The specificity of the double-stranded RNA(dsRNA) used in the RNA interference(RNAi) technique is crucial for the success of sequence-specific gene silencing. Currently, RNAi-mediated insect control is a trending rese...The specificity of the double-stranded RNA(dsRNA) used in the RNA interference(RNAi) technique is crucial for the success of sequence-specific gene silencing. Currently, RNAi-mediated insect control is a trending research topic.However, the off-target effects of the dsRNA in RNAi are a major concern. In this study, the ds Hvβ’COPI(coat protein complex I, β’ subunit)-treated and untreated transcriptomes of the 28-spotted potato lady beetle(Henosepilachna vigintioctopunctata) were compared to understand its off-target gene silencing effects. The RNA-seq results revealed that 63 and 44 differentially expressed genes(DEGs) were upregulated and downregulated, respectively, in the ds Hvβ’COPI treated group as compared with the control. Validation of the differential expressions of some selected DEGs via reverse transcription-quantitative PCR(RT-qPCR) analysis confirmed the reliability of the transcriptome analysis results. Further downstream analysis revealed that there were no genes homologous with Hvβ’COPI in H. vigintioctopunctata. Additionally,no genes with a >11 bp continuous match with ds Hvβ’COPI were found in the H. vigintioctopunctata transcriptome. Six genes(Hvcitron, Hvhelicase, Hvtransposase, Hvserine, Hvdynein, and Hv E3 ubiquitin) were selected to examine the offtarget activity of ds Hvβ’COPI based on their potential involvement in various H. vigintioctopunctata metabolic pathways.The severity of silencing these six off-target genes was evaluated by employing RNAi. The RNAi results confirmed the downregulation of the expression of all six genes, although there was no significant lethality. The findings of this study will be helpful in the risk analysis of future RNAi-mediated pest control experiments.展开更多
As versatile and robust genome editing tools,clustered regularly interspaced short palindromic repeats(CRISPR)technologies have been broadly used in basic research,biotechnology,and therapeutic development.Off-target ...As versatile and robust genome editing tools,clustered regularly interspaced short palindromic repeats(CRISPR)technologies have been broadly used in basic research,biotechnology,and therapeutic development.Off-target mutagenesis by CRISPR systems has been demonstrated,and various methods have been developed to markedly increase their specificity.In this review,we highlight the efforts of producing and modifying guide RNA(gRNA)to minimize off-target activities,including sequence and structure design,tuning expression and chemical modification.The modalities of gRNA engineering can be applied across CRISPR systems.In conjunction with CRISPR protein effectors,the engineered gRNA enables efficient and precise genome editing.展开更多
CRISPR-mediated genome editing is a revolutionary technology for genome manipulation that uses the CRISPR-Cas systems and base editors.Currently,poor efficiency and off-target problems have impeded the application of ...CRISPR-mediated genome editing is a revolutionary technology for genome manipulation that uses the CRISPR-Cas systems and base editors.Currently,poor efficiency and off-target problems have impeded the application of CRISPR systems.The on-target efficiency has been improved in several advanced versions of CRISPR systems,whereas the off-target detection still remains a key challenge.Here,we outline the different versions of CRISPR systems and off-target detection strategies,discuss the merits and limitations of off-target detection methods,and provide potential implications for further gene editing research.展开更多
A recent breakthrough in agricultural biotechnology is the introduction of RNAi-mediated strategies in pest control.However, the off-target effects of RNAi pest control are still not fully understood. Here, we studied...A recent breakthrough in agricultural biotechnology is the introduction of RNAi-mediated strategies in pest control.However, the off-target effects of RNAi pest control are still not fully understood. Here, we studied the off-target effects of two insecticidal siRNAs in both target and non-target insects. The results revealed that off-target effects of insecticidal siRNAs occur widely in both target and non-target insects. We classified the expression-changed genes according to their homology to the siRNA-targeted gene, related KEGG pathways with the siRNA-targeted gene and continuous matches with siRNAs. Surprisingly, the unintended significant changes in gene expression levels did not strictly match with the number of contiguous nucleotides in the siRNAs. As expected, the expression of small portions of the homologous and KEGG-related genes were significantly changed. We calculated the Shannon entropy of the transcriptome profile of the insects after injecting them with insecticidal siRNAs. Though hundreds of genes were affected in their expression levels post siRNAtreatment, the Shannon entropy of the transcriptome remained unchanged, suggesting that the transcriptome expression was balanced. Our results provide evidence that siRNAs cross-reacted with individual genes in non-target species, but did not have significant effects on the integrity of the transcriptome profiles in either target or non-target species on a genomic scale. The metric we proposed can be used to estimate the off-target effects of insecticidal siRNAs, which might be useful for evaluating the safety of RNAi in pest control.展开更多
DNA is the blueprint of life,instructing the growth,development,and reproduction of an organism.Genome sequencing uncovers the codes of life,whereas genome editing could rewrite the codes,thus then leads to revolution...DNA is the blueprint of life,instructing the growth,development,and reproduction of an organism.Genome sequencing uncovers the codes of life,whereas genome editing could rewrite the codes,thus then leads to revolutionary advances in all aspects of life sciences,such as uncovering regulatory network of life,increasing the production of crops,producing new breeds of livestock,and curing genetic disorders(Liu,2017).展开更多
Site-directed RNA editing(SDRE)is invaluable to basic research and clinical applications and has emerged as a new frontier in genome editing.The past few years have witnessed a surge of interest in SDRE,with SDRE tool...Site-directed RNA editing(SDRE)is invaluable to basic research and clinical applications and has emerged as a new frontier in genome editing.The past few years have witnessed a surge of interest in SDRE,with SDRE tools emerging at a breathtaking pace.However,off-target effects of SDRE remain a tough problem,which constitutes a major hurdle to their clinical applications.Here we discuss the diverse strategies for combating off-target editing,drawing lessons from the published studies as well as our ongoing research.Overall,SDRE is still at its infancy,with significant challenges and exciting opportunities ahead.展开更多
