Rice(Oryza sativa),a major staple throughout the world and a model system for plant genomics and breeding,was the first crop genome sequenced almost two decades ago.However,reference genomes for all higher organisms t...Rice(Oryza sativa),a major staple throughout the world and a model system for plant genomics and breeding,was the first crop genome sequenced almost two decades ago.However,reference genomes for all higher organisms to date contain gaps and missing sequences.Here,we report the assembly and analysis of gap-free reference genome sequences for two elite O.sativa xian/indica rice varieties,Zhenshan 97 and Minghui 63,which are being used as a model system for studying heterosis and yield.Gap-free reference genomes provide the opportunity for a global view of the structure and function of centromeres.We show that all rice centromeric regions share conserved centromere-specific satellite motifs with different copy numbers and structures.In addition,the similarity of CentO repeats in the same chromosome is higher than across chromosomes,supporting a model of local expansion and homogenization.Both genomes have over 395 non-TE genes located in centromere regions,of which∼41%are actively transcribed.Two large structural variants at the end of chromosome 11 affect the copy number of resistance genes between the two genomes.The availability of the two gap-free genomes lays a solid foundation for further understanding genome structure and function in plants and breeding climate-resilient varieties.展开更多
Anthocyanins are biosynthesized on the cytosolic surface of the endoplasmic reticulum and then transported into the vacuole for storage.Glutathione S-transferases(GSTs)are considered to be responsible for the transpor...Anthocyanins are biosynthesized on the cytosolic surface of the endoplasmic reticulum and then transported into the vacuole for storage.Glutathione S-transferases(GSTs)are considered to be responsible for the transport of anthocyanins into the vacuole.However,the regulatory mechanisms of GSTs in plants are still unclear.Here,we performed a genome-wide analysis and identified 69 GST genes in apple.The expression of MdGSTF6 was positively correlated with the anthocyanin content(r=0.949)during‘Yanfu 8’fruit development.The overexpression of MdGSTF6 in the Arabidopsis thaliana tt19 mutant resulted in seedlings of 35S::MdGSTF6-GFP/tt19 that could accumulate anthocyanin and rescue its phenotype,suggesting that MdGSTF6 was an anthocyanin transporter.The silencing of MdGSTF6 affected anthocyanin accumulation in apple fruit.Moreover,the knockdown of MdGSTF6 by RNA interference in cultured‘Gala’seedlings inhibited anthocyanin accumulation.The interaction experiments showed that MdMYB1 could bind directly to the MdGSTF6 promoter to transcriptionally activate its expression.Collectively,our results demonstrate that MdGSTF6 encodes an important GST transporter of anthocyanins in apple fruit and provide evidence for the associated regulatory mechanisms.Therefore,MdMYB1 can not only regulate anthocyanin synthesis,but also control the transport of anthocyanin in apples.This information may be useful for further clarifying the regulation of anthocyanin transport in apple.展开更多
目的研发基于人工智能深度学习技术的全髋关节置换术(total hip arthroplasty,THA)髋臼假体型号算法并进行初步验证。方法回顾性分析2019年4月至2020年4月30例股骨头坏死患者资料,其中男15例,女15例;年龄(54.8±10.5)岁(范围33~72...目的研发基于人工智能深度学习技术的全髋关节置换术(total hip arthroplasty,THA)髋臼假体型号算法并进行初步验证。方法回顾性分析2019年4月至2020年4月30例股骨头坏死患者资料,其中男15例,女15例;年龄(54.8±10.5)岁(范围33~72岁),左侧13髋,右侧17髋,均接受初次单侧THA。在完成髋关节图像手工标注的基础上,训练人工智能深度学习卷积神经网络对患者髋关节CT骨质进行分割,而后识别骨盆解剖标志位点,并对骨盆位置进行矫正并模拟安放髋臼杯,分别采用dice overlap coefficients(DOC)、平均误差等参数对上述步骤的精度进行评估,最终形成人工智能髋臼假体型号算法。并使用该算法与Orthoview二维术前规划软件分别对患者髋臼杯大小进行规划,将两组规划结果与已完成的实际手术结果进行比对,分别计算其符合率,从而回顾性验证本算法的规划效果。结果在算法方面,与其他经典分割网络相比,G-net网络可更精准的完成对股骨头坏死髋关节骨质的分割,DOC为92.51%±6.70%,且具有更好的鲁棒性(robustness),点识别网络平均误差为0.87个像素值。在临床应用效果方面,人工智能组完全符合率为96.7%(29/30),较Orthoview组的73.3%(22/30)高23.4%,差异有统计学意义(χ^2=6.405,P=0.011)。结论深度学习技术可精准分割患者髋关节CT图像,识别髋关节特征点,人工智能THA髋臼杯放置算法与传统二维术前规划方式相比具有较高的准确性。此算法有望实现准确、快速的THA三维术前规划。展开更多
Numerous studies on eutrophication remediation have mainly focused on purifying water first, then restoring submerged macrophytes. A restoration-promoting integrated floating bed （RPIFB） was designed to combine the ...Numerous studies on eutrophication remediation have mainly focused on purifying water first, then restoring submerged macrophytes. A restoration-promoting integrated floating bed （RPIFB） was designed to combine the processes of water purification and macrophyte restoration simultaneously. Two outdoor experiments were conducted to evaluate the ecological functions of the RP1FB. Trial 1 was conducted to compare the eutrophication purification among floating bed, gradual-submerging bed （GSB） and RPIFB technologies. The results illustrated that RPIFB has the best purification capacity. Removal efficiencies of RPIFB for TN, TP,NH4＋-N, NO3-N, CODcr, Chlorophyll-a and turbidity were 74.45%, 98.31%, 74.71%, 88.81%, 71.42%, 90.17% and 85%, respectively. In trial 2, influences of depth of GSB and photic area in RPIFB on biota were investigated. When the depth of GSB decreased and the photic area of RPIFB grew, the height of Potamogeton crispus Linn. increased, but the biomass of Canna indica Linn. was reduced. The mortalities of Misgurnus anguillicaudatus and Bellamya aeruginosa in each group were all less than 7%. All results indicated that when the RPIFB was embedded into the eutrophic water, the regime shift from phytoplankton-dominated to macrophyte-dominated state could be promoted. Thus, the RPIFB is a promising remediation technology for eutrophication and submerged macrophyte restoration.展开更多
Flavonoids play essential roles in human health.Apple(Malus domestica Borkh.),one of the most widely produced and economically important fruit crops in temperate regions,is a significant source of flavonoids in the hu...Flavonoids play essential roles in human health.Apple(Malus domestica Borkh.),one of the most widely produced and economically important fruit crops in temperate regions,is a significant source of flavonoids in the human diet and is among the top nutritionally rated and most widely consumed fruits worldwide.Epidemiological studies have shown that the consumption of apples,which are rich in a variety of free and easily absorbable flavonoids,is associated with a decreased risk of various diseases.However,apple production is challenged by serious inbreeding problems.The narrowing of the hereditary base has resulted in apples with poor nutritional quality and low flavonoid contents.Recently,there have been advances in our understanding of the roles that Malus sieversii(Ledeb.)M.Roem has played in the process of apple domestication and breeding.In this study,we review the origin of cultivated apples and red-fleshed apples,and discuss the genetic diversity and construction of the core collections of M.sieversii.We also discuss current research progress and breeding programs on red-skinned and red-fleshed apples and summarize the exploitation and utilization of M.sieversii in the breeding of high-flavonoid,and red-fleshed apples.This study highlights a valuable pattern of horticultural crop breeding using wild germplasm resources.The future challenges and directions of research on the molecular mechanisms of flavonoid accumulation and high-flavonoid apple breeding are discussed.展开更多
Esophageal squamous cell carcinoma continues to heavily burden clinicians worldwide. Researchers have discovered the genomic landscape of esophageal squamous cell carcinoma, which holds promise for an era of personali...Esophageal squamous cell carcinoma continues to heavily burden clinicians worldwide. Researchers have discovered the genomic landscape of esophageal squamous cell carcinoma, which holds promise for an era of personalized oncology care. One of the most pressing problems facing this issue is to improve the understanding of the newly available genomic data, and identify the driver-gene mutations, pathways, and networks. The emergence of a legion of novel targeted agents has generated much hope and hype regarding more potent treatment regimens, but the accuracy of drug selection is still arguable. Other problems, such as cancer heterogeneity, drug resistance, exceptional responders, and side effects, have to be surmounted. Evolving topics in personalized oncology, such as interpretation of genomics data, issues in targeted therapy, research approaches for targeted therapy, and future perspectives, will be discussed in this editorial.展开更多
