Nanoparticles for the treatment of spinal cord injury

Spinal cord injuries lead to significant loss of motor, sensory, and autonomic functions, presenting major challenges in neural regeneration. Achieving effective therapeutic concentrations at injury sites has been a slow process, partly due to the difficulty of delivering drugs effectively. Nanoparticles, with their targeted delivery capabilities, biocompatibility, and enhanced bioavailability over conventional drugs, are garnering attention for spinal cord injury treatment. This review explores the current mechanisms and shortcomings of existing treatments, highlighting the benefits and progress of nanoparticle-based approaches. We detail nanoparticle delivery methods for spinal cord injury, including local and intravenous injections, oral delivery, and biomaterial-assisted implantation, alongside strategies such as drug loading and surface modification. The discussion extends to how nanoparticles aid in reducing oxidative stress, dampening inflammation, fostering neural regeneration, and promoting angiogenesis. We summarize the use of various types of nanoparticles for treating spinal cord injuries, including metallic, polymeric, protein-based, inorganic non-metallic, and lipid nanoparticles. We also discuss the challenges faced, such as biosafety, effectiveness in humans, precise dosage control, standardization of production and characterization, immune responses, and targeted delivery in vivo. Additionally, we explore future directions, such as improving biosafety, standardizing manufacturing and characterization processes, and advancing human trials. Nanoparticles have shown considerable progress in targeted delivery and enhancing treatment efficacy for spinal cord injuries, presenting significant potential for clinical use and drug development.

Temperature-dependent solubility of Rebaudioside A in methanol/ethanol and ethyl acetate mixtures:Experimental measurements and thermodynamic modeling

The equilibrium solubility of Rebaudioside A(Reb A)FormⅡin binary mixtures of methanol/ethanol and ethyl acetate was quantitatively determined within the temperature range of 283.15—328.15 K at ambient pressure.The experimental findings indicate a positive correlation between the solubility of Reb A(FormⅡ)and both the temperature and the methanol/ethanol content in the solvent system.To describe the solubility data,six distinct models were employed:the modified Apelblat equation,theλh model,the combined nearly ideal binary solvent/Redlich—Kister(CNIBS/R—K)model,the van't HoffJouyban-Acree(VJA)model,the Apelblat-Jouyban-Acree(AJA)model,and the non-random two-liquid(NRTL)model.The combined nearly ideal binary solvent/Redlich—Kister model exhibited the most precise fit for solubility in methanol+ethyl acetate mixtures,reflected by an average relative deviation(ARD)of 0.0011 and a root mean square deviation(RMSD)of 12×10^(-7).Conversely,for ethanol+ethyl acetate mixtures,the modified Apelblat equation provided a superior correlation(ARD=0.0014,RMSD=4×10^(-7)).Furthermore,thermodynamic parameters associated with the dissolution of Reb A(FormⅡ),including enthalpy,entropy,and the Gibbs energy change,were inferred from the data.The findings underscore that the dissolution process is predominantly endothermic across the solvent systems examined.Notably,the entropy changes appear to have a significant influence on the Gibbs free energy associated with the dissolution of Reb A(FormⅡ),suggesting that entropic factors may play a pivotal role in the studied systems.

TDERS,an exosome RNA-derived signature predicts prognosis and immunotherapeutic response in clear cell renal cell cancer:a multicohort study

