Oxidative catalysis enables lignin depolymerization to yield carbonyl-containing aromatic chemicals for sustainable lignocellulose valorization.The oxidative depolymerization of lignin requires high oxygen pressure an...Oxidative catalysis enables lignin depolymerization to yield carbonyl-containing aromatic chemicals for sustainable lignocellulose valorization.The oxidative depolymerization of lignin requires high oxygen pressure and harsh conditions to trade off lignin’s structural complexity and limited solubility.Herein,we developed an oxidation system for lignin depolymerization using a single phosphomolybdic acid(H_(3)PMo_(12)O_(40))catalyst in acetic acid solvent to address the aforementioned issues.The entire catalytic system was operated under only 0.1 MPa O_(2) pressure,providing over 20 wt% of aromatic compounds containing aldehydes and carboxylic acids.Theoretical calculations combined with experimental analyses reveal structural transformations and redox behavior driven by the synergistic interaction between H_(3)PMo_(12)O_(40) and acetic acid.Mechanistic studies detected superoxide radicals,confirming the joint role of catalyst and solvent in oxygen activation,radicals stabilization,and enhanced reaction efficiency.A low-cost,commercially available catalyst with minimal oxygen demand offers a promising route to industrial-scale biomass refining.展开更多
LIM zinc finger domain containing 1(LIMS1),an evolutionarily conserved LIM domain adaptor protein,is implicated in diverse pathologies,including cancer and neurological disorders.However,its roles in cardiac diseases ...LIM zinc finger domain containing 1(LIMS1),an evolutionarily conserved LIM domain adaptor protein,is implicated in diverse pathologies,including cancer and neurological disorders.However,its roles in cardiac diseases and the underlying mechanisms remain unclear.Here,we explore the functions and mechanisms of LIMS1 in cardiac remodeling and heart failure.We identify the elevated LIMS1 expression in patients with dilated cardiomyopathy and murine cardiomyocytes,suggesting that LIMS1 dysregulation contributes to cardiac pathology.Using CRISPR/Cas9 technology,we generate a zebrafish model of lims1 loss-offunction mutant,which exhibits severe cardiac chamber remodeling,systolic dysfunction,and premature mortality,demonstrating the essential role of lims1 in maintaining cardiac integrity.Transcriptomic profiling reveals the activation of the gp130/Jak1/Stat3 signaling in the lims1-deficient hearts.Strikingly,pharmacological inhibition of Stat3 or c-Fos partially rescues cardiomyopathy phenotypes.Our findings reveal the underlying mechanism of lims1 deficiency-caused heart failure through gp130/Jak1/Stat3 hyperactivation,offering insights into cardiac remodeling and potential therapeutic strategies.展开更多
Temperature is a key meteorological factor that affects tropospheric ozone(O_(3)),with both humid-heat(sauna days)and dry-heat(roast days)conditions leading to O_(3) exceedances.However,the mechanisms influencing O_(3...Temperature is a key meteorological factor that affects tropospheric ozone(O_(3)),with both humid-heat(sauna days)and dry-heat(roast days)conditions leading to O_(3) exceedances.However,the mechanisms influencing O_(3) formation and degradation under these two weather conditions remain unclear.Therefore,experiments were conducted in Beijing from 2019 to 2021 to observe O_(3),its precursors,and related meteorological elements.A total of 18 days with O_(3) exceedances were selected,including 10 sauna days and 8 roast days.The results of this study revealed that on roast days,the sensible heat flux was 143.5 W/m^(2) greater and the wind speed gradient was 0.018 s^(-1) greater than those on sauna days,indicating more intense thermal and dynamic turbulence.The strong turbulence enhanced the vertical cycle of nitrogen dioxide(NO_(2))and O_(3),resulting in a 58.2μg/(m^(2)·h)increase in NO_(2) upward transport rate and a 1034.4μg/(m^(2)·h)increase in O_(3) downward transport rate on roast days than sauna days.Subsequently,a box model analysis was used to examine O_(3) formation under the two types of weather conditions,revealing that the NO_(2)-O_(3) vertical cycling speed dominated the O_(3) sensitivity.The O_(3) sensitivity was synergistically controlled by nitrogen oxides(NO_(x))and volatile organic compounds on sauna days,while it tended to be NO_(x)-limited on roast days.The aim of this study was to provide a scientific theoretical basis for the control of O_(3) under different types of high temperature weather conditions.展开更多