AIM: To study the anti-HBV effect of liposome-encapsulated matrine (Lip-M) in vitro and in vivo. METHODS: 2.2.15 cell line was cultured in vitro observe the effect of Lip-M and matrine on the secretion of HBsAg and HB...AIM: To study the anti-HBV effect of liposome-encapsulated matrine (Lip-M) in vitro and in vivo. METHODS: 2.2.15 cell line was cultured in vitro observe the effect of Lip-M and matrine on the secretion of HBsAg and HBeAg. The toxicity of Lip-M and matrine to 2.2.15 cell line was also studied by MTT method. In in vivo study, drug treatment experiment was carried out on the 13th day after ducks were infected with duck hepatitis B virus (DHBV). The ducks were randomly divided into 4 groups with 5-6 ducks in each group. Lip-M and matrine were given to DHBV-infected ducks respectively by gastric perfusion. Four groups were observed: group of Lip-M (20 mg/kg), group of Lip-M (10 mg/kg), group of matrine (20 mg/kg) and group of blank model. The drug was given once daily for 20 d continuously, and normal saline was used as control. The blood was drawn from the posterior tibial vein of all ducks before treatment (T0), after the medication for 5 (T5), 10 (T10), 15 (T15), 20 (T20) d and withdrawl of the drug for 3 d (P3). The serum samples were separated and stored at -70 ℃, DHBV-DNA was detected by the dot-blot hybridization. RESULTS: After addition of Lip-M and matrine to 2.2.15 cell line for eleven d, the median toxic concentration (TC50) of Lip-M and matrine was 7.29 mg/mL and 1.33 mg/mL respectively. The median concentration (IC50) of Lip-M to inhibit HBsAg and HBeAg expression was 0.078 mg/mL and 3.35 mg/mL respectively. The treatment index (TI) value of Lip-M for HBsAg and HBeAg was 93.46 and 2.17 respectively, better than that of matrine. The DHBV-infected duck model treatment test showed that the duck serum DHBV-DNA levels were markedly reduced in the group of Lip-M (20 mg/kg) after treated by gastric perfusion for 10, 15 and 20 d (0.43±0.22 vs 0.95±0.18, t = 4.70, P= 0.001<0.01.0.40±0.12 vs 0.95±0.18, t = 6.34, P= 0.000<0.01. 0.22±0.10 vs 0.95±0.18, t = 8.30, P= 0.000<0.01), compared to the group of matrine (20 mg/kg) (0.43±0.22 vs 0.79±0.19, t = 3.17, P= 0.01<0.05. 0.40±0.12 vs 0.73±0.24, t = 3.21, P=展开更多
The immune system initiates robust immune responses to defend against invading pathogens or tumor cells and protect the body from damage,thus acting as a fortress of the body.However,excessive responses cause detrimen...The immune system initiates robust immune responses to defend against invading pathogens or tumor cells and protect the body from damage,thus acting as a fortress of the body.However,excessive responses cause detrimental effects,such as inflammation and autoimmune diseases.To balance the immune responses and maintain immune homeostasis,there are immune checkpoints to terminate overwhelmed immune responses.Pathogens and tumor cells can also exploit immune checkpoint pathways to suppress immune responses,thus escaping immune surveillance.As a consequence,therapeutic antibodies that target immune checkpoints have made great breakthroughs,in particular for cancer treatment.While the overall efficacy of immune checkpoint blockade(ICB)is unsatisfactory since only a small group of patients benefted from ICB treatment.Hence,there is a strong need to search for other targets that improve the efficacy of ICB.Ubiquitination is a highly conserved process which participates in numerous biological activities,including innate and adaptive immunity.A growing body of evidence emphasizes the importance of ubiquitination and its reverse process,deubiquitination,on the regulation of immune responses,providing the rational of simultaneous targeting of immune checkpoints and ubiquitination/deubiquitination pathways to enhance the therapeutic efficacy.Our review will summarize the latest findings of ubiquitination/deubiquitination pathways for anti-tumor immunity,and discuss therapeutic significance of targeting ubiquitination/deubiquitination pathways in the future of immunotherapy.展开更多
Exercise training is beneficial to the cardiovascular system. MicroRNAs （miRNAs, miRs） are a class of conserved non-coding RNAs and play a wide-ranging role in the regulation of eukaryotic gene expression. Exercise ...Exercise training is beneficial to the cardiovascular system. MicroRNAs （miRNAs, miRs） are a class of conserved non-coding RNAs and play a wide-ranging role in the regulation of eukaryotic gene expression. Exercise training alters the expression levels of large amounts ofmiRNAs in the heart. In addition, circulating miRNAs appear to be regulated by exercise training. In this review, we will summarize recent advances in the regulation of miRNAs during physical exercise intervention in various cardiovascular diseases, including pathologic cardiac hypertrophy, myocardial fibrosis, ischemia-reperfusion injury, myocardial infarction, and heart failure. The regulatory role of circulating miRNAs after exercise training was also reviewed. In conclusion, miRNAs might be a valuable target for treatment of cardiovascular diseases and have great potential as biomarkers for assessment of physical performance.2018 Published by Elsevier B.V.on behalf of Shanghai University of Sport. This is an open access article under the CC BY-NC-ND license. （http：//creativecommons.org/licenses/by-nc-nd/4.0/）.展开更多
Apple ring rot,which is caused by Botryosphaeria dothidea,severely affects apple production.The mechanisms employed in apple cells against B.dothidea remain unknown.In this research,the pathogen infection mode and the...Apple ring rot,which is caused by Botryosphaeria dothidea,severely affects apple production.The mechanisms employed in apple cells against B.dothidea remain unknown.In this research,the pathogen infection mode and the relationship between cell death and disease resistance in‘Fuji’/B.dothidea interaction pathosystem were investigated.By using transmission electron microscopy(TEM),our research showed that the pathogen infects apple cells both intracellularly and extracellularly.However,compared with that in immature fruit,the incidence of hyphae in the interior of mature apple fruit cells increased dramatically,suggesting that cell wall-mediated penetration resistance could be important in apple resistance against B.dothidea.TEM ultrastructural characterization identified the nuclear morphology of programmed cell death induction in both apple fruit and callus cells under B.dothidea infection.Overexpression of MdVDAC2(MDP0000271281),which encodes an outer-membrane localized anion channel protein in mitochondria,significantly promoted cell death under B.dothidea infection and simultaneously inhibited pathogen infection,suggesting that cell death represents a disease resistance mechanism in apple against B.dothidea infection.Furthermore,BdCatalase(KAF4307763),a cytochromeP450 family protein BdCYP52A4(KAF4300696),and subtilisin-domain containing proteinswere identified fromB.dothidea-secreted proteins,which suggested the potential involvement of active oxygen species and phytoalexins in combating B.dothidea infection and triggering or dampening apple resistance.Collectively,our research suggested that cell wall-mediated penetration resistance,programmed cell death machinery and microbial effector-interrelated signaling were among strategies recruited in apple to combat B.dothidea.The current research laid the foundation for further investigations into resistance mechanisms in apple.展开更多
The recycling and reutilization of spent lithium-ion batteries(LIBs)have become an important measure to alleviate problems like resource scarcity and environmental pollution.Although some progress has been made,batter...The recycling and reutilization of spent lithium-ion batteries(LIBs)have become an important measure to alleviate problems like resource scarcity and environmental pollution.Although some progress has been made,battery recycling technology still faces challenges in terms of efficiency,effectiveness and environmental sustainability.This review aims to systematically review and analyze the current status of spent LIB recycling,and conduct a detailed comparison and evaluation of different recycling processes.In addition,this review introduces emerging recycling techniques,including deep eutectic solvents,molten salt roasting,and direct regeneration,with the intent of enhancing recycling efficiency and diminishing environmental repercussions.Furthermore,to increase the added value of recycled materials,this review proposes the concept of upgrading recycled materials into high value-added functional materials,such as catalysts,adsorbents,and graphene.Through life cycle assessment,the paper also explores the economic and environmental impacts of current battery recycling and highlights the importance that future recycling technologies should achieve a balance between recycling efficiency,economics and environmental benefits.Finally,this review outlines the opportunities and challenges of recycling key materials for next-generation batteries,and proposes relevant policy recommendations to promote the green and sustainable development of batteries,circular economy,and ecological civilization.展开更多