Background:Tumor-derived exosomes are involved in tumor progression and immune invasion and might func-tion as promising noninvasive approaches for clinical management.However,there are few reports on exosom-based markers for predicting the progression and adjuvant therapy response rate among patients with clear cell renal cell carcinoma(ccRCC).Methods:The signatures differentially expressed in exosomes from tumor and normal tissues from ccRCC pa-tients were correspondingly deregulated in ccRCC tissues.We adopted a two-step strategy,including Lasso and bootstrapping,to construct a novel risk stratification system termed the TDERS(Tumor-Derived Exosome-Related Risk Score).During the testing and validation phases,we leveraged multiple external datasets containing over 2000 RCC cases from eight cohorts and one inhouse cohort to evaluate the accuracy of the TDERS.In addition,enrichment analysis,immune infiltration signatures,mutation landscape and therapy sensitivity between the high and low TDERS groups were compared.Finally,the impact of TDERS on the tumor microenvironment(TME)was also analysed in our single-cell datasets.Results:TDERS consisted of 12 mRNAs deregulated in both exosomes and tissues from patients with ccRCC.TDERS achieved satisfactory performance in both prognosis and immune checkpoint inhibitor(ICI)response across all ccRCC cohorts and other pathological types,since the average area under the curve(AUC)to predict 5-year overall survival(OS)was larger than 0.8 across the four cohorts.Patients in the TDERS high group were resistant to ICIs,while mercaptopurine might function as a promising agent for those patients.Patients with a high TDERS were characterized by coagulation and hypoxia,which induced hampered tumor antigen presentation and relative resistance to ICIs.In addition,single cells from 12 advanced samples validated this phenomenon since the interaction between dendritic cells and macrophages was limited.Finally,PLOD2,which is highly expressed in fibro-and epi-tissue,could be a potential therapeutic target for ccRCC patients since inhibiting PLOD2 altered the malignant phenotype of ccRCC in vitro.Conclusion:As a novel,non-invasive,and repeatable monitoring tool,the TDERS could work as a robust risk stratification system for patients with ccRCC and precisely inform treatment decisions about ICI therapy.

Nickel single atom overcoordinated active sites to accelerate the electrochemical reaction kinetics for Li-S cathode

Lithium-sulfur(Li-S)batteries with high theoretical energy density are promising advanced energy storage devices.However,shuttling of dissolute lithium polysulfide(LiPSs)and sluggish conversion kinetics impede their applications.Herein,single nickel(Ni)atoms on two-dimensional(2D)nitrogen(N)-doped carbon with Ni-N_(4)-O overcoordinated structure(SANi-N_(4)-O/NC)are prepared and firstly used as a sulfur host of Li-S batteries.Due to the efficient polysulfides traps and highly LiPSs conversion effect of SANi-N_(4)-O/NC,the electrochemical performance of Li-S batteries obviously improved.The batteries can well operate even under high sulfur loading(5.8 mg cm^(-2))and lean electrolyte(6.1μL mg^(-1))condition.Meanwhile,density functional theory(DFT)calculations demonstrate that Ni single atom’s active sites decrease the energy barriers of conversion reactions from Li_(2)S_(8)to Li2S due to the strong interaction between SANi-N_(4)-O/NC and LiPSs.Thus,the kinetic conversion of LiPSs was accelerated and the shuttle effect is suppressed on SANi-N_(4)-O/NC host.This study provides a new design strategy for a 2D structure with single-atom overcoordinated active sites to facilitate the fast kinetic conversion of LiPSs for Li-S cathode.

客体溶剂导向策略构筑异构的金属有机框架材料实现二氧化碳和甲烷的动力学分离

利用吸附分离技术实现二氧化碳和甲烷的分离是提高天然气品质的一种有效手段。然而,基于热力学分离的吸附剂对二氧化碳往往表现出很强的亲和力,因此再生过程会产生巨大的能耗。相较而言,尽管精准调控吸附剂孔径以实现吸附质扩散速率的巨大差异仍具有巨大挑战,动力学分离技术仍是变压吸附(PSA)过程的首选。本文报道了一种用于在亚埃尺度精准调控吸附剂孔径的客体溶剂导向策略,实现了二氧化碳和甲烷的高效动力学分离。基于4,4-(六氟异丙基亚甲基)-双(苯甲酸)和双核铜的轮桨型结构单元,我们构筑了一系列异构的金属有机框架材料。结果表明,得益于周期性扩张和收缩的孔道以及理想的孔径尺寸,CuFMOF·CH_(3)OH(CuFMOF-c)能够有效地捕获二氧化碳并阻碍甲烷的扩散,从而表现出优异的动力学分离性能,其具有极高的动力学选择性(273.5)和平衡-动力学综合选择性(64.2)。分子动力学(MD)模拟阐明了分离机制,固定床穿透实验验证了材料优异的分离性能。

