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
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
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
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
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
BACKGROUND Sensitivity to stress is essential in the onset,clinical symptoms,course,and prognosis of major depressive disorder(MDD).Meanwhile,it was unclear how variously classified but connected stress-sensitivity va...BACKGROUND Sensitivity to stress is essential in the onset,clinical symptoms,course,and prognosis of major depressive disorder(MDD).Meanwhile,it was unclear how variously classified but connected stress-sensitivity variables affect MDD.We hypothesize that high-level trait-and state-related stress-sensitivity factors may have different cumulative effects on the clinical symptoms and follow-up outcomes of MDD.AIM To investigate how stress-sensitivity factors added up and affected MDD clinical symptoms and follow-up results.METHODS In this prospective study,281 MDD patients were enrolled from a tertiary care setting.High-level stress-sensitivity factors were classified as trait anxiety,state anxiety,perceived stress,and neuroticism,with a total score in the top quartile of the research cohort.The cumulative effects of stress-sensitivity factors on cognitive dysfunction,disability and functional impairment,suicide risk,and depressive and anxiety symptoms were examined using an analysis of variance with linear trend analysis.Correlations were investigated further using multiple regression analysis.RESULTS Regarding high-level stress-sensitivity factors,53.40%of patients had at least one at baseline,and 29.61%had two or more.Four high-level stress-sensitivity components had significant cumulative impacts on MDD symptoms at baseline(all P<0.001).Perceived stress predicted the greatest effect sizes of state-related factors on depressive symptoms(partialη^(2)=0.153;standardizedβ=0.195;P<0.05).The follow-up outcomes were significantly impacted only by the high-level trait-related components,mainly when it came to depressive symptoms and suicide risk,which were predicted by trait anxiety and neuroticism,respectively(partialη^(2)=0.204 and 0.156;standardizedβ=0.247 and 0.392;P<0.05).CONCLUSION To enhance outcomes of MDD and lower the suicide risk,screening for stress-sensitivity factors and considering multifaceted measures,mainly focusing on trait-related ones,should be addressed clinically.展开更多
Natural cemented calcareous sand and limestone are highly complex and not well understood in terms of the me-chanical behavior due to the difficulty of obtaining undisturbed samples from far sea.This paper proposes an...Natural cemented calcareous sand and limestone are highly complex and not well understood in terms of the me-chanical behavior due to the difficulty of obtaining undisturbed samples from far sea.This paper proposes an artificial method in a laboratory setting using microbial-induced carbonate precipitation(MICP)to simulate the natural process of cementation of limestone.The artificially cemented sand has a high degree of similarity with the natural weakly limestone in three aspects:(1)the mineral composition of the cemented material is also granular calcite and acicular aragonite;(2)the microstructure in interconnected open pore network can be gradually closed and contracted with cementation.The porosity reaches to approximately 9.2%;(3)both the stress-strain relationship and the unconfined strength closely resemble that of natural weakly limestone.Furthermore,both static and dynamic behaviors of artificial limestone were studied by quasi-static compression tests and Split Hopkinson Pressure Bar(SHPB)tests,finding that the unconfined strength of weakly artifical limestone exponentially increases with increasing strain rate.A rate-dependent bond strength was proposed and implemented in software to reveal the mechanism of strain rate effects.It is found that the loading velocity is too high to keep in sync with the initiation and propagation of cracks under impact loading.This delay-induced viscosity may restrict the movement of the surrounding balls,thus increasing resistance.展开更多
β-Ga_(2)O_(3),as one of the important 4th generation semiconductors,is widely used in solar-blind ultraviolet(UV)detectors with a short detection range of 200-280 nm benefiting from its ultra-wide bandgap,strong radi...