饱和的碳氢键氧化是合成化学和化学工业中一类重要的化学反应.然而,饱和C(sp^(3))−H键离解能(BDEs)较高、极性较弱,导致了底物难以活化和催化转化效率较低等问题.在过去的几十年,C(sp^(3))−H键的定向活化转化取得了重要的进展.其中,关于...饱和的碳氢键氧化是合成化学和化学工业中一类重要的化学反应.然而,饱和C(sp^(3))−H键离解能(BDEs)较高、极性较弱,导致了底物难以活化和催化转化效率较低等问题.在过去的几十年,C(sp^(3))−H键的定向活化转化取得了重要的进展.其中,关于C(sp^(3))−H键催化氧化的研究主要涉及一些键能低的、预活化的C−H键,包括苄基型、亚甲基型、脂肪族X−CH_(2)(X=O,N)和甲苯等,含有未活化C(sp^(3))−H键的复杂化合物的选择性氧化仍具有挑战性.例如,芳基醚C(sp^(3))−H键功能化通常采用计量的过氧化物氧化剂,或者通过单电子氧化和碱促进的去质子化进一步构建C−C/C−N键,产物选择性较低,也带来了一些不利的环境影响.因此,有必要开发高效、温和的芳基醚C(sp^(3))−H键选择氧化方法,并将其应用于有机合成和药物开发.近年来,光催化C(sp^(3))−H键氧化因其操作简便、氧化还原中性等优点,已发展成为一种有用且多样的催化研究工具.本文发展了一种利用氧气作为氧化剂,在可见光驱动下选择性地将芳基醚C(sp^(3))−H键氧化成为甲酸苯酯类产物的新方法.使用Mes-10-phenyl-Acr^(+)−BF_(4)^(-)光催化剂,高效活化多种氯源(如盐酸、无机氯盐和有机氯化物)得到氯自由基,由于其具有较高的氧化能力(+2.03 V vs.SCE)和对氢原子的亲和力,能够通过氢原子转移过程活化芳基醚C(sp^(3))−键,攫取氢自由基得到相应的烷基碳自由基(•CH_(2)OPh)中间体,进一步被分子氧选择氧化得到酯类目标产物.研究结果表明,多种链状芳基醚和不同取代(如给电子基和吸电子基)芳基醚均可发生氧化反应,高收率地合成了一系列官能团丰富的甲酸苯酯类化合物.本文方法具有反应条件温和、操作简单、官能团耐受性好以及可规模化放大等优点,并且少量的水对反应没有明显影响.机理实验研究结果表明,芳基醚C(sp^(3))−H键的断裂是反应过程的决速步骤.紫外可见吸收光谱结果表明,氯离子与催化剂之间的相互作用强于底物,并且自由基捕获实验证实反应体系中存在氯自由基和烷基碳自由基物种,表明反应经历自由基路径.此外,电子顺磁共振测试结果表明,反应过程中存在单线态氧物种,可能是激发态的光催化剂直接与氧气发生能量转移得到;同位素实验(18O)揭示了甲酸苯酯类化合物氧的来源.综上,本文实现了温和条件下光催化芳基醚C(sp^(3))−H键选择氧化反应,高收率合成了一系列甲酸苯酯类化合物.该方法避免了化学计量的过氧化物和碱等添加剂的使用以及底物的过度氧化,阐明了催化反应机制,为其他醚类化合物的C(sp^(3))−H键氧化功能化提供了新思路,为后续化学合成和药物开发提供了参考和启示.展开更多
Bacillus thuringiensis(Bt)cotton production is challenged by two main problems,i.e.,the low concentration of Bt protein at the boll setting stage and the lowest insect resistance in bolls among all the cotton plant’s...Bacillus thuringiensis(Bt)cotton production is challenged by two main problems,i.e.,the low concentration of Bt protein at the boll setting stage and the lowest insect resistance in bolls among all the cotton plant’s organs.Therefore,increasing the Bt protein concentration at the boll stage,especially in bolls,has become the main goal for increasing insect resistance in cotton.In this study,two protein degradation inhibitors(ethylene diamine tetra acetic acid(EDTA)and leupeptin)were sprayed on the bolls,subtending leaves,and whole cotton plants at the peak flowering stage of two Bt cultivars(medium maturation Sikang 1(SK1))and early maturation Zhongmian 425(ZM425)in 2019 and 2020.The Bt protein content and protein degradation metabolism were assessed.The results showed that the Bt protein concentrations were enhanced by 21.3 to 38.8%and 25.0 to 38.6%in the treated bolls of SK1 and ZM425 respectively,while they were decreased in the subtending leaves of these treated bolls.In the treated leaves,the Bt protein concentrations increased by 7.6 to 23.5%and 11.2 to 14.9%in SK1 and ZM425,respectively.The combined application of EDTA and leupeptin to the whole cotton plant increased the Bt protein concentrations in both bolls and subtending leaves.The Bt protein concentrations in bolls were higher,increasing by 22.5 to 31.0%and 19.6 to 32.5%for SK1 and ZM425,respectively.The organs treated with EDTA or/and leupeptin showed reduced free amino acid contents,protease and peptidase activities and significant enhancements in soluble protein contents.These results indicated that inhibiting protein degradation could improve the protein content,thus increasing the Bt protein concentrations in the bolls or/and leaves of cotton plants.Therefore,the increase in the Bt protein concentration without yield reduction suggested that these two protein degradation inhibitors may be applicable for improving insect resistance in cotton production.展开更多
The equilibrium optimizer(EO)represents a new,physics-inspired metaheuristic optimization approach that draws inspiration from the principles governing the control of volume-based mixing to achieve dynamic mass equili...The equilibrium optimizer(EO)represents a new,physics-inspired metaheuristic optimization approach that draws inspiration from the principles governing the control of volume-based mixing to achieve dynamic mass equilibrium.Despite its innovative foundation,the EO exhibits certain limitations,including imbalances between exploration and exploitation,the tendency to local optima,and the susceptibility to loss of population diversity.To alleviate these drawbacks,this paper introduces an improved EO that adopts three strategies:adaptive inertia weight,Cauchy mutation,and adaptive sine cosine mechanism,called SCEO.Firstly,a new update formula is conceived by incorporating an adaptive inertia weight to reach an appropriate balance between exploration and exploitation.Next,an adaptive sine cosine mechanism is embedded to boost the global exploratory capacity.Finally,the Cauchy mutation is utilized to prevent the loss of population diversity during searching.To validate the efficacy of the proposed SCEO,a comprehensive evaluation is conducted on 15 classical benchmark functions and the CEC2017 test suite.The outcomes are subsequently benchmarked against both the conventional EO,its variants,and other cutting-edge metaheuristic techniques.The comparisons reveal that the SCEO method provides significantly superior results against the standard EO and other competitors.In addition,the developed SCEO is implemented to deal with a mobile robot path planning(MRPP)task,and compared to some classical metaheuristic approaches.The analysis results demonstrate that the SCEO approach provides the best performance and is a prospective tool for MRPP.展开更多