Hybridization of metal–organic framework and monodisperse spherical silica for chromatographic separation of xylene isomers

Metal–organic frameworks(MOFs) packed in the column have been a promising candidate as the stationary phase for high performance liquid chromatography(HPLC). However, the direct packing of irregular MOF powder could raise some problems like high back pressure and low column efficiency in the HPLC separation. In this work, UiO-66 capable of separating xylenes was supported effectively on the surface of the monodisperse spherical silica microspheres by one-pot method. The hybridization of Ui O-66 and silica microspheres(termed UiO-66@SiO2 shell–core composite) was prepared by stirring the suspension of the precursors of Ui O-66 and\\COOH terminated silica in the N,N-dimethylformamide with heating. The shell–core composite material UiO66@SiO2 was characterized by SEM, TEM, PXRD and FTIR. Then, it was used as a packing material for the chromatographic separation of xylene isomers. Xylene isomers including o-xylene, m-xylene and p-xylene were efficiently separated on the column with high resolution and good reproducibility. Moreover, the Ui O-66@SiO2 shell–core composites packed column still remained reverse shape selectivity as Ui O-66 possessed, and the retention of xylenes was probably ascribed to the hydrophobic effect between analytes and the aromatic rings of the Ui O-66 shell. The Ui O-66@SiO2 shell–core composites obtained in this study have some potential for the separation of structural isomers in HPLC.

Dynamic immune recovery process after liver transplantation revealed by single-cell multi-omics analysis

Elucidating the temporal process of immune remodeling under immunosuppressive treatment after liver transplantation(LT)is critical for precise clinical management strategies.Here,we performed a single-cell multi-omics analysis of peripheral blood mononuclear cells(PBMCs)collected from LT patients(with and without acute cellular rejection[ACR])at 13 time points.Validation was performed in two independent cohorts with additional LT patients and healthy controls.Our study revealed a four-phase recovery process after LT and delineated changes in immune cell composition,expression programs,and interactions along this process.The intensity of the immune response differs between the ACR and non-ACR patients.Notably,the newly identified inflamed NK cells,CD14+RNASE2+monocytes,and FOS-expressing monocytes emerged as predictive indicators of ACR.This study illuminates the longitudinal evolution of the immune cell landscape under tacrolimus-based immunosuppressive treatment during LT recovery,providing a four-phase framework that aids the clinical management of LT patients.

Migration and transformation of Pb,Cu,and Zn during co-combustion of high-chlorine-alkaline coal and Si/Al dominated coal

Shaerhu(SEH)coal is abundant in Xinjiang,China.The utilization of SEH suffers from severe ash deposition,slagging,and fouling problems due to its high-chlorine-alkaline characteristics.The co-combustion of high-alkaline coal and other type coals containing high Si/Al oxides has been proven to be a simple and effective method that will alleviate ash-related problems,but the risk of heavy metals(HMs)contamination in this process is nonnegligible.Hence,the volatilization rates and chemical speciation of Pb,Cu,and Zn in co-combusting SEH and a high Si/Al oxides coal,i.e.,Yuanbaoshan(YBS)coal were investigated in this study.The results showed that the addition of SEH increased the volatilization rates of Pb,Cu,and Zn during the co-combustion at 800℃from 23.70%,23.97%,and 34.98%to 82.31%,30.01%,and 44.03%,respectively,and promoted the extractable state of Cu and Zn.In addition,the interaction between SEH and YBS inhibited the formation of the Pb residue state.SEM-EDS mapping results showed that compared to Zn and Cu,the signal intensity of Pb was extremely weak in regions where some of the Si and Al signal distributions overlap.The DFT results indicated that the O atoms of the metakaolin(Al_(2)O_(3)·2SiO_(2))(001)surface were better bound to the Zn and Cu than Pb atoms after adsorption of the chlorinated HMs.These results contribute to a better understanding of the effects of high-alkaline coal blending combustion on Pb,Cu,and Zn migration and transformation.