Agglomeration supports the high-quality development of the manufacturing industry,and its associated resource and environmental effects play a crucial role in driving green economic development.Based on data from pref...Agglomeration supports the high-quality development of the manufacturing industry,and its associated resource and environmental effects play a crucial role in driving green economic development.Based on data from prefecture-level cities in China from 2005 to 2019,this study employs the inverse distance weighting method,the bivariate local indicator of spatial association model,the spatial Durbin model,and other techniques to explore the relationship between manufacturing agglomeration and PM_(2.5)concentrations,and to assess the impact of its manufacturing agglomeration.Four correlation patterns are observed:high-high,low-low,high-low,and low-high.Among these,high-high and low-low patterns dominate in terms of number of cities.These correlation patterns demonstrate strong temporal stability,with a clear“Matthew effect”.The effect of manufacturing agglomeration on PM_(2.5)levels is significantly negative and helps reduce concentrations regionally,indicating the need to further enhance agglomeration levels regionally.However,it can increase PM_(2.5)levels in neighboring areas due to a siphon effect,and the impact of varies across regions.Compared with levels in 2005-2013,the significance of the relationship between manufacturing agglomeration and PM_(2.5)weakened in the 2013-2019 period.Accordingly,this study proposes countermeasures and policy recommendations aimed at strengthening regional collaborative governance and inspiring differentiated agglomeration strategies to support sustainable economic development in China.展开更多
The dried fruit of Forsythia suspensa(Oleaceae),also known as Forsythia,is a traditional Chinese medicinal herb known for its heat-clearing and detoxifying properties.It is used to disperse nodules,reduce swelling,rem...The dried fruit of Forsythia suspensa(Oleaceae),also known as Forsythia,is a traditional Chinese medicinal herb known for its heat-clearing and detoxifying properties.It is used to disperse nodules,reduce swelling,remove toxins,clear heat,and alleviate wind-heat syndromes.It also has hepatoprotective,anti-inflammatory,antiviral,antibacterial,anticancer,antioxidant,antiaging,and anti-obesity effects,as well as potential therapeutic effects on Alzheimer’s disease and diabetic nephropathy.It is used to treat scrofula,mastitis,wind-heat common cold,and other ailments.The review summarizes the chemical constituents and pharmacological effects of F.suspensa,aiming to provide a scientific foundation for its future development,research,and clinical utilization.展开更多
Beam-tracking simulations have been extensively utilized in the study of collective beam instabilities in circular accelerators.Traditionally,many simulation codes have relied on central processing unit(CPU)-based met...Beam-tracking simulations have been extensively utilized in the study of collective beam instabilities in circular accelerators.Traditionally,many simulation codes have relied on central processing unit(CPU)-based methods,tracking on a single CPU core,or parallelizing the computation across multiple cores via the message passing interface(MPI).Although these approaches work well for single-bunch tracking,scaling them to multiple bunches significantly increases the computational load,which often necessitates the use of a dedicated multi-CPU cluster.To address this challenge,alternative methods leveraging General-Purpose computing on Graphics Processing Units(GPGPU)have been proposed,enabling tracking studies on a standalone desktop personal computer(PC).However,frequent CPU-GPU interactions,including data transfers and synchronization operations during tracking,can introduce communication overheads,potentially reducing the overall effectiveness of GPU-based computations.In this study,we propose a novel approach that eliminates this overhead by performing the entire tracking simulation process exclusively on the GPU,thereby enabling the simultaneous processing of all bunches and their macro-particles.Specifically,we introduce MBTRACK2-CUDA,a Compute Unified Device Architecture(CUDA)ported version of MBTRACK2,which facilitates efficient tracking of single-and multi-bunch collective effects by leveraging the full GPU-resident computation.展开更多
Preferential magnesium(Mg)electrodeposition on separators is a ubiquitous yet poorly understood phenomenon in rechargeable Mg-metal batteries,posing a fundamental challenge to their development.In this work,the synerg...Preferential magnesium(Mg)electrodeposition on separators is a ubiquitous yet poorly understood phenomenon in rechargeable Mg-metal batteries,posing a fundamental challenge to their development.In this work,the synergy effects of interface-accelerating desolvation and spatial confinement have been demonstrated as the essential causation of this counterintuitive experimental phenomenon.At the molecular level,the imide ring(-CO-NR-CO-,in which R represents the phenyl)groups in an artificially introduced polyimide(PI)interlayer facilitate the strong electrostatic affinity towards Mg^(2+),which accelerates the desolvation process for Mg^(2+)solvation structures at the inner Helmholtz plane.At the nucleation scale,the wedge-like concave geometry formed at the PI/current collector interface provides energetically favorable sites for Mg nucleation.This unique architecture reduces the critical nucleus size,thereby significantly lowering nucleation energy barriers.As a result,the satisfactory Coulombic efficiency for Mg plating/stripping(98.22%)and cycle lifespan(1200 cycles,above 100 days)have been achieved,outperforming most of the previous results.This work pioneers a molecular-level understanding of separator-directed Mg deposition and resolves a long-standing confusion in Mg-metal batteries.展开更多
Understanding Cd contamination in the soil-rice ecosystem and the underlying its threshold and interaction effects is crucial for controlling Cd pollution and ensuring food safety.Although the quantitative relationshi...Understanding Cd contamination in the soil-rice ecosystem and the underlying its threshold and interaction effects is crucial for controlling Cd pollution and ensuring food safety.Although the quantitative relationships between Cd and environmental variables have been extensively studied,the threshold and interaction effects of multi-source environmental variables remain largely unexplored.This study employs a combination of random forest analysis and a human health risk model to investigate the effects of variables on Cd levels in rice grains,with the goal of quantifying their contributions and elucidating their relationships.The results indicated that the 15 selected variables collectively explained 47.36%of the variation in Cd content,with the top three variables being soil pH,distance from industrial park,and soil Zn.The majority of variables exhibited threshold effects on Cd levels in rice grains.By visualizing the interaction between Soil pH,distance from industrial park,and soil Zn with Cd levels in rice,we demonstrate the threshold effects of them on Cd level in rice grains,thereby providing further insight into the variation observed.Furthermore,oral intake of rice has been identified as the primary route of human exposure,significantly contributing to overall exposure pathways.Understanding these interactions is crucial for gaining insights into the underlying processes driving Cd pollution and fostering sustainable development within the industry.Our findings underscore the crucial need to consider multiple environmental variables and their interactions when managing heavy metals(HMs)contamination and mitigating health risks.展开更多