Event detection(ED)is aimed at detecting event occurrences and categorizing them.This task has been previously solved via recognition and classification of event triggers(ETs),which are defined as the phrase or word m...Event detection(ED)is aimed at detecting event occurrences and categorizing them.This task has been previously solved via recognition and classification of event triggers(ETs),which are defined as the phrase or word most clearly expressing event occurrence.Thus,current approaches require both annotated triggers as well as event types in training data.Nevertheless,triggers are non-essential in ED,and it is time-wasting for annotators to identify the“most clearly”word from a sentence,particularly in longer sentences.To decrease manual effort,we evaluate event detectionwithout triggers.We propose a novel framework that combines Type-aware Attention and Graph Convolutional Networks(TA-GCN)for event detection.Specifically,the task is identified as a multi-label classification problem.We first encode the input sentence using a novel type-aware neural network with attention mechanisms.Then,a Graph Convolutional Networks(GCN)-based multilabel classification model is exploited for event detection.Experimental results demonstrate the effectiveness.展开更多
Dysregulated lineage commitment of mesenchymal stem cells(MSCs)contributes to impaired bone formation and an imbalance between adipogenesis and osteogenesis during skeletal aging and osteoporosis.The intrinsic cellula...Dysregulated lineage commitment of mesenchymal stem cells(MSCs)contributes to impaired bone formation and an imbalance between adipogenesis and osteogenesis during skeletal aging and osteoporosis.The intrinsic cellular mechanism that regulates MSC commitment remains unclear.Here,we identified Cullin 4B(CUL4B)as a critical regulator of MSC commitment.CUL4B is expressed in bone marrow MSCs(BMSCs)and downregulated with aging in mice and humans.Conditional knockout of Cul4b in MSCs resulted in impaired postnatal skeletal development with low bone mass and reduced bone formation.Moreover,depletion of CUL4B in MSCs aggravated bone loss and marrow adipose accumulation during natural aging or after ovariectomy.In addition,CUL4B deficiency in MSCs reduced bone strength.Mechanistically,CUL4B promoted osteogenesis and inhibited adipogenesis of MSCs by repressing KLF4 and C/EBPδexpression,respectively.The CUL4B complex directly bound to Klf4 and Cebpd and epigenetically repressed their transcription.Collectively,this study reveals CUL4B-mediated epigenetic regulation of the osteogenic or adipogenic commitment of MSCs,which has therapeutic implications in osteoporosis.展开更多
Eradication of MRSA osteomyelitis requires elimination of distinct biofilms.To overcome this,we developed bisphosphonateconjugated sitafloxacin(BCS,BV600072)and hydroxybisphosphonate-conjugate sitafloxacin(HBCS,BV6307...Eradication of MRSA osteomyelitis requires elimination of distinct biofilms.To overcome this,we developed bisphosphonateconjugated sitafloxacin(BCS,BV600072)and hydroxybisphosphonate-conjugate sitafloxacin(HBCS,BV63072),which achieve“target-and-release”drug delivery proximal to the bone infection and have prophylactic efficacy against MRSA static biofilm in vitro and in vivo.Here we evaluated their therapeutic efficacy in a murine 1-stage exchange femoral plate model with bioluminescent MRSA(USA300LAC::lux).Osteomyelitis was confirmed by CFU on the explants and longitudinal bioluminescent imaging(BLI)after debridement and implant exchange surgery on day 7,and mice were randomized into seven groups:1)Baseline(harvested at day7,no treatment);2)HPBP(bisphosphonate control for BCS)+vancomycin;3)HPHBP(hydroxybisphosphonate control for HBCS)+vancomycin;4)vancomycin;5)sitafloxacin;6)BCS+vancomycin;and 7)HBCS+vancomycin.BLI confirmed infection persisted in all groups except for mice treated with BCS or HBCS+vancomycin.Radiology revealed catastrophic femur fractures in all groups except mice treated with BCS or HBCS+vancomycin,which also displayed decreases in peri-implant bone loss,osteoclast numbers,and biofilm.To confirm this,we assessed the efficacy of vancomycin,sitafloxacin,and HBCS monotherapy in a transtibial implant model.The results showed complete lack of vancomycin efficacy while all mice treated with HBCS had evidence of infection control,and some had evidence of osseous integrated septic implants,suggestive of biofilm eradication.Taken together these studies demonstrate that HBCS adjuvant with standard of care debridement and vancomycin therapy has the potential to eradicate MRSA osteomyelitis.展开更多
ALKBH1 was recently discovered as a demethylase for DNA N6-methyladenine (N6-mA), a new epigenetic modification, and interacts with the core transcriptional pluripotency network of embryonic stem cells. However, the...ALKBH1 was recently discovered as a demethylase for DNA N6-methyladenine (N6-mA), a new epigenetic modification, and interacts with the core transcriptional pluripotency network of embryonic stem cells. However, the role of ALKBH1 and DNA N6-mA in regulating osteogenic differentiation is largely unknown. In this study, we demonstrated that the expression of ALKBH1 in human mesenchymal stem cells (MSCs) was upregulated during osteogenic induction. Knockdown of ALKBH1 increased the genomic DNA N6-mA levels and significantly reduced the expression of osteogenic-related genes, alkaline phosphatase activity, and mineralization. ALKBHl-depleted MSCs also exhibited a restricted capacity for bone formation in vivo. By contrast, the ectopic overexpression of ALKBH1 enhanced osteoblastic differentiation. Mechanically, we found that the depletion of ALKBH1 resulted in the accumulation of N6-mA on the promoter region of ATF4, which subsequently silenced ATF4 transcription. In addition, restoring the expression of ATP by adenovirus-mediated transduction successfully rescued osteogenic differentiation. Taken together, our results demonstrate that ALKBH1 is indispensable for the osteogenic differentiation of MSCs and indicate that DNA N6-mA modifications area new mechanism for the epigenetic regulation of stem cell differentiation.展开更多
