干性年龄相关性黄斑变性免疫学机制的研究进展

干性年龄相关性黄斑变性(ARMD)是一种发病机制尚不完全明确的退行性眼底病变,可造成中心视力不可逆的损失,以黄斑部色素紊乱、玻璃膜疣生成及地图样萎缩为主要眼底表现。免疫与炎性反应在本病的发展过程中起到关键作用,免疫分子中的补体系统、模式识别受体、炎症小体及多种细胞因子等均与干性ARMD的发生密切相关。现将这些免疫分子与干性ARMD的最新研究进展做一综述。

Surface‑Alloyed Nanoporous Zinc as Reversible and Stable Anodes for High‑Performance Aqueous Zinc‑Ion Battery

Metallic zinc(Zn)is one of the most attractive multivalent-metal anode materials in post-lithium batteries because of its high abundance,low cost and high theoretical capacity.However,it usually suffers from large voltage polarization,low Coulombic efficiency and high propensity for dendritic failure during Zn stripping/plating,hindering the practical application in aqueous rechargeable zinc-metal batteries(AR-ZMBs).Here we demonstrate that anionic surfactant-assisted in situ surface alloying of Cu and Zn remarkably improves Zn reversibility of 3D nanoporous Zn electrodes for potential use as high-performance AR-ZMB anode materials.As a result of the zincophilic ZnxCuy alloy shell guiding uniform Zn deposition with a zero nucleation overpotential and facilitating Zn stripping via the ZnxCuy/Zn galvanic couples,the self-supported nanoporous ZnxCuy/Zn electrodes exhibit superior dendrite-free Zn stripping/plating behaviors in ambient aqueous electrolyte,with ultralow polarizations under current densities up to 50 mA cm^(‒2),exceptional stability for 1900 h and high Zn utilization.This enables AR-ZMB full cells constructed with nanoporous ZnxCuy/Zn anode and K_(z)MnO_(2)cathode to achieve specific energy of as high as~430 Wh kg^(‒1)with~99.8%Coulombic efficiency,and retain~86%after long-term cycles for>700 h.

Mechanism of CO_(2) enhanced oil recovery in shale reservoirs

Combined with NMR,core experiment,slim-tube tests,nano-CT and oil composition analysis,the mechanism of CO(2) enhanced oil recovery had been studied.CO_(2) flooding under supercritical state could achieve higher oil recovery.In the process of crude oil displaced by supercritical CO2,the average oil recovery was 46.98% at low displacement pressures and 73.35% at high displacement pressures.The permeability of cores after CO2 flooding was only 28%-64% of those before flooding.As to the expelled oil,the contents of asphaltenes and non-hydrocarbons decreased,and saturated hydrocarbons of above C25 were absent in some samples,indicating that they had been retained in cores as demonstrated by CT and NMR experiments.In slim-tube tests,the heavy components of oil were expelled when the pressure increased to 30 MPa.There was a reasonable bottom hole pressure(BHP) below which the heavy components driven out from the far-well zone would deposit in the near-well zone,and when the pressure was too high,the nonhydrocarbon detention may cause block.The smaller throat and worse physical properties the porous media had,the higher displacement pressure would be required to achieve a good oil displacement efficiency.The increase in displacement pressure or time of interaction between oil and CO2 could effectively enhance oil recovery.

Painlevé integrability of the supersymmetric Ito equation

A supersymmetric version of the Ito equation is proposed by extending the independent and dependent variables for the classic Ito equation.To investigate the integrability of the N = 1 supersymmetric Ito(sIto) equation, a singularity structure analysis for this system is carried out.Through a detailed analysis in two cases by using Kruskal's simplified method, the sIto system is found to pass the Painleve test, and thus is Painlevé integrable.