β-Ga_(2)O_(3),as one of the important 4th generation semiconductors,is widely used in solar-blind ultraviolet(UV)detectors with a short detection range of 200-280 nm benefiting from its ultra-wide bandgap,strong radiation resistance,and excellent chemical and thermal stabilities.Here,a self-powered photodetector(PD)based on an Ag/β-Ga_(2)O_(3) Schottky heterojunction was designed and fabricated.Through a subtle design of electrodes,the pyro-phototronic effect was discovered,which can be coupled to the common photovoltaic effect and further enhance the performance of the PD.Compared to traditional Ga_(2)O_(3)-based PD,the as-used PD exhibited a self-driving property and a broadband response beyond the bandgap lim-itations,ranging from 200 nm(deep UV)to 980 nm(infrared).Moreover,the photoresponse time was greatly shrunk owing to the coupling effect.Under laser irradiation,with a wavelength of 450 nm and a power density of 8 mW cm-2,the photocurrent could be improved by around 41 times compared with the sole photovoltaic effect.Besides,the performances of the Schottky PD were enhanced at both high and low temperatures.The device also possessed long-term working stability.This paper not only re-veals basic physics lying in the 4th generation semiconductor Ga_(2)O_(3) but also sheds light on the multi-encryption transmission of light information using this PD.展开更多
The highly selective catalytic hydrogenation of halogenated nitroaromatics was achieved by employing Pd‑based catalysts that were co‑modified with organic and inorganic ligands.It was demonstrated that the catalysts c...The highly selective catalytic hydrogenation of halogenated nitroaromatics was achieved by employing Pd‑based catalysts that were co‑modified with organic and inorganic ligands.It was demonstrated that the catalysts contained Pd species in mixed valence states,with high valence Pd at the metal‑support interface and zero valence Pd at the metal surface.While the strong coordination of triphenylphosphine(PPh3)to Pd0 on the Pd surface prevents the adsorption of halogenated nitroaromatics and thus dehalogenation,the coordination of sodium metavanadate(NaVO3)to high‑valence Pd sites at the interface helps to activate H2 in a heterolytic pathway for the selective hydrogenation of nitro‑groups.The excellent catalytic performance of the interfacial active sites enables the selective hydrogenation of a wide range of halogenated nitroaromatics.展开更多
Roads are a leading cause of habitat fragmentation and may reduce bird populations by increasing nest predation rates.However,few studies have investigated the effects of traffic volume on the reproductive success of ...Roads are a leading cause of habitat fragmentation and may reduce bird populations by increasing nest predation rates.However,few studies have investigated the effects of traffic volume on the reproductive success of roadside birds in the neotropics.Our goal was to evaluate the effects of spatial,temporal,and vehicle flow variations on the survival of artificial open-cup nests.The study was carried out in a nature reserve on the side of a highway during the breeding season(from October to March)in two restinga(sand-coastal plain)phytophysiognomies in southeastern Brazil:non-floodable(open)and floodable(closed).One hundred thirty nests were distributed along transects ranging from 3 m to 300 m from the highway in each vegetation type(totaling 260 nests).The nests were checked every three days for their status(depredated or intact)over 12 days,and new nests were subsequently placed near sampling points of depredated or successful nests.We estimated survival using logistic exposure generalized linear and additive mixed models.At the end of the 180 days of the experiment,33%of 6202 nests were successful.Nest survival was higher in open restinga than in closed restinga.In both habitats,nest survival was lowest mid-season and highest at the beginning and end.Survival rates peaked near the highway,declined up to 50 m away,then showed a slight increase.Finally,survival increased at moderate-to-high traffic volumes(∼22,000 vehicles/day),particularly in open restinga.We suggest that spatial,temporal,and habitat-specific highway impacts(e.g.,noise,vibration,visual stimuli)can lead to variations in the activity of nest predators,generating fluctuations in nest survival associated with predator behavior.展开更多
Thermally activated delayed fluorescence(TADF)molecules have outstanding potential for applications in organic light-emitting diodes(OLEDs).Due to the lack of systematic studies on the correlation between molecular st...Thermally activated delayed fluorescence(TADF)molecules have outstanding potential for applications in organic light-emitting diodes(OLEDs).Due to the lack of systematic studies on the correlation between molecular structure and luminescence properties,TADF molecules are far from meeting the needs of practical applications in terms of variety and number.In this paper,three twisted TADF molecules are studied and their photophysical properties are theoretically predicted based on the thermal vibrational correlation function method combined with multiscale calculations.The results show that all the molecules exhibit fast reverse intersystem crossing(RISC)rates(kRISC),predicting their TADF luminescence properties.In addition,the binding of DHPAzSi as the donor unit with different acceptors can change the dihedral angle between the ground and excited states,and the planarity of the acceptors is positively correlated with the reorganization energy,a property that has a strong influence on the non-radiative process.Furthermore,a decrease in the energy of the molecular charge transfer state and an increase in the kRISC were observed in the films.This study not only provides a reliable explanation for the observed experimental results,but also offers valuable insights that can guide the design of future TADF molecules.展开更多
