1.Introduction Cities are responsible for approximately 70%of all anthropogenic greenhouse gas(GHG)emissions and about 60%of all anthropogenic methane(CH4)emissions[1,2].Solid waste disposal sites(including landfills ...1.Introduction Cities are responsible for approximately 70%of all anthropogenic greenhouse gas(GHG)emissions and about 60%of all anthropogenic methane(CH4)emissions[1,2].Solid waste disposal sites(including landfills and dumpsites),which are prevalent in global cities,emit CH4 generated from the anaerobic biodegradation of municipal solid waste(MSW).Notably,the proportions of CH4 emissions from disposal sites surpass 50%of the total CH4 emissions in some megalopolises[3].CH4 has a high global warming potential(GWP),being 28 times stronger than carbon dioxide(CO_(2))over a 100-year period and 80 times stronger over a 20-year period[4].Understanding and mitigating CH4 emissions from solid waste disposal sites is particularly pertinent and pressing,considering that the latest Synthesis Report from the Intergovernmental Panel on Climate Change(IPCC)emphasizes that the current pace of mitigation and adaptation policies and measures falls short of restraining global temperature rise to under 1.5℃ within the 21st century[4].More than 150 countries signed the Global Methane Pledge at the United Nations Climate Change Conference in Glasgow(COP26),which aims to reduce global annual CH4 emissions by 30%by 2030,compared with emissions in 2020[5].展开更多
In the last decade,Pakistan has experienced multidemics of HIV in key populations,namely:injecting drug users,male sex with male,female sex workers,transgender sex workers,and transgenders.According to recent reports,...In the last decade,Pakistan has experienced multidemics of HIV in key populations,namely:injecting drug users,male sex with male,female sex workers,transgender sex workers,and transgenders.According to recent reports,in Pakistan,210000 people with HIV accounts for less than 0.2%of the general population.展开更多
Attribute-based encryption is cryptographic techniques that provide flexible data access control to encrypted data content in cloud storage.Each trusted authority needs proper management and distribution of secret key...Attribute-based encryption is cryptographic techniques that provide flexible data access control to encrypted data content in cloud storage.Each trusted authority needs proper management and distribution of secret keys to the user’s to only authorized user’s attributes.However existing schemes cannot be applied multiple authority that supports only a single keywords search compare to multi keywords search high computational burden or inefficient attribute’s revocation.In this paper,a ciphertext policy attribute-based encryption(CP-ABE)scheme has been proposed which focuses on multi-keyword search and attribute revocation by new policy updating feathers under multiple authorities and central authority.The data owner encrypts the keywords index under the initial access policy.Moreover,this paper addresses further issues such as data access,search policy,and confidentiality against unauthorized users.Finally,we provide the correctness analysis,performance analysis and security proof for chosen keywords attack and search trapdoor in general group model using DBDH and DLIN assumption.展开更多
Heat storage properties of phase change materials(PCMs) are essential characteristics that perform a key role in thermal heat energy storage systems.The thermal properties of PCMs can be improved by developing metal f...Heat storage properties of phase change materials(PCMs) are essential characteristics that perform a key role in thermal heat energy storage systems.The thermal properties of PCMs can be improved by developing metal foam/PCM composites.The addition of metal foam in PCMs has a significant effect on the thermal characteristics of PCMs.In this paper,the heat storage properties of two different metal foam/PCM composites were experimentally examined.The behavior of paraffin in metal foam(copper and iron-nickel)/paraffin composites concerning pure paraffin at a constant heat flux of 1000 W/m^(2) in three directions simultaneously(x,y,and z) was studied.Paraffin was infiltrated into copper and iron-nickel foams to develop composite materials which resulted in enhancing the thermal conductivity of the paraffin.A comparative analysis is made on the heat storage properties of paraffin in copper and iron-nickel foams/paraffin composites.Inner temperature distribution during the phase transition process is experimentally evaluated.This comparison indicates that temperature uniformity in copper foam/paraffin composite is better than in iron-nickel foam/paraffin composite and pure paraffin at the same heat flux.Experimental results show that at heat flux of 1000 W/m^(2),the heat storage time for copper foam/paraffin composite is 20.63% of that of iron-nickel foam/paraffin composite.展开更多
