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
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
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
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
Bacille Calmette-Guérin(BCG)vaccine is designed to provide protection against tuberculosis(TB).However,numerous epidemiological,clinical,and immunological studies have shown that BCG vaccination affects neonatal ...Bacille Calmette-Guérin(BCG)vaccine is designed to provide protection against tuberculosis(TB).However,numerous epidemiological,clinical,and immunological studies have shown that BCG vaccination affects neonatal and infant mortality,which may be related to the reduction of TB-unrelated infections and diseases by BCG vaccine.We aimed to discuss the off-target effects of BCG vaccine on un-TB infections and diseases,as well as the potential mechanism and influencing factors.Literature was retrieved mainly from PubMed using medical subject headings"BCG,variations,and non-specific,heterologous or off-target".Studies have showed that BCG vaccination can prevent various heterologous infections,including respiratory tract infections,leprosy,and malaria,treat viral infections including human papillomavirus and herpes simplex virus infection as immunotherapy,and improve the immune responses as vaccine adjuvant.Besides,BCG vaccine can reduce the recurrence rate of non-muscle-invasive bladder cancer,and may provide protection against autoimmune diseases.These off-target effects of BCG vaccine are thought to be achieved by modulating heterologous lymphocyte responses or inducing trained immunity,which were found to be sex-differentiated and affected by the BCG vaccine strains,sequence or time of vaccination.展开更多
Small interfering RNA(siRNA)is often used for function study and expression regulation of specific genes,as well as the development of small molecule drugs.Selecting siRNAs with high inhibition and low off-target effe...Small interfering RNA(siRNA)is often used for function study and expression regulation of specific genes,as well as the development of small molecule drugs.Selecting siRNAs with high inhibition and low off-target effects from massive can-didates is always a great challenge.Increasing experimentally-validated samples can prompt the development of machine-learning-based algorithms,including Support Vector Machine(SVM),Convolutional Neural Network(CNN),and Graph Neural Network(GNN).However,these methods still suffer from limited accuracy and poor generalization in designing potent and specific siRNAs.In this study,we propose a novel approach for siRNA inhibition and off-target effect prediction,named AttSiOff.It combines a self-attention-based siRNA inhibition predictor with an mRNA searching package and an off-target filter.The predictor gives the inhibition score via analyzing the embedding of siRNA and local mRNA sequences,generated from the pre-trained RNA-FM model,as well as other meaningful prior-knowledge-based features.Self-attention mechanism can detect potentially decisive features,which may determine the inhibition of siRNA.It captures global and local dependencies more efficiently than normal convolutions.The tenfold cross-validation results indicate that our model outperforms all existing methods,achieving PCC of 0.81,SPCC of 0.84,and AUC of 0.886.It also reaches better performance of generalization and robustness on cross-dataset validation.In addition,the mRNA searching package could find all mature mRNAs for a given gene name from the GENOMES database,and the off-target filter can calculate the amount of unwanted off-target binding sites,which affects the specificity of siRNA.Experiments on five mature siRNA drugs,as well as a new target gene(AGT),show that AttSioff has excellent convenience and operability in practical applications.展开更多
The flexoelectric effect refers to the electromechanical coupling between electric polarization and mechanical strain gradient.It universally exists in a variety of materials in any space group,such as liquid crystals...The flexoelectric effect refers to the electromechanical coupling between electric polarization and mechanical strain gradient.It universally exists in a variety of materials in any space group,such as liquid crystals,dielectrics,biological materials,and semiconductors.Because of its unique size effect,nanoscale flexoelectricity has shown novel phenomena and promising applications in electronics,optronics,mechatronics,and photovoltaics.In this review,we provide a succinct report on the discovery and development of the flexoelectric effect,focusing on flexoelectric materials and related applications.Finally,we discuss recent flexoelectric research progress and still‐unsolved problems.展开更多
Agricultural intensification has led to an increase in monoculture and the use of chemical pesticides,resulting in a decline in biodiversity and a reduction in ecosystem services,particularly biological pest managemen...Agricultural intensification has led to an increase in monoculture and the use of chemical pesticides,resulting in a decline in biodiversity and a reduction in ecosystem services,particularly biological pest management.However,studies have shown that agroforestry can not only improve land productivity and biodiversity but also regulate some ecosystem services.This study reviews the impacts of physical and biological factors on herbivorous pests,parasites,and predatory natural enemies in fruit-crop agroforestry systems.Fruit-crop agroforestry systems provide high spatial heterogeneity by altering crop layouts,regulating the microclimate and soil quality,and offering food resources and shelter for natural enemies,thus promoting biological pest control.This enhances biological control and makes the agrocomplex system an effective tool for sustainable agriculture.Our research shows that volatile plant substances attract or repel pests and natural enemies based on the characteristics of the insects themselves.When scientifically designed,fruit-crop agroforestry systems provide high spatial heterogeneity and favorable microclimatic conditions,which enhance biological pest control and make the agroforestry system an effective tool for sustainable agriculture.Our research shows that fruit-crop agroforestry systems can provide richer food resources and habitat,enhancing biological pest control and improving pest management.展开更多
