Fudan multi-purpose active target time projection chamber(fMeta-TPC)for photonuclear reaction experiments

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.

Studies of the 2α and 3α channels of the ^(12)C+^(12)C reaction in the range of E_(c.m.)=8.9 MeV to 21 MeV using the active target Time Projection Chamber

The ^(12)C+^(12)C fusion reaction was studied in the range of E_(c.m.)=8.9 to 21 MeV using the active-target Time Projection Chamber.With full information on all tracks of the reaction products,cross sections of the^(12)C(^(12)C,^(8)Be)^(16)O_(g.s.)channel and the ^(12)C(^(12)C,3a)^(12)C channel could be measured down to the level of a few milibarns.The ^(12)C(^(12)C,^(8)Be)^(16)O_(g.s.)reaction channel was determined to be 10_(-8)^(+24) mb at E_(c.m.)=11.1 MeV,supporting the direct a transfer reaction mechanism.The ^(12)C(^(12)C,3α)^(12)C reaction channel was studied for the first time using an exclusive measurement.Our result does not confirm the anomaly behavior reported in the previous inclusive measurement by Kolata et al.[Phys.Rev.C 21,579(1980)].Our comparisons with statistical model calculations suggest that the 3 a channel is dominated by the fusion evaporation process at E_(c.m.)>19 MeV.The additional contribution of the 3 a channel increases the fusion reaction cross section by 10% at energies above 20 MeV.We also find that an additional reaction mechanism is needed to explain the measured cross section at E_(c.m.)<15 MeV at which point the statistical model prediction vanishes.

Research Progress on Novel Carrier-modified Methods and Evaluation of Active Targeting Antitumor Preparation

This article mainly introduced novel carrier-modified methods for active targeting antitumor preparation as well as their evaluation methodology in recent years. By reviewing related domestic and overseas literatures, the up-to-date scientific researches concerning active targeting antitumor preparation were elaborated and the problems existing in present studies were discussed. Numerous valid vector- embellished methods had been discovered with excellent targeting effects, and the significant progress was acquired for the evaluation tools in vitroand in vivo. The active targeting agent would be a major direction in prospective tumor or cancer therapeutic regimen.

Is active targeting of brain metastases of breast cancer superior to passive targeting?

Brain metastasis is a major cause of death in patients with solid cancers. Breast cancer cells have high tendency to migrate towards brain. Cancer cells within brain are characterized by severe aggressiveness and inaccessibility. Currently, breast cancer and its metastasis are the second leading cause of death among women. Tumor microenvironment and blood brain barrier (BBB) represent great obstacles in targeting breast cancer and its metastasis. Chemotherapy is a safer treatment modality for brain metastasis compared with risky surgical resection and brain radiotherapy. Unfortunately, conventional chemotherapy lack penetration of BBB and suffer from multiple resistance mechanisms. Current treatment technologies for brain metastases of breast cancer have limited long-term success and numerous side effects, illustrating the urgent need for novel smart strategies. Various novel drug entities and nanosystems have been employed to improve diagnosis and targeted treatment of breast cancer and its metastasis. Immunotherapy agents and small tyrosine kinase inhibitors have been shown to reduce tumor size and increase survival in patients with breast cancer, but still poorly penetrate BBB. Tailored sized nanoparticles to some extent crossed brain tumor barrier and enhanced drug accumulation in tumors by taking advantage of enhanced permeability and retention. Furthermore, various active targeting strategies have been adopted to improve accessibility to brain malignancies. Therefore, to achieve enhanced antitumor therapy against ;breast cancer and its brain metastasis, multi-talented delivery systems are urgently needed for optimal treatment. This review focuses on the various active and passive targeting technologies for the treatment of breast cancer brain metastases in the past decade. A comprehensive summary and examples along with pros and cons of each system will be discussed. Different treatment modalities and nanotechnology facilities will be demonstrated to aid in designing the optimal smart, safe, targeted and effective systems to combat brain metastases of breast cancer.

Macrophage membrane-mediated targeted drug delivery for treatment of spinal cord injury regardless of the macrophage polarization states

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.

Tumor Microenvironment Cascade‑Responsive Nanodrug with Self‑Targeting Activation and ROS Regeneration for Synergistic Oxidation‑Chemotherapy

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.

Conversion of a normal maize hybrid into a waxy version using in vivo CRISPR/Cas9 targeted mutation activity

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.

Why Has China Become a Target of Anti-dumping Activities?

Although the benefits of China’s trade expansion have been distributed much more broadly than those of some early industrialized nations,China has become the primary target of anti-dumping activities.Being a new and relatively efficient new rival in the global market may be an important reason for this.On the other hand,China’s development stage and her trade structure also place her in a disadvantageous position when it comes to anti-dumping activities.

