Utilizing engineered extracellular vesicles as delivery vectors in the management of ischemic stroke:a special outlook on mitochondrial delivery

Ischemic stroke is a secondary cause of mortality worldwide,imposing considerable medical and economic burdens on society.Extracellular vesicles,serving as natural nanocarriers for drug delivery,exhibit excellent biocompatibility in vivo and have significant advantages in the management of ischemic stroke.However,the uncertain distribution and rapid clearance of extracellular vesicles impede their delivery efficiency.By utilizing membrane decoration or by encapsulating therapeutic cargo within extracellular vesicles,their delivery efficacy may be greatly improved.Furthermore,previous studies have indicated that microvesicles,a subset of large-sized extracellular vesicles,can transport mitochondria to neighboring cells,thereby aiding in the restoration of mitochondrial function post-ischemic stroke.Small extracellular vesicles have also demonstrated the capability to transfer mitochondrial components,such as proteins or deoxyribonucleic acid,or their sub-components,for extracellular vesicle-based ischemic stroke therapy.In this review,we undertake a comparative analysis of the isolation techniques employed for extracellular vesicles and present an overview of the current dominant extracellular vesicle modification methodologies.Given the complex facets of treating ischemic stroke,we also delineate various extracellular vesicle modification approaches which are suited to different facets of the treatment process.Moreover,given the burgeoning interest in mitochondrial delivery,we delved into the feasibility and existing research findings on the transportation of mitochondrial fractions or intact mitochondria through small extracellular vesicles and microvesicles to offer a fresh perspective on ischemic stroke therapy.

Exploring negative ion behaviors and their influence on properties of DC magnetron sputtered ITO films under varied power and pressure conditions

We deposited indium-tin-oxide(ITO)films on silicon and quartz substrates by magnetron sputtering technology in pure argon.Using electrostatic quadrupole plasma diagnostic technology,we investigate the effects of discharge power and discharge pressure on the ion flux and energy distribution function of incidence on the substrate surface,with special attention to the production of high-energy negative oxygen ions,and elucidate the mechanism behind its production.At the same time,the structure and properties of ITO films are systematically characterized to understand the potential effects of high energy oxygen ions on the growth of ITO films.Combining with the kinetic property analysis of sputtering damage mechanism of transparent conductive oxide(TCO)thin films,this study provides valuable physical understanding of optimization of TCO thin film deposition process.

Effects of power on ion behaviors in radio-frequency magnetron sputtering of indium tin oxide(ITO)

This study delves into ion behavior at the substrate position within RF magnetron discharges utilizing an indium tin oxide(ITO)target.The positive ion energies exhibit an upward trajectory with increasing RF power,attributed to heightened plasma potential and initial emergent energy.Simultaneously,the positive ion flux escalates owing to amplified sputtering rates and electron density.Conversely,negative ions exhibit broad ion energy distribution functions(IEDFs)characterized by multiple peaks.These patterns are clarified by a combination of radiofrequency oscillation of cathode voltage and plasma potential,alongside ion transport time.This elucidation finds validation in a one-dimensional model encompassing the initial ion energy.At higher RF power,negative ions surpassing 100 e V escalate in both flux and energy,posing a potential risk of sputtering damages to ITO layers.

Explaining the dynamics of the sub-relativistic electron third belt in the Earth's radiation belts by using medium Earth orbit satellite observations

The Earth's electron radiation belts typically exhibit a two-belt structure.However,observations from the Van Allen Probes revealed the existence of a three-belt structure.This structure consists of an inner belt,a slot region,a remnant belt,a“second slot,”and a new outer belt(or the“third belt”).The formation of the structure involves both the partial loss of the original outer belts and the formation of the third belts.These processes are likely associated with radial diffusion induced by ultra-low-frequency(ULF)waves.In this study,we mainly analyzed electron flux data from medium Earth orbit(MEO)navigation satellites M17–M19 to supplement the observational evidence for the sub-relativistic electron(~100–500 keV)three-belt structure.Evidence of substorm injections and ULF waves during the three-belt event was identified,suggesting they played significant roles in the formation and evolution of the third belt.Substorm injections may introduce new electron populations to the third belt,whereas ULF waves may influence the evolution of the third belt through radial diffusion.Toward the end of the three-belt event,the compression of the magnetosphere by shocks may lead to the dropout of the third belt because of the magnetopause shadowing effect and outward radial diffusion,ultimately disrupting the three-belt structure.This study provides more evidence for the presence of a sub-relativistic electron three-belt structure and offers an analysis of the evolutionary mechanisms of the third belt,which may contribute to a comprehensive understanding of the electron three-belt structure in the radiation belts.

