PAN-POSS接枝共聚物改性聚环氧乙烷/离子液体凝胶电解质的制备及性能

采用自由基聚合法成功合成了聚丙烯腈与笼型倍半硅氧烷的接枝共聚物(PAN-POSS),并将其引入聚环氧乙烷(PEO)/1-乙基-3-甲基咪唑双三氟甲磺酰亚胺盐([EMIM][TFSI])/双三氟甲磺酰亚胺锂(LiTFSI)体系,通过溶剂挥发法制备具有自支撑性的凝胶电解质(GPEs)。采用差示扫描量热分析、热分析、拉伸测试和电化学性能测试等进行表征,研究了PAN-POSS含量对PEO基电解质结晶性能、力学性能、热稳定性和电化学性能的影响。结果表明,在PEO/[EMIM][TFSI]/LiTFSI凝胶电解质体系中,随PAN-POSS含量增加,PEO的结晶度逐渐降低,当质量分数为9%时,结晶度从初始的25.7%降至11.6%。此时,GPEs的室温离子电导率为2.87×10^(-4) S/cm,在0.1 C充电速率下,电池的容量达到130 mAh/g。PAN-POSS的添加提高了GPEs的热稳定性,热降解温度可达到380.6℃,力学性能略有下降,但是仍然达到3.3 MPa,具有良好的自支撑特性。

Fundamental and Technical Challenges for a Compatible Design Scheme of Oxyfuel Combustion Technology

Oxyfuel combustion with carbon capture and sequestration(CCS) is a carbon-reduction technology for use in large-scale coal-fired power plants. Significant progress has been achieved in the research and development of this technology during its scaling up from 0.4 MWth to 3 MWth and 35 MWth by the combined efforts of universities and industries in China. A prefeasibility study on a 200 MWe large-scale demonstration has progressed well, and is ready for implementation. The overall research development and demonstration(RD&D) roadmap for oxyfuel combustion in China has become a critical component of the global RD&D roadmap for oxyfuel combustion. An air combustion/oxyfuel combustion compatible design philosophy was developed during the RD&D process. In this paper, we briefly address fundamental research and technology innovation efforts regarding several technical challenges, including combustion stability, heat transfer, system operation, mineral impurities, and corrosion. To further reduce the cost of carbon capture, in addition to the large-scale deployment of oxyfuel technology, increasing interest is anticipated in the novel and nextgeneration oxyfuel combustion technologies that are briefly introduced here, including a new oxygen-production concept and flameless oxyfuel combustion.

DBU-based CO2 absorption-mineralization system: Reaction process,feasibility and process intensification

Amine-based carbon dioxide(CO2)capture is still limited by high desorption energy consumption.Fixing CO2 into carbonate is a safer and more permanent method.In this work,calcium oxide(CaO)is introduced to perform chemical desorption instead of thermal desorption on 1,8-diazabicyclo[5.4.0]undec-7-ene(DBU)aqueous solution after CO2 absorption.The X-ray diffraction(XRD)patterns of solid products show the formation of calcite calcium carbonate(CaCO3),which prove the feasibility of this method.The effects of reaction temperature,reaction time and Ca2+/CO32-molar ratios on the related reactions in CO2 absorption-mineralization process and CaCO3 precipitation are discussed,and purer CaCO3 is obtained by ultrasonic treatment.The CaCO3 content can be increased to 95.8%and the CO2 desorption ratio can achieve 80%by 30 min ultrasonic dispersion treatment under the conditions(40℃,180 min,Ca2+/CO32-molar ratio=1.0).After five cycles,DBU aqueous solution shows stable CO2 absorption and mineralization ability.Fourier transform infrared spectroscopy(FT-IR)spectra of the reaction process also indicate the regeneration of the solvent.Compared with thermal desorption,this process is exothermic,almost without no additional heat.

