Climate extremes for agriculture-pasture transitional zone, northern China, are analyzed on the basis of daily mean temperature and precipitation observations for 31 stations in the period 1956-2001. Analysis season f...Climate extremes for agriculture-pasture transitional zone, northern China, are analyzed on the basis of daily mean temperature and precipitation observations for 31 stations in the period 1956-2001. Analysis season for precipitation is May-September, i.e., the rainy season. For temperature is the hottest three months, i.e., June through August. Heavy rain events, defined as those with daily precipitation equal to or larger than 50 mm, show no significant secular trend. A jump-like change, however, is found occurring in about 1980. For the period 1980-1993, the frequency of heavy rain events is significantly lower than the previous periods. Simultaneously, the occurring time of heavy rains expanded, commencing about one month early and ending one month later. Long dry spells are defined as those with longer than 10 days without rainfall. The frequency of long dry spells displays a significant (at the 99% confidence level) trend at the value of +8.3% /10a. That may be one of the major causes of the frequent droughts emerging over northern China during the last decades. Extremely hot and low temperature events are defined as the uppermost 10% daily temperatures and the lowest 10% daily temperatures, respectively. There is a weak and non-significant upward trend in frequency of extremely high temperatures from the 1950s to the mid-1990s. But the number of hot events increases as much as twice since 1997. That coincides well with the sudden rise in mean summer temperature for the same period. Contrary to that, the frequency of low temperature events have been decreasing steadily since the 1950s, with a significant linear trend of-15%/10a.展开更多
Laparoscopic radical gastrectomy has been increasingly applied in China. However, how to reduce surgery-related trauma, shorten operative time and achieve the long-term prognosis equal to the conventional open surgery...Laparoscopic radical gastrectomy has been increasingly applied in China. However, how to reduce surgery-related trauma, shorten operative time and achieve the long-term prognosis equal to the conventional open surgery is still hot research topics. Along with the change in learning curve and the optimization of endoscopic techniques, laparoscopic lymph node dissection can achieve or even exceed the extent that can be achieved in open surgery. Therefore, it has gradually replaced the conventional digestive tract reconstruction using an auxiliary incision. By completing the laparoscopic digestive tract reconstruction with EndoGIA, we describe the laparoscopy-assisted D2 radical distal gastrectomy for gastric cancer （Billroth Ⅱ anastomosis）.展开更多
Hyperlipidemia is a kind of pancreatitis caused by high triglyceride levels in the blood. The morbidity and mortality of this disease continue to increase worldwide, and it has become one of the most common gastrointe...Hyperlipidemia is a kind of pancreatitis caused by high triglyceride levels in the blood. The morbidity and mortality of this disease continue to increase worldwide, and it has become one of the most common gastrointestinal diseases in developed countries worldwide. Although many studies have been conducted, the pathogenesis still cannot be defined. Many studies have shown that this may be related to the triglyceride decomposition products free fatty acids are the main toxic substances, which can directly damage pancreatic acinar cells and vascular endothelial cells, causing tissue ischemia and acidic environment. Therefore, this paper focuses on the correlation of triglycerides and their decomposition products in plasma and provides evidence on the pathogenesis of AP and the disease progression of AP. Finally, the future potential to prevent and treat acute pancreatitis by some new drugs to reduce plasma triglycerides is summarized.展开更多
Multi-fluid k-e-kp, two phase turbulence model is used to simulate charged gas-liquid two phase coaxial jet, which is the transorting flow field in electrostatic spraying. Compared with the results of experiment, cha...Multi-fluid k-e-kp, two phase turbulence model is used to simulate charged gas-liquid two phase coaxial jet, which is the transorting flow field in electrostatic spraying. Compared with the results of experiment, charged gas-liquid two-phase turbulence can be well predicted by this model.展开更多
Dear Editor,Most human genetic diseases arise from mutations such as insertion,deletion,or point mutations(Landrum et al.,2016).CRISPRCas system has been repurposed to correct pathogenic mutations in a variety of gene...Dear Editor,Most human genetic diseases arise from mutations such as insertion,deletion,or point mutations(Landrum et al.,2016).CRISPRCas system has been repurposed to correct pathogenic mutations in a variety of genetic diseases(Choi et al.,2022).There are many concerns about using CRISPR-mediated double-stranded DNA breaks(DSBs)for therapeutic purposes,primarily due to off-targeted mutations(Kosicki et al.,2018).Nevertheless,base editing cannot correct deletions,insertions,or some point mutations such as transversion mutations.Prime editing has its advantages of precisely correct point mutations,small insertions,or deletions in animal cells(Anzalone et al.,2019)and plants(Lin et al.,2020).However,prime editing efficiency varies among genomic sites or cell types(Chen et al.,2021;Nelson et al.,2022).展开更多
Remote organ injury,which is a common secondary complication of sterile tissue damage,is a major cause of poor prognosis and is difficult to manage.Here,we report the critical role of tissue-resident macrophages in lu...Remote organ injury,which is a common secondary complication of sterile tissue damage,is a major cause of poor prognosis and is difficult to manage.Here,we report the critical role of tissue-resident macrophages in lung injury after trauma or stroke through the inflammatory response.We found that depleting tissue-resident macrophages rather than disrupting the recruitment of monocyte-derived macrophages attenuated lung injury after trauma or stroke.Our findings revealed that the release of circulating alarmins from sites of distant sterile tissue damage triggered an inflammatory response in lung-resident macrophages by binding to receptor for advanced glycation end products(RAGE)on the membrane,which activated epidermal growth factor receptor(EGFR).Mechanistically,ligand-activated RAGE triggered EGFR activation through an interaction,leading to Rab5-mediated RAGE internalization and EGFR phosphorylation,which subsequently recruited and activated P38;this,in turn,promoted RAGE translation and trafficking to the plasma membrane to increase the cellular response to RAGE ligands,consequently exacerbating inflammation.Our study also showed that the loss of RAGE or EGFR expression by adoptive transfer of macrophages,blocking the function of RAGE with a neutralizing antibody,or pharmacological inhibition of EGFR activation in macrophages could protect against trauma-or stroke-induced remote lung injury.Therefore,our study revealed that targeting the RAGE-EGFR signaling pathway in tissue-resident macrophages is a potential therapeutic approach for treating secondary complications of sterile damage.展开更多
