Prodrugs need to be converted to active drugs to exert their pharmacological activities.Identifying the direct targets of active drugs is essential to elucidate the pharmacological mechanisms of prodrugs,but remains c...Prodrugs need to be converted to active drugs to exert their pharmacological activities.Identifying the direct targets of active drugs is essential to elucidate the pharmacological mechanisms of prodrugs,but remains challenging,especially for active drugs with low stability.展开更多
This article provides a comprehensive review of various approaches to targeted drug delivery for liver cancer, an area of significant need due to the limited effectiveness of current treatments. The article begins by ...This article provides a comprehensive review of various approaches to targeted drug delivery for liver cancer, an area of significant need due to the limited effectiveness of current treatments. The article begins by highlighting the role of the liver in metabolism and discusses the high mortality associated with hepatocellular carcinoma (HCC). The shortcomings of traditional chemotherapy, such as multidrug resistance and off-target effects, necessitate the exploration of novel therapeutic strategies, with a focus on targeted approaches. The review details both passive and active targeting strategies. Passive targeting leverages the enhanced permeability and retention (EPR) effect and unique features of the tumor microenvironment, while active targeting employs specific ligands, such as peptides, antibodies, and proteins, to bind to overexpressed receptors on liver and tumor cells. The article further details many examples of active targeting using the asialoglycoprotein receptor (ASGPR), glycyrrhetinic acid (GA), transferrin receptor (TfR), and folate receptor (FR) on hepatocytes and tumor cells, demonstrating that there has been significant research effort put into this field. The importance of non-parenchymal cells in the liver is also discussed, and the article examines methods of targeting Kupffer cells, sinusoidal endothelial cells, and hepatic stellate cells for therapeutic benefit. The review goes on to cover the emerging field of subcellular targeting, including specific strategies to target the nucleus, mitochondria, and the endoplasmic reticulum/Golgi apparatus, noting that although there has been some progress, further research is needed in this area. The text finishes with a summary which acknowledges that while targeted therapies, including enzyme-activated prodrugs, such as Pradefovir, and other novel methods for drug delivery have shown significant promise, challenges remain in translating these therapies into clinical use due to limitations in understanding the sequential transport and the mechanisms of action. Ultimately, the article emphasizes the need for in-depth research to fully realize the potential of precision cancer therapies for liver cancer.展开更多
Objective:To improve the efficiency of drug delivery,a mannose vinyl stearate mannose ligand(Man ligand)with active liver-targeting properties was synthesized.Methods:Non-aqueous enzymatic synthesis was used to modify...Objective:To improve the efficiency of drug delivery,a mannose vinyl stearate mannose ligand(Man ligand)with active liver-targeting properties was synthesized.Methods:Non-aqueous enzymatic synthesis was used to modify the structure of mannose.Glycyrrhetinic acid-tanshinone lipid nanoparticles(GT-LN)and liver-targeted glycyrrhetinic acid-tanshinone mannose-modified lipid nanoparticles(GT-MLN)were prepared.The physicochemical properties and release profiles of both formulations were evaluated,and their pharmacokinetic behavior and tissue distribution were investigated.Results:The average particle sizes of GT-LN and GT-MLN were 190.20±1.35 and 204.83±3.86 nm,respectively,with corresponding surface Zeta potentials of-28.0±1.68 and-30.24±2.10 mV.The drug release profile of GT-LN conformed to the Higuchi equation,whereas that of GT-MLN followed both the first-order kinetic and RitgerePeppas equations.Both formulations significantly enhanced the gastrointestinal stability of the drug.In vivo studies in mice demonstrated that hepatic GA and TSN concentrations in both groups were significantly higher than those in the original drug suspension group(P=.01).Notably,the concentrations in the GT-MLN group were significantly higher compared to the GTLN group(P=.01).Conclusion:Man ligand was formed via the linkage of vinyl stearate with the hydroxyl group at C-6 in mannose.The Manligand endowed these lipid nanoparticles with obvious active liver-targeting properties.Our results provide an efficient and stable route of drug delivery to the liver with improved drug availability.展开更多
Waxy maize is a specialty maize that produces mainly amylopectin starch with special food or industrial values. The objective of this study was to overcome the limitations of wx mutant allele acquisition and breeding ...Waxy maize is a specialty maize that produces mainly amylopectin starch with special food or industrial values. The objective of this study was to overcome the limitations of wx mutant allele acquisition and breeding efficiency by conversion of parental lines from normal to waxy maize. The intended mutation activity was achieved by in vivo CRISPR/Cas9 machinery involving desired-target mutation of the Wx locus in the ZC01 background,abbreviated as ZC01-DTM^(wx). Triple selection was applied to segregants to obtain high genome background recovery with transgene-free wx mutations. The targeted mutation was identified, yielding six types of mutations among progeny crossed with ZC01-DTM^(wx).The amylopectin contents of the endosperm starch in mutant lines and hybrids averaged94.9%, while those of the wild-type controls were significantly(P < 0.01) lower, with an average of 76.9%. Double selection in transgene-free lines was applied using the Bar strip test and Cas9 PCR screening. The genome background recovery ratios of the lines were determined using genome-wide SNP data. That of lines used as male parents was as high as98.19% and that of lines used as female parents was as high as 86.78%. Conversion hybrids and both parental lines showed agronomic performance similar to that of their wild-type counterparts. This study provides a practical example of the efficient extension of CRISPR/Cas9 targeted mutation to industrial hybrids for transformation of a recalcitrant species.展开更多
The presence of hydroxyl groups at the C4 and C7 positions in coumarin backbone has been proposed as a potential modification site for providing excellent bioactivity according to previous studies. A series of novel c...The presence of hydroxyl groups at the C4 and C7 positions in coumarin backbone has been proposed as a potential modification site for providing excellent bioactivity according to previous studies. A series of novel coumarin derivatives were rationally designed and synthesized by use of a complex catalytic system for a targeted modification at the above sites. These derivatives were assayed for nematicidal activity. As predicted, the derivatization enhanced the activity of the coumarins against five nematodes.Compounds 7b, 9a, 10 c and 11 c showed significant strong nematicidal broad spectrum activity against all tested nematodes. Compound 10 c was the most effective with the lowest LC50 values against Meloidogyne incognita（5.1 mmol/L）, Ditylenchus destructor（3.7 mmol/L）, Bursaphelenchus mucronatus（6.4 mmol/L）, Bursaphelenchus B. xylophilus（2.5 mmol/L） and Aphelenchoides besseyi（3.1 mmol/L）,respectively. A brief investigation on the structure–activity relationships（SAR） revealed that the targeted modification by a C7 hydroxyl was optimum compared with that of a C4 hydroxyl and that the coupling chain length was crucial for the nematicidal activity.展开更多