The char combustion mechanisms were analyzed and a comprehensive fractal char combustion model was developed to give a better understanding and better predictions of the char combustion characteristics. Most of the co...The char combustion mechanisms were analyzed and a comprehensive fractal char combustion model was developed to give a better understanding and better predictions of the char combustion characteristics. Most of the complex factors affecting the char combustion were included, such as the coupling effects between the pore diffusion and the chemical reactions, the evolution of the char pore structures and the variation of the apparent reaction order during combustion, the CO/CO_2 ratio in the combustion products and the correction for oxy-char combustion. Eleven different chars were then combusted in two drop tube furnaces with the conversions of the partly burned char samples measured by thermogravimetric analysis. The combustion processes of these chars were simulated with the predicted char conversions matching very well with the measured data which shows that this char combustion model has good accuracy. The apparent reaction order of the char combustion decreases, stabilizes and then increases during the combustion process. The combustion rates in the oxy-mode are generally slower than in the air-mode and the effect of the char-CO_2 gasification reaction becomes obvious only when the temperature is relatively high and the O_2 concentration is relatively low.展开更多
Diabetes is a chronic disease recognized by the World Health Organization,which is harmful to human life and health.With the improvement of people's quality of life,people's diet structure has changed greatly,...Diabetes is a chronic disease recognized by the World Health Organization,which is harmful to human life and health.With the improvement of people's quality of life,people's diet structure has changed greatly,and the primary"three high"prevalence rate has risen sharply.The main reason for the impaired life expectancy of a large number of diabetic patients is the threat of a series of cardiovascular complications.According to statistics,the risk of cardiovascular disease in diabetic patients are 2-4 times higher than that in non-diabetic patients.More than 80% of patients with type 2 diabetes die of cardiovascular disease every year,and 75% of them have ischemic heart disease[1].All kinds of data show that diabetes mellitus complicated with cardiovascular diseases have become a worldwide public health problem.We must try our best to find a cure mechanism and give patients a healthy life.In order to effectively curb the threat of diabetes complicated with cardiovascular disease patients,we should strengthen the research in this field.Through the analysis of the risk factors of diabetic cardiovascular disease,we can let the majority of medical workers understand the superficial and potential risk factors,to formulate scientific and reasonable treatment plan,for further improving the quality of life of patients.In the following,the author first introduces the basic situation of diabetes and cardiovascular complications,then introduces the main risk factors of diabetic cardiovascular disease one by one,hoping that this study can help to improve the cure rate of diabetes complicated with cardiovascular disease.展开更多
Doxorubicin(DOX)-mediated cardiotoxicity can exacerbate mortality in oncology patients,but related pharmacotherapeutic measures are relatively limited.Ferroptosis was recently identified as a major mechanism of DOX-in...Doxorubicin(DOX)-mediated cardiotoxicity can exacerbate mortality in oncology patients,but related pharmacotherapeutic measures are relatively limited.Ferroptosis was recently identified as a major mechanism of DOX-induced cardiotoxicity.Idebenone,a novel ferroptosis inhibitor,is a well-described clinical drug widely used.However,its role and pathological mechanism in DOX-induced cardiotoxicity are still unclear.In this study,we demonstrated the effects of idebenone on DOX-induced cardiotoxicity and elucidated its underlying mechanism.A single intraperitoneal injection of DOX(15 mg/kg)was administrated to establish DOX-induced cardiotoxicity.The results showed that idebenone significantly attenuated DOX-induced cardiac dysfunction due to its ability to regulate acute DOX-induced Fe^(2+)and ROS overload,which resulted in ferroptosis.CESTA and BLI further revealed that idebenone's anti-ferroptosis effect was mediated by FSP1.Interestingly,idebenone increased FSP1 protein levels but did not affect Fsp1 mRNA levels in the presence of DOX.Idebenone could form stable hydrogen bonds with FSP1 protein at K355,which may influence its association with ubiquitin.The results confirmed that idebenone stabilized FSP1 protein levels by inhibiting its ubiquitination degradation.In conclusion,this study demonstrates idebenone attenuated DOX-induced cardiotoxicity by inhibiting ferroptosis via regulation of FSP1,making it a potential clinical drug for patients receiving DOX treatment.展开更多