Effective waste management is a major challenge for Small Island Developing States (SIDS) like Maldives due to limited land availability. Maldives exemplifies these issues as one of the most geographically dispersed c...Effective waste management is a major challenge for Small Island Developing States (SIDS) like Maldives due to limited land availability. Maldives exemplifies these issues as one of the most geographically dispersed countries, with a population unevenly distributed across numerous islands varying greatly in size and population density. This study provides an in-depth analysis of the unique waste management practices across different regions of Maldives in relation to its natural and socioeconomic context. Data shows Maldives has one of the highest population density and per capita waste generation among SIDS, despite its small land area and medium GDP per capita. Large disparities exist between the densely populated capital Male’ with only 5.8 km2 area generating 63% of waste and the ~194 scattered outer islands with ad hoc waste management practices. Given Male’s dense population and high calorific waste, incineration could generate up to ~30 GW/a energy and even increase Maldives’ renewable energy supply by 200%. In contrast, decentralized anaerobic digestion presents an optimal solution for outer islands to reduce waste volume while providing over 40%–100% energy supply for daily cooking in local families. This timely study delivers valuable insights into designing context-specific waste-to-energy systems and integrated waste policies tailored to Maldives’ distinct regions. The framework presented can also guide other SIDS facing similar challenges as Maldives in establishing sustainable, ecologically sound waste management strategies.展开更多
Emerging and recurrent infectious diseases caused by human coronaviruses(HCoVs)continue to pose a significant threat to global public health security.In light of this ongoing threat,the development of a broad-spectrum...Emerging and recurrent infectious diseases caused by human coronaviruses(HCoVs)continue to pose a significant threat to global public health security.In light of this ongoing threat,the development of a broad-spectrum drug to combat HCoVs is an urgently priority.Herein,we report a series of anti-pan-coronavirus ssDNA aptamers screened using Systematic Evolution of Ligands by Exponential Enrichment(SELEX).These aptamers have nanomolar affinity with the nucleocapsid protein(NP)of Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and also show excellent binding efficiency to the N proteins of both SARS,MERS,HCoV-OC43 and-NL63 with affinity KD values of 1.31 to 135.36 nM.Such aptamer-based therapeutics exhibited potent antiviral activity against both the authentic SARS-CoV-2 prototype strain and the Omicron variant(BA.5)with EC50 values at 2.00 nM and 41.08 nM,respectively.The protein docking analysis also evidenced that these aptamers exhibit strong affinities for N proteins of pan-coronavirus and other HCoVs(−229E and-HKU1).In conclusion,we have identified six aptamers with a high pan-coronavirus antiviral activity,which could potentially serve as an effective strategy for preventing infections by unknown coronaviruses and addressing the ongoing global health threat.展开更多