多极性位点的杂化氢键有机框架吸附分离CO_(2)/CH_(4)

氢键有机框架(HOFs)是极具研究价值的新型多孔材料,但稳定、永久多孔且富含功能位点的HOFs的构筑难题制约了其在气体吸附分离领域的应用.本文采用具有轮桨立体构型和多氢键位点的金属-核碱基构造体构筑了一类稳定的微孔杂化HOFs材料(HOF-ZJU-201、HOF-ZJU-202和HOF-ZJU-203),框架内的无机阴离子、氨基以及电荷差异性分布孔道作为多重极性位点实现了CO_(2)的选择性吸附和CO_(2)/CH_(4)的吸附分离.在298 K和1 bar(1 bar=105 Pa)条件下,杂化HOFs材料的CO_(2)吸附量为2.31~3.35 mmol/g,对CO_(2)/CH_(4)(50/50,v:v)的分离选择性为7.3~9.0.通过色散矫正的密度泛函理论计算和Hirshfeld表面分析明确了杂化HOFs材料通过氢键、静电偶极作用以及范德华力选择性捕获CO_(2)的作用机理.固定床穿透实验进一步验证了杂化HOFs材料对CO_(2)/CH_(4)的动态吸附性能,能够从等摩尔二元混合气中直接获得纯度99.9%的甲烷,具有低浓度甲烷气高效提浓的应用潜力.杂化HOFs材料良好的空气、水汽、热稳定性以及优异的循环稳定性和化学稳定性使其具备工业化应用潜力.

超微孔碳吸附剂实现天然气中丙烷和乙烷的高选择性提取

轻烃混合物分离以及从天然气中提取C3H8和C2H6对天然气纯化及劣质天然气升级意义重大.微孔碳吸附剂在轻烃分离中潜力巨大,然而构筑孔径均一的超微孔从而增强分离选择性仍是巨大挑战.在本文中,我们采取无活化剂热解法制备了一系列孔径均一(5.2到5.3?)的聚偏二氯乙烯树脂(PVDC)衍生的超微孔碳吸附剂.与已报道的吸附剂相比,优选的C-PVDC-800对C3H8/CH4及C2H6/CH4在298 K和1.0 bar下表现出更高的理想吸附溶液理论(IAST)选择性(分别为3387和75),对C3H8/CH4具有最高的Henry系数选择性(369).此外,C-PVDC-800在低压下对C3H8和C2H6具有极高的吸附量.更重要的是,该材料对所有气体分子都实现了快速的动力学吸附,有利于应用于固定床吸附过程.固定床穿透实验及循环测试进一步证实了该材料从天然气中选择性提取C3H8和C2H6的优异性能.

Boosting xenon adsorption with record capacity in microporous carbon molecular sieves

Xenon/krypton(Xe/Kr)separation is an important task in industry,yet it remains challenging to develop adsorbents with high Xe/Kr selectivity and adsorption capacity of Xe,especially at low partial pressures.Herein,we report a series of microporous carbon molecular sieves(CMSs)for Xe/Kr separation.Those materials have ideal bimodal pore size distributions that not only provide substantial space for the accommodation of gas molecules,but also allow selective diffusion of gas molecules.Additionally,the carbon frameworks decorated with polar oxygen-containing functional groups afford higher affinity for Xe than Kr,which is proven by density functional theory(DFT)calculations and charge density difference analysis.The optimal CPVDC-700 exhibits a high selectivity of Xe/Kr and,more importantly,a record-high uptake of Xe(2.93 mmol g^(-1))at 0.2 bar and298 K,which is the highest among all the reported carbon adsorbents.Breakthrough experiments confirm the excellent performance of such CMSs for Xe/Kr separation,and the dynamic adsorption uptake of Xe and productivity of high-purity Kr are calculated to be 2.91 mmol g^(-1)and 208 m L g^(-1)(9.29 mmol g^(-1)),respectively,which also set up a new benchmark for Xe/Kr separation of carbon adsorbents.