The increased incidence ofNHL(non-Hodgkin's lymphoma),along with its high mortality rate and pronounced resistance to therapy pose an enormous challenge.Both traditional therapeutic strategies and recently develop...The increased incidence ofNHL(non-Hodgkin's lymphoma),along with its high mortality rate and pronounced resistance to therapy pose an enormous challenge.Both traditional therapeutic strategies and recently developed therapeutic strategies against NHL such as chemoimmunotherapy and targeted therapy have drawbacks.Therefore,novel therapeutic approaches for NHL are urgently needed.Maytansine-loaded PLA-TPGS(polyethylene glycol 1000 succinate-polylactide)nanoparticles were synthesized.And then,rituximab targeting NHL was conjugated together by using EDC(1-ethyl-3-(3-dimethylaminopropyl)carbodiimide)as a coupling agent.The in vitro/vivo antitumor activity was evaluated by Raji cell proliferation inhibition and nude mice xenograft tumor models for NHL.Both the rituximab-conjugated and maytansine-loaded PLA-TPGS nanoparticles(maytansine-NPs(Nanoparticles)-rituximab)and maytansine-loaded PLA-TPGS nanoparticles(maytansine-NPs)presented significant inhibition effect on Raji cell proliferation in a concentration-dependent manner.Compared with conventional maytansine and maytansine-NPs,maytansine-NPs-rituximab showed significantly enhanced cytotoxicity and increased cell apoptosis in Raji cells.The maytansine-NPs-rituximab described in this paper might be a potential formulation for targeting chemotherapy and immunotherapy to CD20+B cell malignancies.展开更多
Active target time projection chambers are state-of-the-art tools in the field of low-energy nuclear physics and are particularly suitable for experiments using low-intensity radioactive ion beams or gamma rays.The Fu...Active target time projection chambers are state-of-the-art tools in the field of low-energy nuclear physics and are particularly suitable for experiments using low-intensity radioactive ion beams or gamma rays.The Fudan multi-purpose active target time projection chamber(fMeta-TPC)with 2048 channels was developed to studyα-clustering nuclei.This study focused on the photonuclear reaction with a laser Compton scattering gamma source,particularly for the decay of the highly excitedαcluster state.The design of fMeta-TPC is described in this paper.A comprehensive evaluation of its offline performance was conducted using an ultraviolet laser and ^(241)Amαsource.The results showed that the intrinsic angular resolution of the detector was within 0.30°,and the detector had an energy resolution of 6.85%for 3.0 MeVαparticles.The gain uniformity of the detector was approximately 10%(RMS/Mean),as tested by the ^(55)Fe X-ray source.展开更多
A charged particle array named MATE-PA,which serves as an auxiliary detector system for a Multi-purpose Active-target Time projection chamber used in nuclear astrophysical and exotic beam Experiments(MATE),was constru...A charged particle array named MATE-PA,which serves as an auxiliary detector system for a Multi-purpose Active-target Time projection chamber used in nuclear astrophysical and exotic beam Experiments(MATE),was constructed.The array comprised of 20 single-sided strip-silicon detectors covering approximately 10%of the solid angle.The detectors facilitated the detection of reaction-induced charged particles that penetrate the active volume of the MATE.The performance of MATE-PA has been experimentally studied using an alpha source and a 36-MeV 14 N beam injected into the MATE chamber on the radioactive ion beam line in Lanzhou(RIBLL).The chamber was filled with a gas mixture of 95%4 He and 5%CO_(2) at a pressure of 500 mbar.The results indicated good separation of light-charged particles using the forward double-layer silicon detectors of MATE-PA.The energy resolution of the Si detectors was deduced to be approximately 1%(σ)for an energy loss of approximately 10 MeV caused by theαparticles.The inclusion of MATE-PA improves particle identification and increases the dynamic range of the kinetic energy of charged particles,particularly that of theαparticles,up to approximately 15 MeV.展开更多
Proton exchange membrane fuel cells(PEMFC)have attracted much attention because of their high energy conversion efficiency,high power density and zero emission of pollutants.However,the high cost of the cathode platin...Proton exchange membrane fuel cells(PEMFC)have attracted much attention because of their high energy conversion efficiency,high power density and zero emission of pollutants.However,the high cost of the cathode platinum group metal(PGM)catalysts creates a barrier for the large-scale application of PEMFC.Tremendous efforts have been devoted to the development of low-cost PGM-free catalysts,especially the Fe-N-C catalysts,to replace the expensive PGM catalysts.However,the characterization methods and evaluation standards of the catalysts varies,which is not conducive to the comparison of PGM-free catalysts.U.S.Department of energy(DOE)is the only authority that specifies the testing standards and activity targets for PGM-free catalysts.In this review,the major breakthroughs of Fe-N-C catalysts are outlined with the reference of DOE standards and targets.The preparation and characteristics of these highly active Fe-N-C catalysts are briefly introduced.Moreover,the efforts on improving the mass transfer and the durability issue of Fe-N-C fuel cell are discussed.Finally,the prospective directions concerning the comprehensive evaluation of the Fe-N-C catalysts are proposed.展开更多
Objective:To compare the targeting effects of lactosarninated alginate(AlgNP)、polyethylene glycol - coated hydroxyapatite- poly- L- lysine nanoparticles (PLL- PCHNP)and relative nonlactosaminated ones load ed with ex...Objective:To compare the targeting effects of lactosarninated alginate(AlgNP)、polyethylene glycol - coated hydroxyapatite- poly- L- lysine nanoparticles (PLL- PCHNP)and relative nonlactosaminated ones load ed with exogenous gene on liver via peripheral intravenous route. Methods:Preparation of AlgNP based on control of gelification phenomenon of algiante by calcium ions and HA- PLLNP with collosol - gel method, both further modified with lactosaminated - poly- L - lysine synthesized by reductive lactosamination . We used pEGFPCl as the reporter gene to establish receptor- mediated and positive liver targeting nanoparticles- gene model. The potential of adsorbing DNA on nanoparticles was analysed by electrophoresis and spectrophotometer. Then different complexes were transferred into the rat's body by peripheral intravenous route and their targeting characteristics in liver were investigated by using radioisotope tracing assay. Results: PCHNP presented as needle - like particles with a diameter of 20nm by TEM and could be effectively combined with PLL. The diameter of AlgNP was 280nm. Agarpse gel electrophoresis showed both nanoparticles could effectively combine with DNA and the optimal proportion of PLLPCHNP and DNA was 30:1 (w/w); DNA mixed ratio of AlgPLL was 68.3 % by spectrophotometer. The radioactivities in liver for the two lactosaminated nanoparticles were higher than the nonlactosaminated ones. No statistic difference between AlgNP and AlgLacNP could be found . Conclusions: Lactosaminated naroparticles can target to liver more effectively by peripheral intravenous route than nonlactosaminated ones, which is closely concerned with the characteritics of the nanopartide complex.展开更多