Ni-catalyzed carbon–carbon bonds cleavage of mixed polyolefin plastics waste

The inert carbon–carbon(C–C) bonds cleavage is a main bottleneck in the chemical upcycling of recalcitrant polyolefin plastics waste. Here we develop an efficient strategy to catalyze the complete cleavage of C–C bonds in mixed polyolefin plastics over non-noble metal catalysts under mild conditions. The nickelbased catalyst involving Ni_(2)Al_(3) phase enables the direct transformation of mixed polyolefin plastics into natural gas, and the gas carbon yield reaches up to 89.6%. Reaction pathway investigation reveals that natural gas comes from the stepwise catalytic cleavage of C–C bonds in polypropylene, and the catalyst prefers catalytic cleavage of terminal C–C bond in the side-chain with the low energy barrier.Additionally, our developed approach is evaluated by the technical economic analysis for an economically competitive production process.

Donkey whey proteins ameliorate dextran sulfate sodium-induced ulcerative colitis in mice by downregulating the S100A8-TRAF6-NF-κB axis-mediated inflammatory response

Donkey milk has a variety of physiological functions, including antibacterial and anti-inflammatory. Donkey whey proteins(DWPs), as the main functional component in donkey milk, its inhibitory effect on colitis is still unclear. In this study, the inhibitory effect and potential mechanism of DWPs on dextran sulfate sodium(DSS)-induced colitis were investigated. Firstly, the DWPs and bovine milk whey proteins(BWPs)were characterized using proteomics. Then, we administered DWPs and BWPs to mice with colitis via oral gavage. The results of immunohistochemistry and flow cytometry indicated that DWPs increased T regulatory cell accumulation and increased the abundance of the cluster of differentiation 205+(CD205+)macrophages compared to those with BWPs and in model groups. In addition, DWPs exhibited a more remarkable ability to inhibit pro-inflammatory proteins(S100A8, TRAF6, and NF-κB)expression and inflammatory secretion than BWPs. In addition, DWPs significantly decreased NF-κB and CD86 levels more than BWPs or the negative control in both LPS-stimulated human peripheral blood mononuclear cells or cell lines. These findings indicate that DWPs comprise a promising anti-colitis functional food, and this work has established a foundation for future research on these compounds.

Identification of 13th-14th Century Chinese Handmade Paper Fibers Collected in Yuan Dynasty Paper Currencies

The earliest paper currencies in existence in China were handcrafted during the Yuan dynasty.These currencies were scientifically excavated from different ruins or tombs,whereas scientific analyses of the papers are rare.This study used optical and scanning electron microscopy to examine the fibers collected in Yuan dynasty paper currencies in conjunction with the Herzberg staining method.Despite differences in circulation period,paper fibers in both Zhi Yuan Tong Xing Bao Chao(two Guan)and Zhong Tong Yuan Bao Jiao Chao(one Guan and 500 Wen,issued in Zhi Zheng period)were identified as similar papermaking materials,bast fibers of mulberry bark.The results indicate that mulberry bark,a durable papermaking material used since ancient times,was mainly utilized as a raw material in these Yuan dynasty paper currency.This fiber identification work solved the critical problem of papermaking material in the Yuan dynasty paper currency and provided important information for conserving these precious cultural relics.