Liver cancer is the fourth cause of cancer-related deaths and the primary cause of death in patients with compensated cirrhosis.In recent years,the role of traditional Chinese medicine in the treatment of liver cancer...Liver cancer is the fourth cause of cancer-related deaths and the primary cause of death in patients with compensated cirrhosis.In recent years,the role of traditional Chinese medicine in the treatment of liver cancer has attracted more and more attention and recognition.Luteolin(LUT)and glycyrrhetinic(GA)are natural compounds extracted from Chinese herbal medicine.LUT exhibits various biological activity including anti-inflammatory,antibacterial,antiviral,anti-tumor,and neuroprotective effects.GA significantly inhibits the growth and metastasis of cancer cells.However,the low water solubility of both compounds hinders their clinical applications.In this study,rod-shaped nanoparticles(NPs)self-assembled from LUT and GA were designed to enhance drug solubility and tumor-targeting capability.We verified that the assembly mechanism of the NPs was π-π stacking.These NPs significantly inhibited the proliferation of liver cancer cells while had no significant effect on normal liver cells.In a mouse model of liver cancer,these NPs demonstrated superior tumor-targeting ability due to the enhanced permeability and retention effect,and the affinity of GA for liver cancer cells,resulting in better therapeutic efficacy with lower systemic toxicity.Results of network pharmacology analysis showed that LUT and GA respectively targeted estrogen receptor 1(ESR1)protein and cyclin-dependent kinase 1(CDK1)protein to corporately induce tumor cell cycle arrest,which induced the inhibition of tumor cell proliferation.In conclusion,this study provides a novel reference for the treatment of liver cancer.展开更多
Fertilization or atmospheric deposition of nitrogen(N)and phosphorus(P)to terrestrial ecosystems can alter soil N(P)availability and the nature of nutrient limitation for plant growth.Changing the allocation of leaf P...Fertilization or atmospheric deposition of nitrogen(N)and phosphorus(P)to terrestrial ecosystems can alter soil N(P)availability and the nature of nutrient limitation for plant growth.Changing the allocation of leaf P fractions is potentially an adaptive strategy for plants to cope with soil N(P)availability and nutrient-limiting conditions.However,the impact of the interactions between imbalanced anthropogenic N and P inputs on the concentrations and allocation proportions of leaf P fractions in forest woody plants remains elusive.We conducted a metaanalysis of data about the concentrations and allocation proportions of leaf P fractions,specifically associated with individual and combined additions of N and P in evergreen forests,the dominant vegetation type in southern China where the primary productivity is usually considered limited by P.This assessment allowed us to quantitatively evaluate the effects of N and P additions alone and interactively on leaf P allocation and use strategies.Nitrogen addition(exacerbating P limitation)reduced the concentrations of leaf total P and different leaf P fractions.Nitrogen addition reduced the allocation to leaf metabolic P but increased the allocation to other fractions,while P addition showed opposite trends.The simultaneous additions of N and P showed an antagonistic(mutual suppression)effect on the concentrations of leaf P fractions,but an additive(summary)effect on the allocation proportions of leaf P fractions.These results highlight the importance of strategies of leaf P fraction allocation in forest plants under changes in environmental nutrient availability.Importantly,our study identified critical interactions associated with combined N and P inputs that affect leaf P fractions,thus aiding in predicting plant acclimation strategies in the context of intensifying and imbalanced anthropogenic nutrient inputs.展开更多
In the practice of healthcare,patient-reported outcomes(PROs)and PRO measures(PROMs)are used as an attempt to observe the changes in complex clinical situations.They guide us in making decisions based on the evidence ...In the practice of healthcare,patient-reported outcomes(PROs)and PRO measures(PROMs)are used as an attempt to observe the changes in complex clinical situations.They guide us in making decisions based on the evidence regarding patient care by recording the change in outcomes for a particular treatment to a given condition and finally to understand whether a patient will benefit from a particular treatment and to quantify the treatment effect.For any PROM to be usable in health care,we need it to be reliable,encapsulating the points of interest with the potential to detect any real change.Using structured outcome measures routinely in clinical practice helps the physician to understand the functional limitation of a patient that would otherwise not be clear in an office interview,and this allows the physician and patient to have a meaningful conver-sation as well as a customized plan for each patient.Having mentioned the rationale and the benefits of PROMs,understanding the quantification process is crucial before embarking on management decisions.A better interpretation of change needs to identify the treatment effect based on clinical relevance for a given condition.There are a multiple set of measurement indices to serve this effect and most of them are used interchangeably without clear demarcation on their differences.This article details the various quantification metrics used to evaluate the treatment effect using PROMs,their limitations and the scope of usage and implementation in clinical practice.展开更多