[Objectives]To explore the control mode of farmland drainage pollutants and investigate the effects of ecological ditch and wetland on reducing farmland drainage pollutants in Hetao Irrigation District.[Methods]Based ...[Objectives]To explore the control mode of farmland drainage pollutants and investigate the effects of ecological ditch and wetland on reducing farmland drainage pollutants in Hetao Irrigation District.[Methods]Based on the demonstration construction project of the ecological ditch-constructed wetland system in the Hetao Irrigation District,an experimental study was conducted from July to September 2023 to investigate the interception and purification effects of ecological ditches,constructed wetlands,and the combined ecological ditch-constructed wetland system on farmland drainage pollutants.Key water quality parameters measured included total nitrogen(TN)concentration and total phosphorus(TP)concentration.[Results]Different treatment modes of ecological ditches and constructed wetlands have a certain removal effect on nitrogen and phosphorus pollutants in water bodies.The ecological ditches treated with Astragalus laxmannii,Melilotus officinalis,Medicago sativa,bio-ball substrate,and bio-sheet substrate showed reduction efficiencies for TN and TP of 21.09% and 23.84%,12.06% and 26.67%,20.08% and 34.15%,23.65% and 20.56%,and 19.92% and 25.83%,respectively.The emergent plant area showed reduction efficiencies of 24.28%for TN and 17.89%for TP,while the submerged plant area achieved a reduction efficiency of 10.21%for both TN and TP.Among the different treatment modes,the ecological ditch with M.sativa performed better in TP removal,whereas the bio-ball substrate treatment mode showed higher effectiveness in TN removal.In addition,the emergent plant area exhibited better TP removal performance,while the submerged plant area was more effective in TN removal.The combined system of ecological ditch and constructed wetland achieved removal rates of 37.55% for TN and 11.47% for TP.It effectively facilitates the step-by-step interception and adsorption purification of pollutants,thereby showing significant removal and purification effects on nitrogen and phosphorus contaminants.This contributes to mitigating agricultural non-point source pollution.[Conclusions]The combined ecological ditch-constructed wetland system serves dual functions of agricultural drainage and pollutant interception and purification.It reduces the pollution load of farmland drainage on receiving water bodies to some extent and mitigates agricultural non-point source pollution.Therefore,it is a relatively suitable technology for managing agricultural non-point source pollution in the Hetao Irrigation District.展开更多
Inflammatory bowel disease(IBD),which includes Crohn’s disease(CD)and ulcerative colitis(UC),is a chronic inflammatory condition affecting the gastrointestinal tract.The global incidence and prevalence of IBD continu...Inflammatory bowel disease(IBD),which includes Crohn’s disease(CD)and ulcerative colitis(UC),is a chronic inflammatory condition affecting the gastrointestinal tract.The global incidence and prevalence of IBD continue to increase.While multiple clinical treatments exist,conventional therapies frequently present limitations and adverse effects.Natural polysaccharides(PSs)have emerged as a significant focus of research interest due to their therapeutic potential and applications in functional foods and health products.This review synthesizes current understanding of IBD pathophysiology and the mechanisms by which natural PSs counter IBD,including their capacity to restore immune homeostasis and intestinal barrier function,modulate gut microbiota and metabolites,reduce oxidative stress,and address irregularities in autophagy and endoplasmic reticulum stress(ERS).The review examines the structure-activity relationships of PSs demonstrating anti-IBD effects and identifies promising therapeutic products.The discussion encompasses pharmacokinetics,safety evaluations,and clinical applications of these compounds.This comprehensive review establishes a theoretical foundation for developing natural PS-based therapeutic approaches for IBD management.展开更多
Existing studies on the Regional Comprehensive Economic Partnership(RCEP)mainly focused on institutional features,macro-economic impacts,and trade-network structures,while its geographic attributes and their implicati...Existing studies on the Regional Comprehensive Economic Partnership(RCEP)mainly focused on institutional features,macro-economic impacts,and trade-network structures,while its geographic attributes and their implications remain underexplored.Taking the RCEP as a case,this paper examines how the FTA reshapes China’s trade geography and validates these effects with an enhanced GTAP model,providing an empirical basis for advancing trade-geography theory.Key findings include:(1)RCEP significantly reduces regional trade costs.After full implementation of the agreement,the average tariffs among member countries will decrease to 40.5%of the pre-implementation level,while import and export trade facilitation levels improve by 34.3%and 29.6%,respectively.However,these improvements exhibit marked regional disparities.(2)RCEP asymmetrically promotes China’s foreign trade growth,with stronger import stimulation than export expansion,alongside significant product-specific variations.(3)The agreement reshapes China’s trade geography,driving a 7.66%increase in intra-RCEP trade while reducing extra-RCEP trade by 0.80%.(4)The restructuring of China’s trade patterns under RCEP emerges from the complex interplay of trade creation,diversion,and crowding-out effects.Accordingly,China should further harmonize regional tariff schedules,enhance trade-facilitation mechanisms,strengthen industrial competitiveness and expand multilateral partnerships.展开更多
Aerodynamic performances of axial compressors are significantly affected by variation of Reynolds number in aero-engines.In the design and analysis of compressors,previous correction methods for cascades and stages ha...Aerodynamic performances of axial compressors are significantly affected by variation of Reynolds number in aero-engines.In the design and analysis of compressors,previous correction methods for cascades and stages have difficulties in predicting comprehensively Reynolds number effects on airfoils,matching and characteristics curves.This study proposes Re-correction models for loss,deviation angle and endwall blockage based on classical theories and cascade tests,and loss and deviation models show good agreement in test data of NACA65 and C4 cascades.Throughflow method considering Reynolds number effects is developed by integrating the correction models into a verified Streamline Curvature(SLC)tool.A three-stage axial compressor is investigated through SLC and CFD methods from design Reynolds number(Red=2106)to low Re=4104,and the numerical methods are validated with test data of characteristic curves and spanwise distributions at Red.With Re reduction,SLC method with correction models well predicts variation in overall performances compared with CFD calculations and Wassell's model.Streamwise and spanwise matching such as total pressure and loss distributions in SLC predictions are basically consistent with those in CFD results at near-stall points under design and low Reynolds numbers.SLC and CFD methods share similar detections of stall risks in the third stage(Stg3),and their analyses of diffusion processes deviate to some extent due to different predictions in separated endwall flow.The correction models can be adopted to consider Reynolds number effects in through-flow design and analysis of axial compressors.展开更多