Validation of neuropathic pain assessment tools among Chinese patients with painful diabetic peripheral neuropathy

Objective:This study aims to evaluate the reliability and validity of neuropathic pain assessment tools among Chinese patients with painful diabetic peripheral neuropathy(PDPN).Methods:One hundred patients with PDPN and 70 patients with non-neuropathic pain were recruited from five grade III general hospitals in Guangzhou.Pain was assessed using the Leeds Assessment of Neuropathic Symptoms and Signs(LANSS),Douleur Neuropathique 4 questionnaire(DN4),and Brief Pain Inventory for Painful Diabetic Peripheral Neuropathy(BPI-DPN).Reliability was evaluated by internal consistency of the Cronbach's a coefficient and Guttman split-half.Construct validity was analyzed by factor analysis and Spearman correlation coefficients.Sensitivity and specificity were also assessed.Results:The Cronbach's a coefficients of the LANSS,DN4,and BPI-DPN were 0.735,0.750,and 0.898,respectively.The Guttman split-half coefficients of the LANSS,DN4,and BPIDPN were 0.660,0.726,and 0.849,respectively.The cumulative contributions of the LANSS,DN4,and BPI-DPN to the total variance were 61.945%,57.010%,and 66.056%,respectively.The items of the LANSS,DN4,and BPI-DPN presented high factorial loads,ranging from 0.387 to 0.841,0.137 to 0.948,and 0.487 to 0.953,respectively.The LANSS and DN4 exhibited sensitivities of 58.0%and 82.7%,respectively,and specificity of 97.1%.Conclusions:The LANSS or DN4 can be used to detect neuropathic pain in Chinese patients with PDPN.The BPI-DPN can be employed to monitor the effectiveness of pain intervention.

The properties of N-doped diamond-like carbon films prepared by helicon wave plasma chemical vapor deposition

In this paper, N-doped diamond-like carbon(DLC) films were deposited on silicon substrates by using helicon wave plasma chemical vapor deposition(HWP-CVD) with the Ar/CH_4/N_2 mixed gas. The surface morphology, structural and mechanical properties of the N-doped DLC films were investigated in detail by scanning electron microscopy(SEM), x-ray photoelectron spectroscopy(XPS), Raman spectra, and atomic force microscopy(AFM). It can be observed from SEM images that surface morphology of the films become compact and uniform due to the incorporation of N. The maximum of the deposition rate of the films is 143 nm min^(-1), which is related to the high plasma density. The results of XPS show that the N incorporates in the films and the C-C sp^3 bond content increases firstly up to the maximum(20%) at 10 sccm of N_2 flow rate, and then decreases with further increase in the N_2 flow rate. The maximum Young's modulus of the films is obtained by the doping of N and reaches 80 GPa at 10 sccm of N_2 flow rate, which is measured by AFM in the scanning probe microscope mode. Meanwhile, friction characteristic of the N-doped DLC films reaches a minimum value of 0.010.

Photonic-plasmonic hybrid microcavities: Physics and applications

Photonic-plasmonic hybrid microcavities,which possess a higher figure of merit Q/V(the ratio of quality factor to mode volume)than that of pure photonic microcavities or pure plasmonic nano-antennas,play key roles in enhancing light–matter interaction.In this review,we summarize the typical photonic-plasmonic hybrid microcavities,such as photonic crystal microcavities combined with plasmonic nano-antenna,whispering gallery mode microcavities combined with plasmonic nano-antenna,and Fabry–Perot microcavities with plasmonic nano-antenna.The physics and applications of each hybrid photonic-plasmonic system are illustrated.The recent developments of topological photonic crystal microcavities and topological hybrid nano-cavities are also introduced,which demonstrates that topological microcavities can provide a robust platform for the realization of nanophotonic devices.This review can bring comprehensive physical insights of the hybrid system,and reveal that the hybrid system is a good platform for realizing strong light–matter interaction.

Thermal stability and thermoelectric properties of Cd-doped nano-layered Cu2Se prepared using NaCl flux method

Cu2Se is a promising"phonon liquid-electron crystal"thermoelectric material with excellent thermoelectric performance.In this work,Cd-doped Cu2-xSeCdx(x=0,0.0075,0.01,and 0.02)samples were prepared using NaCl flux method.The solubility of Cd in Cu2Se at room temperature was less than 6%,and a second phase of CdSe was found in the samples with large initial Cd content(x=0.01 and 0.02).Field-emission scanning electron microscopic image showed that the arranged lamellae formed a large-scale layered structure with an average thickness of approximately 100 nm.Transmission electron microscopy demonstrated that doping of Cd atoms did not destroy the crystal integrity of Cu2Se.A small amount of Cd in Cu2Se could reduce the electrical and thermal conductivities of the material,thus significantly enhancing its thermoelectric performance.With the increase in Cd content in the sample,the carrier concentration decreased and the mobility increased gradually.Thermogravimetric differential thermal analysis showed that no weight loss occurred below the melting point.Excessive Cd doping led to the emergence of the second phase of CdSe in the sample,thus significantly increasing the thermal conductivity of the material.A maximum ZT value of 1.67 at 700 K was obtained in the Cu1.9925SeCd0.0075 sample.