Structural regulation of Pd-based electrocatalytic hydrodechlorination(EHDC)catalyst for constructing high-efficient cathode materials with low noble metal content and high atom utilization is crucial but still challe...Structural regulation of Pd-based electrocatalytic hydrodechlorination(EHDC)catalyst for constructing high-efficient cathode materials with low noble metal content and high atom utilization is crucial but still challenging.Herein,a support electron inductive effect of Pd-Mn/Ni foam catalyst was proposed via in-situ Mn doping to optimize the electronic structure of the Ni foam(NF),which can inductive regulation of Pd for improving the EHDC performance.The mass activity and current efficiency of Pd-Mn/NF catalyst are 2.91 and 1.34 times superior to that of Pd/NF with 2,4-dichlorophenol as model compound,respectively.The Mn-doped interlayer optimized the electronic structure of Pd by bringing the d-state closer to the Fermi level than Pd on the NF surface,which optimizied the binding of EHDC intermediates.Additionally,the Mn-doped interlayer acted as a promoter for generating H∗and accelerating the EHDC reaction.This work presents a simple and effective regulation strategy for constructing high-efficient cathode catalyst for the EHDC of chlorinated organic compounds.展开更多
Low-electrode capacitive deionization(FCDI)is an emerging desalination technology with great potential for removal and/or recycling ions from a range of waters.However,it still suffers from inefficient charge transfer...Low-electrode capacitive deionization(FCDI)is an emerging desalination technology with great potential for removal and/or recycling ions from a range of waters.However,it still suffers from inefficient charge transfer and ion transport kinetics due to weak turbulence and low electric intensity in flow electrodes,both restricted by the current collectors.Herein,a new tip-array current collector(designated as T-CC)was developed to replace the conventional planar current collectors,which intensifies both the charge transfer and ion transport significantly.The effects of tip arrays on flow and electric fields were studied by both computational simulations and electrochemical impedance spectroscopy,which revealed the reduction of ion transport barrier,charge transport barrier and internal resistance.With the voltage increased from 1.0 to 1.5 and 2.0 V,the T-CC-based FCDI system(T-FCDI)exhibited average salt removal rates(ASRR)of 0.18,0.50,and 0.89μmol cm^(-2) min^(-1),respectively,which are 1.82,2.65,and 2.48 folds higher than that of the conventional serpentine current collectors,and 1.48,1.67,and 1.49 folds higher than that of the planar current collectors.Meanwhile,with the solid content in flow electrodes increased from 1 to 5 wt%,the ASRR for T-FCDI increased from 0.29 to 0.50μmol cm^(-2) min^(-1),which are 1.70 and 1.67 folds higher than that of the planar current collectors.Additionally,a salt removal efficiency of 99.89%was achieved with T-FCDI and the charge efficiency remained above 95%after 24 h of operation,thus showing its superior long-term stability.展开更多
Objective The use of lasers has been an important part of urology in the treatment of stone and prostate disease.The thermal effects of lasers in lithotripsy have been a subject of debate over the years.The objective ...Objective The use of lasers has been an important part of urology in the treatment of stone and prostate disease.The thermal effects of lasers in lithotripsy have been a subject of debate over the years.The objective of this review was to assess the current state of knowledge available on the thermal effects of lasers in lithotripsy,as well as explore any new areas where studies are needed.Methods In August 2022,a keyword search on Google Scholar,PubMed,and Scopus for all papers containing the phrases“thermal effects”AND“laser”AND“lithotripsy”AND“urology”was done followed by citation jumping to other studies pertaining to the topic and 35 relevant papers were included in our study.The data from relevant papers were segregated into five groups according to the factor studied and type of study,and tables were created for a comparison of data.Results Temperature above the threshold of 43℃ was reached only when the power was>40 W and when there was adequate irrigation(at least 15–30 mL/min).Shorter lasing time divided by lithotripsy time or operator duty cycles less than 70%also resulted in a smaller temperature rise.Conclusion At least eight factors modify the thermal effects of lasers,and most importantly,the use of chilled irrigation at higher perfusion rates,lower power settings of<40 W,and with a shorter operator duty cycle will help to prevent thermal injuries from occurring.Stones impacted in the ureter or pelvi-ureteric junction further increase the probability of thermal injuries during laser firing.展开更多