Tropospheric ozone(O3)is a trace gas of great significance for air quality and climate change.In recent years,due to the extensive implementation of emission reduction policies,the concentration of fine particulate ma...Tropospheric ozone(O3)is a trace gas of great significance for air quality and climate change.In recent years,due to the extensive implementation of emission reduction policies,the concentration of fine particulate matter in many countries has decreased significantly^([1]).In contrast,the global ground-level O3 concentration has increased by approximately 0.25 ppbv/a^([2]).Research shows that developed countries are experiencing a rebound in O3 levels while developing countries are facing more severe O3 pollution problems^([3,4]).Therefore,the prevention and control of O3 pollution is the top priority at this stage and will play a vital role in the longterm improvement of air quality.展开更多
Due to the similarity of conditioning factors,the aggregation feature of landslides and the multi-temporal landslide inventory,the spatial and temporal effects of landslides need to be considered in landslide suscepti...Due to the similarity of conditioning factors,the aggregation feature of landslides and the multi-temporal landslide inventory,the spatial and temporal effects of landslides need to be considered in landslide susceptibility prediction(LSP).The ignorance of this issue will result in some biases and time-invariance in landslide susceptibility.Hence,a novel framework has been proposed to update landslide susceptibility by simultaneously considering the spatial and temporal effects of landslides at the regional scale.In this framework,the landslide inventory of Chongyi County has been divided into pre-and fresh-landslide inventories.According to the LSP results predicted by the support vector machine(SVM)model using the slope unit-based conditioning factors and pre-landslide inventory,a normalized spatial distance index(NSDI)is calculated to quantitatively represent the spatial correlation between landslides and surrounding slope units to develop the SVM-NSDI model.Furthermore,the SVM-Updating model,which incorporates the LSP results of the SVM-NSDI model and fresh-landslide inventory,could be developed to update the LSP results.Subsequently,the confusion matrix,the area under the receiver operating characteristic curve(AUC)and frequency ratio(FR)accuracy are used to evaluate the prediction performance of the above LSP models.The F1-score values of the SVM,SVM-NSDI and SVM-Updating models are 0.776,0.816 and 0.831,respectively.The AUC values are 0.869,0.903 and 0.914 and the FR accuracies are 0.795,0.853 and 0.873.It can be concluded that landslide susceptibility is a time-variant variable,which can be updated by considering the spatial correlation between landslides and surrounding slope units as well as the temporal effects of multi-temporal landslide inventory.This study provides a new framework to update landslide susceptibility over time and also provides more accurate LSP results for decisionmakers.展开更多
Dear Editor,Hyperactivation of the type I interferon(IFN)signature has been observed in several systemic autoimmune conditions,and the type I IFN receptor antagonist Saphnelo(anifrolumab-fnia)has been approved in 2021...Dear Editor,Hyperactivation of the type I interferon(IFN)signature has been observed in several systemic autoimmune conditions,and the type I IFN receptor antagonist Saphnelo(anifrolumab-fnia)has been approved in 2021 by the Food and Drug Administration(FDA)in the US.The launch of Saphnelo marked the only new treatment approved for systemic lupus erythematosus(SLE)in more than 10 years.展开更多
We report an all-fiber telecom-band energy-time entangled biphoton source with all physical elements integrated into a compact cabinet.At a pump power of 800μW,the photon pairs generation rate reaches 6.9 MHz with th...We report an all-fiber telecom-band energy-time entangled biphoton source with all physical elements integrated into a compact cabinet.At a pump power of 800μW,the photon pairs generation rate reaches 6.9 MHz with the coincidence-toaccidental ratio[CAR]better than 1150.The long-term stability of the biphoton source is characterized by measuring the Hong-Ou-Mandel interference visibility and CAR within a continuous operation period of more than 10 h.Benefiting from the advantages of compact size,light weight,and high stability,this device provides a convenient resource for various field turnkey quantum communication and metrology applications.展开更多
Polyploidy is a major factor in the evolution of plants,yet we know little about the origin and evolution of polyploidy in intertidal species.This study aimed to identify the evolutionary transitions in three truemang...Polyploidy is a major factor in the evolution of plants,yet we know little about the origin and evolution of polyploidy in intertidal species.This study aimed to identify the evolutionary transitions in three truemangrove species of the genus Acanthus distributed in the Indo-West Pacific region.For this purpose,we took an integrative approach that combined data on morphology,cytology,climatic niche,phylogeny,and biogeography of 493 samples from 42 geographic sites.Our results show that the Acanthus ilicifolius lineage distributed east of the Thai-Malay Peninsula possesses a tetraploid karyotype,which is morphologically distinct from that of the lineage on the west side.The haplotype networks and phylogenetic trees for the chloroplast genome and eight nuclear genes reveal that the tetraploid species has two sub-genomes,one each from A.ilicifolius and A.ebracteatus,the paternal and maternal parents,respectively.Population structure analysis also supports the hybrid speciation history of the new tetraploid species.The two sub-genomes of the tetraploid species diverged from their diploid progenitors during the Pleistocene.Environmental niche models revealed that the tetraploid species not only occupied the near-entire niche space of the diploids,but also expanded into novel environments.Our findings suggest that A.ilicifolius species distributed on the east side of the Thai-Malay Peninsula should be regarded as a new species,A.tetraploideus,which originated from hybridization between A.ilicifolius and A.ebracteatus,followed by chromosome doubling.This is the first report of a true-mangrove allopolyploid species that can reproduce sexually and clonally reproduction,which explains the long-term adaptive potential of the species.展开更多