Wavefront sensing is the simultaneous measurement of the amplitude and phase of an incoming optical field.Traditional wavefront sensors such as Shack-Hartmann wavefront sensor(SHWFS)suffer from a fundamental tradeoff ...Wavefront sensing is the simultaneous measurement of the amplitude and phase of an incoming optical field.Traditional wavefront sensors such as Shack-Hartmann wavefront sensor(SHWFS)suffer from a fundamental tradeoff between spatial resolution and phase estimation and consequently can only achieve a resolution of a few thousand pixels.To break this tradeoff,we present a novel computational-imaging-based technique,namely,the Wavefront Imaging Sensor with High resolution(WISH).We replace the microlens array in SHWFS with a spatial light modulator(SLM)and use a computational phase-retrieval algorithm to recover the incident wavefront.This wavefront sensor can measure highly varying optical fields at more than 10-megapixel resolution with the fine phase estimation.To the best of our knowledge,this resolution is an order of magnitude higher than the current noninterferometric wavefront sensors.To demonstrate the capability of WISH,we present three applications,which cover a wide range of spatial scales.First,we produce the diffraction-limited reconstruction for long-distance imaging by combining WISH with a large-aperture,low-quality Fresnel lens.Second,we show the recovery of high-resolution images of objects that are obscured by scattering.Third,we show that WISH can be used as a microscope without an objective lens.Our study suggests that the designing principle of WISH,which combines optical modulators and computational algorithms to sense high-resolution optical fields,enables improved capabilities in many existing applications while revealing entirely new,hitherto unexplored application areas.展开更多
Background:Burn shock caused by vascular leakage is one of the main causes of high mortality in severe burn injury.However,the pathophysiological mechanism of vascular leakage is still unclear.The purpose of this stud...Background:Burn shock caused by vascular leakage is one of the main causes of high mortality in severe burn injury.However,the pathophysiological mechanism of vascular leakage is still unclear.The purpose of this study was to explore the molecular mechanism of vascular leakage in the early stage of severe burn and provide a new target for the treatment of severe burns.Methods:Neutrophils were isolated from human peripheral blood by magnetic beads sorting.ELISA was used to detect neutrophil-derived granule proteins and glycocalyx injury products in plasma.The vascular leakage and neutrophil movement were assessed by in vivo laser confocal imaging in mice,and high-quality video were provided.Adhesion-related molecules were investigated by qRT-PCR.The damage to glycocalyx of mice vascular endothelial cellswas observed by transmission electron microscope and scanning electron microscope.Proteomic analysis,flow cytometry and immunofluorescence were used to further study the relationship between human peripheral blood neutrophil-derived hypochlorite(HOCl)and CD44 of human vascular endothelial cells.Results:In this study,we found that rapidly increasing activated neutrophils secrete heparin binding protein(HBP)andmyeloperoxidase(MPO)after severe burn injury.Increased HBP triggers vascular leakage with synergy of MPO,results in systemic edema and burn shock.Furthermore,we found that the MPO catalytic product HOCl but not MPO triggers CD44 extracellular domain shedding from vascular endothelial cells to damage the glycocalyx.Damage to the glycocalyx results in firm adhesion of neutrophils and increases vascular leakage.However,MPO inhibitors partially protect the glycocalyx of vascular endothelial cells.The combination of HBP and MPO inhibitors markedly reduces vascular leakage and systemic edema in the early stage of severe burns.Conclusions:Taken together,these data reveal that neutrophil-derived HBP and MPO play an important synergies role in triggering vascular leakage at the early stage of severe burns.Targeted inter展开更多
Anthocyanin biosynthesis and sugar metabolism are important processes during plant growth,but the molecular interactions underlying these pathways are still unclear.In this work,we analyzed the anthocyanin and soluble...Anthocyanin biosynthesis and sugar metabolism are important processes during plant growth,but the molecular interactions underlying these pathways are still unclear.In this work,we analyzed the anthocyanin and soluble sugar contents,as well as the transcript levels of transcription factors that are known to be related to the biosynthesis of anthocyanin in‘Hongcui 1’apple flesh during fruit development.Overexpression of MdMYB6 in red-fleshed calli was found to reduce anthocyanin content and result in downregulated expression of the MdANS and MdGSTF12 proteins.Yeast one-hybrid and electrophoretic mobility shift analyses showed that MdMYB6 could directly bind to the promoters of MdANS and MdGSTF12,indicating that MdMYB6 could inhibit anthocyanin biosynthesis by regulating MdANS and MdGSTF12.Overexpression of MdTMT1 in the Arabidopsis tmt1 mutant restored the glucose and fructose contents to the wild-type levels,while overexpression of MdTMT1 in red-fleshed calli increased the contents of glucose and fructose but reduced the contents of UDP-glucose,UDP-galactose,and anthocyanin.Using a GUS reporter system,yeast one-hybrid,chromatin immunoprecipitation-PCR and electrophoretic mobility shift analyses,we found that MdMYB6 could bind to the promoter of MdTMT1,resulting in increased promoter activity.Overexpression of MdMYB6 in calli overexpressing MdTMT1 increased the expression of MdTMT1,which led to reduced contents of UDP-glucose and UDP-galactose and decreased anthocyanin content compared to those of the calli that overexpressed MdTMT1.This finding suggested that MdMYB6 could also inhibit anthocyanin biosynthesis by regulating MdTMT1 to decrease the contents of UDP-glucose and UDP-galactose.Taken together,these results showed that MdMYB6 and MdTMT1 play key roles in both anthocyanin biosynthesis and sugar transport.展开更多
Metallic Sn has provoked tremendous progress as an anode material for sodium-ion batteries(SIBs).However,Sn anodes suffer from a dramatic capacity fading,owing to pulverization induced by drastic volume expansion duri...Metallic Sn has provoked tremendous progress as an anode material for sodium-ion batteries(SIBs).However,Sn anodes suffer from a dramatic capacity fading,owing to pulverization induced by drastic volume expansion during cycling.Herein,a flexible three-dimensional(3D)hierarchical conductive network electrode is designed by constructing Sn quantum dots(QDs)encapsulated in one-dimensional N,S codoped carbon nanofibers(NS-CNFs)sheathed within two-dimensional(2D)reduced graphene oxide(rGO)scrolls.In this ingenious strategy,1D NS-CNFs are regarded as building blocks to prevent the aggregation and pulverization of Sn QDs during sodiation/desodiation,2D rGO acts as electrical roads and“bridges”among NS-CNFs to improve the conductivity of the electrode and enlarge the contact area with electrolyte.Because of the unique structural merits,the flexible 3D hierarchical conductive network was directly used as binder-and current collectorfree anode for SIBs,exhibiting ultra-long cycling life(373 mAh g?1 after 5000 cycles at 1 A g?1),and excellent high-rate capability(189 mAh g?1 at 10 A g?1).This work provides a facile and efficient engineering method to construct 3D hierarchical conductive electrodes for other flexible energy storage devices.展开更多
Coal is widely utilized as an important energy source,but coal-fired power plant was considered to be an important anthropogenic lead emission source.In the present study,the distribution characteristics of lead in co...Coal is widely utilized as an important energy source,but coal-fired power plant was considered to be an important anthropogenic lead emission source.In the present study,the distribution characteristics of lead in coal and combustion by-products are reviewed.Specifically,lead is mainly transferred to ash particles and the formation and migration mechanisms of particulate lead are summarized.Also,targeted measures are proposed to control the formation of fine particulate lead as well as to increase the removal efficiency during the low-temperature flue gas clean process.In detail,interactions between gaseous lead and some coal-bearing minerals or added adsorbents could obviously suppress the formation of fine particulate lead.On the other hand,some efforts(including promoting capture of fine particles,reducing resistivity of particles and strengthening the gas-liquid contact)could be made to improve the fine particulate lead removal capacity.Notably,the formation mechanism of fine particulate lead is still unclear due to the limitations of research methods.Some differences in the removal principles of fine particles and particulate lead make the lead emission precisely control a great challenge.Finally,the environmental potential risk of lead emission from flue gas and ash residues is addressed and further discussed.展开更多