The homogeneously dispersed, less agglomerated YAG nanopowders are synthesized by the citrate-gel method followed by low-temperature self-propagating combustion reaction, using Y2O3, Al(NO3)3?9H2O and citric acid as s...The homogeneously dispersed, less agglomerated YAG nanopowders are synthesized by the citrate-gel method followed by low-temperature self-propagating combustion reaction, using Y2O3, Al(NO3)3?9H2O and citric acid as starting materials. This method effectively solves the problems caused by solid-state reaction at high temperature and the hard ag-glomerates brought by the chemical precipitation method. The powders are characterized by TG-DTA, XRD, FT-IR and TEM respectively. The experiments show that the forming temperature of YAG crystal phase is 850°C and the pseudo-YAG crystalline appears during the calcination and transforms to pure YAG at 1050°C. The powders with sizes less than 50 nm are observed by TEM micrography, which is consistent with the result calculated by Scherrer's formula. The powders consist of single grains.展开更多
One concern about the application of medical artificial intelligence(AI)regards the“black box”feature which can only be viewed in terms of itsinputs and outputs,with no way to understand the AI’s algorithm.Thisis p...One concern about the application of medical artificial intelligence(AI)regards the“black box”feature which can only be viewed in terms of itsinputs and outputs,with no way to understand the AI’s algorithm.Thisis problematic because patients,physicians,and even designers,do not understand why or how a treatment recommendation is produced by AI technologies.One view claims that the worry about black-box medicine is unreasonable because AI systems outperform human doctors in identifying the disease.Furthermore,under the medical AI-physicianpatient model,the physician can undertake the responsibility of interpreting the medical AI’s diagnosis.In this study,we focus on the potential harm caused by the unexplainability feature of medical AI and try to show that such possible harm is underestimated.We will seek to contribute to the literature from three aspects.First,we appealed to a thought experiment to show that although the medical AI systems perform better on accuracy,the harm caused by medical AI’s misdiagnoses may be more serious than that caused by human doctors’misdiagnoses in some cases.Second,in patient-centered medicine,physicians were obligated to provide adequate information to their patients in medical decision-making.However,the unexplainability feature of medical AI systems would limit the patient’s autonomy.Last,we tried to illustrate the psychological and financial burdens that may be caused by the unexplainablity feature of medical AI systems,which seems to be ignored by the previous ethical discussions.展开更多
The wrong Supplementary file was originally published with this article;it has now been replaced with the correct file.In detail,the western blotting of t-EGFR in Supplementary Fig.14a was mistakenly presented with an...The wrong Supplementary file was originally published with this article;it has now been replaced with the correct file.In detail,the western blotting of t-EGFR in Supplementary Fig.14a was mistakenly presented with an incorrect image.Supplementary Fig.14a has been corrected.The corrected Supplementary Figure 14 is shown below.展开更多
HMGA2,a pivotal transcription factor,functions as a versatile regulator implicated in the progression of diverse aggressive malignancies.In this study,mass spectrometry was employed to identify ubiquitin-specific prot...HMGA2,a pivotal transcription factor,functions as a versatile regulator implicated in the progression of diverse aggressive malignancies.In this study,mass spectrometry was employed to identify ubiquitin-specific proteases that potentially interact with HMGA2,and USP48 was identified as a deubiquitinating enzyme of HMGA2.The enforced expression of USP48 significantly increased HMGA2 protein levels by inhibiting its degradation,while the deprivation of USP48 promoted HMGA2 degradation,thereby suppressing tumor invasion and metastasis.We discovered that USP48 undergoes SUMOylation at lysine 258,which enhances its binding affinity to HMGA2.Through subsequent phenotypic screening of small molecules,we identified DUB-IN-2 as a remarkably potent pharmacological inhibitor of USP48.Interestingly,the small-molecule inhibitor targeting USP48 induces destabilization of HMGA2.Clinically,upregulation of USP48 or HMGA2 in cancerous tissues is indicative of poor prognosis for patients with colorectal cancer(CRC).Collectively,our study not only elucidates the regulatory mechanism of DUBs involved in HMGA2 stability and validates USP48 as a potential therapeutic target for CRC,but also identifies DUB-IN-2 as a potent inhibitor of USP48 and a promising candidate for CRC treatment.展开更多
Dear Editor Resistance （R） genes represent one of the most divergent gene families in plants. Novel resistance function might arise through point mutations or sequence exchanges between paralogues （Kuang et al., 20...Dear Editor Resistance （R） genes represent one of the most divergent gene families in plants. Novel resistance function might arise through point mutations or sequence exchanges between paralogues （Kuang et al., 2004; Luo et al., 2011, 2012）.展开更多
Fast and accurate MRI reconstruction is a key concern in modern clinical practice.Recently,numerous Deep-Learning methods have been proposed for MRI reconstruction,however,they usually fail to reconstruct sharp detail...Fast and accurate MRI reconstruction is a key concern in modern clinical practice.Recently,numerous Deep-Learning methods have been proposed for MRI reconstruction,however,they usually fail to reconstruct sharp details from the subsampled k-space data.To solve this problem,we propose a lightweight and accurate Edge Attention MRI Reconstruction Network(EAMRI)to reconstruct images with edge guidance.Specifically,we design an efficient Edge Prediction Network to directly predict accurate edges from the blurred image.Meanwhile,we propose a novel Edge Attention Module(EAM)to guide the image reconstruction utilizing the extracted edge priors,as inspired by the popular self-attention mechanism.EAM first projects the input image and edges into Q_(image),K_(edge),and V_(image),respectively.Then EAM pairs the Q_(image)with K_(edge)along the channel dimension,such that 1)it can search globally for the high-frequency image features that are activated by the edge priors;2)the overall computation burdens are largely reduced compared with the traditional spatial-wise attention.With the help of EAM,the predicted edge priors can effectively guide the model to reconstruct high-quality MR images with accurate edges.Extensive experiments show that our proposed EAMRI outperforms other methods with fewer parameters and can recover more accurate edges.展开更多