When a porous rock is subjected to overall compressive loading,either increasing pore pressure or decreasing confining pressure could result in rock failure.The stress path and the applied pressure change rate may aff...When a porous rock is subjected to overall compressive loading,either increasing pore pressure or decreasing confining pressure could result in rock failure.The stress path and the applied pressure change rate may affect the initiation and propagation of fractures within brittle materials.Understanding the physical mechanisms leading to failure is crucial for underground engineering applications and geo-energy exploration and storage.We conducted triaxial compression experiments on porous Bentheim sandstone samples at different stress paths and pressure change rates.First,at a constant confining pressure of 35 MPa and pore pressure of 5 MPa,intact cylindrical samples were axially loaded up to about 85%of the peak strength.Subsequently,the axial piston position was fixed,and then either the pore pressure was increased or the confining pressure was decreased at two different rates(0.5 MPa/min or 2 MPa/min),leading to final catastrophic failure.The mechanical results revealed that samples subjected to higher rates of decreasing effective confining pressure exhibited larger stress drop rates,higher slip rates,higher total breakdown work,higher rates of acoustic emissions(AEs)before failure,and higher post-failure AE decay rates.In contrast,the applied stress path did not significantly affect rock failure characteristics.Comparison of located AE events with post-mortem microstructures of deformed samples shows a good agreement.The AE source type determined from the P-wave first-motion polarity shows that shear failure dominated the fracture process when approaching failure.Gutenberg-Richter b-values revealed a significant decrease before failure in all tests.Our results indicate that,in contrast to the stress path,the rate of effective stress change strongly affects fracturing behavior and AE rate changes.展开更多
Significant progress has been recently made in studying artemisinin and its derivatives for treating cardiovascular diseases,making this area a prominent research focus.Artemisinin,discovered with great acclaim,was in...Significant progress has been recently made in studying artemisinin and its derivatives for treating cardiovascular diseases,making this area a prominent research focus.Artemisinin,discovered with great acclaim,was initially and widely adopted in antimalarial treatments.As scientific research steadily progressed,its latent potential role in the cardiovascular system gradually captured the attention of the global scientific community.Artemisinin and its derivatives can reportedly play a protective role in the cardiovascular system through various mechanisms,including anti-inflammatory,anti-angiogenic,antioxidant,and anti-fibrotic effects,as well as the regulation of blood lipids and blood pressure.In particular,they have shown promising therapeutic effects in models of cardiovascular diseases such as atherosclerosis,myocardial ischaemia,and cardiac hypertrophy.In addition,artemisinin and its derivatives can improve cardiovascular function and prevent cardiovascular injury by regulating signalling pathways closely related to cardiovascular disease,such as AMPK and NF-kB.Although numerous ex vivo and in vivo experiments have verified the potential role of artemisinin in treating cardiovascular diseases,systematic studies to comprehensively elucidate its specific mechanism of action remain scarce.Further exploration of the precise roles of artemisinin and its derivatives in cardiovascular disease therapy,along with their potential clinical applications,could offer valuable insights for future research and treatment strategies.展开更多
Ensuring national food security amidst rapid population growth and increasing extreme weather events remains a critical global challenge.However,the extent to which agricultural modernization in China enhances grain y...Ensuring national food security amidst rapid population growth and increasing extreme weather events remains a critical global challenge.However,the extent to which agricultural modernization in China enhances grain yield and contributes to food security remains unclear.Therefore,using panel data from 327 Chinese cities(2013–2021),this study employs spatial econometric models to analyze the spatial spillover effects of agricultural modernization level(AML)on grain yield and to reveal regional heterogeneity across nine major agricultural zones.The results showed a cumulative grain yield increase of 23.7 million tons,with peak productivity concentrated along the Hu Line and declining eastward and westward.AML also exhibited a steady increase but a clear spatial gradient,decreasing from coastal to inland regions,with the highest level observed in Southern China(SC).A key finding was that a 1%increase in AML directly raised local grain yield by an average of 4.185%,accompanied by significant positive spillover effects on neighboring regions.Regional variations revealed distinct patterns:the direct effects of AML were more pronounced in southern and eastern zones,while spillover effects dominated in northern and western zones.The largest positive direct impact of AML on grain yield was observed in the SC(8.499%),while Middle-Lower Yangtze Plain ranked second but exhibited the strongest positive spatial spillover effect(4.534%).These findings highlight the critical role of agricultural modernization in promoting grain production and provide a solid basis for optimizing regional agricultural systems,ensuring food security,and advancing sustainable agriculture.展开更多
Integration of natural gas and electricity transmission systems has strengthened interdependence between the two systems.Due to the close interconnection through coupling elements between the power system(PS)and natur...Integration of natural gas and electricity transmission systems has strengthened interdependence between the two systems.Due to the close interconnection through coupling elements between the power system(PS)and natural gas system(NGS)when a disturbance happens in one system,a series of complicated sequences of dependent events may follow in another system.Therefore,an integrated planning model jointing security-constrained considering cascading effects is proposed in this paper.Meanwhile,natural gas and electricity transmission systems considering stochastic failures and various operating characteristics of components can be viewed as a multistate systems.Moreover,power-to-gas(P2G),as a promising technology proposed to store surplus renewable energy,is considered in the integrated planning.First,multi-state models for different components are developed to describe realistic operating conditions in natural gas and electricity transmission systems.Furthermore,a mixed-integer linear programming(MILP)approach considers N-1 contingency and cascading effects between natural gas and the electrical power systems.Therefore,a security-constrained integrated planning model of natural gas and electricity transmission systems is represented.The proposed methods are validated using an integrated gas and power test system.展开更多