The novel coronavirus disease 2019(COVID-19)is still rampant all over the world,causing incalculable losses to the world.Major pharmaceutical organizations around the globe are focusing on vaccine research and drug de...The novel coronavirus disease 2019(COVID-19)is still rampant all over the world,causing incalculable losses to the world.Major pharmaceutical organizations around the globe are focusing on vaccine research and drug development to prevent further damage caused by the pandemic.The messenger RNA(mRNA)technology has got ample of attention after the success of the two very effective mRNA vaccines during the recent pandemic of COVID-19.mRNA vaccine has been promoted to the core stage of pharmaceutical industry,and the rapid development of mRNA technology has exceeded expectations.Beyond COVID-19,the mRNA vaccine has been tested for various infectious diseases and undergoing clinical trials.Due to the ability of constant mutation,the viral infections demand abrupt responses and immediate production,and therefore mRNA-based technology offers best answers to sudden outbreaks.The need for mRNA-based vaccine became more obvious due to the recent emergence of new Omicron variant.In this review,we summarized the unique properties of mRNA-based vaccines for infectious diseases,delivery technologies,discussed current challenges,and highlighted the prospects of this promising technology in the future.We also discussed various clinical studies as well preclinical studies conducted on mRNA therapeutics for diverse infectious diseases.展开更多
With the development of a small interfering RNA(siRNA)delivery strategy,increasing siRNA therapeutics for tumor treatment appeared in clinical trials and pre-clinical development.However,the test results of such thera...With the development of a small interfering RNA(siRNA)delivery strategy,increasing siRNA therapeutics for tumor treatment appeared in clinical trials and pre-clinical development.However,the test results of such therapeutics unveiled that efficient siRNA delivery to tumor tissues is still challenging.Albumin is considered an ideal carrier for delivering hydrophobic agents into tumor tissue because it is highly concentrated and long-circulating in blood and has propensity of tumor enrichment.Herein,we synthesized lipid conjugated siRNAs(LsiRNAs),which showed high affinity to albumin.Mechanistically,LsiRNAs non-covalently bind to the hydrophobic core of albumin through its octadecyl tails.The small size of albumin/LsiRNAs allows the complex to penetrate tumor tissue efficiently.Biodistribution test proved that albumin extremely prolonged circulation time and increased tumor retention of associated LsiRNAs.Notably,LsiRNA against programmed death ligand-1(Pdl1)efficiently suppressed tumor growth as well as prolonged survival time of tumor bearing mice by increasing infiltration of CD8^(+)T cells as well as promoted the maturation of dendritic cells both in tumor and lymph.Together,LsiRNAs provide a simple but effective way for siRNA tumor delivery that“hitchhikes”on albumin.展开更多
CRISPR/Cas9-based gene editing has emerged as a powerful biotechnological tool,that relies on Cas9 protein and single guided RNA(sgRNA)to edit target DNA.However,the lack of safe and efficient delivery carrier is one ...CRISPR/Cas9-based gene editing has emerged as a powerful biotechnological tool,that relies on Cas9 protein and single guided RNA(sgRNA)to edit target DNA.However,the lack of safe and efficient delivery carrier is one of the crucial factors restricting its clinical transformation.Here,we report an ionizable lipid nanoparticle(iLP181,pKa=6.43)based on iLY1809 lipid enabling robust gene editing in vitro and in vivo.The iLP181 effectively encapsulate psgPLK1,the best-performing plasmid expressing for both Cas9 protein and sgRNA targeting Polo-like kinase 1(PLK1).The iLP181/psgPLK1 nanoformulation showed uniformity in size,regular nanostructure and nearly neutral zeta potential at pH 7.4.The nanoformulation effectively triggered editing of PLK1 gene with more than 30%efficiency in HepG2-Luc cells.iLP181/psgPLK1 significantly accumulated in the tumor for more than 5 days after a single intravenous injection.In addition,it also achieved excellent tumor growth suppression compared to other nucleic acid modalities such as siRNA,without inducing adverse effects to the main organs including the liver and kidneys.This study not only provides a clinically-applicable lipid nanocarrier for delivering CRISPR/Cas system(even other bioactive molecules),but also constitutes a potential cancer treatment regimen base on DNA editing of oncogenes.展开更多
