘The application of deep learning is fast developing in climate prediction,in which El Ni?o–Southern Oscillation(ENSO),as the most dominant disaster-causing climate event,is a key target.Previous studies have shown that deep learning methods possess a certain level of superiority in predicting ENSO indices.The present study develops a deep learning model for predicting the spatial pattern of sea surface temperature anomalies(SSTAs)in the equatorial Pacific by training a convolutional neural network(CNN)model with historical simulations from CMIP6 models.Compared with dynamical models,the CNN model has higher skill in predicting the SSTAs in the equatorial western-central Pacific,but not in the eastern Pacific.The CNN model can successfully capture the small-scale precursors in the initial SSTAs for the development of central Pacific ENSO to distinguish the spatial mode up to a lead time of seven months.A fusion model combining the predictions of the CNN model and the dynamical models achieves higher skill than each of them for both central and eastern Pacific ENSO.
基金The National Natural Science Foundation of China under contract Nos 51809047 and U22A20585the Fujian Provincial Natural Science Foundation under contract No.2019J05029.
文摘Mangroves are crucial for protecting coastal areas against extreme disasters such as tsunamis and storm surges.An experimental study was conducted to determine how mangroves can mitigate the tsunami wave propagation.The test was performed in a flume, where mangrove models were installed on a slope, and dam-burst waves were used to simulate tsunami waves. To study how mangrove forests reduce the impact of tsunamis, this paper measured the heights of the incoming waves under different initial conditions(tsunami wave intensity and initial water depth) and plant factors(arrangement and distribution density) and described the reduction process. The results show that, after passing through the mangrove, the tsunami bore height will decrease within a certain range as the initial water depth increases. However, there is no correlation between the increase of inundation level and the drop of water level. The bore height attenuation is more significant at higher density of mangroves,but after tsunami passing through the mangroves, the relative bore height will decrease. When the distribution density of mangroves is constant, the wave attenuation at different locations(before, on and after the slope)shows different relationships with the initial water depth and wave height for different models. The transmission coefficient(K_(i)) shows a parabolic correlation with its density. The proportion of the energy loss caused by the mangrove resistance to the total energy(E_(b)) is defined as C_(m2). The variation trend of C_(m2) corresponds to the tsunami wave energy attenuation rate(C_(a)) and K_(i).
基金supported by NIH grants AR055915 and AR054465 to DC
文摘Osteoarthritis(OA) is the most common degenerative joint disease and a major cause of pain and disability in adult individuals. The etiology of OA includes joint injury, obesity, aging, and heredity. However, the detailed molecular mechanisms of OA initiation and progression remain poorly understood and, currently,there are no interventions available to restore degraded cartilage or decelerate disease progression. The diathrodial joint is a complicated organ and its function is to bear weight, perform physical activity and exhibit a joint-specific range of motion during movement. During OA development, the entire joint organ is affected, including articular cartilage, subchondral bone, synovial tissue and meniscus. A full understanding of the pathological mechanism of OA development relies on the discovery of the interplaying mechanisms among different OA symptoms, including articular cartilage degradation, osteophyte formation, subchondral sclerosis and synovial hyperplasia, and the signaling pathway(s) controlling these pathological processes.
基金supported by grants from the National Nature Science Foundation of China (No. 81200395, 81370632)the National Science and Technology supporting Program (No. 2014BAI09B12)+1 种基金the Fundamental Application and Advanced Technology Research Program of Tianjin (No. 15JCYBJC27900)the National Public Health Grand Research Foundation (No. 201202017)
文摘Objective:This study aims to evaluate the natural history of patients with chronic lymphocytic leukemia(CLL)and a 17p deletion(17p-)and identify the predictive factors within this subgroup.Methods:The sample of patients with CLL were analyzed by fluorescence in situ hybridization for deletions in chromosome bands 11q22,13q14 and 17p13;trisomy of bands 12q13;and translocation involving band 14q32.The data from 456 patients with or without a 17p-were retrospectively collected and analyzed.Results:The overall response rate(ORR)in patients with a 17p-was 56.9%,and patients with a high percentage of 17p-(defined as more than 25%of cells harbouring a 17p-)had a lower ORR.The median overall survival(OS)in patients with a 17p-was 78.0 months,which was significantly shorter than the OS in patients without this genetic abnormality(median 162.0 months,P<0.001).Within the subgroup with a 17p-,the progression-free survival was significantly shorter in patients at Binet stage B-C and patients with elevated lactate dehydrogenase(LDH),B symptoms,unmutated IGHV and a high percentage of 17p-.Conclusions:These results indicated that patients with a 17p-CLL have a variable prognosis that might be predicted using simple clinical and laboratory characteristics.