Exosomes(Exos)are extracellular vesicles secreted by cells and serve as crucial mediators of intercellular communication.They play a pivotal role in the pathogenesis and progression of various diseases and offer promi...Exosomes(Exos)are extracellular vesicles secreted by cells and serve as crucial mediators of intercellular communication.They play a pivotal role in the pathogenesis and progression of various diseases and offer promising avenues for therapeutic interventions.Exos derived from mesenchymal stem cells(MSCs)have significant immunomodulatory properties.They effectively regulate immune responses by modulating both innate and adaptive immunity.These Exos can inhibit excessive inflammatory responses and promote tissue repair.Moreover,they participate in antigen presentation,which is essential for activating immune responses.The cargo of these Exos,including ligands,proteins,and microRNAs,can suppress T cell activity or enhance the population of immunosuppressive cells to dampen the immune response.By inhibiting lymphocyte proliferation,acting on macrophages,and increasing the population of regulatory T cells,these Exos contribute to maintaining immune and metabolic homeostasis.Furthermore,they can activate immune-related signaling pathways or serve as vehicles to deliver microRNAs and other bioactive substances to target tumor cells,which holds potential for immunotherapy applications.Given the immense therapeutic potential of MSC-derived Exos,this review comprehensively explores their mechanisms of immune regulation and therapeutic applications in areas such as infection control,tumor suppression,and autoimmune disease management.This article aims to provide valuable insights into the mechanisms behind the actions of MSC-derived Exos,offering theoretical references for their future clinical utilization as cell-free drug preparations.展开更多
Excellent progress has been made in the last few decades in the cure rates of pediatric malignancies,with more than 80%of children with cancer who have access to contemporary treatment being cured.However,the therapie...Excellent progress has been made in the last few decades in the cure rates of pediatric malignancies,with more than 80%of children with cancer who have access to contemporary treatment being cured.However,the therapies responsible for this survival can also produce adverse physical and psychological long-term outcomes,referred to as late effects,which appear months to years after the completion of cancer treatment.Research has shown that 60%to 90%of childhood cancer survivors(CCSs)develop one or more chronic health conditions,and 20%to 80%of survivors experience severe or life-threatening complications during adulthood.Therefore,understanding the late side effects of such treatments is important to improve the health and quality of life of the growing population of CCSs.展开更多
Mn-based layered oxides(KMO)have emerged as one of the promising low-cost cathodes for potassiumion batteries(PIBs).However,due to the multiple-phase transitions and the distortion in the MnO6structure induced by the ...Mn-based layered oxides(KMO)have emerged as one of the promising low-cost cathodes for potassiumion batteries(PIBs).However,due to the multiple-phase transitions and the distortion in the MnO6structure induced by the Jahn-Teller(JT)effect associated with Mn-ion,the cathode exhibits poor structural stability.Herein,we propose a strategy to enhance structural stability by introducing robust metal-oxygen(M-O)bonds,which can realize the pinning effect to constrain the distortion in the transition metal(TM)layer.Concurrently,all the elements employed have exceptionally high crustal abundance.As a proof of concept,the designed K_(0.5)Mn_(0.9)Mg_(0.025)Ti_(0.025)Al_(0.05)O_(2)cathode exhibited a discharge capacity of approximately 100 mA h g^(-1)at 20 mA g^(-1)with 79%capacity retention over 50 cycles,and 73%capacity retention over 200 cycles at 200 mA g^(-1),showcased much better battery performance than the designed cathode with less robust M-O bonds.The properties of the formed M-O bonds were investigated using theoretical calculations.The enhanced dynamics,mitigated JT effect,and improved structural stability were elucidated through the in-situ X-ray diffractometer(XRD),in-situ electrochemical impedance spectroscopy(EIS)(and distribution of relaxation times(DRT)method),and ex-situ X-ray absorption fine structure(XAFS)tests.This study holds substantial reference value for the future design of costeffective Mn-based layered cathodes for PIBs.展开更多
With the rapid development of artificial intelligence,magnetocaloric materials as well as other materials are being developed with increased efficiency and enhanced performance.However,most studies do not take phase t...With the rapid development of artificial intelligence,magnetocaloric materials as well as other materials are being developed with increased efficiency and enhanced performance.However,most studies do not take phase transitions into account,and as a result,the predictions are usually not accurate enough.In this context,we have established an explicable relationship between alloy compositions and phase transition by feature imputation.A facile machine learning is proposed to screen candidate NiMn-based Heusler alloys with desired magnetic entropy change and magnetic transition temperature with a high accuracy R^(2)≈0.98.As expected,the measured properties of prepared NiMn-based alloys,including phase transition type,magnetic entropy changes and transition temperature,are all in good agreement with the ML predictions.As well as being the first to demonstrate an explicable relationship between alloy compositions,phase transitions and magnetocaloric properties,our proposed ML model is highly predictive and interpretable,which can provide a strong theoretical foundation for identifying high-performance magnetocaloric materials in the future.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 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.