Although crop domestication has greatly aided human civilization,the sequential domestication and regulation of most quality traits remain poorly understood.Here,we report the stepwise selection and regulation of majo...Although crop domestication has greatly aided human civilization,the sequential domestication and regulation of most quality traits remain poorly understood.Here,we report the stepwise selection and regulation of major fruit quality traits that occurred during watermelon evolution.The levels of fruit cucurbitacins and flavonoids were negatively selected during speciation,whereas sugar and carotenoid contents were positively selected during domestication.Interestingly,fruit malic acid and citric acid showed the opposite selection trends during the improvement.We identified a novel gene cluster(CGC1,cucurbitacin gene cluster on chromosome 1)containing both regulatory and structural genes involved in cucurbitacin biosynthesis,which revealed a cascade of transcriptional regulation operating mechanisms.In the CGC1,an allele caused a single nucleotide change in Cl ERF1 binding sites(GCC-box)in the promoter of Cl Bh1,which resulted in reduced expression of Cl Bh1 and inhibition of cucurbitacin synthesis in cultivated watermelon.Functional analysis revealed that a rare insertion of 244 amino acids,which arose in C.amarus and became fixed in sweet watermelon,in Cl OSC(oxidosqualene cyclase)was critical for the negative selection of cucurbitacins during watermelon evolution.This research provides an important resource for metabolomics-assisted breeding in watermelon and for exploring metabolic pathway regulation mechanisms.展开更多
Tantalum carbon(TaC)alternate coatings with sublayers comprised of different crystallite morphologies were prepared on carbon/carbon composites by chemical vapor deposition.Their ablative behaviors and defending mecha...Tantalum carbon(TaC)alternate coatings with sublayers comprised of different crystallite morphologies were prepared on carbon/carbon composites by chemical vapor deposition.Their ablative behaviors and defending mechanisms were both investigated.The specimen with the sublayer composed of columnar crystals exhibited a better ablation resistance due to the toughness enhancement induced by the lami-nated structure.However,the mechanical denudation of the sample only containing acicular crystals and the coating spallation caused by superfluous gaseous products of the sample with the sublayer composed of nanocrystals both indicate their inferior anti-ablation properties.It is believed that the results will be helpful for the structural design and practical application of chemical vapor deposition(CVD)alternate coatings.展开更多
A filtered density function (FDF) transport equation was derived for the fluid velocity seen by the particles in gas-particle two-phase flow. An LES/FDF simulation of a two-phase plane wake flow was carried out. The s...A filtered density function (FDF) transport equation was derived for the fluid velocity seen by the particles in gas-particle two-phase flow. An LES/FDF simulation of a two-phase plane wake flow was carried out. The simulation results were compared with both the experimental photograph and the simulation results without using the FDF model, and proved that the LES/FDF model can clearly improve the spatial dispersion of the particle phase.展开更多
The human genome can be demarcated into domains based on distinct epigenetic states.The trimethylation of histone H3 lysine 9(H3K9me3)is essential for the formation of constitutive heterochromatin nanodomains.However,...The human genome can be demarcated into domains based on distinct epigenetic states.The trimethylation of histone H3 lysine 9(H3K9me3)is essential for the formation of constitutive heterochromatin nanodomains.However,the extent to which genomic regions require specific densities or degrees of H3K9me3 for stable interactions remains unclear.Here,we utilize CRISPR-based DNA imaging to investigate the role of endogenous or ectopic H3K9me3 in chromatin dynamics and genomic interactions.We select three loci(IDR3,TCF3,and PR1)with distinct levels of H3K9me3 to examine the genomic interactions and association with endogenous Heterochromatin Protein 1(HP1α)condensates.Our results demonstrate a positive correlation between the levels of H3K9me3 at the loci and their association with HP1αcondensates.By dual-color labeling and long-term tracking of IDR3 and PR1 loci,we find a periodical association between the two ranging from one to three hours.Epigenetic perturbation-induced Genome organization(EpiGo)-KRAB introduces∼20 kilobases of H3K9me3 at the TCF3 locus,which is sufficient to establish a stable association between TCF3 and HP1αcondensates.In addition,EpiGo-mediated H3K9me3 also leads to stable genomic interaction between IDR3 and TCF3.Briefly,these data suggest that the density of H3K9me3 could dictate the stability of interactions between genomic loci and HP1αcondensates.展开更多
Background:Previous studies have examined the bulk transcriptome of peripheral blood immune cells in acquired immunodeficiency syndrome patients experiencing immunological non-responsiveness.This study aimed to invest...Background:Previous studies have examined the bulk transcriptome of peripheral blood immune cells in acquired immunodeficiency syndrome patients experiencing immunological non-responsiveness.This study aimed to investigate the characteristics of specific immune cell subtypes in acquired immunodeficiency syndrome patients who exhibit immunological non-responsiveness.Methods:A single-cell transcriptome sequencing of peripheral blood mononuclear cells obtained from both immunological responders(IRs)(CD4^(+)T-cell count>500)and immunological non-responders(INRs)(CD4^(+)T-cell count<300)was conducted.The transcriptomic profiles were used to identify distinct cell subpopulations,marker genes,and differentially expressed genes aiming to uncover potential genetic factors associated with immunological non-responsiveness.Results:Among the cellular subpopulations analyzed,the ratios of monocytes,CD16^(+)monocytes,and exhausted B cells demonstrated the most substantial differences between INRs and IRs,with fold changes of 39.79,11.08,and 2.71,respectively.In contrast,the CD4^(+)T cell ratio was significantly decreased(0.39-fold change)in INRs compared with that in IRs.Similarly,the ratios of natural killer cells and terminal effector CD8^(+)T cells were also lower(0.37-fold and 0.27-fold,respectively)in the INRs group.In addition to several well-characterized immune cell-specific markers,we identified a set of 181 marker genes that were enriched in biological pathways associated with human immunodeficiency virus(HIV)replication.Notably,ISG15,IFITM3,PLSCR1,HLA-DQB1,CCL3L1,and DDX5,which have been demonstrated to influence HIV replication through their interaction with viral proteins,emerged as significant monocyte marker genes.Furthermore,the differentially expressed genes in natural killer cells were also enriched in biological pathways associated with HIV replication.Conclusions:We generated an atlas of immune cell transcriptomes in HIV-infected IRs and INRs.Host genes associated with HIV replication were identified as mark展开更多