基金supported by the National Institutes of Health Grants R01 AR054465 and R01 AR070222 to D.Cpartially supported by the Natural Science Foundation of China(NSFC)(grant#81371999)to D.C+2 种基金partially supported by the State Scholarship Fund(No.201406240061)partially sponsored by a grant from Shenzhen Science and Technology Innovation Committee(JCYJ20160331114205502 and JCYJ20150626090344603)partially supported by NSFC grants(grant#81301531 and 81572104),China
文摘β-Catenin plays a critical role in cartilage formation and development. To further understand the role of β-catenin in osteoarthritis(OA) development in temporomandibular joint(TMJ), we have generated β-catenin conditional activation mice(β-cat(ex3)^(Agc1CreER))by breeding Agc1-CreER mice with β-catenin^(flox(ex3)/+)mice. Results of histologic analysis showed the progressive TMJ defects in 3-and 6-month-old β-cat(ex3)^(Agc1CreER)mice(tamoxifen induction was performed at 2 weeks of age), including decreased chondrocyte numbers in the superficial layer associated with less Alcian blue staining, increased numbers of hypertrophic chondrocytes in deep layers, and rough articular surface. Compared to the TMJ phenotype of β-cat(ex3)^(Col2CreER)mice, β-cat(ex3)^(Agc1CreER)mice showed much severe morphological defects in the superficial layer of TMJ. This may reflect that Agc1-CreER mice could efficiently target cells in the superficial layer of TMJ. Results of immunostaining showed significantly increased expression of MMP13, Col-X, Adamts4,and Adamts5 in TMJ of β-cat(ex3)^(Agc1CreER)mice. Results of proliferating cell nuclear antigen(PCNA), Ki67, and terminal deoxinucleotidyl transferase-mediated d UTP-fluorescein nick end labeling(TUNEL) staining further demonstrated that cell proliferation was decreased and cell apoptosis was increased in condylar cartilage of β-cat(ex3)^(Agc1CreER)mice. Our findings indicate that abnormal upregulation of β-catenin in TMJ leads to defects assembling to OA-like phenotype, further demonstrating that β-catenin plays a critical role in TMJ pathogenesis.
基金supported by National Institutes of Health Grants, R01 AR054465, R01 AR070222, and R01 AR070222supported by the grants of Natural Science Foundation of China (NSFC) to TW (grants No. 81301531 and 81572104)+1 种基金supported by the grant from Shenzhen Science and Technology Innovation Committee, China (grant No. JCYJ20160331114205502)the grant from Shenzhen Development and Reform Committee, China for Shenzhen Engineering Laboratory of Orthopedic Regenerative Technologies
文摘Carboxyl terminus of Hsp70-interacting protein(CHIP or STUB1) is an E3 ligase and regulates the stability of several proteins which are involved in different cellular functions. Our previous studies demonstrated that Chip deficient mice display bone loss phenotype due to increased osteoclast formation through enhancing TRAF6 activity in osteoclasts. In this study we provide novel evidence about the function of CHIP. We found that osteoblast differentiation and bone formation were also decreased in Chip KO mice. In bone marrow stromal(BMS) cells derived from Chip^(-/-) mice, expression of a panel of osteoblast marker genes was significantly decreased. ALP activity and mineralized bone matrix formation were also reduced in Chip-deficient BMS cells. We also found that in addition to the regulation of TRAF6, CHIP also inhibits TNFα-induced NF-κB signaling through promoting TRAF2 and TRAF5 degradation. Specific deletion of Chip in BMS cells downregulated expression of osteoblast marker genes which could be reversed by the addition of NF-κB inhibitor. These results demonstrate that the osteopenic phenotype observed in Chip^(-/-) mice was due to the combination of increased osteoclast formation and decreased osteoblast differentiation. Taken together, our findings indicate a significant role of CHIP in bone remodeling.