The palladium/kieselguhr composites(Pd/K)were prepared by the PdCl_(2) dipping-reducing method.The effects of the preparation conditions on the Pd/K were studied,such as the heat treatment,dipping time,palladium conce...The palladium/kieselguhr composites(Pd/K)were prepared by the PdCl_(2) dipping-reducing method.The effects of the preparation conditions on the Pd/K were studied,such as the heat treatment,dipping time,palladium concentration in solution and number of loading cycles.The pore structure and palladium content of the Pd/K were measured by the Brunauer-Emmett-Teller method and an inductively coupled plasma mass spectrometry.The appearance and palladium element distribution were measured by a scanning electron microscope.It is found that the palladium element is more densely distributed in the irregular and porous parts of the kieselguhr particles,so the kieselguhr is superior to Al_(2)O_(3) as the carrier material.The heat treatment can improve the pore permeability and increase the palladium content for the Pd/K.Increasing the dipping time,palladium concentration in solution and number of loading cycles is beneficial to increase the palladium content of the Pd/K,but more loading cycles may lead to the pore collapse,which obstructs the interaction with the hydrogen isotope gases.A kind of Pd/K was prepared under a set of optimized conditions and was packed in a separation column.This Pd/K was proved to be of high performance and durable by some hydrogen-deuterium separation experiments.展开更多
Offline policy evaluation,evaluating and selecting complex policies for decision-making by only using offline datasets is important in reinforcement learning.At present,the model-based offline policy evaluation(MBOPE)...Offline policy evaluation,evaluating and selecting complex policies for decision-making by only using offline datasets is important in reinforcement learning.At present,the model-based offline policy evaluation(MBOPE)is widely welcomed because of its easy to implement and good performance.MBOPE directly approximates the unknown value of a given policy using the Monte Carlo method given the estimated transition and reward functions of the environment.Usually,multiple models are trained,and then one of them is selected to be used.However,a challenge remains in selecting an appropriate model from those trained for further use.The authors first analyse the upper bound of the difference between the approximated value and the unknown true value.Theoretical results show that this difference is related to the trajectories generated by the given policy on the learnt model and the prediction error of the transition and reward functions at these generated data points.Based on the theoretical results,a new criterion is proposed to tell which trained model is better suited for evaluating the given policy.At last,the effectiveness of the proposed criterion is demonstrated on both benchmark and synthetic offline datasets.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
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
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
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
During the boll formation stage,cotton bolls exhibit the lowest expression of Bacillus thuringiensis(Bt)insecticidal proteins.Resistance to insects varies notably among different organs,which poses challenges for cont...During the boll formation stage,cotton bolls exhibit the lowest expression of Bacillus thuringiensis(Bt)insecticidal proteins.Resistance to insects varies notably among different organs,which poses challenges for controlling cotton bollworms.Consequently,an experimental strategy was designed in the 2020-2021 cotton growing season to coordinate the enhancement of protein synthesis and the attenuation of degradation.Two Bt cultivars of Gossypium hirsutum,namely the hybrid Sikang 3 and the conventional Sikang 1,were used as test materials.Three treatments were applied at the peak flowering period:CK(the control),T1(amino acids),and T2(amino acids and EDTA).The results show that,in comparison to the CK group,the Bt protein contents were significantly increased in both cotton bolls and their subtending leaves under the T1 and T2 treatments.The maximum levels of increase observed were 67.5%in cotton bolls and 21.7%in leaves.Moreover,the disparity in Bt protein content between cotton bolls and their subtending leaves notably decreased by 31.2%.Correlation analysis suggested that the primary physiological mechanisms for augmenting Bt protein content involve increased protein synthesis and reduced protein catabolism,which are independent of Bt gene expression levels.Stepwise regression and path analysis revealed that elevating the soluble protein content and transaminase activity,while reducing the catabolic enzyme activities,are instrumental in enhancing the Bt protein content.Consequently,the coordinated application of amino acids and EDTA emerges as a strategy that can improve the overall resistance of Bt cotton and mitigate the spatiotemporal variations in Bt toxin concentrations in both cotton bolls and leaves.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
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