The law of anti-VCAM-1 targeted microbubbles adhesion to activated endothelial cells under controlled shear flow

Microbubbles can enhance the detection in noninvasive ultrasound imaging.Recently,targeted microbubbles have been developed to selectively adhere to specific and overexpressed p molecules in endothelial cells in some pathologic conditions.However,the law of

Construction and performance test of charged particle detector array for MATE

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.

An ATF24 peptide-functionalized β-elemene-nanostructured lipid carrier combined with cisplatin for bladder cancer treatment

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.

乳糖化修饰纳米基因载体的肝靶向性研究(英文)

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.

Application of sialic acid/polysialic acid in the drug delivery systems

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.

Designed fabrication of active tumor targeting covalent organic framework nanotherapeutics via a simple post-synthetic strategy

Developing agents that can accurately differentiate tumors from normal healthy tissues is of utmost importance for safe cancer therapy.Active targeting has been considered as an effective technique for tumor recognition.In this work,we demonstrate a folate-functionalized nanoscale covalent organic framework(FATD nCOF)highly specific to cancer cells through active targeting of their enriched folate receptors(FRs).The FATD nCOF prepared by simple post-synthetic modification of the COF surface defeats disperses well in water and exhibits a high loading capacity for various anticancer drugs.The biocompatible FATD nCOF is selectively internalized by FR-harboring cancer cells and consequently augments the efficacy of the loaded drug,Withaferin A(Wi-A),for targeted cancer cell killing.In biomolecular mechanism studies,Wi-A-loaded FATD(FATD@Wi-A)nanocomposites show remarkably a higher rate of apoptosis in FR-enriched cancer cells.Comparative analyses of FR-positive and FR-negative tumor xenografts reveal enhanced selective antitumor activity of FATD@Wi-A nanotherapeutics.Taken together,the study findings suggest that FATD nCOF holds great promise for active targeting of tumors in vivo.Our simple yet effective technology might be valuable for creating new state-of-the-art COFs for chemical and biomedical applications.

Folate-conjugated pH-responsive nanocarrier designed for active tumor targeting and controlled release of doxorubicin

A novel type of amphiphilic pH-responsive folate-poly（ε-caprolactone）- block-poly（ 2-hydroxyethylmethacrylate ）-co-poly（ 2-（ dimethylamino ）-ethylmethacrylate ） （FA-PCL-b-P（HEMA-co-DMAEMA）） （MFP） block copolymers were designed and synthe- sized via atom transfer radical polymerization （ATRP） and ring opening polymerization （ROP） techniques. The molecular structures of the copolymers were confirmed with IH NMR, FTIR and GPC measurements. The critical micelle concentration （CMC） of MFP in aqueous solution was extremely low （about 6.54 mglL）. The in vitro release behavior of DOX-Ioaded micelles was significantly accelerated when the pH value of solution decreased from 7.4 to 5.0. In vitro antitumor efficiency was evaluated by incubating DOX- loaded micelles with Hela cells. The results demonstrated that this copolymer possessed excellent biocompatibility, and FA-decorated micelles MFP showed higher cellular uptake than those micelles without the FA moiety, indicating their unique targetability. These folate-conjugated biodegradable micelles are highly promising for targeted cancer chemothe-rapy.

Superior Antitumor Activity of Rituximab-Conjugated and Maytansine-Loaded PLA-TPGS Nanoparticles in Xenograft Models for Non-Hodgkin＇s Lymphoma

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.

Fe-N-C catalysts for PEMFC: Progress towards the commercial application under DOE reference

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.

Molecular Biological Mechanisms of Yuan Zhi Powder in the Treatment of Alzheimer's Disease: an Analysis Based on Network Pharmacology

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.

A tracking filter method of active sonar subject to unknown target maneuver

A tracking filter algorithm based on the maneuvering detection delay is presented in order to solve the fuzzy problem of target maneuver decision introduced by the measure？ment errors of active sonar. When the maneuvering detection is unclear, two target moving hypotheses, the uniform and the maneuver, derived from the method of multiple hypothesis tracking, are generated to delay the final decision time. Then the hypothesis test statistics is constructed by using the residual sequence. The active sonar？s tracking ability of unknown prior information targets is improved due to the modified sequential probability ratio test and the integration of the advantages of strong tracking filter and the Kalman filter. Simulation results show that the algorithm is able to not only track the uniform targets accurately, but also track the maneuvering targets steadily. The effectiveness of the algorithm for real underwater acoustic targets is further verified by the sea trial data processing results.

Inhibiting Human Copper Transfer and Tumor Growth

Copper is a trace element that is required by almost all forms of life.Acting as cofactors for various key metabolism enzymes,copper takes part in many vital biological processes.Previous studies have found the concentration of copper is significantly higher in tumor cells than in normal cells.In addition,copper can promote angiogenesis by activating VEGF and FGF signaling.