基金supported by the National Natural Science Foundation of China(31972269 and 32172500)the National Key R&D Program of China(2017YFD0200900)。
文摘The specificity of the double-stranded RNA(dsRNA) used in the RNA interference(RNAi) technique is crucial for the success of sequence-specific gene silencing. Currently, RNAi-mediated insect control is a trending research topic.However, the off-target effects of the dsRNA in RNAi are a major concern. In this study, the ds Hvβ’COPI(coat protein complex I, β’ subunit)-treated and untreated transcriptomes of the 28-spotted potato lady beetle(Henosepilachna vigintioctopunctata) were compared to understand its off-target gene silencing effects. The RNA-seq results revealed that 63 and 44 differentially expressed genes(DEGs) were upregulated and downregulated, respectively, in the ds Hvβ’COPI treated group as compared with the control. Validation of the differential expressions of some selected DEGs via reverse transcription-quantitative PCR(RT-qPCR) analysis confirmed the reliability of the transcriptome analysis results. Further downstream analysis revealed that there were no genes homologous with Hvβ’COPI in H. vigintioctopunctata. Additionally,no genes with a >11 bp continuous match with ds Hvβ’COPI were found in the H. vigintioctopunctata transcriptome. Six genes(Hvcitron, Hvhelicase, Hvtransposase, Hvserine, Hvdynein, and Hv E3 ubiquitin) were selected to examine the offtarget activity of ds Hvβ’COPI based on their potential involvement in various H. vigintioctopunctata metabolic pathways.The severity of silencing these six off-target genes was evaluated by employing RNAi. The RNAi results confirmed the downregulation of the expression of all six genes, although there was no significant lethality. The findings of this study will be helpful in the risk analysis of future RNAi-mediated pest control experiments.
基金supported by the National Key Research and Development Program of China(2018YFA0801401 and 2019YFA0802801)the National Natural Science Foundation of China 31871345+1 种基金the Young Thousand Talented Program from Wuhan Universitythe startup funding from Wuhan University to H.Y.
文摘As versatile and robust genome editing tools,clustered regularly interspaced short palindromic repeats(CRISPR)technologies have been broadly used in basic research,biotechnology,and therapeutic development.Off-target mutagenesis by CRISPR systems has been demonstrated,and various methods have been developed to markedly increase their specificity.In this review,we highlight the efforts of producing and modifying guide RNA(gRNA)to minimize off-target activities,including sequence and structure design,tuning expression and chemical modification.The modalities of gRNA engineering can be applied across CRISPR systems.In conjunction with CRISPR protein effectors,the engineered gRNA enables efficient and precise genome editing.
基金supported by the grants 81771230(W.C.),31922048(E.Z.)and 31522037(H.Y.)from the National Natural Science Foundation of China.
文摘CRISPR-mediated genome editing is a revolutionary technology for genome manipulation that uses the CRISPR-Cas systems and base editors.Currently,poor efficiency and off-target problems have impeded the application of CRISPR systems.The on-target efficiency has been improved in several advanced versions of CRISPR systems,whereas the off-target detection still remains a key challenge.Here,we outline the different versions of CRISPR systems and off-target detection strategies,discuss the merits and limitations of off-target detection methods,and provide potential implications for further gene editing research.
基金funded by grants from the National Science and Technology Major Project of China(2016ZX08011002)。
文摘A recent breakthrough in agricultural biotechnology is the introduction of RNAi-mediated strategies in pest control.However, the off-target effects of RNAi pest control are still not fully understood. Here, we studied the off-target effects of two insecticidal siRNAs in both target and non-target insects. The results revealed that off-target effects of insecticidal siRNAs occur widely in both target and non-target insects. We classified the expression-changed genes according to their homology to the siRNA-targeted gene, related KEGG pathways with the siRNA-targeted gene and continuous matches with siRNAs. Surprisingly, the unintended significant changes in gene expression levels did not strictly match with the number of contiguous nucleotides in the siRNAs. As expected, the expression of small portions of the homologous and KEGG-related genes were significantly changed. We calculated the Shannon entropy of the transcriptome profile of the insects after injecting them with insecticidal siRNAs. Though hundreds of genes were affected in their expression levels post siRNAtreatment, the Shannon entropy of the transcriptome remained unchanged, suggesting that the transcriptome expression was balanced. Our results provide evidence that siRNAs cross-reacted with individual genes in non-target species, but did not have significant effects on the integrity of the transcriptome profiles in either target or non-target species on a genomic scale. The metric we proposed can be used to estimate the off-target effects of insecticidal siRNAs, which might be useful for evaluating the safety of RNAi in pest control.
基金supported by the National Key R&D Program of China(2017YFC1001901)the National Natural Science Foundation(31971365 and 31601196)the Guangzhou Science and Technology Project(201803010020 and 201707010085).
文摘DNA is the blueprint of life,instructing the growth,development,and reproduction of an organism.Genome sequencing uncovers the codes of life,whereas genome editing could rewrite the codes,thus then leads to revolutionary advances in all aspects of life sciences,such as uncovering regulatory network of life,increasing the production of crops,producing new breeds of livestock,and curing genetic disorders(Liu,2017).
基金supported by the start-up package of the ShanghaiTech University.
文摘Site-directed RNA editing(SDRE)is invaluable to basic research and clinical applications and has emerged as a new frontier in genome editing.The past few years have witnessed a surge of interest in SDRE,with SDRE tools emerging at a breathtaking pace.However,off-target effects of SDRE remain a tough problem,which constitutes a major hurdle to their clinical applications.Here we discuss the diverse strategies for combating off-target editing,drawing lessons from the published studies as well as our ongoing research.Overall,SDRE is still at its infancy,with significant challenges and exciting opportunities ahead.
基金supported by the National Natural Science Foundation of China“Research on the Multi-scale Regional Industrial Spatial Evolution Mechanism,Resource and Environmental Effects,and Green Transformation in the Yellow River Basin”[Grant No.42371194]Taishan Scholar Foundation of Shandong Province[Grant Nos.tsqn202408148 and tstp20240821].