基金The work was supported by the Central University Fundamental Research Funds Special Fund Project[2572016AA03,25720171118]Harbin Applied Technology Research and Development Project[2016RAXXJ035]the Central Financial Forest Science and Technology Promotion Demonstration Fund Project[JLT[2016]13].
文摘We optimized the extraction process of Lysurus mokusin(L.)Fr.insecticidal compound(LMIC)using response surface methodology with ultrasonic extraction(UE).The surface morphologies of maceration extract(ME)and UE residues were compared by scanning electron microscopy,and then the activity of LMIC on Lymantria dispar(Asian gypsy moths)larvae was determined.Results showed that the optimal condition of UE was followed by 80 min of extraction time,60%of ethanol concentration and 80 mL g^-1 of liquid–solid ratio.The surface morphologies of UE residue were looser and rougher than ME residue.The corrected mortalities of LMIC on L.dispar larvae was 59.77%.This result indicated that L.mokusin was a good candidate as pesticide for pest management.
基金supported by the National Key Research and Development Program of China(No.2021YFA1201601)the National Natural Science Foundation of China(No.52192610).
文摘As extremely important physiological indicators,respiratory signals can often reflect or predict the depth and urgency of various diseases.However,designing a wearable respiratory monitoring system with convenience,excellent durability,and high precision is still an urgent challenge.Here,we designed an easy-fabricate,lightweight,and badge reel-like retractable selfpowered sensor(RSPS)with high precision,sensitivity,and durability for continuous detection of important indicators such as respiratory rate,apnea,and respiratory ventilation.By using three groups of interdigital electrode structures with phase differences,combined with flexible printed circuit boards(FPCBs)processing technology,a miniature rotating thin-film triboelectric nanogenerator(RTF-TENG)was developed.Based on discrete sensing technology,the RSPS has a sensing resolution of 0.13 mm,sensitivity of 7 P·mm^(−1),and durability more than 1 million stretching cycles,with low hysteresis and excellent anti-environmental interference ability.Additionally,to demonstrate its wearability,real-time,and convenience of respiratory monitoring,a multifunctional wearable respiratory monitoring system(MWRMS)was designed.The MWRMS demonstrated in this study is expected to provide a new and practical strategy and technology for daily human respiratory monitoring and clinical diagnosis.
文摘Osteoarthritis(OA)is a painful degenerative joint disease and is the leading cause of chronic disability among elderly individuals.To improve the quality of life for patients with OA,the primary goal for OA treatment is to relieve the pain.During OA progression,nerve ingrowth was observed in synovial tissue and articular cartilage.These abnormal neonatal nerves act as nociceptors to detect OA pain signals.The molecular mechanisms for transmitting OA pain in the joint tissues to the central nerve system(CNS)is currently unknown.MicroRNA miR-204 has been demonstrated to maintain the homeostasis of joint tissues and have chondro-protective effect on OA pathogenesis.However,the role of miR-204 in OA pain has not been determined.In this study,we investigated interactions between chondrocytes and neural cells and evaluated the effect and mechanism of miR-204 delivered by exosome in the treatment of OA pain in an experimental OA mouse model.Our findings demonstrated that miR-204 could protect OA pain by inhibition of SP1-LDL Receptor Related Protein 1(LRP1)signaling and blocking neuro-cartilage interaction in the joint.Our studies defined novel molecular targets for the treatment of OA pain.
基金the National Natural Science Foundation of China(81970187,82170193,81920108006,and 81900203)Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2021-I2M-C&T-B-081).