TP53 gene alteration confers inferior prognosis in refractory/relapse aggressive B-cell non-Hodgkin lymphoma(r/r B-NHL).From September 2016 to September 2020,257 r/r B-NHL patients were assessed for eligibility for tw...TP53 gene alteration confers inferior prognosis in refractory/relapse aggressive B-cell non-Hodgkin lymphoma(r/r B-NHL).From September 2016 to September 2020,257 r/r B-NHL patients were assessed for eligibility for two trials in our center,assessing anti-CD19 and anti-CD22 chimeric antigen receptor(CAR19/22)T-cell cocktail treatment alone or in combination with autologous stem cell transplantation(ASCT).TP53 alterations were screened in 123 enrolled patients and confirmed in 60.CAR19/22 T-cell administration resulted in best objective(ORR)and complete(CRR)response rate of 87.1%and 45.2%in patients with TP53 alterations.展开更多
AIM:To facilitate translational research on cholelithiasis,we have developed a rat model of human gallstones by exploiting the unique biliopancreatic features of this species.METHODS:Under anesthesia,16 adult rats of ...AIM:To facilitate translational research on cholelithiasis,we have developed a rat model of human gallstones by exploiting the unique biliopancreatic features of this species.METHODS:Under anesthesia,16 adult rats of equal genders underwent two times of abdominal surgery.First,their common bile duct(CBD)was ligated to cause cholestasis by total biliary obstruction(TBO).On day 0,1,3,7,14,21 and 28 after TBO,magnetic resonance imaging(MRI)was conducted to monitor the dilatation of the CBD,and blood was sampled to analyze total serum bilirubin(TSB).Secondly,on day 30,the abdomen was re-opened and gallstone(s)collected from human patients were implanted in the dilated CBD asa virtual gallbladder(VGB),which was closed by suture ligation.This rat cholelithiasis model was examined by MRI,clinical observation,microcholangiography and histology.RESULTS:All rats survived two laparotomies.After ligation,the CBD was dilated to a stable size of 4 to30 mm in diameter on day 21-28,which became a VGB.The rats initially showed signs of jaundice that diminished over time,which paralleled with the evolving TSB levels from 0.6±0.3 mg/d L before ligation,through a peak of 10.9±1.9 mg/dL on day 14,until a nearly normalized value after day 28.The dilated CBD with thickened wall allowed an incision for implantation of human gallstones of 1-10 mm in diameter.The rat cholelithiasis was proven by in vivo MRI and postmortem microcholangiography and histomorphology.CONCLUSION:A rat model cholelithiasis with human gallstones has been established,which proves feasible,safe,reliable,nontoxic and cost-effective.Given the gallstones of human origin,applications of this model may be of help in translational research such as optical detection and lysis of gallstones by systemic drug administration.展开更多
Electric vehicles(EVs)have garnered significant attention as a vital driver of economic growth and environmental sustainability.Nevertheless,ensuring the safety of high-energy batteries is now a top priority that cann...Electric vehicles(EVs)have garnered significant attention as a vital driver of economic growth and environmental sustainability.Nevertheless,ensuring the safety of high-energy batteries is now a top priority that cannot be overlooked during large-scale applications.This paper proposes an innovative active protection and cooling integrated battery module using smart materials,magneto-sensitive shear thickening fluid(MSTF),which is specifically designed to address safety threats posed by lithium-ion batteries(LIBs)exposed to harsh mechanical and environmental conditions.The theoretical framework introduces a novel approach for harnessing the smoothed-particle hydrodynamics(SPH)methodology that incorporates the intricate interplay of non-Newtonian fluid behavior,capturing the fluid-structure coupling inherent to the MSTF.This approach is further advanced by adopting an enhanced Herschel-Bulkley(H-B)model to encapsulate the intricate rheology of the MSTF under the influence of the magnetorheological effect(MRE)and shear thickening(ST)behavior.Numerical simulation results show that in the case of cooling,the MSTF is an effective cooling medium for rapidly reducing the temperature.In terms of mechanical abuse,the MSTF solidifies through actively applying the magnetic field during mechanical compression and impact within the battery module,resulting in 66%and 61.7%reductions in the maximum stress within the battery jellyroll,and 31.1%and 23%reductions in the reaction force,respectively.This mechanism effectively lowers the risk of short-circuit failure.The groundbreaking concepts unveiled in this paper for active protection battery modules are anticipated to be a valuable technological breakthrough in the areas of EV safety and lightweight/integrated design.展开更多
Mechanical pretreatment is an indispensable process in biological treatment plants that remove plastics and other impurities from household biogenic waste(HBW).However,the imperfect separation of plastics in these pre...Mechanical pretreatment is an indispensable process in biological treatment plants that remove plastics and other impurities from household biogenic waste(HBW).However,the imperfect separation of plastics in these pretreatment methods has raised concerns that they pose a secondary formation risk for microplastics(MPs).To validate this presumption,herein,quantities and properties of plastic debris and MPs larger than 50 μm were examined in the full chain of three different pretreatment methods in six plants.These facilities received HBW with or without prior depackaging at the source.The key points in the secondary formation of MPs were identified.Moreover,flux estimates of MPs were released,and an analysis of MPs sources was provided to develop an overview of their fate in HBW pretreatment.Pretreated output can contain a maximum of(1673±279) to(3198±263) MP particles per kilogram of wet weight(particles·kg^(-1)ww) for those undepackaged at source,and secondary MPs formation is primarily attributed to biomass crushers,biohydrolysis reactors,and rough shredders.Comparatively,HBW depackaged at the source can greatly reduce MPs by 8%-72%,regardless of pretreatment processes.Before pretreatment,4.6-205.6 million MP particles were present in 100 tonnes of HBW.MPs are produced at a rate of 741.11-33124.22 billion MP particles annually in anaerobic digester feedstock(ADF).This study demonstrated that HBW pretreatment is a competitive source of MPs and emphasized the importance of implementing municipal solid waste segregation at the source.Furthermore,depackaging biogenic waste at the source is recommended to substantially alleviate the negative effect of pretreatment on MPs formation.展开更多
基金This research was supported by the Natinal Key Research and Development Program of China(2016YFD0100904 and 2016YFD0100802)the National Natural Science Foundation of China(31871269)+1 种基金the Hubei Provincial Natural Science Foundation of China(2019CFA014)Fundamental Research Funds for the Central Universities(2662020SKPY010 to J.Z.).
文摘Rice(Oryza sativa),a major staple throughout the world and a model system for plant genomics and breeding,was the first crop genome sequenced almost two decades ago.However,reference genomes for all higher organisms to date contain gaps and missing sequences.Here,we report the assembly and analysis of gap-free reference genome sequences for two elite O.sativa xian/indica rice varieties,Zhenshan 97 and Minghui 63,which are being used as a model system for studying heterosis and yield.Gap-free reference genomes provide the opportunity for a global view of the structure and function of centromeres.We show that all rice centromeric regions share conserved centromere-specific satellite motifs with different copy numbers and structures.In addition,the similarity of CentO repeats in the same chromosome is higher than across chromosomes,supporting a model of local expansion and homogenization.Both genomes have over 395 non-TE genes located in centromere regions,of which∼41%are actively transcribed.Two large structural variants at the end of chromosome 11 affect the copy number of resistance genes between the two genomes.The availability of the two gap-free genomes lays a solid foundation for further understanding genome structure and function in plants and breeding climate-resilient varieties.