文摘Agglomeration supports the high-quality development of the manufacturing industry,and its associated resource and environmental effects play a crucial role in driving green economic development.Based on data from prefecture-level cities in China from 2005 to 2019,this study employs the inverse distance weighting method,the bivariate local indicator of spatial association model,the spatial Durbin model,and other techniques to explore the relationship between manufacturing agglomeration and PM_(2.5)concentrations,and to assess the impact of its manufacturing agglomeration.Four correlation patterns are observed:high-high,low-low,high-low,and low-high.Among these,high-high and low-low patterns dominate in terms of number of cities.These correlation patterns demonstrate strong temporal stability,with a clear“Matthew effect”.The effect of manufacturing agglomeration on PM_(2.5)levels is significantly negative and helps reduce concentrations regionally,indicating the need to further enhance agglomeration levels regionally.However,it can increase PM_(2.5)levels in neighboring areas due to a siphon effect,and the impact of varies across regions.Compared with levels in 2005-2013,the significance of the relationship between manufacturing agglomeration and PM_(2.5)weakened in the 2013-2019 period.Accordingly,this study proposes countermeasures and policy recommendations aimed at strengthening regional collaborative governance and inspiring differentiated agglomeration strategies to support sustainable economic development in China.
文摘The dried fruit of Forsythia suspensa(Oleaceae),also known as Forsythia,is a traditional Chinese medicinal herb known for its heat-clearing and detoxifying properties.It is used to disperse nodules,reduce swelling,remove toxins,clear heat,and alleviate wind-heat syndromes.It also has hepatoprotective,anti-inflammatory,antiviral,antibacterial,anticancer,antioxidant,antiaging,and anti-obesity effects,as well as potential therapeutic effects on Alzheimer’s disease and diabetic nephropathy.It is used to treat scrofula,mastitis,wind-heat common cold,and other ailments.The review summarizes the chemical constituents and pharmacological effects of F.suspensa,aiming to provide a scientific foundation for its future development,research,and clinical utilization.
基金supported by the National Research Foundation of Korea(NRF)funded by the Ministry of Science and ICT(MSIT)(No.RS-2022-00143178)the Ministry of Education(MOE)(Nos.2022R1A6A3A13053896 and 2022R1F1A1074616),Republic of Korea.
文摘Beam-tracking simulations have been extensively utilized in the study of collective beam instabilities in circular accelerators.Traditionally,many simulation codes have relied on central processing unit(CPU)-based methods,tracking on a single CPU core,or parallelizing the computation across multiple cores via the message passing interface(MPI).Although these approaches work well for single-bunch tracking,scaling them to multiple bunches significantly increases the computational load,which often necessitates the use of a dedicated multi-CPU cluster.To address this challenge,alternative methods leveraging General-Purpose computing on Graphics Processing Units(GPGPU)have been proposed,enabling tracking studies on a standalone desktop personal computer(PC).However,frequent CPU-GPU interactions,including data transfers and synchronization operations during tracking,can introduce communication overheads,potentially reducing the overall effectiveness of GPU-based computations.In this study,we propose a novel approach that eliminates this overhead by performing the entire tracking simulation process exclusively on the GPU,thereby enabling the simultaneous processing of all bunches and their macro-particles.Specifically,we introduce MBTRACK2-CUDA,a Compute Unified Device Architecture(CUDA)ported version of MBTRACK2,which facilitates efficient tracking of single-and multi-bunch collective effects by leveraging the full GPU-resident computation.
基金supported by the National Natural Science Foundation of China(22279068,52374306)the Taishan Scholars of Shandong Province(tsqn202408202)the Qingdao New Energy Shandong Laboratory Open Project(QNESL OP202312)。
文摘Preferential magnesium(Mg)electrodeposition on separators is a ubiquitous yet poorly understood phenomenon in rechargeable Mg-metal batteries,posing a fundamental challenge to their development.In this work,the synergy effects of interface-accelerating desolvation and spatial confinement have been demonstrated as the essential causation of this counterintuitive experimental phenomenon.At the molecular level,the imide ring(-CO-NR-CO-,in which R represents the phenyl)groups in an artificially introduced polyimide(PI)interlayer facilitate the strong electrostatic affinity towards Mg^(2+),which accelerates the desolvation process for Mg^(2+)solvation structures at the inner Helmholtz plane.At the nucleation scale,the wedge-like concave geometry formed at the PI/current collector interface provides energetically favorable sites for Mg nucleation.This unique architecture reduces the critical nucleus size,thereby significantly lowering nucleation energy barriers.As a result,the satisfactory Coulombic efficiency for Mg plating/stripping(98.22%)and cycle lifespan(1200 cycles,above 100 days)have been achieved,outperforming most of the previous results.This work pioneers a molecular-level understanding of separator-directed Mg deposition and resolves a long-standing confusion in Mg-metal batteries.
基金supported by the GDAS’Project of Science and Technology Development(No.2022GDASZH-2022010104-2)Guangdong Major Project of Basic and Applied Basic Research(No.2023B0303000006).
文摘Understanding Cd contamination in the soil-rice ecosystem and the underlying its threshold and interaction effects is crucial for controlling Cd pollution and ensuring food safety.Although the quantitative relationships between Cd and environmental variables have been extensively studied,the threshold and interaction effects of multi-source environmental variables remain largely unexplored.This study employs a combination of random forest analysis and a human health risk model to investigate the effects of variables on Cd levels in rice grains,with the goal of quantifying their contributions and elucidating their relationships.The results indicated that the 15 selected variables collectively explained 47.36%of the variation in Cd content,with the top three variables being soil pH,distance from industrial park,and soil Zn.The majority of variables exhibited threshold effects on Cd levels in rice grains.By visualizing the interaction between Soil pH,distance from industrial park,and soil Zn with Cd levels in rice,we demonstrate the threshold effects of them on Cd level in rice grains,thereby providing further insight into the variation observed.Furthermore,oral intake of rice has been identified as the primary route of human exposure,significantly contributing to overall exposure pathways.Understanding these interactions is crucial for gaining insights into the underlying processes driving Cd pollution and fostering sustainable development within the industry.Our findings underscore the crucial need to consider multiple environmental variables and their interactions when managing heavy metals(HMs)contamination and mitigating health risks.