The types of mutations and their corresponding frequencies are difficult to measure in complex genomes. In this study, a high-throughput method was developed to identify spontaneous loss-of-function alleles for the re...The types of mutations and their corresponding frequencies are difficult to measure in complex genomes. In this study, a high-throughput method was developed to identify spontaneous loss-of-function alleles for the resistance gene N and the transgenic avirulence gene P50 in allotetraploid tobacco. A total of 2134 loss- of-function alleles of the N gene were identified after screening 14 million F1 hybrids. Analysis of these mutants revealed striking evolutionary patterns for genes in polyploids. Only 14 of the loss-of-function mutations were caused by spontaneous point mutations or indels, while the others were caused by home- ologous recombination （with a frequency of 1/12 000） or chromosome loss （1/15 000）. Loss of the chromosome with the PS0 insertion occurred at a similar frequency （1/13 000）, and the frequency of spon- taneous segmental deletion in this chromosome was 1/16 000. Both homeologous recombination and chromosome loss considerably decreased the viability of the mutants. Our data suggest that the high mutation rate in polyploids is probably due to the occurrence of homeologous recombination and the toler- ance of large mutations such as chromosome loss in polyploid genomes. Frequent mutations tend to drive polyploids to extinction unless a novel mutation helps the polyploid to effectively compete with diploids or find a new ecological niche.展开更多
Betula L.(birch)is a pioneer hardwood tree species with ecological,economic,and evolutionary importance in the Northern Hemisphere.We sequenced the Betula platyphylla genome and assembled the sequences into 14 chromos...Betula L.(birch)is a pioneer hardwood tree species with ecological,economic,and evolutionary importance in the Northern Hemisphere.We sequenced the Betula platyphylla genome and assembled the sequences into 14 chromosomes.The Betula genome lacks evidence of recent whole-genome duplication and has the same paleoploidy level as Vitis vinifera and Prunus mume.Phylogenetic analysis of lignin pathway genes coupled with tissue-specific expression patterns provided clues for understanding the formation of higher ratios of syringyl to guaiacyl lignin observed in Betula species.Our transcriptome analysis of leaf tissues under a time-series cold stress experiment revealed the presence of the MEKK1–MKK2–MPK4 cascade and six additional mitogen-activated protein kinases that can be linked to a gene regulatory network involving many transcription factors and cold tolerance genes.Our genomic and transcriptome analyses provide insight into the structures,features,and evolution of the B.platyphylla genome.The chromosome-level genome and gene resources of B.platyphylla obtained in this study will facilitate the identification of important and essential genes governing important traits of trees and genetic improvement of B.platyphylla.展开更多
Understanding the energy balance on the Tibetan Plateau is important for better prediction of global climate change. To characterize the energy balance on the Plateau, we examined the radiation balance and the respons...Understanding the energy balance on the Tibetan Plateau is important for better prediction of global climate change. To characterize the energy balance on the Plateau, we examined the radiation balance and the response of albedo to environmental factors above an alpine meadow and an alpine wetland surfaces in the eastern Tibetan Plateau, using 2014 data. Although our two sites belong to the same climatic background, and are close geographically, the annual incident solar radiation at the alpine meadow site(6,447 MJ/(m2·a)) was about 1.1 times that at the alpine wetland site(6,012 MJ/(m2·a)),due to differences in the cloudiness between our two sites. The alpine meadow and the alpine wetland emitted about 38%and 42%, respectively, of annual incident solar radiation back into atmosphere in the form of net longwave radiation; and they reflected about 22% and 18%, respectively, of the annual incident solar radiation back into atmosphere in the form of shortwave radiation. The annual net radiation was 2,648 and 2,544 MJ/(m2·a) for the alpine meadow site and the alpine wetland site, respectively, accounting for only about 40% of the annual incident solar radiation, significantly lower than the global mean. At 30-min scales, surface albedo exponentially decreases with the increase of the solar elevation angle; and it linearly decreases with the increase of soil-water content for our two sites. But those relationships are significantly influenced by cloudiness and are site-specific.展开更多
文摘Climate extremes for agriculture-pasture transitional zone, northern China, are analyzed on the basis of daily mean temperature and precipitation observations for 31 stations in the period 1956-2001. Analysis season for precipitation is May-September, i.e., the rainy season. For temperature is the hottest three months, i.e., June through August. Heavy rain events, defined as those with daily precipitation equal to or larger than 50 mm, show no significant secular trend. A jump-like change, however, is found occurring in about 1980. For the period 1980-1993, the frequency of heavy rain events is significantly lower than the previous periods. Simultaneously, the occurring time of heavy rains expanded, commencing about one month early and ending one month later. Long dry spells are defined as those with longer than 10 days without rainfall. The frequency of long dry spells displays a significant (at the 99% confidence level) trend at the value of +8.3% /10a. That may be one of the major causes of the frequent droughts emerging over northern China during the last decades. Extremely hot and low temperature events are defined as the uppermost 10% daily temperatures and the lowest 10% daily temperatures, respectively. There is a weak and non-significant upward trend in frequency of extremely high temperatures from the 1950s to the mid-1990s. But the number of hot events increases as much as twice since 1997. That coincides well with the sudden rise in mean summer temperature for the same period. Contrary to that, the frequency of low temperature events have been decreasing steadily since the 1950s, with a significant linear trend of-15%/10a.