Objective:In this study,we aimed to develop an amino-terminal fragment(ATF)peptide-targeted liposome carryingβ-elemene(ATF24-PEG-Lipo-β-E)for targeted delivery into urokinase plasminogen activator receptor-overexpre...Objective:In this study,we aimed to develop an amino-terminal fragment(ATF)peptide-targeted liposome carryingβ-elemene(ATF24-PEG-Lipo-β-E)for targeted delivery into urokinase plasminogen activator receptor-overexpressing bladder cancer cells combined with cisplatin(DDP)for bladder cancer treatment.Methods:The liposomes were prepared by ethanol injection and high-pressure microjet homogenization.The liposomes were characterized,and the drug content,entrapment efficiency,andin vitro release were studied.The targeting efficiency was investigated using confocal microscopy,ultra-fast liquid chromatography,and an orthotopic bladder cancer model.The effects of ATF24-PEG-Lipo-β-E combined with DDP on cell viability and proliferation were evaluated by a Cell Counting Kit-8(CCK-8)assay,a colony formation assay,and cell apoptosis and cell cycle analyses.The anticancer effects were evaluated in a KU-19-19 bladder cancer xenograft model.Results:ATF24-PEG-Lipo-β-E had small and uniform sizes(~79 nm),high drug loading capacity(~5.24 mg/mL),high entrapment efficiency(98.37±0.95%),and exhibited sustained drug release behavior.ATF24-PEG-Lipo-β-E had better targeting efficiency and higher cytotoxicity than polyethylene glycol(PEG)ylatedβ-elemene liposomes(PEG-Lipo-β-E).DDP,combined with ATF24-PEG-Lipo-β-E,exerted a synergistic effect on cellular apoptosis and cell arrest at the G2/M phase,and these effects were dependent on the caspase-dependent pathway and Cdc25C/Cdc2/cyclin B1 pathways.Furthermore,thein vivo antitumor activity showed that the targeted liposomes effectively inhibited the growth of tumors,using the combined strategy.Conclusions:The present study provided an effective strategy for the targeted delivery ofβ-elemene(β-E)to bladder cancer,and a combined strategy for bladder cancer treatment.展开更多
Targeted delivery of therapeutics for spinal cord injury(SCI)has been a long-term challenge due to the complexity of the pathological procession.Macrophage,as an immune cell,can selectively accumulate at the trauma si...Targeted delivery of therapeutics for spinal cord injury(SCI)has been a long-term challenge due to the complexity of the pathological procession.Macrophage,as an immune cell,can selectively accumulate at the trauma site after SCI.This intrinsic targeting,coupled with good immune-escaping capacity makes macrophages an ideal source of biomimetic delivery carrier for SCI.Worth mentioning,macrophages have multiple polarization states,which may not be ignored when designing macrophage-based delivery systems.Herein,we fabricated macrophage membrane-camouflaged liposomes(RM-LIPs)and evaluated their abilities to extend drug circulation time and target the injured spinal cord.Specially,we detected the expression levels of the two main targeted receptors Mac-1 and integrinα4 in three macrophage subtypes,including unactivated(M0)macrophages,classically activated(M1)macrophages and alternatively activated(M2)macrophages,and compared targeting of these macrophage membrane-coated nanoparticles for SCI.The macrophage membrane camouflage decreased cellular uptake of liposomes in RAW264.7 immune cells and strengthened binding of the nanoparticle to the damaged endothelial cells in vitro.RM-LIPs can prolong drug circulation time and actively accumulate at the trauma site of the spinal cord in vivo.Besides,RM-LIPs loaded with minocycline(RM-LIP/MC)showed a comprehensive therapeutic effect on SCI mice,and the anti-pyroptosis was found to be a novel mechanism of RM-LIP/MC treatment of SCI.Moreover,the levels of Mac-1 and integrinα4 in macrophages and the targeting of RM-LIP for SCI were found to be independent of macrophage polarization states.Our study provided a biomimetic strategy via the biological properties of macrophages for SCI targeting and treatment.展开更多
The properties of modified biomaterial are gaining more and more importance in drug delivery systems.Sialic acid(SA)and polysialic acid(PSA)serve as endogenous substances,which are non-immunogenic and biodegradable.At...The properties of modified biomaterial are gaining more and more importance in drug delivery systems.Sialic acid(SA)and polysialic acid(PSA)serve as endogenous substances,which are non-immunogenic and biodegradable.At the same time,SA modification of the drugs/carriers can enhance the uptake of tumor cell and retention in brain;PSA modifi-cation can reduce the immunogenicity of the proteins or polypeptides and increase circulation time of the modified drugs/carriers in the blood,thus achieving active targeting effect.These properties offer a variety of opportunities for applications in drug delivery systems.This article summarizes the biological functions of SA and PSA and presents the technologies of SA/PSA modified small molecule drugs,proteins and carriers in drug delivery systems.展开更多
Extensive research has been performed on cell membrane camouflaged-based drug delivery systems in recent years.Herein,we provide an overview of the challenges in system preparation,functional design,continuous industr...Extensive research has been performed on cell membrane camouflaged-based drug delivery systems in recent years.Herein,we provide an overview of the challenges in system preparation,functional design,continuous industrial production of these systems,and solution strategies for these challenges.Further,we analyze and discuss the frontier medical applications of cell membrane-camouflaged drug delivery systems in anti-inflammatory,anti-pathogenic microorganisms,and biological detoxification.This review takes a challenge-oriented perspective and seeks innovative strategies,provides a literature review of research into cell membrane-camouflaged drug delivery systems,and promotes the development of personalized clinical treatments.展开更多
It was reported that a 5-amino acid peptide Ala-Pro-Arg-Pro-Gly （APRPG） could specifically bind to the tumor angiogenic site. We investigated the antitumor efficacy of doxorubicin （DOX） encapsulated in APRPG modif...It was reported that a 5-amino acid peptide Ala-Pro-Arg-Pro-Gly （APRPG） could specifically bind to the tumor angiogenic site. We investigated the antitumor efficacy of doxorubicin （DOX） encapsulated in APRPG modified liposome （APRPG-LP） compared with DOX encapsulated in non-APRPG modified liposomes （LP） and DOX solution （flee DOX） on Lewis lung carcinoma （LLC） bearing mice. APRPG-LP could efficiently suppress the tumor growth of the experimental mice, compared with LP （P〈0.001）, free DOX （P〈0.001） and saline of negative control （P〈0.001）. The present results demonstrated that the APRPG modified liposomes exhibited a much better therapeutic efficacy over the non-modified liposomes and the DOX solution, because of the effect of targeted tumor angiogenesis disruption. Thus, APRPG-LP could be a promising active-targeting drug carrier to tumor angiogenic site.展开更多
Carrier-free nanodrug with exceptionally high drug payload has attracted increasing attentions.Herein,we construct a pH/ROS cascade-responsive nanodrug which could achieve tumor acidity-triggered targeting activation ...Carrier-free nanodrug with exceptionally high drug payload has attracted increasing attentions.Herein,we construct a pH/ROS cascade-responsive nanodrug which could achieve tumor acidity-triggered targeting activation followed by circularly amplified ROS-triggered drug release via positive-feedback loop.The di-selenide-bridged prodrug synthesized from vitamin E succinate and methotrexate(MTX)self-assembles into nanoparticles(VSeM);decorating acidity-cleavable PEG onto VSeM surface temporarily shields the targeting ability of MTX to evade immune clearance and consequently elongate circulation time.Upon reaching tumor sites,acidity-triggered detachment of PEG results in targeting recovery to enhance tumor cell uptake.Afterward,the VSeM could be dissociated in response to intracellular ROS to trigger VES/MTX release;then the released VES could produce extra ROS to accelerate the collapse of VSeM.Finally,the excessive ROS produced from VES could synergize with the released MTX to efficiently suppress tumor growth via orchestrated oxidation-chemotherapy.Our study provides a novel strategy to engineer cascade-responsive nanodrug for synergistic cancer treatment.展开更多