文摘Bacille Calmette-Guérin(BCG)vaccine is designed to provide protection against tuberculosis(TB).However,numerous epidemiological,clinical,and immunological studies have shown that BCG vaccination affects neonatal and infant mortality,which may be related to the reduction of TB-unrelated infections and diseases by BCG vaccine.We aimed to discuss the off-target effects of BCG vaccine on un-TB infections and diseases,as well as the potential mechanism and influencing factors.Literature was retrieved mainly from PubMed using medical subject headings"BCG,variations,and non-specific,heterologous or off-target".Studies have showed that BCG vaccination can prevent various heterologous infections,including respiratory tract infections,leprosy,and malaria,treat viral infections including human papillomavirus and herpes simplex virus infection as immunotherapy,and improve the immune responses as vaccine adjuvant.Besides,BCG vaccine can reduce the recurrence rate of non-muscle-invasive bladder cancer,and may provide protection against autoimmune diseases.These off-target effects of BCG vaccine are thought to be achieved by modulating heterologous lymphocyte responses or inducing trained immunity,which were found to be sex-differentiated and affected by the BCG vaccine strains,sequence or time of vaccination.
基金supported by grants from the National Natural Science Foundation of China(No.62103262)the Shanghai Pujiang Programme(No.21PJ1407700)。
文摘Small interfering RNA(siRNA)is often used for function study and expression regulation of specific genes,as well as the development of small molecule drugs.Selecting siRNAs with high inhibition and low off-target effects from massive can-didates is always a great challenge.Increasing experimentally-validated samples can prompt the development of machine-learning-based algorithms,including Support Vector Machine(SVM),Convolutional Neural Network(CNN),and Graph Neural Network(GNN).However,these methods still suffer from limited accuracy and poor generalization in designing potent and specific siRNAs.In this study,we propose a novel approach for siRNA inhibition and off-target effect prediction,named AttSiOff.It combines a self-attention-based siRNA inhibition predictor with an mRNA searching package and an off-target filter.The predictor gives the inhibition score via analyzing the embedding of siRNA and local mRNA sequences,generated from the pre-trained RNA-FM model,as well as other meaningful prior-knowledge-based features.Self-attention mechanism can detect potentially decisive features,which may determine the inhibition of siRNA.It captures global and local dependencies more efficiently than normal convolutions.The tenfold cross-validation results indicate that our model outperforms all existing methods,achieving PCC of 0.81,SPCC of 0.84,and AUC of 0.886.It also reaches better performance of generalization and robustness on cross-dataset validation.In addition,the mRNA searching package could find all mature mRNAs for a given gene name from the GENOMES database,and the off-target filter can calculate the amount of unwanted off-target binding sites,which affects the specificity of siRNA.Experiments on five mature siRNA drugs,as well as a new target gene(AGT),show that AttSioff has excellent convenience and operability in practical applications.
基金support of the National Natural Science Foundation of China(Grant Nos.52192611,51872031,61904013,and 62405157)China Postdoctoral Science Foundation(Nos.2023M741890 and GZC20231215)the Fundamental Research Funds for the Central Universities.
文摘The flexoelectric effect refers to the electromechanical coupling between electric polarization and mechanical strain gradient.It universally exists in a variety of materials in any space group,such as liquid crystals,dielectrics,biological materials,and semiconductors.Because of its unique size effect,nanoscale flexoelectricity has shown novel phenomena and promising applications in electronics,optronics,mechatronics,and photovoltaics.In this review,we provide a succinct report on the discovery and development of the flexoelectric effect,focusing on flexoelectric materials and related applications.Finally,we discuss recent flexoelectric research progress and still‐unsolved problems.
文摘Agricultural intensification has led to an increase in monoculture and the use of chemical pesticides,resulting in a decline in biodiversity and a reduction in ecosystem services,particularly biological pest management.However,studies have shown that agroforestry can not only improve land productivity and biodiversity but also regulate some ecosystem services.This study reviews the impacts of physical and biological factors on herbivorous pests,parasites,and predatory natural enemies in fruit-crop agroforestry systems.Fruit-crop agroforestry systems provide high spatial heterogeneity by altering crop layouts,regulating the microclimate and soil quality,and offering food resources and shelter for natural enemies,thus promoting biological pest control.This enhances biological control and makes the agrocomplex system an effective tool for sustainable agriculture.Our research shows that volatile plant substances attract or repel pests and natural enemies based on the characteristics of the insects themselves.When scientifically designed,fruit-crop agroforestry systems provide high spatial heterogeneity and favorable microclimatic conditions,which enhance biological pest control and make the agroforestry system an effective tool for sustainable agriculture.Our research shows that fruit-crop agroforestry systems can provide richer food resources and habitat,enhancing biological pest control and improving pest management.