文摘Laparoscopic radical gastrectomy has been increasingly applied in China. However, how to reduce surgery-related trauma, shorten operative time and achieve the long-term prognosis equal to the conventional open surgery is still hot research topics. Along with the change in learning curve and the optimization of endoscopic techniques, laparoscopic lymph node dissection can achieve or even exceed the extent that can be achieved in open surgery. Therefore, it has gradually replaced the conventional digestive tract reconstruction using an auxiliary incision. By completing the laparoscopic digestive tract reconstruction with EndoGIA, we describe the laparoscopy-assisted D2 radical distal gastrectomy for gastric cancer （Billroth Ⅱ anastomosis）.
文摘Hyperlipidemia is a kind of pancreatitis caused by high triglyceride levels in the blood. The morbidity and mortality of this disease continue to increase worldwide, and it has become one of the most common gastrointestinal diseases in developed countries worldwide. Although many studies have been conducted, the pathogenesis still cannot be defined. Many studies have shown that this may be related to the triglyceride decomposition products free fatty acids are the main toxic substances, which can directly damage pancreatic acinar cells and vascular endothelial cells, causing tissue ischemia and acidic environment. Therefore, this paper focuses on the correlation of triglycerides and their decomposition products in plasma and provides evidence on the pathogenesis of AP and the disease progression of AP. Finally, the future potential to prevent and treat acute pancreatitis by some new drugs to reduce plasma triglycerides is summarized.
基金This project is supported by Provincial Basic Application Granting of Jiangsu(No. B197063
文摘Multi-fluid k-e-kp, two phase turbulence model is used to simulate charged gas-liquid two phase coaxial jet, which is the transorting flow field in electrostatic spraying. Compared with the results of experiment, charged gas-liquid two-phase turbulence can be well predicted by this model.
基金funded by National Natural Science Foundation of China(No.31970591 to H.Ma)the Shanghai Pujiang program(19PJ1408000 to H.Ma)Shanghai Science and Technology Innovation Action Plan(21JC1404800 to H.Ma).
文摘Dear Editor,Most human genetic diseases arise from mutations such as insertion,deletion,or point mutations(Landrum et al.,2016).CRISPRCas system has been repurposed to correct pathogenic mutations in a variety of genetic diseases(Choi et al.,2022).There are many concerns about using CRISPR-mediated double-stranded DNA breaks(DSBs)for therapeutic purposes,primarily due to off-targeted mutations(Kosicki et al.,2018).Nevertheless,base editing cannot correct deletions,insertions,or some point mutations such as transversion mutations.Prime editing has its advantages of precisely correct point mutations,small insertions,or deletions in animal cells(Anzalone et al.,2019)and plants(Lin et al.,2020).However,prime editing efficiency varies among genomic sites or cell types(Chen et al.,2021;Nelson et al.,2022).
基金supported by the National Key R&D Program of China(2021YFC2701700 to JT and XYH)the National Natural Science Foundation of China(81671957 and 81873951 to JT,82200093 to HHZ)+1 种基金the Guangdong Natural Science Foundation(2023A1515012498 to HHZ)the Medical Scientific Research Foundation of Guangdong Province(A2022256 to HHZ).
文摘Remote organ injury,which is a common secondary complication of sterile tissue damage,is a major cause of poor prognosis and is difficult to manage.Here,we report the critical role of tissue-resident macrophages in lung injury after trauma or stroke through the inflammatory response.We found that depleting tissue-resident macrophages rather than disrupting the recruitment of monocyte-derived macrophages attenuated lung injury after trauma or stroke.Our findings revealed that the release of circulating alarmins from sites of distant sterile tissue damage triggered an inflammatory response in lung-resident macrophages by binding to receptor for advanced glycation end products(RAGE)on the membrane,which activated epidermal growth factor receptor(EGFR).Mechanistically,ligand-activated RAGE triggered EGFR activation through an interaction,leading to Rab5-mediated RAGE internalization and EGFR phosphorylation,which subsequently recruited and activated P38;this,in turn,promoted RAGE translation and trafficking to the plasma membrane to increase the cellular response to RAGE ligands,consequently exacerbating inflammation.Our study also showed that the loss of RAGE or EGFR expression by adoptive transfer of macrophages,blocking the function of RAGE with a neutralizing antibody,or pharmacological inhibition of EGFR activation in macrophages could protect against trauma-or stroke-induced remote lung injury.Therefore,our study revealed that targeting the RAGE-EGFR signaling pathway in tissue-resident macrophages is a potential therapeutic approach for treating secondary complications of sterile damage.