Effect of different organic compounds on the preparation of CaO-based CO_(2) sorbents derived from wet mixing combustion synthesis

CaO based sorbents have great potential for commercial use to capture CO_(2) of power plants.In the demand of producing sorbents with better cyclic performance,CaO-based sorbents derived from different kinds of calcium precursors,containing calcium carbonate(CC-CaO),calcium gluconate monohydrate(CG-CaO),calcium citrate(CCi-CaO)and calcium acetate monohydrate(CA-CaO),were tested cyclically and compared using simultaneous thermal analyzer(STA).And further study was conducted on the sorbents modified with citric acid monohydrate and 50%gluconic acid solution by wet mixing combustion synthesis.The modified sorbents showed better performance and higher pore parameters as well as porous microstructure with more organic acid added.After 20 cycles of carbonation and calcination,the C2CCi8(CaO:citric acid=2:8 by mass ratio)and C2G8(CaO:gluconic acid=2:8 by mass ratio)sorbent possess CO_(2) capture capacity of 0.45g·g^(-1)(g CO_(2) per g sorbents)and 0.52 g·g^(-1) respectively.The citric acid was more effective for modification than gluconic acid for extended 50 cycles.Furthermore,good linear relationship between CaO conversion and specific surface area as well as pore volume were determined,of which the specific surface area showed closer correlation with CaO conversion。

Elaborately engineering of a dual-drug co-assembled nanomedicine for boosting immunogenic cell death and enhancing triple negative breast cancer treatment

Pure drug-assembled nanosystem provides a facile and promising solution for simple manufacturing of nanodrugs,whereas a lack of understanding of the underlying assembly mechanism and the inefficient and uncontrollable drug release still limits the development and application of this technology.Here,a simple and practical nanoassembly of DOX and DiR is constructed on basis of their co-assembly characteristics.Multiple interaction forces are found to drive the co-assembly process.Moreover,DOX release from the nanoassembly can bewell controlled by the acidic tumormicroenvironment and laser irradiation,resulting in favorable delivery efficiency of DiR and DOX in vitro and in vivo.As expected,the nanoassembly with high therapeutic safety completely eradicated the mice triple negative breast cancer cells(4T1)on BALB/c mice,owing to synergistic chemo-photothermal therapy.More interestingly,DiR and DOX synergistically induce immunogenic cell death(ICD)of tumor cells after treatment,enabling the mice to acquire immune memory against tumor growth and recurrence.Such a facile nanoassembly technique provides a novelmultimodal cancer treatment platform of chemotherapy/phototherapy/immunotherapy.

Investigating the crucial roles of aliphatic tails in disulfide bond-linked docetaxel prodrug nanoassemblies

Disulfide bond-bridging strategy has been extensively utilized to construct tumor specificity-responsive aliphatic prodrug nanoparticles(PNPs) for precise cancer therapy. Yet, there is no research shedding light on the impacts of the saturation and cis-trans configuration of aliphatic tails on the self-assembly capacity of disulfide bond-linked prodrugs and the in vivo delivery fate of PNPs. Herein, five disulfide bond-linked docetaxelfatty acid prodrugs are designed and synthesized by using stearic acid, elaidic acid, oleic acid, linoleic acid and linolenic acid as the aliphatic tails, respectively. Interestingly, the cistrans configuration of aliphatic tails significantly influences the self-assembly features of prodrugs, and elaidic acid-linked prodrug with a trans double bond show poor self-assembly capacity. Although the aliphatic tails have almost no effect on the redox-sensitive drug release and cytotoxicity, different aliphatic tails significantly influence the chemical stability of prodrugs and the colloidal stability of PNPs, thus affecting the in vivo pharmacokinetics, biodistribution and antitumor efficacy of PNPs. Our findings illustrate how aliphatic tails affect the assembly characteristic of disulfide bond-linked aliphatic prodrugs and the in vivo delivery fate of PNPs, and thus provide theoretical basis for future development of disulfide bond-bridged aliphatic prodrugs.