Feeding experiments using three strains ofentomopathogenic fungi, Beauveria bassiana, Metarhizium anisopliae and Isaria fumosorosea were conducted with newly moulted 3rd-5th instar Ocinara varians Walker larvae in the...Feeding experiments using three strains ofentomopathogenic fungi, Beauveria bassiana, Metarhizium anisopliae and Isaria fumosorosea were conducted with newly moulted 3rd-5th instar Ocinara varians Walker larvae in the laboratory. The mortality of larvae immersed individually in spore suspension (1 × 10^7 spores/mL) of all the strains was 〉 80% except 5th instar larvae treated with M. anisopliae which transformed into pupae, but did not result in adult emergence. The growth (total body mass), consumption, relative consumption rate and relative growth rate, were reduced at all three larval stages, while developmental time was extended in infected larvae with concurrent significant increase in approximate digestibility in infected larvae. Conversion of digested food (ECD) and ingested food (ECI) values declined in infected larvae as compared to the healthy larvae (control). The 5th instar larvae treated with M. anisopliae showed higher ECD and ECI values than control. Based on mortality and growth inhibition it can be suggested that all the studied fungal strains have a high potential for biocontrol and could be developed into biocontrol agents against O. varians.展开更多
Attaching DNA/RNA to nanomaterials is the basis for nucleic acid-based assembly and drug delivery.Herein,we report that small interfering RNA(siRNA)effectively coordinates with ligand-free lanthanide nanoparticles(NaG...Attaching DNA/RNA to nanomaterials is the basis for nucleic acid-based assembly and drug delivery.Herein,we report that small interfering RNA(siRNA)effectively coordinates with ligand-free lanthanide nanoparticles(NaGdF4 NPs),and forms siRNA/NaGdF4 spherical nucleic acids(SNA).The coordination is primarily attributed to the interaction between Gd and phosphate backbone of the siRNA.Surprisingly,an efficient encapsulation and rapid endosomal escape of siRNA from the endosome/lysosome were achieved,due to its flexible ability to bound to phospholipid head of endosomal membrane,thereby disrupting the membrane structure.Resorting to the dual properties of NaGdF4 NPs,siRNA loading,and endosomal escape,siRNA targeting programmed cell death-ligand 1(siPD-L1)/NaGdF4 SNA triggers significant gene silencing in vitro and in vivo,and effectively represses the tumor growth in both CT26 tumor model and 4T1 orthotopic murine model.展开更多
Vulnerable atherosclerotic plaque(VASPs)is the major pathological cause of acute cardiovascular event.Early detection and precise intervention of VASP hold great clinical significance,yet remain a major challenge.Phot...Vulnerable atherosclerotic plaque(VASPs)is the major pathological cause of acute cardiovascular event.Early detection and precise intervention of VASP hold great clinical significance,yet remain a major challenge.Photodynamic therapy(PDT)realizes potent ablation efficacy under precise manipulation of laser irradiation.In this study,we constructed theranostic nanoprobes(NPs),which could precisely regress VASPs through a cascade of synergistic events triggered by local irradiation of lasers under the guidance of fluorescence/MR imaging.The NPs were formulated from human serum albumin(HSA)conjugated with a high affinity-peptide targeting osteopontin(OPN)and encapsulated with photosensitizer IR780 and hypoxia-activatable tirapazamine(TPZ).After intravenous injection into atherosclerotic mice,the OPN-targeted NPs demonstrated high specific accumulation in VASPs due to the overexpression of OPN in activated foamy macrophages in the carotid artery.Under the visible guidance of fluorescence and MR dual-model imaging,the precise near-infrared(NIR)laser irradiation generated massive reactive oxygen species(ROS),which resulted in efficient plaque ablation and amplified hypoxia within VASPs.In response to the elevated hypoxia,the initially inactive TPZ was successively boosted to present potent biological suppression of foamy macrophages.After therapeutic administration of the NPs for 2 weeks,the plaque area and the degree of carotid artery stenosis were markedly reduced.Furthermore,the formulated NPs displayed excellent biocompatibility.In conclusion,the developed HSA-based NPs demonstrated appreciable specific identification ability of VASPs and realized precise synergistic regression of atherosclerosis.展开更多
基金Nanyang Technological University(NTU),Singapore,for providing research scholarships for this study.The authors thank the supports from Debris of the Anthropocene to Resources(DotA2)Lab at NTU.