Meta-analysis of traditional Chinese medicine and western medicine in treating retinal vein occlusion complicated by macular edema

Objective:TMeta-analysis was performed to evaluate the clinical efficacy of the combination of traditional Chinese medicine and western medicine in treating patients with retinal vein occlusion(RVO)complicated by macular edema(ME).Methods:We searched The CNKI,Wanfang Data,PubMed and Cochrane Library from database.All of randomized controlled trials(RCTs)of the combination of traditional Chinese medicine and western medicine in treating patients with RVO complicated by ME were searched.The Revman5.3 software were used for meta-analysis.Results:A total of 30 trials involving 1943 patients and 1976 eyes were included.Meta-analysis showed that compared with western medicine,the combination of traditional Chinese medicine and western medicine can significantly improve the best corrected visual acuity[(MD=0.08,95%CI=0.07~0.10,P<0.00001)(MD=-0.16,95%CI=-0.24^-0.08,P=0.0002)(MD=5.78,95%CI=1.30~10.25,P=0.01)],reduce the central macular thickness(MD=-54.6,95%CI=-73.76^-35.43,P<0.00001),and improve the clinical effective rate(RR=1.32,95%CI=1.22~1.43,P<0.00001).Conclusion:The combination of traditional Chinese and western medicine in treating patients with RVO complicated by ME was superior to western medicine in improving the best corrected visual acuity,reducing the thickness of macular fovea and improving the clinical efficacy.

Remote substituent effects on catalytic activity of metal-organic frameworks: a linker orbital energy model

The Hammett equation is commonly used to theoretically depict the remote electronic effects of substituents on catalytic activitiesof metal nodes of metal-organic frameworks (MOFs). However, the application of the theory to MOF catalysts usually encountersproblems because it relies heavily on empirical parameters with unknown transferability. To develop an alternative predictiontheory, the linker orbital energy model has been proposed by density functional theory calculations. The model provides a simplemethod to approximately depict the remote electronic substituent effects on catalytic activities of metal nodes of MOFs, and itsgeneral applicability to MOFs is supported by extensively revisiting the structure-activity relationships reported in the literatures.The model can be used to design catalytic activity of metal nodes of MOFs by engineering the electronic properties of linkers andsubstituents.

Enrichment of nano delivery platforms for mRNA-based nanotherapeutics

Lipid-based nanoparticles(LNP)have shown significant progress in delivering mRNA for therapeutics,particularly with the success of coronavirus disease 2019(COVID-19)vaccines.However,there are still challenges,such as organ-specific targeting,sustained protein expression,immunogenicity,and storage that need to be addressed.Therefore,there is interest in developing additional nano drug delivery systems(DDS)to complement LNP technology.Some of these include polymer,lipid-polymer hybrid,organic/inorganic hybrid nanostructure,and inorganic nanoparticle.In our opinion,LNP technology may not be suitable for every disease scenario in categories such as infection disease,cancer,pulmonary disease,autoimmune disorders and genetic rare disease(among others).This is because different diseases may require distinct administration routes,doses,and treatment durations,as well as considerations for biological barriers that may lower the efficacy and/or exert safety concern.In this perspective,we will highlight the need and potential for enhancing the diversity of nano delivery platforms for mRNA-based nanotherapeutics.

联合递送IDO抑制剂和紫杉醇用于癌症治疗

为实现化学疗法与免疫疗法的联合应用,本研究合成了具有还原响应性的紫杉醇(Paclitaxel,PTX)前药PEG-SS-PTX,并以此为载体包载吲哚胺2,3-双加氧酶(Indoleamine2,3-dioxygenase,IDO)抑制剂CY-1-4制备PEG-SS-PTX/CY-1-4NPs。通过细胞毒作用、免疫原性细胞死亡(Immunogeniccell death,ICD)诱导能力和抗肿瘤功效对PEG-SS-PTX/CY-1-4NPs进行评估。动态光散射(Dynamic light scattering,DLS)结果显示PEG-SS-PTX/CY-1-4 NPs粒径约为149 nm。体外实验结果表明PEG-SS-PTX/CY-1-4NPs的细胞毒性具有浓度依赖性,并且能够引发B16-F10细胞的ICD。体内实验结果表明PEG-SS-PTX/CY-1-4 NPs在小鼠黑色素瘤模型中能够显著抑制肿瘤生长,降低IDO在肿瘤组织中的表达,并且能够增加脾脏中CD8+T细胞比例。综上,PEG-SS-PTX/CY-1-4 NPs达到良好抗肿瘤效果的同时降低了化疗药物的给药剂量,是一种安全有效的联合递送平台。

Linking, thinking & fixing:the story about the 2015 Chemistry Nobel Prize and the future of science