文摘饱和的碳氢键氧化是合成化学和化学工业中一类重要的化学反应.然而,饱和C(sp^(3))−H键离解能(BDEs)较高、极性较弱,导致了底物难以活化和催化转化效率较低等问题.在过去的几十年,C(sp^(3))−H键的定向活化转化取得了重要的进展.其中,关于C(sp^(3))−H键催化氧化的研究主要涉及一些键能低的、预活化的C−H键,包括苄基型、亚甲基型、脂肪族X−CH_(2)(X=O,N)和甲苯等,含有未活化C(sp^(3))−H键的复杂化合物的选择性氧化仍具有挑战性.例如,芳基醚C(sp^(3))−H键功能化通常采用计量的过氧化物氧化剂,或者通过单电子氧化和碱促进的去质子化进一步构建C−C/C−N键,产物选择性较低,也带来了一些不利的环境影响.因此,有必要开发高效、温和的芳基醚C(sp^(3))−H键选择氧化方法,并将其应用于有机合成和药物开发.近年来,光催化C(sp^(3))−H键氧化因其操作简便、氧化还原中性等优点,已发展成为一种有用且多样的催化研究工具.本文发展了一种利用氧气作为氧化剂,在可见光驱动下选择性地将芳基醚C(sp^(3))−H键氧化成为甲酸苯酯类产物的新方法.使用Mes-10-phenyl-Acr^(+)−BF_(4)^(-)光催化剂,高效活化多种氯源(如盐酸、无机氯盐和有机氯化物)得到氯自由基,由于其具有较高的氧化能力(+2.03 V vs.SCE)和对氢原子的亲和力,能够通过氢原子转移过程活化芳基醚C(sp^(3))−键,攫取氢自由基得到相应的烷基碳自由基(•CH_(2)OPh)中间体,进一步被分子氧选择氧化得到酯类目标产物.研究结果表明,多种链状芳基醚和不同取代(如给电子基和吸电子基)芳基醚均可发生氧化反应,高收率地合成了一系列官能团丰富的甲酸苯酯类化合物.本文方法具有反应条件温和、操作简单、官能团耐受性好以及可规模化放大等优点,并且少量的水对反应没有明显影响.机理实验研究结果表明,芳基醚C(sp^(3))−H键的断裂是反应过程的决速步骤.紫外可见吸收光谱结果表明,氯离子与催化剂之间的相互作用强于底物,并且自由基捕获实验证实反应体系中存在氯自由基和烷基碳自由基物种,表明反应经历自由基路径.此外,电子顺磁共振测试结果表明,反应过程中存在单线态氧物种,可能是激发态的光催化剂直接与氧气发生能量转移得到;同位素实验(18O)揭示了甲酸苯酯类化合物氧的来源.综上,本文实现了温和条件下光催化芳基醚C(sp^(3))−H键选择氧化反应,高收率合成了一系列甲酸苯酯类化合物.该方法避免了化学计量的过氧化物和碱等添加剂的使用以及底物的过度氧化,阐明了催化反应机制,为其他醚类化合物的C(sp^(3))−H键氧化功能化提供了新思路,为后续化学合成和药物开发提供了参考和启示.
基金supported by the National Natural Science Foundation of China (31901462 and 31671613).
文摘Bacillus thuringiensis(Bt)cotton production is challenged by two main problems,i.e.,the low concentration of Bt protein at the boll setting stage and the lowest insect resistance in bolls among all the cotton plant’s organs.Therefore,increasing the Bt protein concentration at the boll stage,especially in bolls,has become the main goal for increasing insect resistance in cotton.In this study,two protein degradation inhibitors(ethylene diamine tetra acetic acid(EDTA)and leupeptin)were sprayed on the bolls,subtending leaves,and whole cotton plants at the peak flowering stage of two Bt cultivars(medium maturation Sikang 1(SK1))and early maturation Zhongmian 425(ZM425)in 2019 and 2020.The Bt protein content and protein degradation metabolism were assessed.The results showed that the Bt protein concentrations were enhanced by 21.3 to 38.8%and 25.0 to 38.6%in the treated bolls of SK1 and ZM425 respectively,while they were decreased in the subtending leaves of these treated bolls.In the treated leaves,the Bt protein concentrations increased by 7.6 to 23.5%and 11.2 to 14.9%in SK1 and ZM425,respectively.The combined application of EDTA and leupeptin to the whole cotton plant increased the Bt protein concentrations in both bolls and subtending leaves.The Bt protein concentrations in bolls were higher,increasing by 22.5 to 31.0%and 19.6 to 32.5%for SK1 and ZM425,respectively.The organs treated with EDTA or/and leupeptin showed reduced free amino acid contents,protease and peptidase activities and significant enhancements in soluble protein contents.These results indicated that inhibiting protein degradation could improve the protein content,thus increasing the Bt protein concentrations in the bolls or/and leaves of cotton plants.Therefore,the increase in the Bt protein concentration without yield reduction suggested that these two protein degradation inhibitors may be applicable for improving insect resistance in cotton production.
基金support from the National Natural Science Foundation of China[Grant Nos.61461053,61461054,and 61072079]Yunnan Provincial Education Department Scientific Research Fund Project[2022Y008].
文摘The equilibrium optimizer(EO)represents a new,physics-inspired metaheuristic optimization approach that draws inspiration from the principles governing the control of volume-based mixing to achieve dynamic mass equilibrium.Despite its innovative foundation,the EO exhibits certain limitations,including imbalances between exploration and exploitation,the tendency to local optima,and the susceptibility to loss of population diversity.To alleviate these drawbacks,this paper introduces an improved EO that adopts three strategies:adaptive inertia weight,Cauchy mutation,and adaptive sine cosine mechanism,called SCEO.Firstly,a new update formula is conceived by incorporating an adaptive inertia weight to reach an appropriate balance between exploration and exploitation.Next,an adaptive sine cosine mechanism is embedded to boost the global exploratory capacity.Finally,the Cauchy mutation is utilized to prevent the loss of population diversity during searching.To validate the efficacy of the proposed SCEO,a comprehensive evaluation is conducted on 15 classical benchmark functions and the CEC2017 test suite.The outcomes are subsequently benchmarked against both the conventional EO,its variants,and other cutting-edge metaheuristic techniques.The comparisons reveal that the SCEO method provides significantly superior results against the standard EO and other competitors.In addition,the developed SCEO is implemented to deal with a mobile robot path planning(MRPP)task,and compared to some classical metaheuristic approaches.The analysis results demonstrate that the SCEO approach provides the best performance and is a prospective tool for MRPP.