文摘1.Introduction Cities are responsible for approximately 70%of all anthropogenic greenhouse gas(GHG)emissions and about 60%of all anthropogenic methane(CH4)emissions[1,2].Solid waste disposal sites(including landfills and dumpsites),which are prevalent in global cities,emit CH4 generated from the anaerobic biodegradation of municipal solid waste(MSW).Notably,the proportions of CH4 emissions from disposal sites surpass 50%of the total CH4 emissions in some megalopolises[3].CH4 has a high global warming potential(GWP),being 28 times stronger than carbon dioxide(CO_(2))over a 100-year period and 80 times stronger over a 20-year period[4].Understanding and mitigating CH4 emissions from solid waste disposal sites is particularly pertinent and pressing,considering that the latest Synthesis Report from the Intergovernmental Panel on Climate Change(IPCC)emphasizes that the current pace of mitigation and adaptation policies and measures falls short of restraining global temperature rise to under 1.5℃ within the 21st century[4].More than 150 countries signed the Global Methane Pledge at the United Nations Climate Change Conference in Glasgow(COP26),which aims to reduce global annual CH4 emissions by 30%by 2030,compared with emissions in 2020[5].
文摘In the last decade,Pakistan has experienced multidemics of HIV in key populations,namely:injecting drug users,male sex with male,female sex workers,transgender sex workers,and transgenders.According to recent reports,in Pakistan,210000 people with HIV accounts for less than 0.2%of the general population.
基金supported by the Foundational Research Funds for the Central University(No.30918012204).
文摘Attribute-based encryption is cryptographic techniques that provide flexible data access control to encrypted data content in cloud storage.Each trusted authority needs proper management and distribution of secret keys to the user’s to only authorized user’s attributes.However existing schemes cannot be applied multiple authority that supports only a single keywords search compare to multi keywords search high computational burden or inefficient attribute’s revocation.In this paper,a ciphertext policy attribute-based encryption(CP-ABE)scheme has been proposed which focuses on multi-keyword search and attribute revocation by new policy updating feathers under multiple authorities and central authority.The data owner encrypts the keywords index under the initial access policy.Moreover,this paper addresses further issues such as data access,search policy,and confidentiality against unauthorized users.Finally,we provide the correctness analysis,performance analysis and security proof for chosen keywords attack and search trapdoor in general group model using DBDH and DLIN assumption.
文摘Heat storage properties of phase change materials(PCMs) are essential characteristics that perform a key role in thermal heat energy storage systems.The thermal properties of PCMs can be improved by developing metal foam/PCM composites.The addition of metal foam in PCMs has a significant effect on the thermal characteristics of PCMs.In this paper,the heat storage properties of two different metal foam/PCM composites were experimentally examined.The behavior of paraffin in metal foam(copper and iron-nickel)/paraffin composites concerning pure paraffin at a constant heat flux of 1000 W/m^(2) in three directions simultaneously(x,y,and z) was studied.Paraffin was infiltrated into copper and iron-nickel foams to develop composite materials which resulted in enhancing the thermal conductivity of the paraffin.A comparative analysis is made on the heat storage properties of paraffin in copper and iron-nickel foams/paraffin composites.Inner temperature distribution during the phase transition process is experimentally evaluated.This comparison indicates that temperature uniformity in copper foam/paraffin composite is better than in iron-nickel foam/paraffin composite and pure paraffin at the same heat flux.Experimental results show that at heat flux of 1000 W/m^(2),the heat storage time for copper foam/paraffin composite is 20.63% of that of iron-nickel foam/paraffin composite.
文摘Effective waste management is a major challenge for Small Island Developing States (SIDS) like Maldives due to limited land availability. Maldives exemplifies these issues as one of the most geographically dispersed countries, with a population unevenly distributed across numerous islands varying greatly in size and population density. This study provides an in-depth analysis of the unique waste management practices across different regions of Maldives in relation to its natural and socioeconomic context. Data shows Maldives has one of the highest population density and per capita waste generation among SIDS, despite its small land area and medium GDP per capita. Large disparities exist between the densely populated capital Male’ with only 5.8 km2 area generating 63% of waste and the ~194 scattered outer islands with ad hoc waste management practices. Given Male’s dense population and high calorific waste, incineration could generate up to ~30 GW/a energy and even increase Maldives’ renewable energy supply by 200%. In contrast, decentralized anaerobic digestion presents an optimal solution for outer islands to reduce waste volume while providing over 40%–100% energy supply for daily cooking in local families. This timely study delivers valuable insights into designing context-specific waste-to-energy systems and integrated waste policies tailored to Maldives’ distinct regions. The framework presented can also guide other SIDS facing similar challenges as Maldives in establishing sustainable, ecologically sound waste management strategies.