Synthesis of Ag-decorated vertical graphene nanosheets and their electrocatalytic efficiencies

Herein we report the successful preparation of silver(Ag)-decorated vertically oriented graphene sheets(Ag/VGs)via helicon wave plasma chemical vapor deposition(HWP-CVD)and radiofrequency plasma magnetron sputtering(RF-PMS).VGs were synthesized in a mixture of argon and methane(Ar/CH_(4))by HWP-CVD and then the Ag nanoparticles on the prepared VGs were modified using the RF-PMS system for different sputtering times and RF power levels.The morphology and structure of the Ag nanoparticles were characterized by scanning electron microscopy and the results revealed that Ag nanoparticles were evenly dispersed on the mesoporous wall of the VGs.X-ray diffraction results showed that the diameter of the Ag particles increased with the increase in Ag loading,and the average size was between 10.49 nm and 25.9 nm,consistent with the transmission electron microscopy results.Ag/VGs were investigated as effective electrocatalysts for use in an alkaline aqueous system.Due to the uniquely ordered and interconnected wall structure of VGs,the area of active sites increased with the Ag loading,giving the Ag/VGs a good performance in the oxygen evolution reaction.The double-layer capacitance(C_(dl))of the Ag/VGs under different Ag loadings were studied,and the results showed that the highest Ag content gave the best C_(dl)(1.04 mF cm^(-2)).Our results show that Ag/VGs are likely to be credible electrocatalytic materials.

Insight into synergistic antioxidation mechanisms of butyl hydroxyanisole with common synthetic antioxidants

Butyl hydroxyanisole(BHA) is usually blended with other synthetic antioxidants to improve the antioxidative property due to synergistic antioxidation. However, the synergistic antioxidation mechanisms of BHA with synergists have not been revealed yet. Thus, the antioxidation of BHA with butylated hydroxytoluene(BHT), tert-butylhydroquinone(TBHQ), or propyl gallate(PG) was investigated in the 2,2-azobis(2-amidino-propane) dihydrochloride oxidizing system. The contents of BHA, BHT, TBHQ,PG, and transformation products were measured by high-performance liquid chromatography. Transformation products were identified with liquid chromatography-mass spectrometry and gas chromatography–mass spectrometry. Results showed that synergistic antioxidation occurred between BHA and BHT, TBHQ, or PG. The synergistic antioxidation effect of BHA and BHT was attributed to the regeneration of BHA by BHT. Transformation products of BHA and BHT(compounds 6 and 7, dimers of BHA and BHT) had little contribution due to the relatively low content(<0.6%). The synergistic antioxidation effect of BHA and TBHQ or BHA and PG was attributed to the protective mechanism of TBHQ or PG on BHA. No transformation products were detected of BHA and TBHQ. Transformation products of BHA and PG(compounds 9 and 10, dimers of BHA and PG) had limited contribution due to the relatively low percentage(<7%). Therefore, BHA and BHT performed competitive antioxidation,while BHA and TBHQ or PG performed protective antioxidation.

腭裂手术模拟训练的研究进展

腭裂是常见的颌面部先天性发育缺陷,表现为腭部组织结构的不连续性,导致食物反流、发音不清、听力受损等问题,严重影响患者的生存质量。目前,手术治疗是腭裂的主要治疗手段,是颌面外科最重要的一类手术。然而,腭裂手术复杂、手术视野范围小,给手术观摩和学习带来了极大的挑战,且初学者很难在真人患者上进行训练。因此,需要腭裂手术模拟训练帮助口腔医学生了解腭裂的病理结构,掌握腭裂手术流程和手术技法。本文将对目前的腭裂手术模拟器做一综述,旨在为临床上腭裂手术教学和训练提供参考。