基金supported by the Hunan Provincial Natural Science Foundation of China(Grant No.2020JJ4624)the National Social Science Fund of China(Grant No.20&ZD047)+1 种基金the Scientific Research Fund of Hunan Provincial Education Department(Grant No.19A020)the National University of Defense Technology Research Project ZK20-46 and the Young Elite Scientists Sponsorship Program 2021-JCJQ-QT-050.
文摘Event detection(ED)is aimed at detecting event occurrences and categorizing them.This task has been previously solved via recognition and classification of event triggers(ETs),which are defined as the phrase or word most clearly expressing event occurrence.Thus,current approaches require both annotated triggers as well as event types in training data.Nevertheless,triggers are non-essential in ED,and it is time-wasting for annotators to identify the“most clearly”word from a sentence,particularly in longer sentences.To decrease manual effort,we evaluate event detectionwithout triggers.We propose a novel framework that combines Type-aware Attention and Graph Convolutional Networks(TA-GCN)for event detection.Specifically,the task is identified as a multi-label classification problem.We first encode the input sentence using a novel type-aware neural network with attention mechanisms.Then,a Graph Convolutional Networks(GCN)-based multilabel classification model is exploited for event detection.Experimental results demonstrate the effectiveness.
基金supported by grants from the National Key R&D Program of China(2022YFC2703700,2022YFC2703701 to Y.G.and 2022YFC2703700,2022YFC2703703 to G.S.)National Natural Science Foundation of China(31872810,82171851 to Y.G.+3 种基金31970559 to B.J.31970781 to G.S.)Key Research and Development Program of Shandong Province(2016GSF201143 to B.J.)Young Scholars Program of Shandong University(to B.J.)。
文摘Dysregulated lineage commitment of mesenchymal stem cells(MSCs)contributes to impaired bone formation and an imbalance between adipogenesis and osteogenesis during skeletal aging and osteoporosis.The intrinsic cellular mechanism that regulates MSC commitment remains unclear.Here,we identified Cullin 4B(CUL4B)as a critical regulator of MSC commitment.CUL4B is expressed in bone marrow MSCs(BMSCs)and downregulated with aging in mice and humans.Conditional knockout of Cul4b in MSCs resulted in impaired postnatal skeletal development with low bone mass and reduced bone formation.Moreover,depletion of CUL4B in MSCs aggravated bone loss and marrow adipose accumulation during natural aging or after ovariectomy.In addition,CUL4B deficiency in MSCs reduced bone strength.Mechanistically,CUL4B promoted osteogenesis and inhibited adipogenesis of MSCs by repressing KLF4 and C/EBPδexpression,respectively.The CUL4B complex directly bound to Klf4 and Cebpd and epigenetically repressed their transcription.Collectively,this study reveals CUL4B-mediated epigenetic regulation of the osteogenic or adipogenic commitment of MSCs,which has therapeutic implications in osteoporosis.
基金supported by grants from the National Institutes of Health(SBIR R44 AI125060,NIAMS P50 AR072000,and NIAMS P30 AR069655)。
文摘Eradication of MRSA osteomyelitis requires elimination of distinct biofilms.To overcome this,we developed bisphosphonateconjugated sitafloxacin(BCS,BV600072)and hydroxybisphosphonate-conjugate sitafloxacin(HBCS,BV63072),which achieve“target-and-release”drug delivery proximal to the bone infection and have prophylactic efficacy against MRSA static biofilm in vitro and in vivo.Here we evaluated their therapeutic efficacy in a murine 1-stage exchange femoral plate model with bioluminescent MRSA(USA300LAC::lux).Osteomyelitis was confirmed by CFU on the explants and longitudinal bioluminescent imaging(BLI)after debridement and implant exchange surgery on day 7,and mice were randomized into seven groups:1)Baseline(harvested at day7,no treatment);2)HPBP(bisphosphonate control for BCS)+vancomycin;3)HPHBP(hydroxybisphosphonate control for HBCS)+vancomycin;4)vancomycin;5)sitafloxacin;6)BCS+vancomycin;and 7)HBCS+vancomycin.BLI confirmed infection persisted in all groups except for mice treated with BCS or HBCS+vancomycin.Radiology revealed catastrophic femur fractures in all groups except mice treated with BCS or HBCS+vancomycin,which also displayed decreases in peri-implant bone loss,osteoclast numbers,and biofilm.To confirm this,we assessed the efficacy of vancomycin,sitafloxacin,and HBCS monotherapy in a transtibial implant model.The results showed complete lack of vancomycin efficacy while all mice treated with HBCS had evidence of infection control,and some had evidence of osseous integrated septic implants,suggestive of biofilm eradication.Taken together these studies demonstrate that HBCS adjuvant with standard of care debridement and vancomycin therapy has the potential to eradicate MRSA osteomyelitis.