基金This work is financially supported by the Excellent Teachers Fund by the Ministry of Education of China (No. KB200226).
文摘The homogeneously dispersed, less agglomerated YAG nanopowders are synthesized by the citrate-gel method followed by low-temperature self-propagating combustion reaction, using Y2O3, Al(NO3)3?9H2O and citric acid as starting materials. This method effectively solves the problems caused by solid-state reaction at high temperature and the hard ag-glomerates brought by the chemical precipitation method. The powders are characterized by TG-DTA, XRD, FT-IR and TEM respectively. The experiments show that the forming temperature of YAG crystal phase is 850°C and the pseudo-YAG crystalline appears during the calcination and transforms to pure YAG at 1050°C. The powders with sizes less than 50 nm are observed by TEM micrography, which is consistent with the result calculated by Scherrer's formula. The powders consist of single grains.
基金the Young Scholars Program of the National Social Science Fund of China(Grant No.22CZX019).
文摘One concern about the application of medical artificial intelligence(AI)regards the“black box”feature which can only be viewed in terms of itsinputs and outputs,with no way to understand the AI’s algorithm.Thisis problematic because patients,physicians,and even designers,do not understand why or how a treatment recommendation is produced by AI technologies.One view claims that the worry about black-box medicine is unreasonable because AI systems outperform human doctors in identifying the disease.Furthermore,under the medical AI-physicianpatient model,the physician can undertake the responsibility of interpreting the medical AI’s diagnosis.In this study,we focus on the potential harm caused by the unexplainability feature of medical AI and try to show that such possible harm is underestimated.We will seek to contribute to the literature from three aspects.First,we appealed to a thought experiment to show that although the medical AI systems perform better on accuracy,the harm caused by medical AI’s misdiagnoses may be more serious than that caused by human doctors’misdiagnoses in some cases.Second,in patient-centered medicine,physicians were obligated to provide adequate information to their patients in medical decision-making.However,the unexplainability feature of medical AI systems would limit the patient’s autonomy.Last,we tried to illustrate the psychological and financial burdens that may be caused by the unexplainablity feature of medical AI systems,which seems to be ignored by the previous ethical discussions.
文摘The wrong Supplementary file was originally published with this article;it has now been replaced with the correct file.In detail,the western blotting of t-EGFR in Supplementary Fig.14a was mistakenly presented with an incorrect image.Supplementary Fig.14a has been corrected.The corrected Supplementary Figure 14 is shown below.
基金We extend our sincere appreciation to Mingyang Gao,Shuai Zhou,and Wenxiang Fang for their exceptional technical assistance.This research was financially supported by the National Natural Science Foundation of China(No.82103543)the Fundamental Research Funds for the Central Universities(No.WK9110000159,China)+1 种基金Natural Science Foundation of Anhui Province(No.2108085QH340,China)the Postdoctoral Science Foundation of China(No.2021M693082).
文摘HMGA2,a pivotal transcription factor,functions as a versatile regulator implicated in the progression of diverse aggressive malignancies.In this study,mass spectrometry was employed to identify ubiquitin-specific proteases that potentially interact with HMGA2,and USP48 was identified as a deubiquitinating enzyme of HMGA2.The enforced expression of USP48 significantly increased HMGA2 protein levels by inhibiting its degradation,while the deprivation of USP48 promoted HMGA2 degradation,thereby suppressing tumor invasion and metastasis.We discovered that USP48 undergoes SUMOylation at lysine 258,which enhances its binding affinity to HMGA2.Through subsequent phenotypic screening of small molecules,we identified DUB-IN-2 as a remarkably potent pharmacological inhibitor of USP48.Interestingly,the small-molecule inhibitor targeting USP48 induces destabilization of HMGA2.Clinically,upregulation of USP48 or HMGA2 in cancerous tissues is indicative of poor prognosis for patients with colorectal cancer(CRC).Collectively,our study not only elucidates the regulatory mechanism of DUBs involved in HMGA2 stability and validates USP48 as a potential therapeutic target for CRC,but also identifies DUB-IN-2 as a potent inhibitor of USP48 and a promising candidate for CRC treatment.
文摘Dear Editor Resistance （R） genes represent one of the most divergent gene families in plants. Novel resistance function might arise through point mutations or sequence exchanges between paralogues （Kuang et al., 2004; Luo et al., 2011, 2012）.
基金This work is supported in part by the National Key R&D Program of China under Grant 2021YFE0203700 and 2021YFA1003004in part by the Natural Science Foundation of Shanghai under Grand 23ZR1422200+1 种基金in part by the Shanghai Sailing Program under Grant 23YF1412800in part by the NSFC/RGC N CUHK 415/19,Grant ITF MHP/038/20,Grant CRF 8730063,Grant RGC 14300219,14302920,14301121,and CUHK Direct Grant for Research.
文摘Fast and accurate MRI reconstruction is a key concern in modern clinical practice.Recently,numerous Deep-Learning methods have been proposed for MRI reconstruction,however,they usually fail to reconstruct sharp details from the subsampled k-space data.To solve this problem,we propose a lightweight and accurate Edge Attention MRI Reconstruction Network(EAMRI)to reconstruct images with edge guidance.Specifically,we design an efficient Edge Prediction Network to directly predict accurate edges from the blurred image.Meanwhile,we propose a novel Edge Attention Module(EAM)to guide the image reconstruction utilizing the extracted edge priors,as inspired by the popular self-attention mechanism.EAM first projects the input image and edges into Q_(image),K_(edge),and V_(image),respectively.Then EAM pairs the Q_(image)with K_(edge)along the channel dimension,such that 1)it can search globally for the high-frequency image features that are activated by the edge priors;2)the overall computation burdens are largely reduced compared with the traditional spatial-wise attention.With the help of EAM,the predicted edge priors can effectively guide the model to reconstruct high-quality MR images with accurate edges.Extensive experiments show that our proposed EAMRI outperforms other methods with fewer parameters and can recover more accurate edges.