Hyperbranched polysulfonamine （HPSA） is a promising biomaterial due to its highly branched spherical architecture and efficient intracellular translocation. To realize the fianctionalization of HPSA, both N-succinim...Hyperbranched polysulfonamine （HPSA） is a promising biomaterial due to its highly branched spherical architecture and efficient intracellular translocation. To realize the fianctionalization of HPSA, both N-succinimidyl 3-（2- pyridyldithio） propionate （SPDP） for tethering the human-mouse chimeric monoclonal antibody CH12 and N-hydroxy succinimidyl S-acetylmercaptoacetyltriglycinate （NHS-MAG3） for labeling 188Re were sequentially grafted onto the primary amine terminals of HPSA via covalent linkages, attaining the SPDP-HPSA-MAG3 intermediate. In order to reserve the structural integrity of CH12, the fragment crystallizable （Fc） region was also processed by oxidation of oligosaccharide moieties with sodium periodate and then reacted with N-（κ-maleimidoundecanoic acid） hydrazide （KMUH）. After chelating 188Re with MAG3 group, the SPDP was reduced to PDP and connected onto the maleinimide group at the Fc region. As a result, both the epidermal growth factor receptor viii （EGFRvIII） targeted monoclonal antibody CH12 and the radionuclide 188Re were conjugated to the HPSA-based vehicles, forming the 188Re-labeled and CH12-tethered HPSA （CH12-HPSA- 188Re）. The molecular weight and in vitro stability of CH12-HPSA-188Re were evaluated by gel electrophoresis and paper chromatography. On one hand, the CH12-HPSA-188Re could specifically bind to the EGFRvlII-positive human hepatocarcinoma cells in vitro. On the other hand, it could also target at the tumor tissue of nude mice in vivo. Hence, the CH12-HPSA-188Re could effectively target at the human hepatocarcinoma and facilitate the tumor detection and targeted radioimmunotherapy.展开更多
Inflammatory bowel disease(IBD)is a chronic and recurrent disease of the gastrointestinal tract,mainly including Crohn's disease(CD)and ulcerative colitis(UC).However,current approaches against IBD do not precisel...Inflammatory bowel disease(IBD)is a chronic and recurrent disease of the gastrointestinal tract,mainly including Crohn's disease(CD)and ulcerative colitis(UC).However,current approaches against IBD do not precisely deliver drugs to the inflammatory site,which leads to life-long medication and serious side effects that can adversely impact patients’adherence.It is necessary to construct optimal drug delivery systems(DDSs)that can target drugs to the region of inflammation,thereby improve therapeutic efficacy and reduce side effects.With the burgeoning development of nanotechnology-based nanomedicines(NMs)and prodrug strategy,remarkable progresses in the treatment of IBD have been made in recent years.Herein,the latest advances are outlined at the intersection of IBD treatment and nanotherapeutics as well as prodrug therapy.First,the pathophysiological microenvironment of inflammatory sites of IBD is introduced in order to rationally design potential NMs and prodrugs.Second,the necessity of NMs for the IBD therapy is elaborated,and the representative nanotherapeutics via passive targeted and active targeted NMs developed to treat the IBD are overviewed.Furthermore,the emerging prodrug-based therapeutics are summarized,including 5-aminosalicylic acid-,amino acid-,and carbohydrate-conjugated prodrugs.Finally,the design considerations and perspectives of these NMs and prodrugs-driven IBD therapeutics in the clinical translation are spotlighted.展开更多
Objective To predict the main active ingredients,potential targets and molecular mechanisms of Yuan Zhi powder in treatment of dementia by using network pharmacology.Methods A database of chemical constituents of Yuan...Objective To predict the main active ingredients,potential targets and molecular mechanisms of Yuan Zhi powder in treatment of dementia by using network pharmacology.Methods A database of chemical constituents of Yuan Zhi powder was constructed by using databases and literatures.Potential targets were predicted by reverse molecular docking,and then a component-target network was constructed.The target network of Alzheimer's disease(AD)was mapped and analyzed to obtain the“active ingredient-AD target”network.The key targets were screened through network analysis.Finally,the rationality of the prediction was analyzed by comparing with the target reported in the literatures.Results There were180chemical constituents acting on the AD target,and the targets included three key targets(cyclooxygenase-2,muscarinic acetylcholine receptor M1,and muscarinic acetylcholine receptor M2)and an important target(acetylcholine esterase).Alzheimer's disease may be treated by regulating the activity of acetylcholine receptors and the binding toβ-amyloid protein,and its biological process may be concentrated in the acetylcholine receptor signal pathway,negative regulation of synaptic transmission and so on.Conclusion The fact that Yuan Zhi powder can treat AD is consistent with the characteristics of multi-components-multitargets-multiple pathways of traditional Chinese medicine.The important targets obtained from network analysis have a large proportion in literature research,so network analysis have some rationality.展开更多
The microbial quality of urban recreational water is of great concern to public health.The monitoring of indicator organisms and several pathogens alone is not sufficient to accurately and comprehensively identify mic...The microbial quality of urban recreational water is of great concern to public health.The monitoring of indicator organisms and several pathogens alone is not sufficient to accurately and comprehensively identify microbial risks.To assess the levels of bacterial pathogens and health risks in urban recreational water,we analyzed pathogen diversity and quantified four pathogens in 46 water samples collected from waterbodies in Beijing Olympic Forest Park in one year.The pathogen diversity revealed by 16 S r RNA gene targeted next-generation sequencing（NGS） showed that 16 of 40 genera and 13 of 76 reference species were present.The most abundant species were Acinetobacter johnsonii,Mycobacterium avium and Aeromonas spp.Quantitative polymerase chain reaction（q PCR） of Escherichia coli（uid A）,Aeromonas（aer A）,M.avium（16S r RNA）,Pseudomonas aeruginosa（oaa） and Salmonella（inv A） showed that the aer A genes were the most abundant,occurring in all samples with concentrations of 10^（4–6） genome copies/100 m L,followed by oaa,inv A and M.avium.In total,34.8% of the samples harbored all genes,indicating the prevalence of these pathogens in this recreational waterbody.Based on the q PCR results,a quantitative microbial risk assessment（QMRA） showed that the annual infection risks of Salmonella,M.avium and P.aeruginosa in five activities were mostly greater than the U.S.EPA risk limit for recreational contacts,and children playing with water may be exposed to the greatest infection risk.Our findings provide a comprehensive understanding of bacterial pathogen diversity and pathogen abundance in urban recreational water by applying both NGS and q PCR.展开更多
基金support from the National Natural Science Foundation of China(Grant Nos.:U21A20407 and 81973467).