基金supported by grants from the National Natural Science Foundation of China (No.81271178 and 81470777)
文摘ALKBH1 was recently discovered as a demethylase for DNA N6-methyladenine (N6-mA), a new epigenetic modification, and interacts with the core transcriptional pluripotency network of embryonic stem cells. However, the role of ALKBH1 and DNA N6-mA in regulating osteogenic differentiation is largely unknown. In this study, we demonstrated that the expression of ALKBH1 in human mesenchymal stem cells (MSCs) was upregulated during osteogenic induction. Knockdown of ALKBH1 increased the genomic DNA N6-mA levels and significantly reduced the expression of osteogenic-related genes, alkaline phosphatase activity, and mineralization. ALKBHl-depleted MSCs also exhibited a restricted capacity for bone formation in vivo. By contrast, the ectopic overexpression of ALKBH1 enhanced osteoblastic differentiation. Mechanically, we found that the depletion of ALKBH1 resulted in the accumulation of N6-mA on the promoter region of ATF4, which subsequently silenced ATF4 transcription. In addition, restoring the expression of ATP by adenovirus-mediated transduction successfully rescued osteogenic differentiation. Taken together, our results demonstrate that ALKBH1 is indispensable for the osteogenic differentiation of MSCs and indicate that DNA N6-mA modifications area new mechanism for the epigenetic regulation of stem cell differentiation.
基金Supported by the National Natural Science Foundation of China(No.51176096)
文摘The char combustion mechanisms were analyzed and a comprehensive fractal char combustion model was developed to give a better understanding and better predictions of the char combustion characteristics. Most of the complex factors affecting the char combustion were included, such as the coupling effects between the pore diffusion and the chemical reactions, the evolution of the char pore structures and the variation of the apparent reaction order during combustion, the CO/CO_2 ratio in the combustion products and the correction for oxy-char combustion. Eleven different chars were then combusted in two drop tube furnaces with the conversions of the partly burned char samples measured by thermogravimetric analysis. The combustion processes of these chars were simulated with the predicted char conversions matching very well with the measured data which shows that this char combustion model has good accuracy. The apparent reaction order of the char combustion decreases, stabilizes and then increases during the combustion process. The combustion rates in the oxy-mode are generally slower than in the air-mode and the effect of the char-CO_2 gasification reaction becomes obvious only when the temperature is relatively high and the O_2 concentration is relatively low.
文摘Diabetes is a chronic disease recognized by the World Health Organization,which is harmful to human life and health.With the improvement of people's quality of life,people's diet structure has changed greatly,and the primary"three high"prevalence rate has risen sharply.The main reason for the impaired life expectancy of a large number of diabetic patients is the threat of a series of cardiovascular complications.According to statistics,the risk of cardiovascular disease in diabetic patients are 2-4 times higher than that in non-diabetic patients.More than 80% of patients with type 2 diabetes die of cardiovascular disease every year,and 75% of them have ischemic heart disease[1].All kinds of data show that diabetes mellitus complicated with cardiovascular diseases have become a worldwide public health problem.We must try our best to find a cure mechanism and give patients a healthy life.In order to effectively curb the threat of diabetes complicated with cardiovascular disease patients,we should strengthen the research in this field.Through the analysis of the risk factors of diabetic cardiovascular disease,we can let the majority of medical workers understand the superficial and potential risk factors,to formulate scientific and reasonable treatment plan,for further improving the quality of life of patients.In the following,the author first introduces the basic situation of diabetes and cardiovascular complications,then introduces the main risk factors of diabetic cardiovascular disease one by one,hoping that this study can help to improve the cure rate of diabetes complicated with cardiovascular disease.
基金supported by the following grants:the Regional Innovation and Development Joint Fund of the National Natural Science Foundation of China(No.U22A20269)the National Key R&D Program of China(No.2018YFC1311300)the National Natural Science Foundation of China(Nos.82200262 and 82000229).
文摘Doxorubicin(DOX)-mediated cardiotoxicity can exacerbate mortality in oncology patients,but related pharmacotherapeutic measures are relatively limited.Ferroptosis was recently identified as a major mechanism of DOX-induced cardiotoxicity.Idebenone,a novel ferroptosis inhibitor,is a well-described clinical drug widely used.However,its role and pathological mechanism in DOX-induced cardiotoxicity are still unclear.In this study,we demonstrated the effects of idebenone on DOX-induced cardiotoxicity and elucidated its underlying mechanism.A single intraperitoneal injection of DOX(15 mg/kg)was administrated to establish DOX-induced cardiotoxicity.The results showed that idebenone significantly attenuated DOX-induced cardiac dysfunction due to its ability to regulate acute DOX-induced Fe^(2+)and ROS overload,which resulted in ferroptosis.CESTA and BLI further revealed that idebenone's anti-ferroptosis effect was mediated by FSP1.Interestingly,idebenone increased FSP1 protein levels but did not affect Fsp1 mRNA levels in the presence of DOX.Idebenone could form stable hydrogen bonds with FSP1 protein at K355,which may influence its association with ubiquitin.The results confirmed that idebenone stabilized FSP1 protein levels by inhibiting its ubiquitination degradation.In conclusion,this study demonstrates idebenone attenuated DOX-induced cardiotoxicity by inhibiting ferroptosis via regulation of FSP1,making it a potential clinical drug for patients receiving DOX treatment.
基金supported by the Second Tibetan Plateau Scientific Expedition and Research Program(2019QZKK0604)the National Natural Science Foundation of China(42177081)+1 种基金the Beijing Municipal Natural Science Foundation(8222075)the Youth Cross Team Scientific Research Project of the Chinese Academy of Sciences(JCTD-2021-10)。
文摘Tropospheric ozone(O3)is a trace gas of great significance for air quality and climate change.In recent years,due to the extensive implementation of emission reduction policies,the concentration of fine particulate matter in many countries has decreased significantly^([1]).In contrast,the global ground-level O3 concentration has increased by approximately 0.25 ppbv/a^([2]).Research shows that developed countries are experiencing a rebound in O3 levels while developing countries are facing more severe O3 pollution problems^([3,4]).Therefore,the prevention and control of O3 pollution is the top priority at this stage and will play a vital role in the longterm improvement of air quality.