基金supported by the National Natural Science Foundation of China(No.31730080,No.31572091)the Ministry of Science and Technology Key Research and Development Plan(No.SQ2016YFSF030011).
文摘Anthocyanins are biosynthesized on the cytosolic surface of the endoplasmic reticulum and then transported into the vacuole for storage.Glutathione S-transferases(GSTs)are considered to be responsible for the transport of anthocyanins into the vacuole.However,the regulatory mechanisms of GSTs in plants are still unclear.Here,we performed a genome-wide analysis and identified 69 GST genes in apple.The expression of MdGSTF6 was positively correlated with the anthocyanin content(r=0.949)during‘Yanfu 8’fruit development.The overexpression of MdGSTF6 in the Arabidopsis thaliana tt19 mutant resulted in seedlings of 35S::MdGSTF6-GFP/tt19 that could accumulate anthocyanin and rescue its phenotype,suggesting that MdGSTF6 was an anthocyanin transporter.The silencing of MdGSTF6 affected anthocyanin accumulation in apple fruit.Moreover,the knockdown of MdGSTF6 by RNA interference in cultured‘Gala’seedlings inhibited anthocyanin accumulation.The interaction experiments showed that MdMYB1 could bind directly to the MdGSTF6 promoter to transcriptionally activate its expression.Collectively,our results demonstrate that MdGSTF6 encodes an important GST transporter of anthocyanins in apple fruit and provide evidence for the associated regulatory mechanisms.Therefore,MdMYB1 can not only regulate anthocyanin synthesis,but also control the transport of anthocyanin in apples.This information may be useful for further clarifying the regulation of anthocyanin transport in apple.
文摘目的研发基于人工智能深度学习技术的全髋关节置换术(total hip arthroplasty,THA)髋臼假体型号算法并进行初步验证。方法回顾性分析2019年4月至2020年4月30例股骨头坏死患者资料,其中男15例,女15例;年龄(54.8±10.5)岁(范围33~72岁),左侧13髋,右侧17髋,均接受初次单侧THA。在完成髋关节图像手工标注的基础上,训练人工智能深度学习卷积神经网络对患者髋关节CT骨质进行分割,而后识别骨盆解剖标志位点,并对骨盆位置进行矫正并模拟安放髋臼杯,分别采用dice overlap coefficients(DOC)、平均误差等参数对上述步骤的精度进行评估,最终形成人工智能髋臼假体型号算法。并使用该算法与Orthoview二维术前规划软件分别对患者髋臼杯大小进行规划,将两组规划结果与已完成的实际手术结果进行比对,分别计算其符合率,从而回顾性验证本算法的规划效果。结果在算法方面,与其他经典分割网络相比,G-net网络可更精准的完成对股骨头坏死髋关节骨质的分割,DOC为92.51%±6.70%,且具有更好的鲁棒性(robustness),点识别网络平均误差为0.87个像素值。在临床应用效果方面,人工智能组完全符合率为96.7%(29/30),较Orthoview组的73.3%(22/30)高23.4%,差异有统计学意义(χ^2=6.405,P=0.011)。结论深度学习技术可精准分割患者髋关节CT图像,识别髋关节特征点,人工智能THA髋臼杯放置算法与传统二维术前规划方式相比具有较高的准确性。此算法有望实现准确、快速的THA三维术前规划。
基金supported by the National Natural Science Foundation of China(No.41271332the Natural Science Foundation of Hunan Province,China(No.11JJ2031)
文摘Numerous studies on eutrophication remediation have mainly focused on purifying water first, then restoring submerged macrophytes. A restoration-promoting integrated floating bed （RPIFB） was designed to combine the processes of water purification and macrophyte restoration simultaneously. Two outdoor experiments were conducted to evaluate the ecological functions of the RP1FB. Trial 1 was conducted to compare the eutrophication purification among floating bed, gradual-submerging bed （GSB） and RPIFB technologies. The results illustrated that RPIFB has the best purification capacity. Removal efficiencies of RPIFB for TN, TP,NH4＋-N, NO3-N, CODcr, Chlorophyll-a and turbidity were 74.45%, 98.31%, 74.71%, 88.81%, 71.42%, 90.17% and 85%, respectively. In trial 2, influences of depth of GSB and photic area in RPIFB on biota were investigated. When the depth of GSB decreased and the photic area of RPIFB grew, the height of Potamogeton crispus Linn. increased, but the biomass of Canna indica Linn. was reduced. The mortalities of Misgurnus anguillicaudatus and Bellamya aeruginosa in each group were all less than 7%. All results indicated that when the RPIFB was embedded into the eutrophic water, the regime shift from phytoplankton-dominated to macrophyte-dominated state could be promoted. Thus, the RPIFB is a promising remediation technology for eutrophication and submerged macrophyte restoration.
基金This work was supported by the National Key Research Project of China(2016YFC0501505)the National Natural Science Foundation of China(CN)(31572091,31730080).
文摘Flavonoids play essential roles in human health.Apple(Malus domestica Borkh.),one of the most widely produced and economically important fruit crops in temperate regions,is a significant source of flavonoids in the human diet and is among the top nutritionally rated and most widely consumed fruits worldwide.Epidemiological studies have shown that the consumption of apples,which are rich in a variety of free and easily absorbable flavonoids,is associated with a decreased risk of various diseases.However,apple production is challenged by serious inbreeding problems.The narrowing of the hereditary base has resulted in apples with poor nutritional quality and low flavonoid contents.Recently,there have been advances in our understanding of the roles that Malus sieversii(Ledeb.)M.Roem has played in the process of apple domestication and breeding.In this study,we review the origin of cultivated apples and red-fleshed apples,and discuss the genetic diversity and construction of the core collections of M.sieversii.We also discuss current research progress and breeding programs on red-skinned and red-fleshed apples and summarize the exploitation and utilization of M.sieversii in the breeding of high-flavonoid,and red-fleshed apples.This study highlights a valuable pattern of horticultural crop breeding using wild germplasm resources.The future challenges and directions of research on the molecular mechanisms of flavonoid accumulation and high-flavonoid apple breeding are discussed.
基金Supported by Grants from Beijing Academic Leaders Program,NO.2009-2-17Beijing Natural Science Foundation,No.7102029+5 种基金Capital Medical Developed Research Fund,No.2007-1023New Scholar Star Program of Ministry of EducationNational Basic Research Program of China,No.2011CB504300Specialized Research Fund for the Doctoral Program of Higher Education,No.20130001110108National Natural Science Foundation for Distinguished Young Scholars,No.81301748Science Fund for Creative Research Groups of the National Natural Science Foundation of China,No.IRT13003 and No.NIH/NCI U54 CA156735
文摘Esophageal squamous cell carcinoma continues to heavily burden clinicians worldwide. Researchers have discovered the genomic landscape of esophageal squamous cell carcinoma, which holds promise for an era of personalized oncology care. One of the most pressing problems facing this issue is to improve the understanding of the newly available genomic data, and identify the driver-gene mutations, pathways, and networks. The emergence of a legion of novel targeted agents has generated much hope and hype regarding more potent treatment regimens, but the accuracy of drug selection is still arguable. Other problems, such as cancer heterogeneity, drug resistance, exceptional responders, and side effects, have to be surmounted. Evolving topics in personalized oncology, such as interpretation of genomics data, issues in targeted therapy, research approaches for targeted therapy, and future perspectives, will be discussed in this editorial.