文摘Prodrugs need to be converted to active drugs to exert their pharmacological activities.Identifying the direct targets of active drugs is essential to elucidate the pharmacological mechanisms of prodrugs,but remains challenging,especially for active drugs with low stability.
文摘This article provides a comprehensive review of various approaches to targeted drug delivery for liver cancer, an area of significant need due to the limited effectiveness of current treatments. The article begins by highlighting the role of the liver in metabolism and discusses the high mortality associated with hepatocellular carcinoma (HCC). The shortcomings of traditional chemotherapy, such as multidrug resistance and off-target effects, necessitate the exploration of novel therapeutic strategies, with a focus on targeted approaches. The review details both passive and active targeting strategies. Passive targeting leverages the enhanced permeability and retention (EPR) effect and unique features of the tumor microenvironment, while active targeting employs specific ligands, such as peptides, antibodies, and proteins, to bind to overexpressed receptors on liver and tumor cells. The article further details many examples of active targeting using the asialoglycoprotein receptor (ASGPR), glycyrrhetinic acid (GA), transferrin receptor (TfR), and folate receptor (FR) on hepatocytes and tumor cells, demonstrating that there has been significant research effort put into this field. The importance of non-parenchymal cells in the liver is also discussed, and the article examines methods of targeting Kupffer cells, sinusoidal endothelial cells, and hepatic stellate cells for therapeutic benefit. The review goes on to cover the emerging field of subcellular targeting, including specific strategies to target the nucleus, mitochondria, and the endoplasmic reticulum/Golgi apparatus, noting that although there has been some progress, further research is needed in this area. The text finishes with a summary which acknowledges that while targeted therapies, including enzyme-activated prodrugs, such as Pradefovir, and other novel methods for drug delivery have shown significant promise, challenges remain in translating these therapies into clinical use due to limitations in understanding the sequential transport and the mechanisms of action. Ultimately, the article emphasizes the need for in-depth research to fully realize the potential of precision cancer therapies for liver cancer.
基金the High-level construction discipline of the National Administration of Traditional Chinese Medicine(zyyzdxk-2023272).
文摘Objective:To improve the efficiency of drug delivery,a mannose vinyl stearate mannose ligand(Man ligand)with active liver-targeting properties was synthesized.Methods:Non-aqueous enzymatic synthesis was used to modify the structure of mannose.Glycyrrhetinic acid-tanshinone lipid nanoparticles(GT-LN)and liver-targeted glycyrrhetinic acid-tanshinone mannose-modified lipid nanoparticles(GT-MLN)were prepared.The physicochemical properties and release profiles of both formulations were evaluated,and their pharmacokinetic behavior and tissue distribution were investigated.Results:The average particle sizes of GT-LN and GT-MLN were 190.20±1.35 and 204.83±3.86 nm,respectively,with corresponding surface Zeta potentials of-28.0±1.68 and-30.24±2.10 mV.The drug release profile of GT-LN conformed to the Higuchi equation,whereas that of GT-MLN followed both the first-order kinetic and RitgerePeppas equations.Both formulations significantly enhanced the gastrointestinal stability of the drug.In vivo studies in mice demonstrated that hepatic GA and TSN concentrations in both groups were significantly higher than those in the original drug suspension group(P=.01).Notably,the concentrations in the GT-MLN group were significantly higher compared to the GTLN group(P=.01).Conclusion:Man ligand was formed via the linkage of vinyl stearate with the hydroxyl group at C-6 in mannose.The Manligand endowed these lipid nanoparticles with obvious active liver-targeting properties.Our results provide an efficient and stable route of drug delivery to the liver with improved drug availability.
基金supported the National Transgenic Science and Technology Program(2019ZX08010-003)the National Natural Science Foundation of China(31771808)+3 种基金the National Key Research and Development Program of China(2016YFD0101803)the Key Area Research and Development Program of Guangdong Province(2018B020202008)Beijing Municipal Science and Technology Commission(D171100007717001)National Engineering Laboratory for Crop Molecular Breeding。
文摘Waxy maize is a specialty maize that produces mainly amylopectin starch with special food or industrial values. The objective of this study was to overcome the limitations of wx mutant allele acquisition and breeding efficiency by conversion of parental lines from normal to waxy maize. The intended mutation activity was achieved by in vivo CRISPR/Cas9 machinery involving desired-target mutation of the Wx locus in the ZC01 background,abbreviated as ZC01-DTM^(wx). Triple selection was applied to segregants to obtain high genome background recovery with transgene-free wx mutations. The targeted mutation was identified, yielding six types of mutations among progeny crossed with ZC01-DTM^(wx).The amylopectin contents of the endosperm starch in mutant lines and hybrids averaged94.9%, while those of the wild-type controls were significantly(P < 0.01) lower, with an average of 76.9%. Double selection in transgene-free lines was applied using the Bar strip test and Cas9 PCR screening. The genome background recovery ratios of the lines were determined using genome-wide SNP data. That of lines used as male parents was as high as98.19% and that of lines used as female parents was as high as 86.78%. Conversion hybrids and both parental lines showed agronomic performance similar to that of their wild-type counterparts. This study provides a practical example of the efficient extension of CRISPR/Cas9 targeted mutation to industrial hybrids for transformation of a recalcitrant species.
基金the National Natural Science Foundation of China(Nos.31070386,21302195 and 31300290)135 Key Cultivation Program of the Chinese Academy of Sciencesthe Province-Academy Cooperation Program of Henan Province of China(No.102106000021)for financial support
文摘The presence of hydroxyl groups at the C4 and C7 positions in coumarin backbone has been proposed as a potential modification site for providing excellent bioactivity according to previous studies. A series of novel coumarin derivatives were rationally designed and synthesized by use of a complex catalytic system for a targeted modification at the above sites. These derivatives were assayed for nematicidal activity. As predicted, the derivatization enhanced the activity of the coumarins against five nematodes.Compounds 7b, 9a, 10 c and 11 c showed significant strong nematicidal broad spectrum activity against all tested nematodes. Compound 10 c was the most effective with the lowest LC50 values against Meloidogyne incognita（5.1 mmol/L）, Ditylenchus destructor（3.7 mmol/L）, Bursaphelenchus mucronatus（6.4 mmol/L）, Bursaphelenchus B. xylophilus（2.5 mmol/L） and Aphelenchoides besseyi（3.1 mmol/L）,respectively. A brief investigation on the structure–activity relationships（SAR） revealed that the targeted modification by a C7 hydroxyl was optimum compared with that of a C4 hydroxyl and that the coupling chain length was crucial for the nematicidal activity.