In situ apolipoprotein E-enriched corona guides dihydroartemisinin-decorating nanoparticles towards LDLr-mediated tumor-homing chemotherapy

The therapeutic efficiency of active targeting nanoparticulate drug delivery systems(nano-DDS)is highly compromised by the plasma proteins adsorption on nanoparticles(NPs)surface,which significantly hinders cell membrane receptors to recognize the designed ligands,and provokes the off-target toxicity and rapid clearance of NPs in vivo.Herein,we report a novel dihydroartemisinin(DHA)-decorating nano-DDS that in situ specifically recruits endogenous apolipoprotein E(apoE)on the NPs surface.The apoE-anchored corona is able to prolong PLGA-PEG2000-DHA(PPD)NPs circulation capability in blood,facilitate NPs accumulating in tumor cells by the passive enhanced permeability and retention(EPR)effect and low-density lipoprotein receptor(LDLr)-mediated target transport,and ultimately improve the in vivo antitumor activity.Our findings demonstrate that the strategy of in situ regulated apoE-enriched corona ensures NPs an efficient LDLr-mediated tumor-homing chemotherapy.

Integration of phospholipid-drug complex into self-nanoemulsifying drug delivery system to facilitate oral delivery of paclitaxel

Self-nanoemulsifying drug delivery system(SNEDDS) has emerged as a promising platform to improve oral absorption of drugs with poor solubility and low permeability. However,large polarity molecules with insufficient lipid solubility,such as paclitaxel(PTX),would suffer from inferior formulation of SNEDDS due to poor compatibility. Herein,phospholipid-drug complex(PLDC) and SNEDDS were integrated into one system to facilitate oral delivery of PTX. First,PTX was formulated into PLDC in response to its inferior physicochemical properties. Then,the prepared PLDC was further formulated into SNEDDS by integrating these two drug delivery technologies into one system(PLDC-SNEDDS). After PLDC-SNEDDS dispersed in aqueous medium,nanoemulsion was formed immediately with an average particle size of ~30 nm. Furthermore,the nanomulsion of PLDC-SNEDDS showed good colloidal stability in both HCl solution(0.1 mol/l,p H 1.0) and phosphate buffer solution(PBS,p H 6.8). In vivo,PTX-PLDC-SNEDDS showed distinct advantages in terms of oral absorption efficiency,with a3.42-fold and 2.13-fold higher bioavailability than PTX-PLDC and PTX solution,respectively.Our results suggest that the integration of PLDC into SNEDDS could be utilized to facilitate the oral delivery of hydrophobic drugs with large polarity.

Development and evaluation of taste-masked dry suspension of cefuroxime axetil for enhancement of oral bioavailability

Cefuroxime axetil(CA)is an ester prodrug of cefuroxime with an unpleasant taste when administrated orally.This work was to mask the bitter taste of CA and enhance its oral bioavailability.Dry suspensions were prepared by means of wet granulation method and solid dispersion method.Binders,suspending agents and other compositions involved in the formulation were optimized.The differential scanning calorimetry(DSC)analysis indicated that CA was amorphous in the solid dispersion with stearic acid as the carrier,which contributed to an improvement of the dissolution rate.Taste evaluation was performed by three volunteers and taste masking was successfully achieved by the methods mentioned above.A pH 7.0 phosphate buffer was adopted to study the in vitro dissolution performance of the three formulations,i.e.,two self-made dry suspensions and the commercial one.With a better release characteristic and a satisfying taste masking ability,the solid dispersion suspension was selected as the optimal formulation for the further pharmacokinetic study in beagle dogs.The values of Cmax and AUC0e12 for the solid dispersion suspension were about 1.78-fold and 2.17-fold higher than these of reference suspension,respectively.The obtained results demonstrated that the solid dispersion can efficiently mask the bitter taste of CA and significantly enhance its oral bioavailability.