基金the financial support from Henan Province Natural Science Foundation(No.252300420583)Henan Provincial Science and Technology Research Project(Nos.242102310455,242102310473,242102310517)the Key Project of Science and Technology Research funded by the Henan Provincial Department of Education(No.24A350002)。
文摘Liver cancer is the fourth cause of cancer-related deaths and the primary cause of death in patients with compensated cirrhosis.In recent years,the role of traditional Chinese medicine in the treatment of liver cancer has attracted more and more attention and recognition.Luteolin(LUT)and glycyrrhetinic(GA)are natural compounds extracted from Chinese herbal medicine.LUT exhibits various biological activity including anti-inflammatory,antibacterial,antiviral,anti-tumor,and neuroprotective effects.GA significantly inhibits the growth and metastasis of cancer cells.However,the low water solubility of both compounds hinders their clinical applications.In this study,rod-shaped nanoparticles(NPs)self-assembled from LUT and GA were designed to enhance drug solubility and tumor-targeting capability.We verified that the assembly mechanism of the NPs was π-π stacking.These NPs significantly inhibited the proliferation of liver cancer cells while had no significant effect on normal liver cells.In a mouse model of liver cancer,these NPs demonstrated superior tumor-targeting ability due to the enhanced permeability and retention effect,and the affinity of GA for liver cancer cells,resulting in better therapeutic efficacy with lower systemic toxicity.Results of network pharmacology analysis showed that LUT and GA respectively targeted estrogen receptor 1(ESR1)protein and cyclin-dependent kinase 1(CDK1)protein to corporately induce tumor cell cycle arrest,which induced the inhibition of tumor cell proliferation.In conclusion,this study provides a novel reference for the treatment of liver cancer.
基金supported by the National Natural Science Foundation of China(No.41473068)supported by China Postdoctoral Science Foundation(No.2022M722667)。
文摘Fertilization or atmospheric deposition of nitrogen(N)and phosphorus(P)to terrestrial ecosystems can alter soil N(P)availability and the nature of nutrient limitation for plant growth.Changing the allocation of leaf P fractions is potentially an adaptive strategy for plants to cope with soil N(P)availability and nutrient-limiting conditions.However,the impact of the interactions between imbalanced anthropogenic N and P inputs on the concentrations and allocation proportions of leaf P fractions in forest woody plants remains elusive.We conducted a metaanalysis of data about the concentrations and allocation proportions of leaf P fractions,specifically associated with individual and combined additions of N and P in evergreen forests,the dominant vegetation type in southern China where the primary productivity is usually considered limited by P.This assessment allowed us to quantitatively evaluate the effects of N and P additions alone and interactively on leaf P allocation and use strategies.Nitrogen addition(exacerbating P limitation)reduced the concentrations of leaf total P and different leaf P fractions.Nitrogen addition reduced the allocation to leaf metabolic P but increased the allocation to other fractions,while P addition showed opposite trends.The simultaneous additions of N and P showed an antagonistic(mutual suppression)effect on the concentrations of leaf P fractions,but an additive(summary)effect on the allocation proportions of leaf P fractions.These results highlight the importance of strategies of leaf P fraction allocation in forest plants under changes in environmental nutrient availability.Importantly,our study identified critical interactions associated with combined N and P inputs that affect leaf P fractions,thus aiding in predicting plant acclimation strategies in the context of intensifying and imbalanced anthropogenic nutrient inputs.
文摘In the practice of healthcare,patient-reported outcomes(PROs)and PRO measures(PROMs)are used as an attempt to observe the changes in complex clinical situations.They guide us in making decisions based on the evidence regarding patient care by recording the change in outcomes for a particular treatment to a given condition and finally to understand whether a patient will benefit from a particular treatment and to quantify the treatment effect.For any PROM to be usable in health care,we need it to be reliable,encapsulating the points of interest with the potential to detect any real change.Using structured outcome measures routinely in clinical practice helps the physician to understand the functional limitation of a patient that would otherwise not be clear in an office interview,and this allows the physician and patient to have a meaningful conver-sation as well as a customized plan for each patient.Having mentioned the rationale and the benefits of PROMs,understanding the quantification process is crucial before embarking on management decisions.A better interpretation of change needs to identify the treatment effect based on clinical relevance for a given condition.There are a multiple set of measurement indices to serve this effect and most of them are used interchangeably without clear demarcation on their differences.This article details the various quantification metrics used to evaluate the treatment effect using PROMs,their limitations and the scope of usage and implementation in clinical practice.
基金supported by the National Natural Science Foundation of China(Nos.22178388 and 22108306)Taishan Scholars Program of Shandong Province(No.tsqn201909065)Chongqing Science and Technology Bureau(No.cstc2019jscx-gksb X0032).