羧酸功能化离子液体吸收分离丙炔/丙二烯/丙烯

丙炔/丙二烯/丙烯等C_(3)气体的分离是丙烯纯化过程中的关键环节.以离子液体为分离介质的吸收分离技术能够克服传统有机溶剂的缺点,有望应用于C_(3)气体的分离.本工作测定了C_(3)气体在强氢键碱性羧酸功能化离子液体中的溶解度,结果表明这类离子液体兼具高的丙炔、丙二烯吸收容量和丙炔/丙烯、丙二烯/丙烯选择性,其中[P_(4442)][C_(5)COO]在313.1 K下对丙炔摩尔吸收容量达到0.3 mol/mol,是目前已报道的最高值,同时丙二烯容量也达到0.14 mol/mol,明显高于丙烯吸收容量.不同长度阴离子和不同温度下的溶解度表明,阴离子碳链较短和温度较低时这类离子液体具有更好的丙炔/丙二烯/丙烯分离性能.吸收-解吸循环实验证明所使用的离子液体具备良好的循环再生性能.

Room-temperature hydrogenation of halogenated nitrobenzenes over metal-organic-framework-derived ultra-dispersed Ni stabilized by N-doped carbon nanoneedles

Ultra-dispersed Ni nanoparticles(7.5 nm)on nitrogen-doped carbon nanoneedles(Ni@NCNs)were prepared by simple pyrolysis of Ni-based metal–organic-framework for selective hydrogenation of halogenated nitrobenzenes to corresponding anilines.Two different crystallization methods(stirring and static)were compared and the optimal pyrolysis temperature was explored.Ni@NCNs were systematically characterized by wide analytical techniques.In the hydrogenation of p-chloronitrobenzene,Ni@NCNs-600(pyrolyzed at 600°C)exhibited extraordinarily high performance with 77.9 h^(–1)catalytic productivity and>99%p-chloroaniline selectivity at full p-chloronitrobenzene conversion under mild conditions(90°C,1.5 MPa H2),showing obvious superiority compared with reported Ni-based catalysts.Notably,the reaction smoothly proceeded at room temperature with full conversion and>99%selectivity.Moreover,Ni@NCNs-600 afforded good tolerance to various nitroarenes substituted by sensitive groups(halogen,nitrile,keto,carboxylic,etc.),and could be easily recycled by magnetic separation and reused for 5 times without deactivation.The adsorption tests showed that the preferential adsorption of–NO2 on the catalyst can restrain the dehalogenation of p-chloronitrobenzene,thus achieving high p-chloroaniline selectivity.While the high activity can be attributed to high Ni dispersion,special morphology,and rich pore structure of the catalyst.

Highly efficient and anti-poisoning single-atom cobalt catalyst for selective hydrogenation of nitroarenes

Developing non-precious metal catalysts to selectively reduce functionalized nitroarenes with high efficiency is urgently desirable for the production of value-added amines.Herein,we report a novel,efficient,anti-poisoning single-atom cobalt catalyst(Co-NAC)for the highly selective hydrogenation of the nitro to amino group for nitroarenes baring various functional groups,including vinyl,cyano,and halogen.Using a combination of structure characterization techniques,we have confirmed that the cobalt species are predominantly present in the form of four-coordinated Co single sites anchored on nitrogen-assembly carbon(NAC)as the ordered mesoporous support.Co-NAC catalysts enable the full conversion and>99%selectivity with molecular H2 as a green reductant under mild conditions(80℃,2 MPa H2).As for the selective hydrogenation of 3-nitrostyrene,Co-NAC catalyst affords high catalytic productivity(19.7 h-1),which is superior to the cobalt nanoparticles(NPs)catalysts and most of the recently reported Co-based catalysts.This is attributed to the highly accessible atomically-dispersed Co active sites,the high surface area with ordered-mesoporous morphology and the prominent high content of nitrogen dopants.Notably,Co-NAC catalyst displays resistance towards sulfur-containing poisons(20 equivalents)and strong non-oxidizing acid(8 M),showing great potential for continuous application in the chemical industry.