Did you know there are roughly over 10,000 DNA damages in a cell per day?Do not be too alarmed though,thanks to various vital DNA repair mechanisms we are able to continue function normally as an organism and maintain our genome integrity.It is no wonder then why this year prestigious Chemistry Nobel Prize(s)went to Drs.Thomas Lindahl,Aziz Sancar,and Paul Modrich for their

Bioinspired synthesis of CVD graphene flakes and graphene-supported molybdenum sulfide catalysts for hydrogen evolution reaction

Chemical vapor deposition has been the most-promising approach for growing large-area high-quality graphene films on planar substrates. Beyond the lateral growth, the synthesis of three-dimensional （3D） graphene has also been demon- strated recently on metal foams and insulating nanoparticles for exploring their applications in electrochemical electrodes. However, the existing approaches need either to prefabricate abundant starting substrates, or to construct porous frameworks for graphene growth. Herein, we report a straightforward, bioinspired strategy for growing large-quantity graphene flakes on cuttlebone substrates using the chemical vapor deposition （CVD） method. The separated graphene flakes from growth substrates are highly crystalline and layer-thickness controllable, outperforming the traditional chemically exfoliated graphene with few surface groups. Due to their inheriting the biomineral-derived morphology, the 3D graphene microstructures show a highly exposed and curved surface, which can load more MoSx（x ≥ 2） catalysts than other planar supports for highly efficient hydrogen generation. Briefly, the bioinspired approach is expected to achieve a reasonable balance between quality and quantity for graphene production, thus propelling its wide applications in energy storage and conversion devices.

Efficient nano-enabled therapy for gastrointestinal cancer using silicasome delivery technology

The gastrointestinal tract is an eight-meter-long pathway that includes various organs,which runs from the mouth to the anus.Under certain pathological circumstances,tumors can develop in one of these organs.Although these tumors could be surgically removed at an early stage of their development,the disease could be incurable and fatal if they progress.In this article,we review our recent progress in the development of a series of rationally designed mesoporous silica nanoparticles(MSNP),which includes the use of a supported lipid bilayer(a.k.a.silicasome),to provide more efficacious and well-tolerated chemotherapy and/or chemo-immunotherapy for the different types of gastrointestinal(GIT)cancer,such as pancreatic ductal adenocarcinoma(PDAC)and colorectal cancer(CRC).Through the use of our silicasome platform,we were able to deliver single-drug or synergistic drug combinations to orthotopic PDAC tumors in murine Kras and human-derived PDAC models.We also developed a scalable silicasome formulation for the weak-base anticancer drug,irinotecan,leading to a highly potent treatment option for mice with reduced toxicity.To address the complex and heterogeneous tumor microenvironment(TME),we have discussed the impact of stroma nanoengineering by transcytosis activation or vascular access improvement,which could enhance the effectiveness of nanocarriers in vivo.Recently,we have upgraded our drug-delivering silicasome as a chemoimmunotherapy platform that implements immunogenic cell death(ICD)as an endogenous vaccination approach.When cointerference occurs in regionally overexpressed immune checkpoint pathways,it was possible to generate a"hot"tumor microenvironment and propagate anticancer immunity,leading to long-lasting anticancer effects.These advanced preclinical results are promising and expected to generate a positive impact by providing efficacious and safe nanocarriers that can be placed into the pipeline of novel nanomedicine for the management of GIT cancer.

Immunological effects of nano-enabled hyperthermia for solid tumors: opportunity and challenge

Compared to conventional hyperthermia that is limited by low selectivity and severe side effects,nano-enabled hyperthermia yields great potentials to tackle these limitations for cancer treatment.Another major advance is the observation of immunological responses associated with nano-enabled hyperthermia,which introduces a new avenue,allowing a potential paradigm shift from the acutely effective and cytotoxicity-centric response to the next-phase discovery,i.e.,long-lasting and/or systemic anti-tumor immunity.This perspective first discusses the temperature-gradient and the spatially-structured immunological landscape in solid tumors receiving nano-enabled hyperthermia.This includes the discussion about underlying mechanism such as immunogenic cell death,which initiates a profound immunological chain reaction.In order to propagate the immune activation as a viable therapeutic principle,we further discussed the tumor type-specific complexity in the immunological tumor microenvironment,including the creative design of nano-enabled combination therapy to synergize with nano-enabled hyperthermia.