文摘Structural regulation of Pd-based electrocatalytic hydrodechlorination(EHDC)catalyst for constructing high-efficient cathode materials with low noble metal content and high atom utilization is crucial but still challenging.Herein,a support electron inductive effect of Pd-Mn/Ni foam catalyst was proposed via in-situ Mn doping to optimize the electronic structure of the Ni foam(NF),which can inductive regulation of Pd for improving the EHDC performance.The mass activity and current efficiency of Pd-Mn/NF catalyst are 2.91 and 1.34 times superior to that of Pd/NF with 2,4-dichlorophenol as model compound,respectively.The Mn-doped interlayer optimized the electronic structure of Pd by bringing the d-state closer to the Fermi level than Pd on the NF surface,which optimizied the binding of EHDC intermediates.Additionally,the Mn-doped interlayer acted as a promoter for generating H∗and accelerating the EHDC reaction.This work presents a simple and effective regulation strategy for constructing high-efficient cathode catalyst for the EHDC of chlorinated organic compounds.
基金supported by the Shenzhen Science and Technology Program(JCYJ20230808105111022,JCYJ20220818095806013)Natural Science Foundation of Guangdong(2023A1515012267)+1 种基金the National Natural Science Foundation of China(22178223)the Royal Society/NSFC cost share program(IEC\NSFC\223372).
文摘Low-electrode capacitive deionization(FCDI)is an emerging desalination technology with great potential for removal and/or recycling ions from a range of waters.However,it still suffers from inefficient charge transfer and ion transport kinetics due to weak turbulence and low electric intensity in flow electrodes,both restricted by the current collectors.Herein,a new tip-array current collector(designated as T-CC)was developed to replace the conventional planar current collectors,which intensifies both the charge transfer and ion transport significantly.The effects of tip arrays on flow and electric fields were studied by both computational simulations and electrochemical impedance spectroscopy,which revealed the reduction of ion transport barrier,charge transport barrier and internal resistance.With the voltage increased from 1.0 to 1.5 and 2.0 V,the T-CC-based FCDI system(T-FCDI)exhibited average salt removal rates(ASRR)of 0.18,0.50,and 0.89μmol cm^(-2) min^(-1),respectively,which are 1.82,2.65,and 2.48 folds higher than that of the conventional serpentine current collectors,and 1.48,1.67,and 1.49 folds higher than that of the planar current collectors.Meanwhile,with the solid content in flow electrodes increased from 1 to 5 wt%,the ASRR for T-FCDI increased from 0.29 to 0.50μmol cm^(-2) min^(-1),which are 1.70 and 1.67 folds higher than that of the planar current collectors.Additionally,a salt removal efficiency of 99.89%was achieved with T-FCDI and the charge efficiency remained above 95%after 24 h of operation,thus showing its superior long-term stability.
文摘Objective The use of lasers has been an important part of urology in the treatment of stone and prostate disease.The thermal effects of lasers in lithotripsy have been a subject of debate over the years.The objective of this review was to assess the current state of knowledge available on the thermal effects of lasers in lithotripsy,as well as explore any new areas where studies are needed.Methods In August 2022,a keyword search on Google Scholar,PubMed,and Scopus for all papers containing the phrases“thermal effects”AND“laser”AND“lithotripsy”AND“urology”was done followed by citation jumping to other studies pertaining to the topic and 35 relevant papers were included in our study.The data from relevant papers were segregated into five groups according to the factor studied and type of study,and tables were created for a comparison of data.Results Temperature above the threshold of 43℃ was reached only when the power was>40 W and when there was adequate irrigation(at least 15–30 mL/min).Shorter lasing time divided by lithotripsy time or operator duty cycles less than 70%also resulted in a smaller temperature rise.Conclusion At least eight factors modify the thermal effects of lasers,and most importantly,the use of chilled irrigation at higher perfusion rates,lower power settings of<40 W,and with a shorter operator duty cycle will help to prevent thermal injuries from occurring.Stones impacted in the ureter or pelvi-ureteric junction further increase the probability of thermal injuries during laser firing.
基金Supported by the National Natural Science Foundation of China,No.82072537the General Project of Hunan Natural Science Foundation,No.2022JJ30412 and No.2021JJ30464.