文摘The increased incidence ofNHL(non-Hodgkin's lymphoma),along with its high mortality rate and pronounced resistance to therapy pose an enormous challenge.Both traditional therapeutic strategies and recently developed therapeutic strategies against NHL such as chemoimmunotherapy and targeted therapy have drawbacks.Therefore,novel therapeutic approaches for NHL are urgently needed.Maytansine-loaded PLA-TPGS(polyethylene glycol 1000 succinate-polylactide)nanoparticles were synthesized.And then,rituximab targeting NHL was conjugated together by using EDC(1-ethyl-3-(3-dimethylaminopropyl)carbodiimide)as a coupling agent.The in vitro/vivo antitumor activity was evaluated by Raji cell proliferation inhibition and nude mice xenograft tumor models for NHL.Both the rituximab-conjugated and maytansine-loaded PLA-TPGS nanoparticles(maytansine-NPs(Nanoparticles)-rituximab)and maytansine-loaded PLA-TPGS nanoparticles(maytansine-NPs)presented significant inhibition effect on Raji cell proliferation in a concentration-dependent manner.Compared with conventional maytansine and maytansine-NPs,maytansine-NPs-rituximab showed significantly enhanced cytotoxicity and increased cell apoptosis in Raji cells.The maytansine-NPs-rituximab described in this paper might be a potential formulation for targeting chemotherapy and immunotherapy to CD20+B cell malignancies.
基金supported by the National Key R&D Program of China(Nos.2022YFA1602402,2020YFE0202001,2023YFA1606900)the National Natural Science Foundation of China(NSFC)(Nos.12235003,11835002,11925502,11705031,12275053,12147101).
文摘Active target time projection chambers are state-of-the-art tools in the field of low-energy nuclear physics and are particularly suitable for experiments using low-intensity radioactive ion beams or gamma rays.The Fudan multi-purpose active target time projection chamber(fMeta-TPC)with 2048 channels was developed to studyα-clustering nuclei.This study focused on the photonuclear reaction with a laser Compton scattering gamma source,particularly for the decay of the highly excitedαcluster state.The design of fMeta-TPC is described in this paper.A comprehensive evaluation of its offline performance was conducted using an ultraviolet laser and ^(241)Amαsource.The results showed that the intrinsic angular resolution of the detector was within 0.30°,and the detector had an energy resolution of 6.85%for 3.0 MeVαparticles.The gain uniformity of the detector was approximately 10%(RMS/Mean),as tested by the ^(55)Fe X-ray source.
基金supported by the National Natural Science Foundation of China(Nos.12175280 and 12250610193)the National Key R&D Program of China(No.2016YFA0400500)+1 种基金the support of the CAS“Light of West China”Programthe support of the Natural Science Foundation of Gansu(No.23JRRA676)。
文摘A charged particle array named MATE-PA,which serves as an auxiliary detector system for a Multi-purpose Active-target Time projection chamber used in nuclear astrophysical and exotic beam Experiments(MATE),was constructed.The array comprised of 20 single-sided strip-silicon detectors covering approximately 10%of the solid angle.The detectors facilitated the detection of reaction-induced charged particles that penetrate the active volume of the MATE.The performance of MATE-PA has been experimentally studied using an alpha source and a 36-MeV 14 N beam injected into the MATE chamber on the radioactive ion beam line in Lanzhou(RIBLL).The chamber was filled with a gas mixture of 95%4 He and 5%CO_(2) at a pressure of 500 mbar.The results indicated good separation of light-charged particles using the forward double-layer silicon detectors of MATE-PA.The energy resolution of the Si detectors was deduced to be approximately 1%(σ)for an energy loss of approximately 10 MeV caused by theαparticles.The inclusion of MATE-PA improves particle identification and increases the dynamic range of the kinetic energy of charged particles,particularly that of theαparticles,up to approximately 15 MeV.
基金supported by the National Thousand Talents Plan of Chinathe National Natural Science Foundation of China(Grant Nos.21673014 and U1766216)+1 种基金the 111 project(B17002)funded by the Ministry of Education of Chinathe Fundamental Research Funds for the Central Universities of China
文摘Proton exchange membrane fuel cells(PEMFC)have attracted much attention because of their high energy conversion efficiency,high power density and zero emission of pollutants.However,the high cost of the cathode platinum group metal(PGM)catalysts creates a barrier for the large-scale application of PEMFC.Tremendous efforts have been devoted to the development of low-cost PGM-free catalysts,especially the Fe-N-C catalysts,to replace the expensive PGM catalysts.However,the characterization methods and evaluation standards of the catalysts varies,which is not conducive to the comparison of PGM-free catalysts.U.S.Department of energy(DOE)is the only authority that specifies the testing standards and activity targets for PGM-free catalysts.In this review,the major breakthroughs of Fe-N-C catalysts are outlined with the reference of DOE standards and targets.The preparation and characteristics of these highly active Fe-N-C catalysts are briefly introduced.Moreover,the efforts on improving the mass transfer and the durability issue of Fe-N-C fuel cell are discussed.Finally,the prospective directions concerning the comprehensive evaluation of the Fe-N-C catalysts are proposed.
文摘Objective:To compare the targeting effects of lactosarninated alginate(AlgNP)、polyethylene glycol - coated hydroxyapatite- poly- L- lysine nanoparticles (PLL- PCHNP)and relative nonlactosaminated ones load ed with exogenous gene on liver via peripheral intravenous route. Methods:Preparation of AlgNP based on control of gelification phenomenon of algiante by calcium ions and HA- PLLNP with collosol - gel method, both further modified with lactosaminated - poly- L - lysine synthesized by reductive lactosamination . We used pEGFPCl as the reporter gene to establish receptor- mediated and positive liver targeting nanoparticles- gene model. The potential of adsorbing DNA on nanoparticles was analysed by electrophoresis and spectrophotometer. Then different complexes were transferred into the rat's body by peripheral intravenous route and their targeting characteristics in liver were investigated by using radioisotope tracing assay. Results: PCHNP presented as needle - like particles with a diameter of 20nm by TEM and could be effectively combined with PLL. The diameter of AlgNP was 280nm. Agarpse gel electrophoresis showed both nanoparticles could effectively combine with DNA and the optimal proportion of PLLPCHNP and DNA was 30:1 (w/w); DNA mixed ratio of AlgPLL was 68.3 % by spectrophotometer. The radioactivities in liver for the two lactosaminated nanoparticles were higher than the nonlactosaminated ones. No statistic difference between AlgNP and AlgLacNP could be found . Conclusions: Lactosaminated naroparticles can target to liver more effectively by peripheral intravenous route than nonlactosaminated ones, which is closely concerned with the characteritics of the nanopartide complex.
基金This research was supported by grants from the National Natural Science Foundation of China(Grant Nos.81672932,81730108,81874380,and 81973635)Zhejiang Provincial Natural Science Foundation of China for Distinguished Young Scholars(Grant No.LR18H160001)the Zhejiang Province Science and Technology Project of TCM(Grant No.2019ZZ016).