The effects of mepiquat chloride(DPC)on the Cry1Ac protein content in Bacillus thuringiensis(Bt)cotton boll shells under high temperature and drought stress were investigated to provide a theoretical reference for Bt ...The effects of mepiquat chloride(DPC)on the Cry1Ac protein content in Bacillus thuringiensis(Bt)cotton boll shells under high temperature and drought stress were investigated to provide a theoretical reference for Bt cotton breeding and high-yield and-efficiency cotton cultivation.This study was conducted using Bt cotton cultivar‘Sikang 3'during the 2020 and 2021 growing seasons at Yangzhou University Farm,Yangzhou,Jiangsu Province,China.Potted cotton plants were exposed to high temperature and drought stress,and sprayed with either 20 mg L^(-1)DPC or water(CK).Seven days after treatment,the Cry1Ac protein content,α-ketoglutarate content,pyruvic acid content,glutamate synthase activity,glutamic oxaloacetic transaminase activity,soluble protein content,and amino acid content were measured,and transcriptome sequencing was performed.DESeq was used for differential gene analysis.Under the DPC treatment,the Cry1Ac protein content increased by 4.7-11.9% compared to CK.Theα-ketoglutarate content,pyruvic acid content,glutamate synthase activity,glutamic oxaloacetic transaminase activity,soluble protein content,and amino acid content all increased.Transcriptome analysis revealed 7,542 upregulated genes and 10,449 downregulated genes for DPC vs.CK.Gene ontology(GO)and Kyoto Encyclopedia of Gene and Genomes(KEGG)analyses showed that the differentially expressed genes were mainly involved in biological processes,such as carbon and amino acid metabolism.For example,genes encoding 6-phosphofructokinase,pyruvate kinase,glutamic pyruvate transaminase,pyruvate dehydrogenase,citrate synthase,isocitrate dehydrogenase,2-oxoglutarate dehydrogenase,glutamate synthase,1-pyrroline-5-carboxylate dehydrogenase,glutamic oxaloacetic transaminase,amino-acid N-acetyltransferase,and acetylornithine deacetylase were all significantly upregulated.The DPC treatment increased pyruvate,α-ketoglutarate,and oxaloacetate by increasing the operational rate of the glycolytic pathway of the citric acid cycle.It also significantly upregulated the genes encoding glutamate synthase,pyrrolidine-5-carboxylic acid dehydrogenase,glutamate oxaloacetate transaminase,and N-acetylglutamate synthetase,while it downregulated the genes encoding glutamine synthetase.Therefore,the synthesis of aspartic acid,glutamic acid,pyruvate,and arginine increased after treatment with DPC,and the Cry1Ac protein content was increased by regulating carbon and amino acid metabolism.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
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
文摘Oxidative catalysis enables lignin depolymerization to yield carbonyl-containing aromatic chemicals for sustainable lignocellulose valorization.The oxidative depolymerization of lignin requires high oxygen pressure and harsh conditions to trade off lignin’s structural complexity and limited solubility.Herein,we developed an oxidation system for lignin depolymerization using a single phosphomolybdic acid(H_(3)PMo_(12)O_(40))catalyst in acetic acid solvent to address the aforementioned issues.The entire catalytic system was operated under only 0.1 MPa O_(2) pressure,providing over 20 wt% of aromatic compounds containing aldehydes and carboxylic acids.Theoretical calculations combined with experimental analyses reveal structural transformations and redox behavior driven by the synergistic interaction between H_(3)PMo_(12)O_(40) and acetic acid.Mechanistic studies detected superoxide radicals,confirming the joint role of catalyst and solvent in oxygen activation,radicals stabilization,and enhanced reaction efficiency.A low-cost,commercially available catalyst with minimal oxygen demand offers a promising route to industrial-scale biomass refining.
基金the National Natural Science Foundation of China(82070394,82371863,31970504,82100491,and 82000307)the Hunan Provincial Key Laboratory of Regional Hereditary Birth Defects Prevention and Control project(HPKL2023001)for their support of this research.
文摘LIM zinc finger domain containing 1(LIMS1),an evolutionarily conserved LIM domain adaptor protein,is implicated in diverse pathologies,including cancer and neurological disorders.However,its roles in cardiac diseases and the underlying mechanisms remain unclear.Here,we explore the functions and mechanisms of LIMS1 in cardiac remodeling and heart failure.We identify the elevated LIMS1 expression in patients with dilated cardiomyopathy and murine cardiomyocytes,suggesting that LIMS1 dysregulation contributes to cardiac pathology.Using CRISPR/Cas9 technology,we generate a zebrafish model of lims1 loss-offunction mutant,which exhibits severe cardiac chamber remodeling,systolic dysfunction,and premature mortality,demonstrating the essential role of lims1 in maintaining cardiac integrity.Transcriptomic profiling reveals the activation of the gp130/Jak1/Stat3 signaling in the lims1-deficient hearts.Strikingly,pharmacological inhibition of Stat3 or c-Fos partially rescues cardiomyopathy phenotypes.Our findings reveal the underlying mechanism of lims1 deficiency-caused heart failure through gp130/Jak1/Stat3 hyperactivation,offering insights into cardiac remodeling and potential therapeutic strategies.