A robust ethane-trapping metal-organic framework for efficient purification of ethylene

Owing to the similar physicochemical properties between ethane(C_(2)H_(6))and ethylene(C_(2)H_(4)),obtaining polymerization-grade C_(2)H_(4)(≥99.95%pure)is still a tricky problem in the petrochemical industry.Here,we report a robust scandium-based metalorganic framework(Sc BPDC),which is connected by oxygen-rich phenyl ligand with exceptionally high thermal stability(up to873 K)and capacity of C_(2)H_(6)(4.94 mmol/g at 100 k Pa and 283 K),exhibiting superior separation performance of C_(2)H_(6)/C_(2)H_(4) mixture(the IAST selectivity is up to 1.7 at 283 K).Importantly,Sc BPDC can produce 8.96 L/kg C_(2)H_(4) with≥99.99%purity while the C_(2)H_(4)/C_(2)H_(6)(50:50,v/v)as the mixture injection and the low isosteric heat of Sc BPDC(16.4 k J/mol for C_(2)H_(6))validates the facility of adsorbent regeneration.Furthermore,theoretical calculations demonstrate the C_(2)H_(6) molecules are trapped in the nonpolar pore surface via C–H···πand C–H···O interactions between multiple hydrogen atoms of C_(2)H_(6) and the host framework.

Porous Hydrogen-Bonded Frameworks Assembled from Metal-Nucleobase Entities for Xe/Kr Separation

It is challenging to obtain high-purity xenon(Xe)and krypton(Kr)from the by-products of the air separation process due to their similar atom size and physical properties.Adsorption using porous materials such as metal–organic frameworks(MOFs)has been considered a promising technology to separate Xe/Kr.Herein,we report two novel isostructural ionic supramolecular MOFs(SMOFs;SMOF-PFSIX-1 and SMOF-AsFSIX-1),in which inorganic anions(PF_(6)^(−)or AsF_(6)^(−))and cationic metal–organic entities have self-assembled through hydrogen bonds to give three-dimensional pore channels.The two kinds of SMOFs can efficiently separate Xe/Kr with ideal adsorbed solution theory(IAST)selectivity values of 6.9 and 6.7 under 298 K and 1.0 bar,respectively.The breakthrough experiments further confirm their industrial application potential.The grand canonical Monte Carlo(GCMC)and density functional theory(DFT)calculations revealed that there are multiple adsorptive sites to capture the Xe atom,and the affinity between Xe and frameworks can be attributed to the inorganic anions and amino groups on the ligands.To the best of our knowledge,this was the first report of using SMOFs for Xe/Kr separation,and we proposed a new strategy for Xe/Kr separation based on the synergistic effect of amino and inorganic anions.

Hydrogen-bonded metal-nucleobase frameworks for highly selective capture of ethane/propane from methane and methane/nitrogen separation

The separation of light hydrocarbons,including C_(2)H_(6)and C_(3)H_(8),is essential to natural gas upgrading.Meanwhile,N_(2)removal from CH_(4)is also crucial to concentrating low-quality coalbed methane,but the adsorption process is challenging because of the close kinetic diameter.This work reports two hydrogen-bonded metal-nucleobase frameworks(HOF-ZJU-201 and HOF-ZJU202)capable of efficiently separating C_(3)H_(8)/CH_(4),C_(2)H_(6)/CH_(4),and CH_(4)/N_(2).Due to strong affinity for C_(3)H_(8)and C_(2)H_(6),the lowpressure capacity for C_(3)H_(8)(5 kPa)and C_(2)H_(6)(10 kPa)of HOF-ZJU-201a exceeds most adsorbents.The ideal adsorbed solution theory(IAST)selectivity of C_(3)H_(8)/CH_(4)and C_(2)H_(6)/CH_(4)is 119 and 45 at ambient conditions.According to density functional theory calculations,surface polarization environments formed by electron-rich anions and electron-deficient purine heterocyclic rings contribute to the selective capture of C_(3)H_(8)and C_(2)H_(6)with greater polarizability.Furthermore,the high CH_(4)adsorption capacity(1.73 mmol/g for HOF-ZJU-201a and 1.50 mmol/g for HOF-ZJU-202a at 298 K and 1.0 bar)and excellent CH_(4)/N_(2)selectivity(6.0 for HOF-ZJU-201 at 298 K),as well as dynamic breakthrough experiments of binary CH_(4)/N_(2)gas mixture implied their efficacy in the concentration of low-quality coalbed methane.