基金supported by the Agricultural Science and Technology Innovation Program(CAAS-ASTIP-ZFRI-07)the National Key R&D Program of China(2018YFD0100704)+5 种基金the China Agriculture Research System(CARS-25-03)the National Natural Science Fund for Distinguished Young Scholars(31625021)the National Natural Science Foundation of China(31672178,31471893)the Hainan University Startup Fund KYQD(ZR)1866Project supported by Hainan Yazhou Bay Seed Laboratory(B21Y10901)the Natural Science Foundation of Hainan Province(322RC574)。
文摘Although crop domestication has greatly aided human civilization,the sequential domestication and regulation of most quality traits remain poorly understood.Here,we report the stepwise selection and regulation of major fruit quality traits that occurred during watermelon evolution.The levels of fruit cucurbitacins and flavonoids were negatively selected during speciation,whereas sugar and carotenoid contents were positively selected during domestication.Interestingly,fruit malic acid and citric acid showed the opposite selection trends during the improvement.We identified a novel gene cluster(CGC1,cucurbitacin gene cluster on chromosome 1)containing both regulatory and structural genes involved in cucurbitacin biosynthesis,which revealed a cascade of transcriptional regulation operating mechanisms.In the CGC1,an allele caused a single nucleotide change in Cl ERF1 binding sites(GCC-box)in the promoter of Cl Bh1,which resulted in reduced expression of Cl Bh1 and inhibition of cucurbitacin synthesis in cultivated watermelon.Functional analysis revealed that a rare insertion of 244 amino acids,which arose in C.amarus and became fixed in sweet watermelon,in Cl OSC(oxidosqualene cyclase)was critical for the negative selection of cucurbitacins during watermelon evolution.This research provides an important resource for metabolomics-assisted breeding in watermelon and for exploring metabolic pathway regulation mechanisms.
基金supported by the National Natu-ral Science Foundations of China(Nos.51727804,52130205,and 91860203)the National Key R&D Program of China(No.2021YFA0715803)The authors also thank the Analytical&Testing Center of Northwestern Polytechnical University for the characteri-zation of our samples.
文摘Tantalum carbon(TaC)alternate coatings with sublayers comprised of different crystallite morphologies were prepared on carbon/carbon composites by chemical vapor deposition.Their ablative behaviors and defending mechanisms were both investigated.The specimen with the sublayer composed of columnar crystals exhibited a better ablation resistance due to the toughness enhancement induced by the lami-nated structure.However,the mechanical denudation of the sample only containing acicular crystals and the coating spallation caused by superfluous gaseous products of the sample with the sublayer composed of nanocrystals both indicate their inferior anti-ablation properties.It is believed that the results will be helpful for the structural design and practical application of chemical vapor deposition(CVD)alternate coatings.
基金Supported by the National Natural Science Foundation of China (Grant Nos. 10502044, 10772162, 50736006)
文摘A filtered density function (FDF) transport equation was derived for the fluid velocity seen by the particles in gas-particle two-phase flow. An LES/FDF simulation of a two-phase plane wake flow was carried out. The simulation results were compared with both the experimental photograph and the simulation results without using the FDF model, and proved that the LES/FDF model can clearly improve the spatial dispersion of the particle phase.
基金This work was funded by the National Natural Science Foundation of China(No.31970591 to H.Ma),the Shanghai Pujiang Program(19PJ1408000 to H.Ma)the Shanghai Science and Technology Innovation Action Plan(21JC1404800 to H.Ma)We thank Luke Lavis(Janelia Research Campus,Howard Hughes Medical Institute,Ashburn,VA,USA)for providing the HaloTag JF-549.U2OS Genomic DNA was a gift from Xingxu Huang.We thank Pengwei Zhang and Shuangli Zhang for their help with cell sorting.
文摘The human genome can be demarcated into domains based on distinct epigenetic states.The trimethylation of histone H3 lysine 9(H3K9me3)is essential for the formation of constitutive heterochromatin nanodomains.However,the extent to which genomic regions require specific densities or degrees of H3K9me3 for stable interactions remains unclear.Here,we utilize CRISPR-based DNA imaging to investigate the role of endogenous or ectopic H3K9me3 in chromatin dynamics and genomic interactions.We select three loci(IDR3,TCF3,and PR1)with distinct levels of H3K9me3 to examine the genomic interactions and association with endogenous Heterochromatin Protein 1(HP1α)condensates.Our results demonstrate a positive correlation between the levels of H3K9me3 at the loci and their association with HP1αcondensates.By dual-color labeling and long-term tracking of IDR3 and PR1 loci,we find a periodical association between the two ranging from one to three hours.Epigenetic perturbation-induced Genome organization(EpiGo)-KRAB introduces∼20 kilobases of H3K9me3 at the TCF3 locus,which is sufficient to establish a stable association between TCF3 and HP1αcondensates.In addition,EpiGo-mediated H3K9me3 also leads to stable genomic interaction between IDR3 and TCF3.Briefly,these data suggest that the density of H3K9me3 could dictate the stability of interactions between genomic loci and HP1αcondensates.