Polymeric nanoparticles developed by vitamin E-modified aliphatic polycarbonate polymer to promote oral absorption of oleanolic acid

Oleanolic acid (OA) exhibited good pharmacological activities in the clinical treatment of hypoglycemia, immune regulation, acute jaundice and chronic toxic hepatitis. However, the oral delivery of OA is greatly limited by its inferior water solubility and poor intestinal mucosa permeability. Herein, we developed a novel polymeric nanoparticle (NP) delivery system based on vitamin E modified aliphatic polycarbonate (mPEG-PCC-VE) to facilitate oral absorption of OA. OA encapsulated mPEG-PCC-VE NPs (OA/mPEG-PCC-VE NPs) showed uniform particle size of about 170 nm with high drug loading capability (8.9%). Furthermore, the polymeric mPEG-PCC-VE NPs, with good colloidal stability and pH-sensitive drug release characteristics, significantly enhanced the in vitro dissolution of OA in the alkaline medium. The in situ single pass intestinal perfusion (SPIP) studies performed on rats demonstrated that the OA/m PEG-PCC-VE NPs showed significantly improved permeability in the whole intestinal tract when compared to OA solution, especially for duodenum and colon. As a result, the in vivo pharmacokinetics study indicated that the bioavailability of OA/m PEG-PCC-VE NPs showed 1.5-fold higher than commercially available OA tablets. These results suggest that mPEGPCC-VE NPs are a promising platform to facilitate the oral delivery of OA.

Elaborately engineering of lipid nanoparticle for targeting delivery of siRNA and suppressing acute liver injury

Small interfering RNA(siRNA)-based gene silencing has been considered as a potential therapy modality against inflammatory diseases.Nevertheless,the effective delivery of siRNA to desired destination still remains challenging due to poor stability,high molecular weight and negative charge.Currently,ionizable lipid nanoparticle(LNP)has been extensively used as vector for effective delivery of siRNA.Herein,we report a mannose-modified LNP(M-MC_(3) LNP@TNFα)loading tumor necrosis factorα(TNFα)siRNA for targeting liver macrophages,achieving effectively inhibit acute liver injury.The M-MC_(3) LNP@TNFαnot only increases the internalization of LNP by macrophages,but also enhances the gene silencing efficiency of TNFαin vitro.Additionally,the M-MC_(3) LNP@TNFαexhibits higher accumulation in liver of healthy mice than that of MC_(3) LNP@TNFα(un-modified LNP)owing to the targeting effect of mannose.As expected,the M-MC_(3) LNP@TNFαsignificantly suppresses the expression of TNFαand ameliorates liver damage in acute liver injury model.Such a LNP targeting siRNA delivery holds great potential for the treatment of diseases associated with liver in the future.

Advances of nanoparticles as drug delivery systems for disease diagnosis and treatment

Decades have passed since the first nanoparticles-base medicine was approved for human cancer treatment, and the research and development of nanoparticles for drug delivery are always undergoing.Nowadays, the significant advances complicate nanoparticles’ branches, including liposomes, solid lipid nanoparticles, inorganic nanoparticles, micelles, nanovaccines and nano-antibodies, etc. These nanoparticles show numerous capabilities in treatment and diagnosis of stubborn diseases like cancer and neurodegenerative diseases, emerging as novel drug carriers or therapeutic agents in future. In this review, the complicated branches of nanoparticles are classified and summarized, with their property and functions concluded. Besides, there are also some delivery strategies that make nanoparticles smarter and more efficient in drug delivery, and frontiers in these strategies are also summarized in this review. Except these excellent works in newly-produced drug delivery nanoparticles, some points of view and future expectations are made in the end.

Modularly engineered prodrug-nanoassemblies for cancer therapy:Nonpharmacological moiety dominating delivery fates

Self-engineered small-molecule prodrug-nanoassemblies have emerged as promising nanomedicines for cancer treatment.Modular design of prodrug molecules is crucial to guarantee the favorable assembly stability,tumor-specific prodrug activation,and satisfactory antitumor effect.However,too much attention has been paid to the pharmacophores and chemical linkages in prodrug molecules while neglects the vital roles of nonpharmacological moieties.Herein,we found that iso-carbon fatty acids with different number,position,and cis-trans configuration of double bonds dramatically affect the nanoassembly feature and drug delivery fates of thioether-linked paclitaxel prodrug-nanoassemblies.Particularly,the number and cis-trans configuration of double bonds in fatty acid moieties not only dominate the self-assembly ability and colloidal stability of prodrugs,but also exert significant influences on the pharmacokinetics,prodrug activation,and antitumor activity of prodrug-nanoassemblies.Finally,oleic acid with one cis double bond stands out as the optimal nonpharmacological moiety for thioether-linked paclitaxel prodrugnanoassemblies.This study elucidates the crucial roles of nonpharmacological moieties in prodrugs,and provides new insights into the modular design of prodrug-based nanomedicines for cancer therapy.