基金Supported by the Natural Science Foundation of Guangdong Province, No.B990353
文摘AIM: To study the anti-HBV effect of liposome-encapsulated matrine (Lip-M) in vitro and in vivo. METHODS: 2.2.15 cell line was cultured in vitro observe the effect of Lip-M and matrine on the secretion of HBsAg and HBeAg. The toxicity of Lip-M and matrine to 2.2.15 cell line was also studied by MTT method. In in vivo study, drug treatment experiment was carried out on the 13th day after ducks were infected with duck hepatitis B virus (DHBV). The ducks were randomly divided into 4 groups with 5-6 ducks in each group. Lip-M and matrine were given to DHBV-infected ducks respectively by gastric perfusion. Four groups were observed: group of Lip-M (20 mg/kg), group of Lip-M (10 mg/kg), group of matrine (20 mg/kg) and group of blank model. The drug was given once daily for 20 d continuously, and normal saline was used as control. The blood was drawn from the posterior tibial vein of all ducks before treatment (T0), after the medication for 5 (T5), 10 (T10), 15 (T15), 20 (T20) d and withdrawl of the drug for 3 d (P3). The serum samples were separated and stored at -70 ℃, DHBV-DNA was detected by the dot-blot hybridization. RESULTS: After addition of Lip-M and matrine to 2.2.15 cell line for eleven d, the median toxic concentration (TC50) of Lip-M and matrine was 7.29 mg/mL and 1.33 mg/mL respectively. The median concentration (IC50) of Lip-M to inhibit HBsAg and HBeAg expression was 0.078 mg/mL and 3.35 mg/mL respectively. The treatment index (TI) value of Lip-M for HBsAg and HBeAg was 93.46 and 2.17 respectively, better than that of matrine. The DHBV-infected duck model treatment test showed that the duck serum DHBV-DNA levels were markedly reduced in the group of Lip-M (20 mg/kg) after treated by gastric perfusion for 10, 15 and 20 d (0.43±0.22 vs 0.95±0.18, t = 4.70, P= 0.001<0.01.0.40±0.12 vs 0.95±0.18, t = 6.34, P= 0.000<0.01. 0.22±0.10 vs 0.95±0.18, t = 8.30, P= 0.000<0.01), compared to the group of matrine (20 mg/kg) (0.43±0.22 vs 0.79±0.19, t = 3.17, P= 0.01<0.05. 0.40±0.12 vs 0.73±0.24, t = 3.21, P=
基金This work was supported by grants from the National Natural Science Foundation of China(#81802301 to M.Y.,#81770082 to Y.S.,and#81901046 to Y.C.)the Natural Science Foundation of Jiangsu province(#BK20180290 to M.Y.and#BK20170115 to Y.C.).
文摘The immune system initiates robust immune responses to defend against invading pathogens or tumor cells and protect the body from damage,thus acting as a fortress of the body.However,excessive responses cause detrimental effects,such as inflammation and autoimmune diseases.To balance the immune responses and maintain immune homeostasis,there are immune checkpoints to terminate overwhelmed immune responses.Pathogens and tumor cells can also exploit immune checkpoint pathways to suppress immune responses,thus escaping immune surveillance.As a consequence,therapeutic antibodies that target immune checkpoints have made great breakthroughs,in particular for cancer treatment.While the overall efficacy of immune checkpoint blockade(ICB)is unsatisfactory since only a small group of patients benefted from ICB treatment.Hence,there is a strong need to search for other targets that improve the efficacy of ICB.Ubiquitination is a highly conserved process which participates in numerous biological activities,including innate and adaptive immunity.A growing body of evidence emphasizes the importance of ubiquitination and its reverse process,deubiquitination,on the regulation of immune responses,providing the rational of simultaneous targeting of immune checkpoints and ubiquitination/deubiquitination pathways to enhance the therapeutic efficacy.Our review will summarize the latest findings of ubiquitination/deubiquitination pathways for anti-tumor immunity,and discuss therapeutic significance of targeting ubiquitination/deubiquitination pathways in the future of immunotherapy.
基金supported by grants from the National Natural Science Foundation of China(81722008,91639101,and81570362 to JX and 81800358 to LW)the Innovation Program of Shanghai Municipal Education Commission(2017-01-07-00-09-E00042 to JX)+1 种基金the Science and TechnologyCommission of Shanghai Municipality(17010500100 to JX)the development fund for Shanghai talents(to JX)
文摘Exercise training is beneficial to the cardiovascular system. MicroRNAs （miRNAs, miRs） are a class of conserved non-coding RNAs and play a wide-ranging role in the regulation of eukaryotic gene expression. Exercise training alters the expression levels of large amounts ofmiRNAs in the heart. In addition, circulating miRNAs appear to be regulated by exercise training. In this review, we will summarize recent advances in the regulation of miRNAs during physical exercise intervention in various cardiovascular diseases, including pathologic cardiac hypertrophy, myocardial fibrosis, ischemia-reperfusion injury, myocardial infarction, and heart failure. The regulatory role of circulating miRNAs after exercise training was also reviewed. In conclusion, miRNAs might be a valuable target for treatment of cardiovascular diseases and have great potential as biomarkers for assessment of physical performance.2018 Published by Elsevier B.V.on behalf of Shanghai University of Sport. This is an open access article under the CC BY-NC-ND license. （http：//creativecommons.org/licenses/by-nc-nd/4.0/）.
基金supported by the National Key Research and Development Program of China(Grant No.2018YFD1000307)the Natural Science Foundation in China(Grant Nos.31672136 and 31272132).
文摘Apple ring rot,which is caused by Botryosphaeria dothidea,severely affects apple production.The mechanisms employed in apple cells against B.dothidea remain unknown.In this research,the pathogen infection mode and the relationship between cell death and disease resistance in‘Fuji’/B.dothidea interaction pathosystem were investigated.By using transmission electron microscopy(TEM),our research showed that the pathogen infects apple cells both intracellularly and extracellularly.However,compared with that in immature fruit,the incidence of hyphae in the interior of mature apple fruit cells increased dramatically,suggesting that cell wall-mediated penetration resistance could be important in apple resistance against B.dothidea.TEM ultrastructural characterization identified the nuclear morphology of programmed cell death induction in both apple fruit and callus cells under B.dothidea infection.Overexpression of MdVDAC2(MDP0000271281),which encodes an outer-membrane localized anion channel protein in mitochondria,significantly promoted cell death under B.dothidea infection and simultaneously inhibited pathogen infection,suggesting that cell death represents a disease resistance mechanism in apple against B.dothidea infection.Furthermore,BdCatalase(KAF4307763),a cytochromeP450 family protein BdCYP52A4(KAF4300696),and subtilisin-domain containing proteinswere identified fromB.dothidea-secreted proteins,which suggested the potential involvement of active oxygen species and phytoalexins in combating B.dothidea infection and triggering or dampening apple resistance.Collectively,our research suggested that cell wall-mediated penetration resistance,programmed cell death machinery and microbial effector-interrelated signaling were among strategies recruited in apple to combat B.dothidea.The current research laid the foundation for further investigations into resistance mechanisms in apple.
基金financially supported by the National Natural Science Foundation of China(NSFC)(52274295)the Natural Science Foundation of Hebei Province(E2020501001,E2021501029,A2021501007,E2022501028,E2022501029)+5 种基金the Natural Science Foundation-Steel,the Iron Foundation of Hebei Province(No.E2022501030)the Performance subsidy fund for Key Laboratory of Dielectric and Electrolyte Functional Material Hebei Province(22567627H)the Science and Technology Project of Hebei Education Department(ZD2022158)the Central Guided Local Science and Technology Development Fund Project of Hebei province(226Z4401G)the China Scholarship Council(No.202206080061,202206050119)the 2023 Hebei Provincial Postgraduate Student Innovation Ability training funding project(CXZZSS2023195)。
文摘The recycling and reutilization of spent lithium-ion batteries(LIBs)have become an important measure to alleviate problems like resource scarcity and environmental pollution.Although some progress has been made,battery recycling technology still faces challenges in terms of efficiency,effectiveness and environmental sustainability.This review aims to systematically review and analyze the current status of spent LIB recycling,and conduct a detailed comparison and evaluation of different recycling processes.In addition,this review introduces emerging recycling techniques,including deep eutectic solvents,molten salt roasting,and direct regeneration,with the intent of enhancing recycling efficiency and diminishing environmental repercussions.Furthermore,to increase the added value of recycled materials,this review proposes the concept of upgrading recycled materials into high value-added functional materials,such as catalysts,adsorbents,and graphene.Through life cycle assessment,the paper also explores the economic and environmental impacts of current battery recycling and highlights the importance that future recycling technologies should achieve a balance between recycling efficiency,economics and environmental benefits.Finally,this review outlines the opportunities and challenges of recycling key materials for next-generation batteries,and proposes relevant policy recommendations to promote the green and sustainable development of batteries,circular economy,and ecological civilization.