基金supported by the Joint Research Project of Health and Education in Fujian Province(No.2019-WJ-15)Natural Science Foundation of Fujian Province(Nos.2021J011295 and 2020J011165)Fujian Chinese Traditional Medicine University research funding(No.XB2020147)
文摘Background:Previous studies have examined the bulk transcriptome of peripheral blood immune cells in acquired immunodeficiency syndrome patients experiencing immunological non-responsiveness.This study aimed to investigate the characteristics of specific immune cell subtypes in acquired immunodeficiency syndrome patients who exhibit immunological non-responsiveness.Methods:A single-cell transcriptome sequencing of peripheral blood mononuclear cells obtained from both immunological responders(IRs)(CD4^(+)T-cell count>500)and immunological non-responders(INRs)(CD4^(+)T-cell count<300)was conducted.The transcriptomic profiles were used to identify distinct cell subpopulations,marker genes,and differentially expressed genes aiming to uncover potential genetic factors associated with immunological non-responsiveness.Results:Among the cellular subpopulations analyzed,the ratios of monocytes,CD16^(+)monocytes,and exhausted B cells demonstrated the most substantial differences between INRs and IRs,with fold changes of 39.79,11.08,and 2.71,respectively.In contrast,the CD4^(+)T cell ratio was significantly decreased(0.39-fold change)in INRs compared with that in IRs.Similarly,the ratios of natural killer cells and terminal effector CD8^(+)T cells were also lower(0.37-fold and 0.27-fold,respectively)in the INRs group.In addition to several well-characterized immune cell-specific markers,we identified a set of 181 marker genes that were enriched in biological pathways associated with human immunodeficiency virus(HIV)replication.Notably,ISG15,IFITM3,PLSCR1,HLA-DQB1,CCL3L1,and DDX5,which have been demonstrated to influence HIV replication through their interaction with viral proteins,emerged as significant monocyte marker genes.Furthermore,the differentially expressed genes in natural killer cells were also enriched in biological pathways associated with HIV replication.Conclusions:We generated an atlas of immune cell transcriptomes in HIV-infected IRs and INRs.Host genes associated with HIV replication were identified as mark
文摘The types of mutations and their corresponding frequencies are difficult to measure in complex genomes. In this study, a high-throughput method was developed to identify spontaneous loss-of-function alleles for the resistance gene N and the transgenic avirulence gene P50 in allotetraploid tobacco. A total of 2134 loss- of-function alleles of the N gene were identified after screening 14 million F1 hybrids. Analysis of these mutants revealed striking evolutionary patterns for genes in polyploids. Only 14 of the loss-of-function mutations were caused by spontaneous point mutations or indels, while the others were caused by home- ologous recombination （with a frequency of 1/12 000） or chromosome loss （1/15 000）. Loss of the chromosome with the PS0 insertion occurred at a similar frequency （1/13 000）, and the frequency of spon- taneous segmental deletion in this chromosome was 1/16 000. Both homeologous recombination and chromosome loss considerably decreased the viability of the mutants. Our data suggest that the high mutation rate in polyploids is probably due to the occurrence of homeologous recombination and the toler- ance of large mutations such as chromosome loss in polyploid genomes. Frequent mutations tend to drive polyploids to extinction unless a novel mutation helps the polyploid to effectively compete with diploids or find a new ecological niche.
基金Forestry Industry Research Special Funds for Public Welfare Projects(No.201004046)the National High Technology Research and Development Program(“863”Program)of China(2011AA100202)+1 种基金Heilongjiang Touyan Innovation Team Program(Tree Genetics and Breeding Innovation Team)the 111 Project(B16010).
文摘Betula L.(birch)is a pioneer hardwood tree species with ecological,economic,and evolutionary importance in the Northern Hemisphere.We sequenced the Betula platyphylla genome and assembled the sequences into 14 chromosomes.The Betula genome lacks evidence of recent whole-genome duplication and has the same paleoploidy level as Vitis vinifera and Prunus mume.Phylogenetic analysis of lignin pathway genes coupled with tissue-specific expression patterns provided clues for understanding the formation of higher ratios of syringyl to guaiacyl lignin observed in Betula species.Our transcriptome analysis of leaf tissues under a time-series cold stress experiment revealed the presence of the MEKK1–MKK2–MPK4 cascade and six additional mitogen-activated protein kinases that can be linked to a gene regulatory network involving many transcription factors and cold tolerance genes.Our genomic and transcriptome analyses provide insight into the structures,features,and evolution of the B.platyphylla genome.The chromosome-level genome and gene resources of B.platyphylla obtained in this study will facilitate the identification of important and essential genes governing important traits of trees and genetic improvement of B.platyphylla.
基金supported by the National Natural Science Foundation of China (Grant Nos. 91537106, 41405016, 41275016, 91537104, and 41605011)
文摘Understanding the energy balance on the Tibetan Plateau is important for better prediction of global climate change. To characterize the energy balance on the Plateau, we examined the radiation balance and the response of albedo to environmental factors above an alpine meadow and an alpine wetland surfaces in the eastern Tibetan Plateau, using 2014 data. Although our two sites belong to the same climatic background, and are close geographically, the annual incident solar radiation at the alpine meadow site(6,447 MJ/(m2·a)) was about 1.1 times that at the alpine wetland site(6,012 MJ/(m2·a)),due to differences in the cloudiness between our two sites. The alpine meadow and the alpine wetland emitted about 38%and 42%, respectively, of annual incident solar radiation back into atmosphere in the form of net longwave radiation; and they reflected about 22% and 18%, respectively, of the annual incident solar radiation back into atmosphere in the form of shortwave radiation. The annual net radiation was 2,648 and 2,544 MJ/(m2·a) for the alpine meadow site and the alpine wetland site, respectively, accounting for only about 40% of the annual incident solar radiation, significantly lower than the global mean. At 30-min scales, surface albedo exponentially decreases with the increase of the solar elevation angle; and it linearly decreases with the increase of soil-water content for our two sites. But those relationships are significantly influenced by cloudiness and are site-specific.