基金supported by the National Natural Science Foundation of China(No.42177081)the National Key R&D Program of China(No.2023YFC3706103)+1 种基金Beijing Municipal Natural Science Foundation(No.8222075)the Youth Cross Team Scientific Research Project of the Chinese Academy of Sciences(No.JCTD-2021–10).
文摘Temperature is a key meteorological factor that affects tropospheric ozone(O_(3)),with both humid-heat(sauna days)and dry-heat(roast days)conditions leading to O_(3) exceedances.However,the mechanisms influencing O_(3) formation and degradation under these two weather conditions remain unclear.Therefore,experiments were conducted in Beijing from 2019 to 2021 to observe O_(3),its precursors,and related meteorological elements.A total of 18 days with O_(3) exceedances were selected,including 10 sauna days and 8 roast days.The results of this study revealed that on roast days,the sensible heat flux was 143.5 W/m^(2) greater and the wind speed gradient was 0.018 s^(-1) greater than those on sauna days,indicating more intense thermal and dynamic turbulence.The strong turbulence enhanced the vertical cycle of nitrogen dioxide(NO_(2))and O_(3),resulting in a 58.2μg/(m^(2)·h)increase in NO_(2) upward transport rate and a 1034.4μg/(m^(2)·h)increase in O_(3) downward transport rate on roast days than sauna days.Subsequently,a box model analysis was used to examine O_(3) formation under the two types of weather conditions,revealing that the NO_(2)-O_(3) vertical cycling speed dominated the O_(3) sensitivity.The O_(3) sensitivity was synergistically controlled by nitrogen oxides(NO_(x))and volatile organic compounds on sauna days,while it tended to be NO_(x)-limited on roast days.The aim of this study was to provide a scientific theoretical basis for the control of O_(3) under different types of high temperature weather conditions.
基金financially supported by the National Natural Science Foundation of China(22109145)the Foundation of Science and Technology on Surface Physics and Chemistry Laboratory(WDZC202202)the Natural Science Foundation of Sichuan Province(2024NSFTD0018)。
文摘The palladium/kieselguhr composites(Pd/K)were prepared by the PdCl_(2) dipping-reducing method.The effects of the preparation conditions on the Pd/K were studied,such as the heat treatment,dipping time,palladium concentration in solution and number of loading cycles.The pore structure and palladium content of the Pd/K were measured by the Brunauer-Emmett-Teller method and an inductively coupled plasma mass spectrometry.The appearance and palladium element distribution were measured by a scanning electron microscope.It is found that the palladium element is more densely distributed in the irregular and porous parts of the kieselguhr particles,so the kieselguhr is superior to Al_(2)O_(3) as the carrier material.The heat treatment can improve the pore permeability and increase the palladium content for the Pd/K.Increasing the dipping time,palladium concentration in solution and number of loading cycles is beneficial to increase the palladium content of the Pd/K,but more loading cycles may lead to the pore collapse,which obstructs the interaction with the hydrogen isotope gases.A kind of Pd/K was prepared under a set of optimized conditions and was packed in a separation column.This Pd/K was proved to be of high performance and durable by some hydrogen-deuterium separation experiments.
文摘Offline policy evaluation,evaluating and selecting complex policies for decision-making by only using offline datasets is important in reinforcement learning.At present,the model-based offline policy evaluation(MBOPE)is widely welcomed because of its easy to implement and good performance.MBOPE directly approximates the unknown value of a given policy using the Monte Carlo method given the estimated transition and reward functions of the environment.Usually,multiple models are trained,and then one of them is selected to be used.However,a challenge remains in selecting an appropriate model from those trained for further use.The authors first analyse the upper bound of the difference between the approximated value and the unknown true value.Theoretical results show that this difference is related to the trajectories generated by the given policy on the learnt model and the prediction error of the transition and reward functions at these generated data points.Based on the theoretical results,a new criterion is proposed to tell which trained model is better suited for evaluating the given policy.At last,the effectiveness of the proposed criterion is demonstrated on both benchmark and synthetic offline datasets.