文摘Rituximab maintenance(RM)prolongs the progression-free survival(PFS)of responding patients with follicular lymphoma(FL),but the maintenance efficacy in different Follicular Lymphoma International Prognostic Index(FLIPI)risk group is still confusing.We performed a retrospective analysis of the effect of RM treatments in patients with FL responding to induction therapy based on their FLIPI risk assessment carried out prior to treatment.We identified 93 patients between 2013 and 2019 who received RM every 3 months for≥4 doses(RM group),and 60 patients who did not accept RM or received rituximab less than 4 doses(control group).After a median follow-up of 39 months,neither median overall survival(OS)nor PFS was reached for the entire population.The PFS was significantly prolonged in the RM group compared to the control group(median PFS NA vs 83.1 months,P=.00027).When the population was divided into the 3 FLIPI risk groups,the PFS differed significantly(4-year PFS rates,97.5%vs 88.8%vs 72.3%,P=.01)according to group.There was no significant difference in PFS for FLIPI low-risk patients with RM compared to the control group(4-year PFS rates,100%vs 93.8%,P=.23).However,the PFS of the RM group was significantly prolonged for FLIPI intermediate-risk(4-year PFS rates,100%vs 70.3%,P=.00077)and high-risk patients(4-year PFS rates,86.7%vs 57.1%,P=.023).These data suggest that standard RM significantly prolongs the PFS of patients assigned to intermediate-and high-risk FLIPI groups but not to low-risk FLIPI group,and pending larger-scale studies to validate.
基金National Nature Science Foundation of China(Nos.81900203,81970187,82170193,and 81920108006)Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(Nos.2022-12M-1-022,2021-I2M-C&T-B-081)
文摘To the Editor:As a rare indolent B cell non-Hodgkin lymphoma,lymphoplasmacytic lymphoma/Waldenström’s macroglobulinemia(LPL/WM)has unique clinical and biological characteristics.[1]However,due to the difficulties in obtaining tumor metaphase for karyotyping and slow cell proliferation,only very few studies have detected the cytogenetic aberration of LPL/WM.[2,3]In addition,6q deletion is the most common cytogenetic aberration in WM,with an incidence rate of about 50%.[2]Nevertheless,other cytogenetic aberrations remain largely unclear,and the prognostic role of cytogenetic aberrations needs to be further explored.In the present study,we systematically analyzed 305 LPL/WM cases in China,focusing on the characteristics and cytogenetic aberrations in Chinese patients.
基金supported by the National Natural Science Foundation of China(82170194,81920108006,82270175)the CAMS Innovation Fund for Medical Sciences(CIFMS 2021-I2M-1-040,CIFMS 2022-I2M-022).
文摘MicroRNAs(MiRNAs)carried by exosomes play pivotal roles in the crosstalk between cell components in the tumor microenvironment.Our study aimed at identifying the expression profile of exosomal miRNAs(exo-miRNAs)in the serum of multiple myeloma(MM)patients and investigating the regulation networks and their potential functions by integrated bioinformatics analysis.Exosomes in serum from 19 newly diagnosed MM patients and 9 healthy donors were isolated and the miRNA profile was investigated by small RNA sequencing.Differential expression of exo-miRNAs was calculated and target genes of miRNAs were predicted.CytoHubba was applied to identify the hub miRNAs and core target genes.The LASSO Cox regression model was used to develop the prognostic model,and the ESTIMATE immune score was calculated to investigate the correlation between the model and immune status in MM patients.The top six hub differentially expressed serum exo-miRNAs were identified.513 target genes of the six hub exo-miRNAs were confirmed to be differentially expressed in MM cells in the Zhan Myeloma microarray dataset.Functional enrichment analysis indicated that these target genes were mainly involved in mRNA splicing,cellular response to stress,and deubiquitination.13 core exo-miRNA target genes were applied to create a novel prognostic signature to provide risk stratification for MM patients,which is associated with the immune microenvironment of MM patients.Our study comprehensively investigated the exo-miRNA profiles in MM patients.A novel prognostic signature was constructed to facilitate the risk stratification of MM patients with distinct outcomes.