基金funded by the National Natural Science Foundation of China(Nos.52222905,52179103,41807285,41972280 and 42272326)China Postdoctoral Science Foundation(No.2019M652287)Jiangxi Provincial Natural Science Foundation(Nos.20181ACB20008,20192BBG70078)。
文摘Due to the similarity of conditioning factors,the aggregation feature of landslides and the multi-temporal landslide inventory,the spatial and temporal effects of landslides need to be considered in landslide susceptibility prediction(LSP).The ignorance of this issue will result in some biases and time-invariance in landslide susceptibility.Hence,a novel framework has been proposed to update landslide susceptibility by simultaneously considering the spatial and temporal effects of landslides at the regional scale.In this framework,the landslide inventory of Chongyi County has been divided into pre-and fresh-landslide inventories.According to the LSP results predicted by the support vector machine(SVM)model using the slope unit-based conditioning factors and pre-landslide inventory,a normalized spatial distance index(NSDI)is calculated to quantitatively represent the spatial correlation between landslides and surrounding slope units to develop the SVM-NSDI model.Furthermore,the SVM-Updating model,which incorporates the LSP results of the SVM-NSDI model and fresh-landslide inventory,could be developed to update the LSP results.Subsequently,the confusion matrix,the area under the receiver operating characteristic curve(AUC)and frequency ratio(FR)accuracy are used to evaluate the prediction performance of the above LSP models.The F1-score values of the SVM,SVM-NSDI and SVM-Updating models are 0.776,0.816 and 0.831,respectively.The AUC values are 0.869,0.903 and 0.914 and the FR accuracies are 0.795,0.853 and 0.873.It can be concluded that landslide susceptibility is a time-variant variable,which can be updated by considering the spatial correlation between landslides and surrounding slope units as well as the temporal effects of multi-temporal landslide inventory.This study provides a new framework to update landslide susceptibility over time and also provides more accurate LSP results for decisionmakers.
基金the National Natural Science Foundation of China(Grant Number:81903882,81871240,82001709)the Science and Technology Commission of Shanghai Municipality(Grant Number:22ZR1473700,21S11907700)"Science and Technology Innovation Action Plan"medicine innovation fund by Science and Technology Commission of Shanghai Municipality(Grant Number:21Y31900200).
文摘Dear Editor,Hyperactivation of the type I interferon(IFN)signature has been observed in several systemic autoimmune conditions,and the type I IFN receptor antagonist Saphnelo(anifrolumab-fnia)has been approved in 2021 by the Food and Drug Administration(FDA)in the US.The launch of Saphnelo marked the only new treatment approved for systemic lupus erythematosus(SLE)in more than 10 years.
基金supported by the National Key R&D Program of China(2022YFE0210300,2022YFC2303401,2016YFD0500300,2021YFC0863300,and 2021YFC2300101)the National Natural Science Foundation of China(32070407)the special fund for Science and Technology Innovation Teams of Shanxi Province(202204051001022)。
基金supported by the National Natural Science Foundation of China(Nos.12033007,61875205,91836301,12103058,and 61801458)the Western Young Scholar Project of CAS(Nos.XAB2019B17 and XAB2019B15)+2 种基金the Frontier Science Key Research Project of CAS(No.QYZDB-SSWSLH007)the Strategic Priority Research Program of CAS(No.XDC07020200)the Youth Innovation Promotion Association,CAS(Nos.2022413 and 2021408)。
文摘We report an all-fiber telecom-band energy-time entangled biphoton source with all physical elements integrated into a compact cabinet.At a pump power of 800μW,the photon pairs generation rate reaches 6.9 MHz with the coincidence-toaccidental ratio[CAR]better than 1150.The long-term stability of the biphoton source is characterized by measuring the Hong-Ou-Mandel interference visibility and CAR within a continuous operation period of more than 10 h.Benefiting from the advantages of compact size,light weight,and high stability,this device provides a convenient resource for various field turnkey quantum communication and metrology applications.
基金supported by grants from the National Natural Science Foundation of China (Grant Nos.32160051,42076117,and 41776166)Guangdong Basic and Applied Basic Research Foundation (Grant Nos.2022A1515012015,2023A1515012772)the Foreign Cultural and Educational Experts Project of the Ministry of Science and Technology (No.QNJ2021162001L)。
文摘Polyploidy is a major factor in the evolution of plants,yet we know little about the origin and evolution of polyploidy in intertidal species.This study aimed to identify the evolutionary transitions in three truemangrove species of the genus Acanthus distributed in the Indo-West Pacific region.For this purpose,we took an integrative approach that combined data on morphology,cytology,climatic niche,phylogeny,and biogeography of 493 samples from 42 geographic sites.Our results show that the Acanthus ilicifolius lineage distributed east of the Thai-Malay Peninsula possesses a tetraploid karyotype,which is morphologically distinct from that of the lineage on the west side.The haplotype networks and phylogenetic trees for the chloroplast genome and eight nuclear genes reveal that the tetraploid species has two sub-genomes,one each from A.ilicifolius and A.ebracteatus,the paternal and maternal parents,respectively.Population structure analysis also supports the hybrid speciation history of the new tetraploid species.The two sub-genomes of the tetraploid species diverged from their diploid progenitors during the Pleistocene.Environmental niche models revealed that the tetraploid species not only occupied the near-entire niche space of the diploids,but also expanded into novel environments.Our findings suggest that A.ilicifolius species distributed on the east side of the Thai-Malay Peninsula should be regarded as a new species,A.tetraploideus,which originated from hybridization between A.ilicifolius and A.ebracteatus,followed by chromosome doubling.This is the first report of a true-mangrove allopolyploid species that can reproduce sexually and clonally reproduction,which explains the long-term adaptive potential of the species.