基金supported by the National Key Research&Development Program of China(2021YFA1201000,2021YFC2302400,2023YFC2606004)the Guangxi Science and Technology Development Program(AB20117001)+5 种基金the National Natural Science Foundation of China(82204263,32171394,32001008)the Fundamental Research Funds for the Central Universities(3332022055,2022CX01013)the China Postdoctoral Science Foundation(2022M720438)the Beijing Nova Program(Interdisciplinary Cooperation Project)from Beijing Municipal Science&Technology Commission(20220484207)We knowledge the Beijing Institute of Technology Research Fund Program for Young Scholars(XSQD-6120220072)We thank the Biological and Medical Engineering Core Facilities,and Analysis&Testing Center,Beijing Institute of Technology for supporting experimental equipment,and staffs for valuable help with technical support.
文摘Emerging and recurrent infectious diseases caused by human coronaviruses(HCoVs)continue to pose a significant threat to global public health security.In light of this ongoing threat,the development of a broad-spectrum drug to combat HCoVs is an urgently priority.Herein,we report a series of anti-pan-coronavirus ssDNA aptamers screened using Systematic Evolution of Ligands by Exponential Enrichment(SELEX).These aptamers have nanomolar affinity with the nucleocapsid protein(NP)of Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and also show excellent binding efficiency to the N proteins of both SARS,MERS,HCoV-OC43 and-NL63 with affinity KD values of 1.31 to 135.36 nM.Such aptamer-based therapeutics exhibited potent antiviral activity against both the authentic SARS-CoV-2 prototype strain and the Omicron variant(BA.5)with EC50 values at 2.00 nM and 41.08 nM,respectively.The protein docking analysis also evidenced that these aptamers exhibit strong affinities for N proteins of pan-coronavirus and other HCoVs(−229E and-HKU1).In conclusion,we have identified six aptamers with a high pan-coronavirus antiviral activity,which could potentially serve as an effective strategy for preventing infections by unknown coronaviruses and addressing the ongoing global health threat.
基金This work was supported by the Natural Science Foundation of Guangdong Province(No.2019A1515010776)the Beijing-Tianjin-Hebei Basic Research Cooperation Project(No.19JCZDJC64100)+2 种基金the National Key Research and Development Program of China(Nos.2021YFE0106900,2021YFA1201002,and 2021YFC2302402)the National Natural Science Foundation of China(Nos.31871003 and 3217100573)the Beijing Nova Program from Beijing Municipal Science&Technology Commission(No.Z201100006820005).
文摘The novel coronavirus disease 2019(COVID-19)is still rampant all over the world,causing incalculable losses to the world.Major pharmaceutical organizations around the globe are focusing on vaccine research and drug development to prevent further damage caused by the pandemic.The messenger RNA(mRNA)technology has got ample of attention after the success of the two very effective mRNA vaccines during the recent pandemic of COVID-19.mRNA vaccine has been promoted to the core stage of pharmaceutical industry,and the rapid development of mRNA technology has exceeded expectations.Beyond COVID-19,the mRNA vaccine has been tested for various infectious diseases and undergoing clinical trials.Due to the ability of constant mutation,the viral infections demand abrupt responses and immediate production,and therefore mRNA-based technology offers best answers to sudden outbreaks.The need for mRNA-based vaccine became more obvious due to the recent emergence of new Omicron variant.In this review,we summarized the unique properties of mRNA-based vaccines for infectious diseases,delivery technologies,discussed current challenges,and highlighted the prospects of this promising technology in the future.We also discussed various clinical studies as well preclinical studies conducted on mRNA therapeutics for diverse infectious diseases.