文摘Exosomes(Exos)are extracellular vesicles secreted by cells and serve as crucial mediators of intercellular communication.They play a pivotal role in the pathogenesis and progression of various diseases and offer promising avenues for therapeutic interventions.Exos derived from mesenchymal stem cells(MSCs)have significant immunomodulatory properties.They effectively regulate immune responses by modulating both innate and adaptive immunity.These Exos can inhibit excessive inflammatory responses and promote tissue repair.Moreover,they participate in antigen presentation,which is essential for activating immune responses.The cargo of these Exos,including ligands,proteins,and microRNAs,can suppress T cell activity or enhance the population of immunosuppressive cells to dampen the immune response.By inhibiting lymphocyte proliferation,acting on macrophages,and increasing the population of regulatory T cells,these Exos contribute to maintaining immune and metabolic homeostasis.Furthermore,they can activate immune-related signaling pathways or serve as vehicles to deliver microRNAs and other bioactive substances to target tumor cells,which holds potential for immunotherapy applications.Given the immense therapeutic potential of MSC-derived Exos,this review comprehensively explores their mechanisms of immune regulation and therapeutic applications in areas such as infection control,tumor suppression,and autoimmune disease management.This article aims to provide valuable insights into the mechanisms behind the actions of MSC-derived Exos,offering theoretical references for their future clinical utilization as cell-free drug preparations.
文摘Excellent progress has been made in the last few decades in the cure rates of pediatric malignancies,with more than 80%of children with cancer who have access to contemporary treatment being cured.However,the therapies responsible for this survival can also produce adverse physical and psychological long-term outcomes,referred to as late effects,which appear months to years after the completion of cancer treatment.Research has shown that 60%to 90%of childhood cancer survivors(CCSs)develop one or more chronic health conditions,and 20%to 80%of survivors experience severe or life-threatening complications during adulthood.Therefore,understanding the late side effects of such treatments is important to improve the health and quality of life of the growing population of CCSs.
基金financially supported by the National Natural Science Foundation of China(NSFC)(52274295)the Natural Science Foundation of Hebei Province(E2021501029)+3 种基金the Fundamental Research Funds for the Central Universities(N2423051,N2423053,N2302016,N2423019,N2323013,N2423005)the Science and Technology Project of Hebei Education Department(QN2024238)the Basic Research Program Project of Shijiazhuang City for Universities Stationed in Hebei Province(241790937A)the Science and Technology Project of Qinhuangdao City in 2023.
文摘Mn-based layered oxides(KMO)have emerged as one of the promising low-cost cathodes for potassiumion batteries(PIBs).However,due to the multiple-phase transitions and the distortion in the MnO6structure induced by the Jahn-Teller(JT)effect associated with Mn-ion,the cathode exhibits poor structural stability.Herein,we propose a strategy to enhance structural stability by introducing robust metal-oxygen(M-O)bonds,which can realize the pinning effect to constrain the distortion in the transition metal(TM)layer.Concurrently,all the elements employed have exceptionally high crustal abundance.As a proof of concept,the designed K_(0.5)Mn_(0.9)Mg_(0.025)Ti_(0.025)Al_(0.05)O_(2)cathode exhibited a discharge capacity of approximately 100 mA h g^(-1)at 20 mA g^(-1)with 79%capacity retention over 50 cycles,and 73%capacity retention over 200 cycles at 200 mA g^(-1),showcased much better battery performance than the designed cathode with less robust M-O bonds.The properties of the formed M-O bonds were investigated using theoretical calculations.The enhanced dynamics,mitigated JT effect,and improved structural stability were elucidated through the in-situ X-ray diffractometer(XRD),in-situ electrochemical impedance spectroscopy(EIS)(and distribution of relaxation times(DRT)method),and ex-situ X-ray absorption fine structure(XAFS)tests.This study holds substantial reference value for the future design of costeffective Mn-based layered cathodes for PIBs.
基金supported by the National Key R&D Program of China(No.2022YFE0109500)the National Natural Science Foundation of China(Nos.52071255,52301250,52171190 and 12304027)+2 种基金the Key R&D Project of Shaanxi Province(No.2022GXLH-01-07)the Fundamental Research Funds for the Central Universities(China)the World-Class Universities(Disciplines)and the Characteristic Development Guidance Funds for the Central Universities.
文摘With the rapid development of artificial intelligence,magnetocaloric materials as well as other materials are being developed with increased efficiency and enhanced performance.However,most studies do not take phase transitions into account,and as a result,the predictions are usually not accurate enough.In this context,we have established an explicable relationship between alloy compositions and phase transition by feature imputation.A facile machine learning is proposed to screen candidate NiMn-based Heusler alloys with desired magnetic entropy change and magnetic transition temperature with a high accuracy R^(2)≈0.98.As expected,the measured properties of prepared NiMn-based alloys,including phase transition type,magnetic entropy changes and transition temperature,are all in good agreement with the ML predictions.As well as being the first to demonstrate an explicable relationship between alloy compositions,phase transitions and magnetocaloric properties,our proposed ML model is highly predictive and interpretable,which can provide a strong theoretical foundation for identifying high-performance magnetocaloric materials in the future.