文摘Objective:In this study,we aimed to develop an amino-terminal fragment(ATF)peptide-targeted liposome carryingβ-elemene(ATF24-PEG-Lipo-β-E)for targeted delivery into urokinase plasminogen activator receptor-overexpressing bladder cancer cells combined with cisplatin(DDP)for bladder cancer treatment.Methods:The liposomes were prepared by ethanol injection and high-pressure microjet homogenization.The liposomes were characterized,and the drug content,entrapment efficiency,andin vitro release were studied.The targeting efficiency was investigated using confocal microscopy,ultra-fast liquid chromatography,and an orthotopic bladder cancer model.The effects of ATF24-PEG-Lipo-β-E combined with DDP on cell viability and proliferation were evaluated by a Cell Counting Kit-8(CCK-8)assay,a colony formation assay,and cell apoptosis and cell cycle analyses.The anticancer effects were evaluated in a KU-19-19 bladder cancer xenograft model.Results:ATF24-PEG-Lipo-β-E had small and uniform sizes(~79 nm),high drug loading capacity(~5.24 mg/mL),high entrapment efficiency(98.37±0.95%),and exhibited sustained drug release behavior.ATF24-PEG-Lipo-β-E had better targeting efficiency and higher cytotoxicity than polyethylene glycol(PEG)ylatedβ-elemene liposomes(PEG-Lipo-β-E).DDP,combined with ATF24-PEG-Lipo-β-E,exerted a synergistic effect on cellular apoptosis and cell arrest at the G2/M phase,and these effects were dependent on the caspase-dependent pathway and Cdc25C/Cdc2/cyclin B1 pathways.Furthermore,thein vivo antitumor activity showed that the targeted liposomes effectively inhibited the growth of tumors,using the combined strategy.Conclusions:The present study provided an effective strategy for the targeted delivery ofβ-elemene(β-E)to bladder cancer,and a combined strategy for bladder cancer treatment.
基金supported by the National Natural Science Foundation of China(No.81673376)the National Natural Science Foundation of Chongqing(cstc2015jcyj BX0100)the project for innovative Research Group at Higher Educational Institutions in Chongqing(CXQT20006)。
文摘Targeted delivery of therapeutics for spinal cord injury(SCI)has been a long-term challenge due to the complexity of the pathological procession.Macrophage,as an immune cell,can selectively accumulate at the trauma site after SCI.This intrinsic targeting,coupled with good immune-escaping capacity makes macrophages an ideal source of biomimetic delivery carrier for SCI.Worth mentioning,macrophages have multiple polarization states,which may not be ignored when designing macrophage-based delivery systems.Herein,we fabricated macrophage membrane-camouflaged liposomes(RM-LIPs)and evaluated their abilities to extend drug circulation time and target the injured spinal cord.Specially,we detected the expression levels of the two main targeted receptors Mac-1 and integrinα4 in three macrophage subtypes,including unactivated(M0)macrophages,classically activated(M1)macrophages and alternatively activated(M2)macrophages,and compared targeting of these macrophage membrane-coated nanoparticles for SCI.The macrophage membrane camouflage decreased cellular uptake of liposomes in RAW264.7 immune cells and strengthened binding of the nanoparticle to the damaged endothelial cells in vitro.RM-LIPs can prolong drug circulation time and actively accumulate at the trauma site of the spinal cord in vivo.Besides,RM-LIPs loaded with minocycline(RM-LIP/MC)showed a comprehensive therapeutic effect on SCI mice,and the anti-pyroptosis was found to be a novel mechanism of RM-LIP/MC treatment of SCI.Moreover,the levels of Mac-1 and integrinα4 in macrophages and the targeting of RM-LIP for SCI were found to be independent of macrophage polarization states.Our study provided a biomimetic strategy via the biological properties of macrophages for SCI targeting and treatment.
基金the National Natural Science Foundation of China(Grant No.81373334).
文摘The properties of modified biomaterial are gaining more and more importance in drug delivery systems.Sialic acid(SA)and polysialic acid(PSA)serve as endogenous substances,which are non-immunogenic and biodegradable.At the same time,SA modification of the drugs/carriers can enhance the uptake of tumor cell and retention in brain;PSA modifi-cation can reduce the immunogenicity of the proteins or polypeptides and increase circulation time of the modified drugs/carriers in the blood,thus achieving active targeting effect.These properties offer a variety of opportunities for applications in drug delivery systems.This article summarizes the biological functions of SA and PSA and presents the technologies of SA/PSA modified small molecule drugs,proteins and carriers in drug delivery systems.
基金supported by the National Natural Science Foundation of China (No.82073789)Innovative Research Group at Higher Educational Institutions in Chongqing (No.CXQT20006)。
文摘Extensive research has been performed on cell membrane camouflaged-based drug delivery systems in recent years.Herein,we provide an overview of the challenges in system preparation,functional design,continuous industrial production of these systems,and solution strategies for these challenges.Further,we analyze and discuss the frontier medical applications of cell membrane-camouflaged drug delivery systems in anti-inflammatory,anti-pathogenic microorganisms,and biological detoxification.This review takes a challenge-oriented perspective and seeks innovative strategies,provides a literature review of research into cell membrane-camouflaged drug delivery systems,and promotes the development of personalized clinical treatments.
基金National Natural Science Foundation of China (Grant No.30772665)Beijing Nature Science Foundation(Grant No.7083111).
文摘It was reported that a 5-amino acid peptide Ala-Pro-Arg-Pro-Gly （APRPG） could specifically bind to the tumor angiogenic site. We investigated the antitumor efficacy of doxorubicin （DOX） encapsulated in APRPG modified liposome （APRPG-LP） compared with DOX encapsulated in non-APRPG modified liposomes （LP） and DOX solution （flee DOX） on Lewis lung carcinoma （LLC） bearing mice. APRPG-LP could efficiently suppress the tumor growth of the experimental mice, compared with LP （P〈0.001）, free DOX （P〈0.001） and saline of negative control （P〈0.001）. The present results demonstrated that the APRPG modified liposomes exhibited a much better therapeutic efficacy over the non-modified liposomes and the DOX solution, because of the effect of targeted tumor angiogenesis disruption. Thus, APRPG-LP could be a promising active-targeting drug carrier to tumor angiogenic site.
基金This work was partially supported by the National Natural Science Foundation of China(Grant Nos.81871483,81671813 and 61727823)the open project funding of The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province(Grant No.2018ZDSY2001).
文摘Carrier-free nanodrug with exceptionally high drug payload has attracted increasing attentions.Herein,we construct a pH/ROS cascade-responsive nanodrug which could achieve tumor acidity-triggered targeting activation followed by circularly amplified ROS-triggered drug release via positive-feedback loop.The di-selenide-bridged prodrug synthesized from vitamin E succinate and methotrexate(MTX)self-assembles into nanoparticles(VSeM);decorating acidity-cleavable PEG onto VSeM surface temporarily shields the targeting ability of MTX to evade immune clearance and consequently elongate circulation time.Upon reaching tumor sites,acidity-triggered detachment of PEG results in targeting recovery to enhance tumor cell uptake.Afterward,the VSeM could be dissociated in response to intracellular ROS to trigger VES/MTX release;then the released VES could produce extra ROS to accelerate the collapse of VSeM.Finally,the excessive ROS produced from VES could synergize with the released MTX to efficiently suppress tumor growth via orchestrated oxidation-chemotherapy.Our study provides a novel strategy to engineer cascade-responsive nanodrug for synergistic cancer treatment.