基金Supported by Special Fund Project for the Transformation of Scientific and Technological Achievements in Inner Mongolia Autonomous Region(2021CG0013)Bayannur City Science and Technology Plan Project(K202014)+1 种基金Inner Mongolia Autonomous Region Science and Technology Plan Project(2022YFHH0088)Research Special Project of the Education Department of Inner Mongolia Autonomous Region(STAQZX202320).
文摘[Objectives]To explore the control mode of farmland drainage pollutants and investigate the effects of ecological ditch and wetland on reducing farmland drainage pollutants in Hetao Irrigation District.[Methods]Based on the demonstration construction project of the ecological ditch-constructed wetland system in the Hetao Irrigation District,an experimental study was conducted from July to September 2023 to investigate the interception and purification effects of ecological ditches,constructed wetlands,and the combined ecological ditch-constructed wetland system on farmland drainage pollutants.Key water quality parameters measured included total nitrogen(TN)concentration and total phosphorus(TP)concentration.[Results]Different treatment modes of ecological ditches and constructed wetlands have a certain removal effect on nitrogen and phosphorus pollutants in water bodies.The ecological ditches treated with Astragalus laxmannii,Melilotus officinalis,Medicago sativa,bio-ball substrate,and bio-sheet substrate showed reduction efficiencies for TN and TP of 21.09% and 23.84%,12.06% and 26.67%,20.08% and 34.15%,23.65% and 20.56%,and 19.92% and 25.83%,respectively.The emergent plant area showed reduction efficiencies of 24.28%for TN and 17.89%for TP,while the submerged plant area achieved a reduction efficiency of 10.21%for both TN and TP.Among the different treatment modes,the ecological ditch with M.sativa performed better in TP removal,whereas the bio-ball substrate treatment mode showed higher effectiveness in TN removal.In addition,the emergent plant area exhibited better TP removal performance,while the submerged plant area was more effective in TN removal.The combined system of ecological ditch and constructed wetland achieved removal rates of 37.55% for TN and 11.47% for TP.It effectively facilitates the step-by-step interception and adsorption purification of pollutants,thereby showing significant removal and purification effects on nitrogen and phosphorus contaminants.This contributes to mitigating agricultural non-point source pollution.[Conclusions]The combined ecological ditch-constructed wetland system serves dual functions of agricultural drainage and pollutant interception and purification.It reduces the pollution load of farmland drainage on receiving water bodies to some extent and mitigates agricultural non-point source pollution.Therefore,it is a relatively suitable technology for managing agricultural non-point source pollution in the Hetao Irrigation District.
基金supported by the National Natural Science Foundation of China(Nos.82003977,82274134 and 82274139)the National Key Research and Development Plan(No.2017YFC1702200)+1 种基金the Key Research and Development Program of Zhejiang Province(No.2020C04020)the Science and Technology Program of Zhejiang Province(No.2025C02183).
文摘Inflammatory bowel disease(IBD),which includes Crohn’s disease(CD)and ulcerative colitis(UC),is a chronic inflammatory condition affecting the gastrointestinal tract.The global incidence and prevalence of IBD continue to increase.While multiple clinical treatments exist,conventional therapies frequently present limitations and adverse effects.Natural polysaccharides(PSs)have emerged as a significant focus of research interest due to their therapeutic potential and applications in functional foods and health products.This review synthesizes current understanding of IBD pathophysiology and the mechanisms by which natural PSs counter IBD,including their capacity to restore immune homeostasis and intestinal barrier function,modulate gut microbiota and metabolites,reduce oxidative stress,and address irregularities in autophagy and endoplasmic reticulum stress(ERS).The review examines the structure-activity relationships of PSs demonstrating anti-IBD effects and identifies promising therapeutic products.The discussion encompasses pharmacokinetics,safety evaluations,and clinical applications of these compounds.This comprehensive review establishes a theoretical foundation for developing natural PS-based therapeutic approaches for IBD management.
基金National Natural Science Foundation of China,No.42471202,No.72441005。
文摘Existing studies on the Regional Comprehensive Economic Partnership(RCEP)mainly focused on institutional features,macro-economic impacts,and trade-network structures,while its geographic attributes and their implications remain underexplored.Taking the RCEP as a case,this paper examines how the FTA reshapes China’s trade geography and validates these effects with an enhanced GTAP model,providing an empirical basis for advancing trade-geography theory.Key findings include:(1)RCEP significantly reduces regional trade costs.After full implementation of the agreement,the average tariffs among member countries will decrease to 40.5%of the pre-implementation level,while import and export trade facilitation levels improve by 34.3%and 29.6%,respectively.However,these improvements exhibit marked regional disparities.(2)RCEP asymmetrically promotes China’s foreign trade growth,with stronger import stimulation than export expansion,alongside significant product-specific variations.(3)The agreement reshapes China’s trade geography,driving a 7.66%increase in intra-RCEP trade while reducing extra-RCEP trade by 0.80%.(4)The restructuring of China’s trade patterns under RCEP emerges from the complex interplay of trade creation,diversion,and crowding-out effects.Accordingly,China should further harmonize regional tariff schedules,enhance trade-facilitation mechanisms,strengthen industrial competitiveness and expand multilateral partnerships.