微矿分离:煤炭清洁化与土壤改良的新契机

报道一种新型的矿物分离技术.该技术集成了磨矿、分离、颗粒级配和土壤改良技术,是结合微纳米科学与材料加工技术等开发的一种多学科交叉的能源化工创新性技术.利用此技术可以高效地选择性脱除含碳材料源中的微量元素及矿物质,制备出清洁固体燃料(clean solid fuel,CSF)、清洁类液体燃料(pseudo liquid fuel,PLF)以及土壤改良矿物质(soil remediation minerals,SRM),简称为微矿分离(RMS)技术.该技术主要包括4个工艺步骤:(1)基于矿物嵌布形态解构,采用流体磨实现碳质组分与无机组分的高效解离;(2)采用颗粒表面改性、多相流界面调控及专用助剂等将碳质颗粒和无机颗粒高效分离;(3)分离之后形成的碳质颗粒流,脱水制成CSF,或者进入PLF制备单元,同时无机颗粒流经脱水制成SRM;(4)采用多峰级配将碳质颗粒制成高浓度PLF.RMS工艺技术经小试和工业放大试验,已完成工业放大验证,可燃体回收率大于80%的同时CSF灰分小于7%.SRM制成的天然矿物质肥料和土壤改良剂,可有效缓解表土流失问题,提高植被及作物产量,通过植物及土壤增量固碳,进而达到碳中和目的.RMS技术可生产低成本的清洁燃料并可实现煤基固废的资源化利用,为煤炭的高效清洁化利用和CO2减排提供了可靠的途径.

High-performance porous carbon foams via catalytic pyrolysis of modified isocyanate-based polyimide foams for electromagnetic shielding

Porous carbon skeletons(PCSs)derived from isocyanate-based aromatic polyimide foams(PIFs)by high-temperature pyrolysis are very promising in the fabrication of high-performance polymer composite foams for electromagnetic interference(EMI)shielding due to their efficient conductive networks and facile preparation process.However,severe volumetric shrinkage and low graphitization degree is not conducive to enhancing the shielding efficiency of the PCSs.Herein,ferric acetylacetonate and carbon-nanotube coating have been introduced in isocyanate-based PIFs to greatly suppress the serious shrinkage during pyrolysis and improve the graphitization degree of the final carbon foams through the Fe-catalytic graphitization process,thereby endowing them with better EMI-shielding performance even at lower pyrolysis temperature compared to the control samples.Moreover,compressible polydimethylsiloxane(PDMS)composite foams with the as-prepared carbon foams as prefabricated PCSs have also been fabricated,which could provide not only stable shielding effectiveness(SE)performance even after a thousand compressions,but also multiple functions of Joule heating,thermal insulation and infrared stealth.This study offers a feasible route to prepare high-performance PCSs in a more energy-efficient manner via PIF pyrolysis,which is very promising in the manufacture of multifunctional conductive polymer composite foams.

Efficacy and safety of low-dose interleukin-2 in combination with methotrexate in patients with active rheumatoid arthritis:a randomized,double-blind,placebo-controlled phase 2 trial

Rheumatoid arthritis(RA)is an aggressive autoimmune arthritis,and current therapies remain unsatisfactory due to low remission rate and substantially adverse effects.Low-dose interleukin-2(Ld-IL2)is potentially a therapeutic approach to further improve the disease.This randomized,double-blind,placebo-controlled trial was undertaken to evaluate the efficacy and safety of Ld-IL2 in patients with active RA.Patients were randomly assigned(1:1)to receive Ld-IL2,defined as a dose of 1 million IU,or placebo in a 12-week trial with a 12-week follow-up.Three cycles of Ld-IL2 or placebo were administered subcutaneously every other day for 2 weeks(a total of 7 doses),followed by a 2-week break.All patients received a stable dose of methotrexate(MTX).The primary outcomes were the proportion of patients achieving the ACR20,DAS28-ESR<2.6,and the change from baseline in CDAI or SDAI at week 24.Secondary endpoints included other clinical responses and safety.The primary outcomes were achieved in the perprotocol population.The improvements from baseline in CDAI and SDAI were significantly greater across time points for the LdIL2+MTX group(n=17)than for the placebo+MTX group(n=23)(P=0.018 and P=0.015,respectively).More patients achieved ACR20 response in the Ld-IL2+MTX group than those in the placebo+MTX group at week 12(70.6%vs 43.5%)and at week 24(76.5%vs 56.5%)(P=0.014).In addition,low Treg and high IL-21 were associated with good responses to Ld-IL2.Ld-IL-2 treatment was well-tolerated in this study.These results suggested that Ld-IL2 was effective and safe in RA.ClinicalTrials.gov number:NCT 02467504.