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 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 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 the National Natural Science Foundation of China(31901462 and 31671613)the Natural Science Foundation of the Jiangsu Higher Education Institutions of China(22KJA210005)+1 种基金the China Scholarship Council(202308320440)the Postgraduate Research&Practice Innovation Program of Jiangsu Province,China(KYCX22_3508)。
文摘During the boll formation stage,cotton bolls exhibit the lowest expression of Bacillus thuringiensis(Bt)insecticidal proteins.Resistance to insects varies notably among different organs,which poses challenges for controlling cotton bollworms.Consequently,an experimental strategy was designed in the 2020-2021 cotton growing season to coordinate the enhancement of protein synthesis and the attenuation of degradation.Two Bt cultivars of Gossypium hirsutum,namely the hybrid Sikang 3 and the conventional Sikang 1,were used as test materials.Three treatments were applied at the peak flowering period:CK(the control),T1(amino acids),and T2(amino acids and EDTA).The results show that,in comparison to the CK group,the Bt protein contents were significantly increased in both cotton bolls and their subtending leaves under the T1 and T2 treatments.The maximum levels of increase observed were 67.5%in cotton bolls and 21.7%in leaves.Moreover,the disparity in Bt protein content between cotton bolls and their subtending leaves notably decreased by 31.2%.Correlation analysis suggested that the primary physiological mechanisms for augmenting Bt protein content involve increased protein synthesis and reduced protein catabolism,which are independent of Bt gene expression levels.Stepwise regression and path analysis revealed that elevating the soluble protein content and transaminase activity,while reducing the catabolic enzyme activities,are instrumental in enhancing the Bt protein content.Consequently,the coordinated application of amino acids and EDTA emerges as a strategy that can improve the overall resistance of Bt cotton and mitigate the spatiotemporal variations in Bt toxin concentrations in both cotton bolls and leaves.
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 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.
基金supported by the National Natural Science Foundation of China(31901462)the Natural Science Foundation of the Jiangsu Higher Education Institutions,China(22KJA210005)+1 种基金the Priority Academic Program Development of Jiangsu Higher Education Institutions,China(PAPD)the Brand Professional Construction Program of Jiangsu Higher Education Institutions,China。
文摘The effects of mepiquat chloride(DPC)on the Cry1Ac protein content in Bacillus thuringiensis(Bt)cotton boll shells under high temperature and drought stress were investigated to provide a theoretical reference for Bt cotton breeding and high-yield and-efficiency cotton cultivation.This study was conducted using Bt cotton cultivar‘Sikang 3'during the 2020 and 2021 growing seasons at Yangzhou University Farm,Yangzhou,Jiangsu Province,China.Potted cotton plants were exposed to high temperature and drought stress,and sprayed with either 20 mg L^(-1)DPC or water(CK).Seven days after treatment,the Cry1Ac protein content,α-ketoglutarate content,pyruvic acid content,glutamate synthase activity,glutamic oxaloacetic transaminase activity,soluble protein content,and amino acid content were measured,and transcriptome sequencing was performed.DESeq was used for differential gene analysis.Under the DPC treatment,the Cry1Ac protein content increased by 4.7-11.9% compared to CK.Theα-ketoglutarate content,pyruvic acid content,glutamate synthase activity,glutamic oxaloacetic transaminase activity,soluble protein content,and amino acid content all increased.Transcriptome analysis revealed 7,542 upregulated genes and 10,449 downregulated genes for DPC vs.CK.Gene ontology(GO)and Kyoto Encyclopedia of Gene and Genomes(KEGG)analyses showed that the differentially expressed genes were mainly involved in biological processes,such as carbon and amino acid metabolism.For example,genes encoding 6-phosphofructokinase,pyruvate kinase,glutamic pyruvate transaminase,pyruvate dehydrogenase,citrate synthase,isocitrate dehydrogenase,2-oxoglutarate dehydrogenase,glutamate synthase,1-pyrroline-5-carboxylate dehydrogenase,glutamic oxaloacetic transaminase,amino-acid N-acetyltransferase,and acetylornithine deacetylase were all significantly upregulated.The DPC treatment increased pyruvate,α-ketoglutarate,and oxaloacetate by increasing the operational rate of the glycolytic pathway of the citric acid cycle.It also significantly upregulated the genes encoding glutamate synthase,pyrrolidine-5-carboxylic acid dehydrogenase,glutamate oxaloacetate transaminase,and N-acetylglutamate synthetase,while it downregulated the genes encoding glutamine synthetase.Therefore,the synthesis of aspartic acid,glutamic acid,pyruvate,and arginine increased after treatment with DPC,and the Cry1Ac protein content was increased by regulating carbon and amino acid metabolism.
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 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.