DNA microarray technology is an extremely effective technique for studying gene expression patterns in cells, and the main challenge currently faced by this technology is how to analyze the large amount of gene expres...DNA microarray technology is an extremely effective technique for studying gene expression patterns in cells, and the main challenge currently faced by this technology is how to analyze the large amount of gene expression data generated. To address this, this paper employs a mixed-effects model to analyze gene expression data. In terms of data selection, 1176 genes from the white mouse gene expression dataset under two experimental conditions were chosen, setting up two conditions: pneumococcal infection and no infection, and constructing a mixed-effects model. After preprocessing the gene chip information, the data were imported into the model, preliminary results were calculated, and permutation tests were performed to biologically validate the preliminary results using GSEA. The final dataset consists of 20 groups of gene expression data from pneumococcal infection, which categorizes functionally related genes based on the similarity of their expression profiles, facilitating the study of genes with unknown functions.展开更多
A comprehensive numerical investigation into mixed⁃mode delamination is presented in this study.It aims to assess the impact of thermal and friction effects through mixed⁃mode flexure crack propagation testing.Finite ...A comprehensive numerical investigation into mixed⁃mode delamination is presented in this study.It aims to assess the impact of thermal and friction effects through mixed⁃mode flexure crack propagation testing.Finite element analysis was employed to model the delamination process,incorporating a contact cohesive zone model.This model couples the traction⁃separation law,the contact law,and the Coulomb friction law simultaneously.The thermomechanical analysis in this study is performed using a sequentially coupled approach,implemented with the finite element software ABAQUS.The findings underscore the importance of this study.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.
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.
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Supported by Science and Technology Innovation 2030-Major Projects,No.2021ZD0202000National Key Research and Development Program of China,No.2019YFA0706200+2 种基金National Natural Science Foundation of China,No.82371535Science and Technology Innovation Program of Hunan Province,No.2023RC3083Fundamental Research Funds for the Central Universities of Central South University,No.2023ZZTS0838.
文摘BACKGROUND Sensitivity to stress is essential in the onset,clinical symptoms,course,and prognosis of major depressive disorder(MDD).Meanwhile,it was unclear how variously classified but connected stress-sensitivity variables affect MDD.We hypothesize that high-level trait-and state-related stress-sensitivity factors may have different cumulative effects on the clinical symptoms and follow-up outcomes of MDD.AIM To investigate how stress-sensitivity factors added up and affected MDD clinical symptoms and follow-up results.METHODS In this prospective study,281 MDD patients were enrolled from a tertiary care setting.High-level stress-sensitivity factors were classified as trait anxiety,state anxiety,perceived stress,and neuroticism,with a total score in the top quartile of the research cohort.The cumulative effects of stress-sensitivity factors on cognitive dysfunction,disability and functional impairment,suicide risk,and depressive and anxiety symptoms were examined using an analysis of variance with linear trend analysis.Correlations were investigated further using multiple regression analysis.RESULTS Regarding high-level stress-sensitivity factors,53.40%of patients had at least one at baseline,and 29.61%had two or more.Four high-level stress-sensitivity components had significant cumulative impacts on MDD symptoms at baseline(all P<0.001).Perceived stress predicted the greatest effect sizes of state-related factors on depressive symptoms(partialη^(2)=0.153;standardizedβ=0.195;P<0.05).The follow-up outcomes were significantly impacted only by the high-level trait-related components,mainly when it came to depressive symptoms and suicide risk,which were predicted by trait anxiety and neuroticism,respectively(partialη^(2)=0.204 and 0.156;standardizedβ=0.247 and 0.392;P<0.05).CONCLUSION To enhance outcomes of MDD and lower the suicide risk,screening for stress-sensitivity factors and considering multifaceted measures,mainly focusing on trait-related ones,should be addressed clinically.