基金supported in part by NSF CAREER grant IIS-1652633NSF grant IIS-1730574+1 种基金DARPA REVEAL grant HR0011-16-C-0028DARPA NESD program HR0011-17-C-0026.
文摘Wavefront sensing is the simultaneous measurement of the amplitude and phase of an incoming optical field.Traditional wavefront sensors such as Shack-Hartmann wavefront sensor(SHWFS)suffer from a fundamental tradeoff between spatial resolution and phase estimation and consequently can only achieve a resolution of a few thousand pixels.To break this tradeoff,we present a novel computational-imaging-based technique,namely,the Wavefront Imaging Sensor with High resolution(WISH).We replace the microlens array in SHWFS with a spatial light modulator(SLM)and use a computational phase-retrieval algorithm to recover the incident wavefront.This wavefront sensor can measure highly varying optical fields at more than 10-megapixel resolution with the fine phase estimation.To the best of our knowledge,this resolution is an order of magnitude higher than the current noninterferometric wavefront sensors.To demonstrate the capability of WISH,we present three applications,which cover a wide range of spatial scales.First,we produce the diffraction-limited reconstruction for long-distance imaging by combining WISH with a large-aperture,low-quality Fresnel lens.Second,we show the recovery of high-resolution images of objects that are obscured by scattering.Third,we show that WISH can be used as a microscope without an objective lens.Our study suggests that the designing principle of WISH,which combines optical modulators and computational algorithms to sense high-resolution optical fields,enables improved capabilities in many existing applications while revealing entirely new,hitherto unexplored application areas.
基金supported by the National Natural Science Founda-tion of China,No.82072217,81772135the Jiangsu Natural Science Foundation,No.BK20201178。
文摘Background:Burn shock caused by vascular leakage is one of the main causes of high mortality in severe burn injury.However,the pathophysiological mechanism of vascular leakage is still unclear.The purpose of this study was to explore the molecular mechanism of vascular leakage in the early stage of severe burn and provide a new target for the treatment of severe burns.Methods:Neutrophils were isolated from human peripheral blood by magnetic beads sorting.ELISA was used to detect neutrophil-derived granule proteins and glycocalyx injury products in plasma.The vascular leakage and neutrophil movement were assessed by in vivo laser confocal imaging in mice,and high-quality video were provided.Adhesion-related molecules were investigated by qRT-PCR.The damage to glycocalyx of mice vascular endothelial cellswas observed by transmission electron microscope and scanning electron microscope.Proteomic analysis,flow cytometry and immunofluorescence were used to further study the relationship between human peripheral blood neutrophil-derived hypochlorite(HOCl)and CD44 of human vascular endothelial cells.Results:In this study,we found that rapidly increasing activated neutrophils secrete heparin binding protein(HBP)andmyeloperoxidase(MPO)after severe burn injury.Increased HBP triggers vascular leakage with synergy of MPO,results in systemic edema and burn shock.Furthermore,we found that the MPO catalytic product HOCl but not MPO triggers CD44 extracellular domain shedding from vascular endothelial cells to damage the glycocalyx.Damage to the glycocalyx results in firm adhesion of neutrophils and increases vascular leakage.However,MPO inhibitors partially protect the glycocalyx of vascular endothelial cells.The combination of HBP and MPO inhibitors markedly reduces vascular leakage and systemic edema in the early stage of severe burns.Conclusions:Taken together,these data reveal that neutrophil-derived HBP and MPO play an important synergies role in triggering vascular leakage at the early stage of severe burns.Targeted inter
基金supported by the National Natural Science Foundation of China(No.31730080,No.31572091)the Ministry of Science and Technology Key Research and Development Plan(No.SQ2016YFSF030011)the Shandong Provincial Agricultural Variety Project(2019LZGC007).
文摘Anthocyanin biosynthesis and sugar metabolism are important processes during plant growth,but the molecular interactions underlying these pathways are still unclear.In this work,we analyzed the anthocyanin and soluble sugar contents,as well as the transcript levels of transcription factors that are known to be related to the biosynthesis of anthocyanin in‘Hongcui 1’apple flesh during fruit development.Overexpression of MdMYB6 in red-fleshed calli was found to reduce anthocyanin content and result in downregulated expression of the MdANS and MdGSTF12 proteins.Yeast one-hybrid and electrophoretic mobility shift analyses showed that MdMYB6 could directly bind to the promoters of MdANS and MdGSTF12,indicating that MdMYB6 could inhibit anthocyanin biosynthesis by regulating MdANS and MdGSTF12.Overexpression of MdTMT1 in the Arabidopsis tmt1 mutant restored the glucose and fructose contents to the wild-type levels,while overexpression of MdTMT1 in red-fleshed calli increased the contents of glucose and fructose but reduced the contents of UDP-glucose,UDP-galactose,and anthocyanin.Using a GUS reporter system,yeast one-hybrid,chromatin immunoprecipitation-PCR and electrophoretic mobility shift analyses,we found that MdMYB6 could bind to the promoter of MdTMT1,resulting in increased promoter activity.Overexpression of MdMYB6 in calli overexpressing MdTMT1 increased the expression of MdTMT1,which led to reduced contents of UDP-glucose and UDP-galactose and decreased anthocyanin content compared to those of the calli that overexpressed MdTMT1.This finding suggested that MdMYB6 could also inhibit anthocyanin biosynthesis by regulating MdTMT1 to decrease the contents of UDP-glucose and UDP-galactose.Taken together,these results showed that MdMYB6 and MdTMT1 play key roles in both anthocyanin biosynthesis and sugar transport.
基金financially supported by the Natural Science Foundation of Shandong Province,China(ZR2018JL021,ZR2014EMQ011)the Applied Basic Research Foundation of Qingdao City(17-1-1-84-jch)+2 种基金the National Natural Science Foundation of China(51402160)supported by Taishan Scholar Program of Shandong Province,China,and National Demonstration Center for Experimental Applied Physics Education(Qingdao University)support from the China Postdoctoral Science Foundation Funded Project(2018M630747)and Qingdao Postdoctoral Applied Research Project.
文摘Metallic Sn has provoked tremendous progress as an anode material for sodium-ion batteries(SIBs).However,Sn anodes suffer from a dramatic capacity fading,owing to pulverization induced by drastic volume expansion during cycling.Herein,a flexible three-dimensional(3D)hierarchical conductive network electrode is designed by constructing Sn quantum dots(QDs)encapsulated in one-dimensional N,S codoped carbon nanofibers(NS-CNFs)sheathed within two-dimensional(2D)reduced graphene oxide(rGO)scrolls.In this ingenious strategy,1D NS-CNFs are regarded as building blocks to prevent the aggregation and pulverization of Sn QDs during sodiation/desodiation,2D rGO acts as electrical roads and“bridges”among NS-CNFs to improve the conductivity of the electrode and enlarge the contact area with electrolyte.Because of the unique structural merits,the flexible 3D hierarchical conductive network was directly used as binder-and current collectorfree anode for SIBs,exhibiting ultra-long cycling life(373 mAh g?1 after 5000 cycles at 1 A g?1),and excellent high-rate capability(189 mAh g?1 at 10 A g?1).This work provides a facile and efficient engineering method to construct 3D hierarchical conductive electrodes for other flexible energy storage devices.