Self-adaptive non-covalent albumin-binding near-infrared probe conjugates enabling precise sentinel lymph node metastasis illumination and primary tumor imaging

Tumor sentinel lymph node(SLN)metastasis plays a vital role in tumor staging and therapeutic decision-making process.However,precise diagnosis of primary tumors and lymphatic metastases is still hindered by low imaging resolution and poor photostability of fluorescent probes.Herein,we report three novel IR820-fatty acid(FA)conjugates(IR-OA,IR-LA,and IR-PA)for precise lymphatic metastasis illumination and primary tumor diagnosis.The IR-FA conjugates are able to non-covalently bound to albumin in vivo,and the fluorescence quantum yield is significantly enhanced after incubation with bovine serum albumin(BSA)in vitro.Moreover,the BSA-IR-FA conjugates display large Stokes shift(>120 nm),dramatically improving in vivo imaging resolution.Among them,IR-PA demonstrates distinct advantage over IR-OA,IR-LA,and IR-maleimide(MAL)(fluorescent probe previously reported by our group)in terms of fluorescence quantum yield,photostability,and imaging resolution.As a result,IR-PA exhibits satisfactory imaging results with high fluorescence intensity and imaging resolution in sentinel lymph node metastasis illumination and primary tumor location.Our findings provide a self-adaptive albumin-binding near-infrared probe conjugate for accurate diagnosis of primary tumors and lymphatic metastases.

Technology development and cost analysis of multiple pollutant abatement for ultra-low emission coal-fired power plants in China

The implementation of ultra-low emission(ULE)limits(SO_(2):35 mg/m3,NOx:50 mg/m3,PM:10 mg/m3)promoted the development of flue gas treatment technologies in China.Pollutant control technology development for Chinese coal-fired power plants was summarized and an analysis of the applicability and cost of pollutant control technologies was conducted.Detailed data were collected from 30 ultra-low emission coal-fired units across China.Based on a cost analysis model,the average unit power generation incremental costs were 0.0144and 0.0095 CNY/(kW·hr)for SO_(2)and NOx control technologies,respectively.The unit power generation incremental cost of twin spray tower technology was 7.2%higher than that of dual-loop spray tower technology.The effect of key parameters on operating cost was analyzed.The unit power generation incremental cost increased because of increments in the electricity price for SO_(2)control technology and the price of the reductant in NOx control technology.With high sulfur content or NOx concentration,the unit power generation incremental cost caused by pollutant control increased,whereas the unit pollutant abatement cost decreased.However,the annual operating hours or load increased,thereby leading to a decline in unit power generation incremental cost and unit pollutant abatement cost.

A risk assessment method considering risk attributes and work safety informational needs and its application

The technological revolution has spawned a new generation of industrial systems,but it has also put forward higher requirements for safety management accuracy,timeliness,and systematicness.Risk assessment needs to evolve to address the existing and future challenges by considering the new demands and advancements in safety management.The study aims to propose a systematic and comprehensive risk assessment method to meet the needs of process system safety management.The methodology first incorporates possibility,severity,and dynamicity(PSD)to structure the“51X”evaluation indicator system,including the inherent,management,and disturbance risk factors.Subsequently,the four-tier(risk point-unit-enterprise-region)risk assessment(RA)mathematical model has been established to consider supervision needs.And in conclusion,the application of the PSD-RA method in ammonia refrigeration workshop cases and safety risk monitoring systems is presented to illustrate the feasibility and effectiveness of the proposed PSD-RA method in safety management.The findings show that the PSD-RA method can be well integrated with the needs of safety work informatization,which is also helpful for implementing the enterprise's safety work responsibility and the government's safety supervision responsibility.