Hydrogen-incorporated vanadium dioxide nanosheets enable efficient uranium confinement and photoreduction

Photocatalytic reduction of U(VI)represents a novel and effective manner for the removal of U(VI)pollutant from radioactive wastewater.Herein,we successfully incorporated hydrogen into VO_(2)nanosheets,which strengthened the interaction between VO_(2)and U(VI),thereby achieving a highly active and stable photocatalyst for U(VI)reduction.With the increase of H content in hydric VO_(2)(H_(x)-VO_(2))nanosheets,the bandgap shrank from 2.29 to 1.66 eV,whereas the position of conduction bands remained more negative than the reduction potential of U(VI)/U(IV)(0.41 V vs.NHE).When irradiated by simulated sunlight,the U(VI)removal efficiency over H0.613-VO_(2)nanosheets reached up to 95.4%within 90 min,which largely outperformed 28.3%of pristine VO_(2)nanosheets.The mechanistic study demonstrated that the hydroxylated surface gave rise to the balanced O confinement sites in VO_(2)(011),leading to the stabilized adsorption configuration and increased binding strength of UO_(2)^(2+)on H_(x)-VO_(2)nanosheets.

Biomass-based aligned carbon networks with double-layer construction for tunable electromagnetic shielding with ultra-low reflectivity

Nowadays,carbon frameworks derived from natural biomaterials have attracted extensive attention for electromagnetic interference(EMI)shielding due to their renewability and affordability.However,it is critical and challenging to achieve effective regulation of shielding effectiveness(SE)as well as weaken the strong EM reflection of highly conductive biomass-based carbon materials.Herein,commercial cotton pads with oriented structure were selected as carbonaceous precursor to fabricate aligned carbon networks by pyrolysis,and the EMI SE of the samples with increased temperature of 800-1000℃ can be accurately controlled in the effective range of~21.7-29.1,~27.7-37.1 and~32.7-43.3 d B with high reflection coefficient of>0.8 by changing the cross-angle between the electric-field direction of incident EM waves and the fiber-orientation direction due to the occurrence of opposite internal electric field.Moreover,the further construction of Salisbury absorber-liked double-layer structure could result in an ultralow reflection coefficient of only~0.06 but enhanced SE variation range up to~38.7-49.3 d B during the adjustment of cross-angle,possibly due to the destructive interference of EM waves in the double-layer carbon networks.This work would provide a simple and effective way for constructing high-performance biomass carbon materials with adjustable EMI shielding and ultra-low reflectivity.

Surface charge-convertible quaternary ammonium salt-based micelles for in vivo infection therapy

Quaternary ammonium salts(QASs) are excellent candidates for treating stubborn bacterial infections caused by biofilms due to their high sterilization efficiency and potential inhibition of the development of drug resistance.However,the inherent toxicity of QASs,including cytotoxicity,protein absorption and hemolysis,severely limits their applications in vivo.Herein,a charge-co nvertible quaternary ammonium salt-based micelle(QAS-SL@CM) was constructed by co-assembly of two amphiphiles with opposite charges and shell cross-linking strategy.The toxicity of the QAS-SL@CM could be greatly reduced towa rds human cells contrast to the corresponding QASs.By response to the acidic environment at infection sites,the surface charge of QAS-SL@CM could be immediately changed to positive and then target to negatively charged bacteria.Furthermo re,β-thiopropionate bonds on QAS-SL@CM could also be disintegrated under acid environment to release QASs to kill bacteria.Importantly,the QAS-SL@CM showed significant therapeutic effect in mice subcutaneous abscesses models without interference with normal cells.Therefore,a surface adaptive micelle constructed by charge-convertible strategy has been developed to ove rcome the cytotoxicity of QAS s,and could intelligently respond to the microenvironment of infected wound for in vivo infection therapy,which shows promising application in clinic.