基金supported by the National Science and Tech-nology Major Project of China(Nos.2017-II-0007-0021 and J2019-II-0017-0038)。
文摘Aerodynamic performances of axial compressors are significantly affected by variation of Reynolds number in aero-engines.In the design and analysis of compressors,previous correction methods for cascades and stages have difficulties in predicting comprehensively Reynolds number effects on airfoils,matching and characteristics curves.This study proposes Re-correction models for loss,deviation angle and endwall blockage based on classical theories and cascade tests,and loss and deviation models show good agreement in test data of NACA65 and C4 cascades.Throughflow method considering Reynolds number effects is developed by integrating the correction models into a verified Streamline Curvature(SLC)tool.A three-stage axial compressor is investigated through SLC and CFD methods from design Reynolds number(Red=2106)to low Re=4104,and the numerical methods are validated with test data of characteristic curves and spanwise distributions at Red.With Re reduction,SLC method with correction models well predicts variation in overall performances compared with CFD calculations and Wassell's model.Streamwise and spanwise matching such as total pressure and loss distributions in SLC predictions are basically consistent with those in CFD results at near-stall points under design and low Reynolds numbers.SLC and CFD methods share similar detections of stall risks in the third stage(Stg3),and their analyses of diffusion processes deviate to some extent due to different predictions in separated endwall flow.The correction models can be adopted to consider Reynolds number effects in through-flow design and analysis of axial compressors.
文摘When a porous rock is subjected to overall compressive loading,either increasing pore pressure or decreasing confining pressure could result in rock failure.The stress path and the applied pressure change rate may affect the initiation and propagation of fractures within brittle materials.Understanding the physical mechanisms leading to failure is crucial for underground engineering applications and geo-energy exploration and storage.We conducted triaxial compression experiments on porous Bentheim sandstone samples at different stress paths and pressure change rates.First,at a constant confining pressure of 35 MPa and pore pressure of 5 MPa,intact cylindrical samples were axially loaded up to about 85%of the peak strength.Subsequently,the axial piston position was fixed,and then either the pore pressure was increased or the confining pressure was decreased at two different rates(0.5 MPa/min or 2 MPa/min),leading to final catastrophic failure.The mechanical results revealed that samples subjected to higher rates of decreasing effective confining pressure exhibited larger stress drop rates,higher slip rates,higher total breakdown work,higher rates of acoustic emissions(AEs)before failure,and higher post-failure AE decay rates.In contrast,the applied stress path did not significantly affect rock failure characteristics.Comparison of located AE events with post-mortem microstructures of deformed samples shows a good agreement.The AE source type determined from the P-wave first-motion polarity shows that shear failure dominated the fracture process when approaching failure.Gutenberg-Richter b-values revealed a significant decrease before failure in all tests.Our results indicate that,in contrast to the stress path,the rate of effective stress change strongly affects fracturing behavior and AE rate changes.
基金supported by the Youth Natural Science Foundation of Shandong Province(grant number:ZR2022QH340).
文摘Significant progress has been recently made in studying artemisinin and its derivatives for treating cardiovascular diseases,making this area a prominent research focus.Artemisinin,discovered with great acclaim,was initially and widely adopted in antimalarial treatments.As scientific research steadily progressed,its latent potential role in the cardiovascular system gradually captured the attention of the global scientific community.Artemisinin and its derivatives can reportedly play a protective role in the cardiovascular system through various mechanisms,including anti-inflammatory,anti-angiogenic,antioxidant,and anti-fibrotic effects,as well as the regulation of blood lipids and blood pressure.In particular,they have shown promising therapeutic effects in models of cardiovascular diseases such as atherosclerosis,myocardial ischaemia,and cardiac hypertrophy.In addition,artemisinin and its derivatives can improve cardiovascular function and prevent cardiovascular injury by regulating signalling pathways closely related to cardiovascular disease,such as AMPK and NF-kB.Although numerous ex vivo and in vivo experiments have verified the potential role of artemisinin in treating cardiovascular diseases,systematic studies to comprehensively elucidate its specific mechanism of action remain scarce.Further exploration of the precise roles of artemisinin and its derivatives in cardiovascular disease therapy,along with their potential clinical applications,could offer valuable insights for future research and treatment strategies.
基金National Natural Science Foundation of China,No.42471455,No.42230113National Key Research and Development Program of China,No.2022YFC3800804-01。
文摘Ensuring national food security amidst rapid population growth and increasing extreme weather events remains a critical global challenge.However,the extent to which agricultural modernization in China enhances grain yield and contributes to food security remains unclear.Therefore,using panel data from 327 Chinese cities(2013–2021),this study employs spatial econometric models to analyze the spatial spillover effects of agricultural modernization level(AML)on grain yield and to reveal regional heterogeneity across nine major agricultural zones.The results showed a cumulative grain yield increase of 23.7 million tons,with peak productivity concentrated along the Hu Line and declining eastward and westward.AML also exhibited a steady increase but a clear spatial gradient,decreasing from coastal to inland regions,with the highest level observed in Southern China(SC).A key finding was that a 1%increase in AML directly raised local grain yield by an average of 4.185%,accompanied by significant positive spillover effects on neighboring regions.Regional variations revealed distinct patterns:the direct effects of AML were more pronounced in southern and eastern zones,while spillover effects dominated in northern and western zones.The largest positive direct impact of AML on grain yield was observed in the SC(8.499%),while Middle-Lower Yangtze Plain ranked second but exhibited the strongest positive spatial spillover effect(4.534%).These findings highlight the critical role of agricultural modernization in promoting grain production and provide a solid basis for optimizing regional agricultural systems,ensuring food security,and advancing sustainable agriculture.
基金supported in part by the Key Projects of National Natural Science Foundation of China under Grant 51936003.
文摘Integration of natural gas and electricity transmission systems has strengthened interdependence between the two systems.Due to the close interconnection through coupling elements between the power system(PS)and natural gas system(NGS)when a disturbance happens in one system,a series of complicated sequences of dependent events may follow in another system.Therefore,an integrated planning model jointing security-constrained considering cascading effects is proposed in this paper.Meanwhile,natural gas and electricity transmission systems considering stochastic failures and various operating characteristics of components can be viewed as a multistate systems.Moreover,power-to-gas(P2G),as a promising technology proposed to store surplus renewable energy,is considered in the integrated planning.First,multi-state models for different components are developed to describe realistic operating conditions in natural gas and electricity transmission systems.Furthermore,a mixed-integer linear programming(MILP)approach considers N-1 contingency and cascading effects between natural gas and the electrical power systems.Therefore,a security-constrained integrated planning model of natural gas and electricity transmission systems is represented.The proposed methods are validated using an integrated gas and power test system.