Mucinous colorectal adenocarcinoma:clinical pathology and treatment options

Mucinous colorectal adenocarcinoma is a distinct subtype of colorectal cancer(CRC)characterized by the pres-ence of abundant extracellular mucin which accounts for at least 50%of the tumor volume.Mucinous colorectal adenocarcinoma is found in 10%-20%of CRC patients and occurs more commonly in female and younger patients.Moreover,mucinous colorectal adenocarcinoma is more frequently located in the proximal colon and diagnosed at an advanced stage.Based on its molecular context,mucinous colorectal adenocarcinoma is associated with the over-expression of mucin 2(MUC2)and mucin 5AC(MUC5AC)proteins.At the same time,it shows higher mutation rates in the fundamental genes of the RAS/MAPK and PI3K/Akt/mTOR pathways.Mucinous colorectal adenocarcinoma also shows higher rates of microsatellite instability(MSI)than non-mucinous colorectal adenocarcinoma which might correlate it with Lynch syndrome and the CpG island methylator phenotype.The prognosis of mucinous colorectal adenocarcinoma as to non-mucinous colorectal adenocarcinoma is debatable.Further,the impaired responses of mucinous colorectal adenocarcinoma to palliative or adjuvant chemotherapy warrant more studies to be performed for a specialized treatment for these patients.In this review,we discuss the molecular background and histopathol-ogy of mucinous colorectal adenocarcinoma,and provide an update on its prognosis and therapeutics from recent literatures.

Pure photosensitizer-driven nanoassembly with core-matched PEGylation for imaging-guided photodynamic therapy

Pure drug-assembled nanomedicines(PDANs)are currently under intensive investigation as promising nanoplatforms for cancer therapy.However,poor colloidal stability and less tumor-homing ability remain critical unresolved problems that impede their clinical translation.Herein,we report a core-matched nanoassembly of pyropheophorbide a(PPa)for photodynamic therapy(PDT).Pure PPa molecules are found to self-assemble into nanoparticles(NPs),and an amphiphilic PEG polymer(PPaPEG_(2K))is utilized to achieve core-matched PEGylating modification via the p-p stacking effect and hydrophobic interaction between the PPa core and the PPa-PEG_(2K) shell.Compared to PCL-PEG_(2K) with similar molecular weight,PPa-PEG_(2K) significantly increases the stability,prolongs the systemic circulation and improves the tumor-homing ability and ROS generation efficiency of PPa-nanoassembly.As a result,PPa/PPa-PEG_(2K) NPs exert potent antitumor activity in a 4T1 breast tumor-bearing BALB/c mouse xenograft model.Together,such a core-matched nanoassembly of pure photosensitizer provides a new strategy for the development of imaging-guided theragnostic nanomedicines.

Erythrocyte membrane-camouflaged carrier-free nanoassembly of FRET photosensitizer pairs with high therapeutic efficiency and high security for programmed cancer synergistic phototherapy

Phototherapy has been intensively investigated as a non-invasive cancer treatment option.However,its clinical translation is still impeded by unsatisfactory therapeutic efficacy and severe phototoxicity.To achieve high therapeutic efficiency and high security,a nanoassembly of Forster Resonance Energy Transfer(FRET)photosensitizer pairs is developed on basis of dual-mode photosensitizer co-loading and photocaging strategy.For proof-of-concept,an erythrocyte-camouflaged FRET pair co-assembly of chlorine e6(Ce6,FRET donor)and 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindotricarbocyanine iodide(DiR,FRET acceptor)is investigated for breast cancer treatment.Notably,Ce6 in the nanoassemby is quenched by DiR and could be unlocked for photodynamic therapy(PDT)only when DiR is photobleached by 808-nm laser.As a result,Ce6-caused phototoxicity could be well controlled.Under cascaded laser irradiation(808-660 nm),tumor-localizing temperature rise following laser irradiation on DiR not only induces tumor cell apoptosis but also facilitates the tumor penetration of NPs,relieves tumor hypoxia,and promotes the PDT efficacy of Ce6.Such FRET pair-based nanoassembly provides a new strategy for developing multimodal phototherapy nanomedicines with high efficiency and good security.