基金supported by the Beijing Natural Science Foundation(No.7214302)the Natural Science Foundation of Guangdong Province(No.2019A1515010776)+3 种基金the National Natural Science Foundation of China(Nos.31901053,32001008,32171394)the Beijing-Tianjin-Hebei Basic Research Cooperation Project(No.19JCZDJC64100)the Beijing Nova Program from Beijing Municipal Science&Technology Commission(No.Z201100006820005)the National Key Research&Development Program of China(Nos.2021YFE0106900,2021YFA1201000,2021YFC2302400).
文摘With the development of a small interfering RNA(siRNA)delivery strategy,increasing siRNA therapeutics for tumor treatment appeared in clinical trials and pre-clinical development.However,the test results of such therapeutics unveiled that efficient siRNA delivery to tumor tissues is still challenging.Albumin is considered an ideal carrier for delivering hydrophobic agents into tumor tissue because it is highly concentrated and long-circulating in blood and has propensity of tumor enrichment.Herein,we synthesized lipid conjugated siRNAs(LsiRNAs),which showed high affinity to albumin.Mechanistically,LsiRNAs non-covalently bind to the hydrophobic core of albumin through its octadecyl tails.The small size of albumin/LsiRNAs allows the complex to penetrate tumor tissue efficiently.Biodistribution test proved that albumin extremely prolonged circulation time and increased tumor retention of associated LsiRNAs.Notably,LsiRNA against programmed death ligand-1(Pdl1)efficiently suppressed tumor growth as well as prolonged survival time of tumor bearing mice by increasing infiltration of CD8^(+)T cells as well as promoted the maturation of dendritic cells both in tumor and lymph.Together,LsiRNAs provide a simple but effective way for siRNA tumor delivery that“hitchhikes”on albumin.
基金This work was supported by the Hu-Xiang Young Talent Program(2018RS3094)the Hunan Provincial Natural Science Foundation of China(2019JJ50196,2018JJ1019)+6 种基金the Natural Science Foundation of Guangdong Province(2019A1515010776)the National Natural Science Foundation of China(31901053,32001008,31871003)the Beijing Nova Program from Beijing Municipal Science&Technology Commission(Z201100006820005)the Beijing-Tianjin-Hebei Basic Research Cooperation Project(19JCZDJC64100)the National Key R&D Program of China(2019YFE0133300)the Young Elite Scientist Sponsorship Program of Beijing Association for Science and Technology(2020-2022),and the Postdoctoral Science Foundation of China(2020M670169)We thank Biological&Medical Engineering Core Facilities(Beijing Institute of Technology)for providing advanced equipment.
文摘CRISPR/Cas9-based gene editing has emerged as a powerful biotechnological tool,that relies on Cas9 protein and single guided RNA(sgRNA)to edit target DNA.However,the lack of safe and efficient delivery carrier is one of the crucial factors restricting its clinical transformation.Here,we report an ionizable lipid nanoparticle(iLP181,pKa=6.43)based on iLY1809 lipid enabling robust gene editing in vitro and in vivo.The iLP181 effectively encapsulate psgPLK1,the best-performing plasmid expressing for both Cas9 protein and sgRNA targeting Polo-like kinase 1(PLK1).The iLP181/psgPLK1 nanoformulation showed uniformity in size,regular nanostructure and nearly neutral zeta potential at pH 7.4.The nanoformulation effectively triggered editing of PLK1 gene with more than 30%efficiency in HepG2-Luc cells.iLP181/psgPLK1 significantly accumulated in the tumor for more than 5 days after a single intravenous injection.In addition,it also achieved excellent tumor growth suppression compared to other nucleic acid modalities such as siRNA,without inducing adverse effects to the main organs including the liver and kidneys.This study not only provides a clinically-applicable lipid nanocarrier for delivering CRISPR/Cas system(even other bioactive molecules),but also constitutes a potential cancer treatment regimen base on DNA editing of oncogenes.