文摘Multi-core processor is widely used as the running platform for safety-critical real-time systems such as spacecraft,and various types of real-time tasks are dynamically added at runtime.In order to improve the utilization of multi-core processors and ensure the real-time performance of the system,it is necessary to adopt a reasonable real-time task allocation method,but the existing methods are only for single-core processors or the performance is too low to be applicable.Aiming at the task allocation problem when mixed real-time tasks are dynamically added,we propose a heuristic mixed real-time task allocation algorithm of virtual utilization VU-WF(Virtual Utilization Worst Fit)in multi-core processor.First,a 4-tuple task model is established to describe the fixedpoint task and the sporadic task in a unified manner.Then,a VDS(Virtual Deferral Server)for serving execution requests of fixed-point task is constructed and a schedulability test of the mixed task set is derived.Finally,combined with the analysis of VDS's capacity,VU-WF is proposed,which selects cores in ascending order of virtual utilization for the schedulability test.Experiments show that the overall performance of VU-WF is better than available algorithms,not only has a good schedulable ratio and load balancing but also has the lowest runtime overhead.In a 4-core processor,compared with available algorithms of the same schedulability ratio,the load balancing is improved by 73.9%,and the runtime overhead is reduced by 38.3%.In addition,we also develop a visual multi-core mixed task scheduling simulator RT-MCSS(open source)to facilitate the design and verification of multi-core scheduling for users.As the high performance,VU-WF can be widely used in resource-constrained and safety-critical real-time systems,such as spacecraft,self-driving cars,industrial robots,etc.
基金financially supported by the Fundamental Research Funds for the Central Universities(No.JUSRP51716A)the National Natural Science Foundation of China(Nos.21203077 and 21773099)the financially support from the Qing Lan Project of Jiangsu Province。
文摘A novel 2D/2D Bi_(2)MoO_(6)/g-C_(3)N_(4) step-scheme(S-scheme)composite by loading Au as cocatalyst was successfully fabricated using a photoreduction and hydrothermal route.The obtained Bi_(2)MoO_(6)/g-C_(3)N_(4)/Au photocatalysts were characterized by X-ray diffraction(XRD),transmission electron microscope(TEM),X-ray photo-electron spectroscopy(XPS),UV–vis diffuse reflectance spectra(UV–vis),Fourier transform infrared spectroscopy(FTIR),photoluminescence(PL),photocurrent response(I-t),and electrochemical impedance spectroscopy(EIS).The HRTEM images revealed that an intimate interface in composites were formed.The optimum photocatalytic activity of Rhodamine B degradation over Bi_(2)MoO_(6)/g-C_(3)N_(4)/Au was about 9.7 times and 13.1 times as high as those of Bi_(2)MoO_(6) and g-C_(3)N_(4),respectively.The notably improved photocatalytic activity of Bi_(2)MoO_(6)/g-C_(3)N_(4)/Au could be mainly ascribed to the abundant active sites and the enhanced separation efficiency of photogenerated carriers in Bi_(2)MoO_(6)/g-C_(3)N_(4) S-scheme system.Notably,Au nanoparticles could act as a co-catalyst to further promote electron transfer and separation from the conduction band of g-C_(3)N_(4).Additionally,a possible step-scheme photocatalytic reaction mechanism of Rh B degradation over Bi_(2)MoO_(6)/g-C_(3)N_(4)/Au was tentatively proposed.PL and transient photocurrent analysis implied that Bi_(2)MoO_(6)/g-C_(3)N_(4)/Au photocatalysts possessed the lower recombination rate of photogenerated carriers compared with pure Bi_(2) MoO_(6) and g-C_(3)N_(4),respectively.The present work is expected to provide useful information in designing 2D/2D S-scheme heterojunction photocatalysts.
基金supported by the Clinical Trial Ability Improvement Project of the Cardiovascular Professional Group of the First Affiliated Hospital of Soochow University(No.201900180019)
文摘To the Editor:Creatine kinase(CK),also called creatine phosphokinase,is primarily located in the cytoplasm and mitochondria.It can be used to diagnose cardiac diseases such as myocardial infarction,viral myocarditis,and pericarditis because it is a vital kinase directly related to intracellular energy operation,muscle contraction,and adenosine triphosphate(ATP)regeneration.Several studies have confirmed in recent years that serum biomarkers such as elevated CK are associated with Alzheimer’s disease(AD)and its related pathological protein.[1]Previous research indicated that systemic conditions,particularly cardiovascular and cerebrovascular diseases,are significant risk factors for cognitive impairment,and dysfunction of peripheral organs may also contribute to cognitive decline and AD.[2]However,the connection between CK and AD remains unknown.Therefore,to investigate the association between CK and cerebrospinal fluid(CSF)AD pathology biomarkers,we analyzed data from the Alzheimer’s Disease Neuroimaging Initiative(ADNI),a global multi-centered database.