基金The authors would like to acknowledge the support of the National Natural Science Foundation of China(No.52279097,No.51779264)Blue and Green Project of Jiangsu Province.
文摘Natural cemented calcareous sand and limestone are highly complex and not well understood in terms of the me-chanical behavior due to the difficulty of obtaining undisturbed samples from far sea.This paper proposes an artificial method in a laboratory setting using microbial-induced carbonate precipitation(MICP)to simulate the natural process of cementation of limestone.The artificially cemented sand has a high degree of similarity with the natural weakly limestone in three aspects:(1)the mineral composition of the cemented material is also granular calcite and acicular aragonite;(2)the microstructure in interconnected open pore network can be gradually closed and contracted with cementation.The porosity reaches to approximately 9.2%;(3)both the stress-strain relationship and the unconfined strength closely resemble that of natural weakly limestone.Furthermore,both static and dynamic behaviors of artificial limestone were studied by quasi-static compression tests and Split Hopkinson Pressure Bar(SHPB)tests,finding that the unconfined strength of weakly artifical limestone exponentially increases with increasing strain rate.A rate-dependent bond strength was proposed and implemented in software to reveal the mechanism of strain rate effects.It is found that the loading velocity is too high to keep in sync with the initiation and propagation of cracks under impact loading.This delay-induced viscosity may restrict the movement of the surrounding balls,thus increasing resistance.
基金supported by the National Natural Science Foundation of China(Grant Nos.52192610 and 52192613)the National Key R&D Project from the Minister of Science and Technology(No.2021YFA1201601)the CAS-TWAS President’s Fellow-ship(A.B).
文摘β-Ga_(2)O_(3),as one of the important 4th generation semiconductors,is widely used in solar-blind ultraviolet(UV)detectors with a short detection range of 200-280 nm benefiting from its ultra-wide bandgap,strong radiation resistance,and excellent chemical and thermal stabilities.Here,a self-powered photodetector(PD)based on an Ag/β-Ga_(2)O_(3) Schottky heterojunction was designed and fabricated.Through a subtle design of electrodes,the pyro-phototronic effect was discovered,which can be coupled to the common photovoltaic effect and further enhance the performance of the PD.Compared to traditional Ga_(2)O_(3)-based PD,the as-used PD exhibited a self-driving property and a broadband response beyond the bandgap lim-itations,ranging from 200 nm(deep UV)to 980 nm(infrared).Moreover,the photoresponse time was greatly shrunk owing to the coupling effect.Under laser irradiation,with a wavelength of 450 nm and a power density of 8 mW cm-2,the photocurrent could be improved by around 41 times compared with the sole photovoltaic effect.Besides,the performances of the Schottky PD were enhanced at both high and low temperatures.The device also possessed long-term working stability.This paper not only re-veals basic physics lying in the 4th generation semiconductor Ga_(2)O_(3) but also sheds light on the multi-encryption transmission of light information using this PD.
文摘The highly selective catalytic hydrogenation of halogenated nitroaromatics was achieved by employing Pd‑based catalysts that were co‑modified with organic and inorganic ligands.It was demonstrated that the catalysts contained Pd species in mixed valence states,with high valence Pd at the metal‑support interface and zero valence Pd at the metal surface.While the strong coordination of triphenylphosphine(PPh3)to Pd0 on the Pd surface prevents the adsorption of halogenated nitroaromatics and thus dehalogenation,the coordination of sodium metavanadate(NaVO3)to high‑valence Pd sites at the interface helps to activate H2 in a heterolytic pathway for the selective hydrogenation of nitro‑groups.The excellent catalytic performance of the interfacial active sites enables the selective hydrogenation of a wide range of halogenated nitroaromatics.