基金supported by National Key Research and Development Project of China (No. 2018YFB0605103)Program for Huazhong University of Science and Technology Academic Frontier Youth Team (No. 2018QYTD05)
文摘Coal is widely utilized as an important energy source,but coal-fired power plant was considered to be an important anthropogenic lead emission source.In the present study,the distribution characteristics of lead in coal and combustion by-products are reviewed.Specifically,lead is mainly transferred to ash particles and the formation and migration mechanisms of particulate lead are summarized.Also,targeted measures are proposed to control the formation of fine particulate lead as well as to increase the removal efficiency during the low-temperature flue gas clean process.In detail,interactions between gaseous lead and some coal-bearing minerals or added adsorbents could obviously suppress the formation of fine particulate lead.On the other hand,some efforts(including promoting capture of fine particles,reducing resistivity of particles and strengthening the gas-liquid contact)could be made to improve the fine particulate lead removal capacity.Notably,the formation mechanism of fine particulate lead is still unclear due to the limitations of research methods.Some differences in the removal principles of fine particles and particulate lead make the lead emission precisely control a great challenge.Finally,the environmental potential risk of lead emission from flue gas and ash residues is addressed and further discussed.
基金We are grateful to the faculty and staff of the Clinical and Laboratory Unit of the Department of Hematology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,for clinical and technical support.Wuhan BioRaid Biotechnology CO.,LTD.is acknowledged for cell manufacturing and qualitycontrol.Dr.Pengcheng Wang of Hubei Clinical Research Center for Emergency and Resuscitation,Zhongnan Hospital of Wuhan University,is appreciated for kind assistance in statistical analysis.The current project was funded by the Key Program of the National Natural Science Foundation of China(81830008 and 81630006,to Dr.J.Z.)the National Natural Science Foundation of China(82070211 and 81670152,to Dr.L.H.,82070217 and 81873427,to Dr.J.W.,81770211 to Dr.M.X.)the Young Topnotch Talent Cultivation Program of Hubei Province(to Dr.L.H.)and CHEN XIAO-PING Foundation for the Development of Science and Technology of Hubei Province(CXPJJH12000009-113,to Dr.J.W.).
文摘TP53 gene alteration confers inferior prognosis in refractory/relapse aggressive B-cell non-Hodgkin lymphoma(r/r B-NHL).From September 2016 to September 2020,257 r/r B-NHL patients were assessed for eligibility for two trials in our center,assessing anti-CD19 and anti-CD22 chimeric antigen receptor(CAR19/22)T-cell cocktail treatment alone or in combination with autologous stem cell transplantation(ASCT).TP53 alterations were screened in 123 enrolled patients and confirmed in 60.CAR19/22 T-cell administration resulted in best objective(ORR)and complete(CRR)response rate of 87.1%and 45.2%in patients with TP53 alterations.
基金Supported by Flanders Research Foundation(FWO-42865)the KU Leuven Molecular Small Animal Imaging Center Mo SAIC(KUL EF/05/08)+3 种基金the center of excellence in vivo molecular imaging research(IMIR),KU Leuven projects IOFHB/08/009 and IOF-HB/12/018the European Union(AsiaLink Cf P 2006-Europe Aid/123738/C/ACT/Multi-Proposal No.128-498/111)the National Natural Science Foundation of China No.81071828Jiangsu Province Natural Science Foundation No.BK2010594
文摘AIM:To facilitate translational research on cholelithiasis,we have developed a rat model of human gallstones by exploiting the unique biliopancreatic features of this species.METHODS:Under anesthesia,16 adult rats of equal genders underwent two times of abdominal surgery.First,their common bile duct(CBD)was ligated to cause cholestasis by total biliary obstruction(TBO).On day 0,1,3,7,14,21 and 28 after TBO,magnetic resonance imaging(MRI)was conducted to monitor the dilatation of the CBD,and blood was sampled to analyze total serum bilirubin(TSB).Secondly,on day 30,the abdomen was re-opened and gallstone(s)collected from human patients were implanted in the dilated CBD asa virtual gallbladder(VGB),which was closed by suture ligation.This rat cholelithiasis model was examined by MRI,clinical observation,microcholangiography and histology.RESULTS:All rats survived two laparotomies.After ligation,the CBD was dilated to a stable size of 4 to30 mm in diameter on day 21-28,which became a VGB.The rats initially showed signs of jaundice that diminished over time,which paralleled with the evolving TSB levels from 0.6±0.3 mg/d L before ligation,through a peak of 10.9±1.9 mg/dL on day 14,until a nearly normalized value after day 28.The dilated CBD with thickened wall allowed an incision for implantation of human gallstones of 1-10 mm in diameter.The rat cholelithiasis was proven by in vivo MRI and postmortem microcholangiography and histomorphology.CONCLUSION:A rat model cholelithiasis with human gallstones has been established,which proves feasible,safe,reliable,nontoxic and cost-effective.Given the gallstones of human origin,applications of this model may be of help in translational research such as optical detection and lysis of gallstones by systemic drug administration.
基金Project supported by the National Natural Science Foundation of China(Nos.12072183 and11872236)the Key Research Project of Zhejiang Laboratory(No.2021PE0AC02)。
文摘Electric vehicles(EVs)have garnered significant attention as a vital driver of economic growth and environmental sustainability.Nevertheless,ensuring the safety of high-energy batteries is now a top priority that cannot be overlooked during large-scale applications.This paper proposes an innovative active protection and cooling integrated battery module using smart materials,magneto-sensitive shear thickening fluid(MSTF),which is specifically designed to address safety threats posed by lithium-ion batteries(LIBs)exposed to harsh mechanical and environmental conditions.The theoretical framework introduces a novel approach for harnessing the smoothed-particle hydrodynamics(SPH)methodology that incorporates the intricate interplay of non-Newtonian fluid behavior,capturing the fluid-structure coupling inherent to the MSTF.This approach is further advanced by adopting an enhanced Herschel-Bulkley(H-B)model to encapsulate the intricate rheology of the MSTF under the influence of the magnetorheological effect(MRE)and shear thickening(ST)behavior.Numerical simulation results show that in the case of cooling,the MSTF is an effective cooling medium for rapidly reducing the temperature.In terms of mechanical abuse,the MSTF solidifies through actively applying the magnetic field during mechanical compression and impact within the battery module,resulting in 66%and 61.7%reductions in the maximum stress within the battery jellyroll,and 31.1%and 23%reductions in the reaction force,respectively.This mechanism effectively lowers the risk of short-circuit failure.The groundbreaking concepts unveiled in this paper for active protection battery modules are anticipated to be a valuable technological breakthrough in the areas of EV safety and lightweight/integrated design.
基金financially supported by the National Natural Science Foundation of China (22276140)the Shanghai Municipal Government State-Owned Assets Supervision and Administration Commission, China (2022028)the Key Research and Development Project of Zhejiang Province, China (2021C03024).
文摘Mechanical pretreatment is an indispensable process in biological treatment plants that remove plastics and other impurities from household biogenic waste(HBW).However,the imperfect separation of plastics in these pretreatment methods has raised concerns that they pose a secondary formation risk for microplastics(MPs).To validate this presumption,herein,quantities and properties of plastic debris and MPs larger than 50 μm were examined in the full chain of three different pretreatment methods in six plants.These facilities received HBW with or without prior depackaging at the source.The key points in the secondary formation of MPs were identified.Moreover,flux estimates of MPs were released,and an analysis of MPs sources was provided to develop an overview of their fate in HBW pretreatment.Pretreated output can contain a maximum of(1673±279) to(3198±263) MP particles per kilogram of wet weight(particles·kg^(-1)ww) for those undepackaged at source,and secondary MPs formation is primarily attributed to biomass crushers,biohydrolysis reactors,and rough shredders.Comparatively,HBW depackaged at the source can greatly reduce MPs by 8%-72%,regardless of pretreatment processes.Before pretreatment,4.6-205.6 million MP particles were present in 100 tonnes of HBW.MPs are produced at a rate of 741.11-33124.22 billion MP particles annually in anaerobic digester feedstock(ADF).This study demonstrated that HBW pretreatment is a competitive source of MPs and emphasized the importance of implementing municipal solid waste segregation at the source.Furthermore,depackaging biogenic waste at the source is recommended to substantially alleviate the negative effect of pretreatment on MPs formation.