文摘Feeding experiments using three strains ofentomopathogenic fungi, Beauveria bassiana, Metarhizium anisopliae and Isaria fumosorosea were conducted with newly moulted 3rd-5th instar Ocinara varians Walker larvae in the laboratory. The mortality of larvae immersed individually in spore suspension (1 × 10^7 spores/mL) of all the strains was 〉 80% except 5th instar larvae treated with M. anisopliae which transformed into pupae, but did not result in adult emergence. The growth (total body mass), consumption, relative consumption rate and relative growth rate, were reduced at all three larval stages, while developmental time was extended in infected larvae with concurrent significant increase in approximate digestibility in infected larvae. Conversion of digested food (ECD) and ingested food (ECI) values declined in infected larvae as compared to the healthy larvae (control). The 5th instar larvae treated with M. anisopliae showed higher ECD and ECI values than control. Based on mortality and growth inhibition it can be suggested that all the studied fungal strains have a high potential for biocontrol and could be developed into biocontrol agents against O. varians.
基金supported by the Beijing Nova Program from Beijing Municipal Science&Technology Commission(No.Z201100006820005)the Beijing-Tianjin-Hebei Basic Research Cooperation Project(No.19JCZDJC64100)+2 种基金the National Key Research&Development Program of China(Nos.2018YFE0117800,2021YFA1201000,and 2021YFE0106900)the National Natural Science Foundation of China(Nos.32030060 and 31871003)the Natural Science Foundation of China international collaboration key project(No.51861135103).
文摘Attaching DNA/RNA to nanomaterials is the basis for nucleic acid-based assembly and drug delivery.Herein,we report that small interfering RNA(siRNA)effectively coordinates with ligand-free lanthanide nanoparticles(NaGdF4 NPs),and forms siRNA/NaGdF4 spherical nucleic acids(SNA).The coordination is primarily attributed to the interaction between Gd and phosphate backbone of the siRNA.Surprisingly,an efficient encapsulation and rapid endosomal escape of siRNA from the endosome/lysosome were achieved,due to its flexible ability to bound to phospholipid head of endosomal membrane,thereby disrupting the membrane structure.Resorting to the dual properties of NaGdF4 NPs,siRNA loading,and endosomal escape,siRNA targeting programmed cell death-ligand 1(siPD-L1)/NaGdF4 SNA triggers significant gene silencing in vitro and in vivo,and effectively represses the tumor growth in both CT26 tumor model and 4T1 orthotopic murine model.
基金This work was supported by the National Nature Science Foundation of China(Nos.81820108019,91939303 and 31971302)the National Key Research and Development Program of China(2018YFC0116305)the Science Foundation of PLA General Hospital(2018XXFC-9,CX19028,China).
文摘Vulnerable atherosclerotic plaque(VASPs)is the major pathological cause of acute cardiovascular event.Early detection and precise intervention of VASP hold great clinical significance,yet remain a major challenge.Photodynamic therapy(PDT)realizes potent ablation efficacy under precise manipulation of laser irradiation.In this study,we constructed theranostic nanoprobes(NPs),which could precisely regress VASPs through a cascade of synergistic events triggered by local irradiation of lasers under the guidance of fluorescence/MR imaging.The NPs were formulated from human serum albumin(HSA)conjugated with a high affinity-peptide targeting osteopontin(OPN)and encapsulated with photosensitizer IR780 and hypoxia-activatable tirapazamine(TPZ).After intravenous injection into atherosclerotic mice,the OPN-targeted NPs demonstrated high specific accumulation in VASPs due to the overexpression of OPN in activated foamy macrophages in the carotid artery.Under the visible guidance of fluorescence and MR dual-model imaging,the precise near-infrared(NIR)laser irradiation generated massive reactive oxygen species(ROS),which resulted in efficient plaque ablation and amplified hypoxia within VASPs.In response to the elevated hypoxia,the initially inactive TPZ was successively boosted to present potent biological suppression of foamy macrophages.After therapeutic administration of the NPs for 2 weeks,the plaque area and the degree of carotid artery stenosis were markedly reduced.Furthermore,the formulated NPs displayed excellent biocompatibility.In conclusion,the developed HSA-based NPs demonstrated appreciable specific identification ability of VASPs and realized precise synergistic regression of atherosclerosis.