基金supports were provided by the Concessionária Rodovia do Sol/SA(RodoSol)the Conselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq,grant:45.6446/2014/1)+2 种基金the São Paulo Research Foundation(FAPESP,Process Number#2024/13237-3)PD received a postdoctoral fellowship from the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior(CAPES,grant:88887.469218/2019-00)CD is grateful to CNPq(Bolsa de Produtividade em Pesquisa,grant:308997/2023-9).
文摘Roads are a leading cause of habitat fragmentation and may reduce bird populations by increasing nest predation rates.However,few studies have investigated the effects of traffic volume on the reproductive success of roadside birds in the neotropics.Our goal was to evaluate the effects of spatial,temporal,and vehicle flow variations on the survival of artificial open-cup nests.The study was carried out in a nature reserve on the side of a highway during the breeding season(from October to March)in two restinga(sand-coastal plain)phytophysiognomies in southeastern Brazil:non-floodable(open)and floodable(closed).One hundred thirty nests were distributed along transects ranging from 3 m to 300 m from the highway in each vegetation type(totaling 260 nests).The nests were checked every three days for their status(depredated or intact)over 12 days,and new nests were subsequently placed near sampling points of depredated or successful nests.We estimated survival using logistic exposure generalized linear and additive mixed models.At the end of the 180 days of the experiment,33%of 6202 nests were successful.Nest survival was higher in open restinga than in closed restinga.In both habitats,nest survival was lowest mid-season and highest at the beginning and end.Survival rates peaked near the highway,declined up to 50 m away,then showed a slight increase.Finally,survival increased at moderate-to-high traffic volumes(∼22,000 vehicles/day),particularly in open restinga.We suggest that spatial,temporal,and habitat-specific highway impacts(e.g.,noise,vibration,visual stimuli)can lead to variations in the activity of nest predators,generating fluctuations in nest survival associated with predator behavior.
文摘Thermally activated delayed fluorescence(TADF)molecules have outstanding potential for applications in organic light-emitting diodes(OLEDs).Due to the lack of systematic studies on the correlation between molecular structure and luminescence properties,TADF molecules are far from meeting the needs of practical applications in terms of variety and number.In this paper,three twisted TADF molecules are studied and their photophysical properties are theoretically predicted based on the thermal vibrational correlation function method combined with multiscale calculations.The results show that all the molecules exhibit fast reverse intersystem crossing(RISC)rates(kRISC),predicting their TADF luminescence properties.In addition,the binding of DHPAzSi as the donor unit with different acceptors can change the dihedral angle between the ground and excited states,and the planarity of the acceptors is positively correlated with the reorganization energy,a property that has a strong influence on the non-radiative process.Furthermore,a decrease in the energy of the molecular charge transfer state and an increase in the kRISC were observed in the films.This study not only provides a reliable explanation for the observed experimental results,but also offers valuable insights that can guide the design of future TADF molecules.
文摘DNA microarray technology is an extremely effective technique for studying gene expression patterns in cells, and the main challenge currently faced by this technology is how to analyze the large amount of gene expression data generated. To address this, this paper employs a mixed-effects model to analyze gene expression data. In terms of data selection, 1176 genes from the white mouse gene expression dataset under two experimental conditions were chosen, setting up two conditions: pneumococcal infection and no infection, and constructing a mixed-effects model. After preprocessing the gene chip information, the data were imported into the model, preliminary results were calculated, and permutation tests were performed to biologically validate the preliminary results using GSEA. The final dataset consists of 20 groups of gene expression data from pneumococcal infection, which categorizes functionally related genes based on the similarity of their expression profiles, facilitating the study of genes with unknown functions.
文摘A comprehensive numerical investigation into mixed⁃mode delamination is presented in this study.It aims to assess the impact of thermal and friction effects through mixed⁃mode flexure crack propagation testing.Finite element analysis was employed to model the delamination process,incorporating a contact cohesive zone model.This model couples the traction⁃separation law,the contact law,and the Coulomb friction law simultaneously.The thermomechanical analysis in this study is performed using a sequentially coupled approach,implemented with the finite element software ABAQUS.The findings underscore the importance of this study.