基金financially supported by the National Natural Science Foundation of China (Nos.20974062,30700175)National Basic Research Program (Nos.2009CB930400,2012CB821500)China National Funds for Distinguished Young Scientists (No.21025417)
文摘Hyperbranched polysulfonamine （HPSA） is a promising biomaterial due to its highly branched spherical architecture and efficient intracellular translocation. To realize the fianctionalization of HPSA, both N-succinimidyl 3-（2- pyridyldithio） propionate （SPDP） for tethering the human-mouse chimeric monoclonal antibody CH12 and N-hydroxy succinimidyl S-acetylmercaptoacetyltriglycinate （NHS-MAG3） for labeling 188Re were sequentially grafted onto the primary amine terminals of HPSA via covalent linkages, attaining the SPDP-HPSA-MAG3 intermediate. In order to reserve the structural integrity of CH12, the fragment crystallizable （Fc） region was also processed by oxidation of oligosaccharide moieties with sodium periodate and then reacted with N-（κ-maleimidoundecanoic acid） hydrazide （KMUH）. After chelating 188Re with MAG3 group, the SPDP was reduced to PDP and connected onto the maleinimide group at the Fc region. As a result, both the epidermal growth factor receptor viii （EGFRvIII） targeted monoclonal antibody CH12 and the radionuclide 188Re were conjugated to the HPSA-based vehicles, forming the 188Re-labeled and CH12-tethered HPSA （CH12-HPSA- 188Re）. The molecular weight and in vitro stability of CH12-HPSA-188Re were evaluated by gel electrophoresis and paper chromatography. On one hand, the CH12-HPSA-188Re could specifically bind to the EGFRvlII-positive human hepatocarcinoma cells in vitro. On the other hand, it could also target at the tumor tissue of nude mice in vivo. Hence, the CH12-HPSA-188Re could effectively target at the human hepatocarcinoma and facilitate the tumor detection and targeted radioimmunotherapy.
基金supported by National Key R&D Program of China(No.2021YFA0909900)National Natural Science Foundation of China(No.81773656)+3 种基金Liaoning Revitalization Talents Program(No.XLYC1808017)Shenyang Youth Science and Technology Innovation Talents Program(No.RC190454)China Postdoctoral Science Foundation(No.2020M680986)General Project of Liaoning Provincial Department of Education(Nos.LKZ0927 and LJKQZ2021034)。
文摘Inflammatory bowel disease(IBD)is a chronic and recurrent disease of the gastrointestinal tract,mainly including Crohn's disease(CD)and ulcerative colitis(UC).However,current approaches against IBD do not precisely deliver drugs to the inflammatory site,which leads to life-long medication and serious side effects that can adversely impact patients’adherence.It is necessary to construct optimal drug delivery systems(DDSs)that can target drugs to the region of inflammation,thereby improve therapeutic efficacy and reduce side effects.With the burgeoning development of nanotechnology-based nanomedicines(NMs)and prodrug strategy,remarkable progresses in the treatment of IBD have been made in recent years.Herein,the latest advances are outlined at the intersection of IBD treatment and nanotherapeutics as well as prodrug therapy.First,the pathophysiological microenvironment of inflammatory sites of IBD is introduced in order to rationally design potential NMs and prodrugs.Second,the necessity of NMs for the IBD therapy is elaborated,and the representative nanotherapeutics via passive targeted and active targeted NMs developed to treat the IBD are overviewed.Furthermore,the emerging prodrug-based therapeutics are summarized,including 5-aminosalicylic acid-,amino acid-,and carbohydrate-conjugated prodrugs.Finally,the design considerations and perspectives of these NMs and prodrugs-driven IBD therapeutics in the clinical translation are spotlighted.
基金funding support from the Major new drug creation project (2017ZX09101002-002-008)National Natural Science Foundation of China (81403171)Autonomous Program of China Academy of Chinese Medical Sciences (QZPT001 and 2014065)
文摘Objective To predict the main active ingredients,potential targets and molecular mechanisms of Yuan Zhi powder in treatment of dementia by using network pharmacology.Methods A database of chemical constituents of Yuan Zhi powder was constructed by using databases and literatures.Potential targets were predicted by reverse molecular docking,and then a component-target network was constructed.The target network of Alzheimer's disease(AD)was mapped and analyzed to obtain the“active ingredient-AD target”network.The key targets were screened through network analysis.Finally,the rationality of the prediction was analyzed by comparing with the target reported in the literatures.Results There were180chemical constituents acting on the AD target,and the targets included three key targets(cyclooxygenase-2,muscarinic acetylcholine receptor M1,and muscarinic acetylcholine receptor M2)and an important target(acetylcholine esterase).Alzheimer's disease may be treated by regulating the activity of acetylcholine receptors and the binding toβ-amyloid protein,and its biological process may be concentrated in the acetylcholine receptor signal pathway,negative regulation of synaptic transmission and so on.Conclusion The fact that Yuan Zhi powder can treat AD is consistent with the characteristics of multi-components-multitargets-multiple pathways of traditional Chinese medicine.The important targets obtained from network analysis have a large proportion in literature research,so network analysis have some rationality.
基金supported by the Key Program of the National Natural Science Foundation of China(No.51138006)the National Key Research on Water Environment Pollution Control in China(No.2012ZX07301-001)
文摘The microbial quality of urban recreational water is of great concern to public health.The monitoring of indicator organisms and several pathogens alone is not sufficient to accurately and comprehensively identify microbial risks.To assess the levels of bacterial pathogens and health risks in urban recreational water,we analyzed pathogen diversity and quantified four pathogens in 46 water samples collected from waterbodies in Beijing Olympic Forest Park in one year.The pathogen diversity revealed by 16 S r RNA gene targeted next-generation sequencing（NGS） showed that 16 of 40 genera and 13 of 76 reference species were present.The most abundant species were Acinetobacter johnsonii,Mycobacterium avium and Aeromonas spp.Quantitative polymerase chain reaction（q PCR） of Escherichia coli（uid A）,Aeromonas（aer A）,M.avium（16S r RNA）,Pseudomonas aeruginosa（oaa） and Salmonella（inv A） showed that the aer A genes were the most abundant,occurring in all samples with concentrations of 10^（4–6） genome copies/100 m L,followed by oaa,inv A and M.avium.In total,34.8% of the samples harbored all genes,indicating the prevalence of these pathogens in this recreational waterbody.Based on the q PCR results,a quantitative microbial risk assessment（QMRA） showed that the annual infection risks of Salmonella,M.avium and P.aeruginosa in five activities were mostly greater than the U.S.EPA risk limit for recreational contacts,and children playing with water may be exposed to the greatest infection risk.Our findings provide a comprehensive understanding of bacterial pathogen diversity and pathogen abundance in urban recreational water by applying both NGS and q PCR.
