环醚直接双羰基化合成α,ω-二元羧酸

二元羧酸是制备聚酰胺、聚酯和聚氨酯的重要中间体,其传统合成途径具有一定的局限性.以己二酸为例,其主要工业生产工艺是利用硝酸氧化KA油,该方法存在KA油产量低和产生大量温室气体N2O等问题.因此,探索工艺绿色、原子有效和采用可再生原料的二元羧酸制备方法具有重要意义.环醚和多元醇很容易从生物质原料中得到,以它们为原料,通过双羰基化直接制备二元羧酸,是一种非常有潜力的反应途径.但目前大多数文献报道由环醚或多元醇通过羰基化反应生成的产物主要是C+1单羧酸.本课题组一直致力于碘催化生物质衍生的多元醇的加氢脱氧,研究发现,在特定的反应条件下,多元醇可以选择性地形成多碘取代化合物的中间体.受此启发,本文报道了一种由环醚或多元醇形成二碘代物中间体,然后直接通过双羰基化反应生成对应的C+2二羧酸的新策略.由于己二酸是最重要的二元羧酸之一,且四氢呋喃(THF)可以从丰富的生物质衍生的糠醛中获得,本文重点研究了通过双羰基化反应直接利用THF合成己二酸.在优化的反应条件下,以铑盐为催化剂,碘为促进剂,乙酸和水为混合溶剂,在170℃,CO和H_(2)条件下,THF可以84%的产率转化为己二酸.循环实验结果表明,该催化体系在5次循环后仍能够稳定运行.该催化体系不仅适用于各种环醚,也适用于不同的伯二醇合成对应的C+2α,ω-二元羧酸.通过对反应中间体进行检测以及控制实验研究发现,选择性生成1,4-二碘丁烷中间体是进一步双羰基化制备己二酸的关键,而生成烯烃中间体和单碘代物中间体是形成副产物戊酸的主要原因.在实验结果和文献研究基础上,提出了THF转化为己二酸的反应机理.在反应中,活性铑常以Rh(I)的形式存在,并且从质谱中观察到了[Rh(CO)_(2)I_(2)]−阴离子,它可以在羰基化条件下由不同的铑前体(例如RhCl_(3))经过CO和碘还原后衍生.具体反应步骤为,首先铑催化剂催化H2和I2生成HI,然后THF与HI反应生成1,4-二碘丁烷中间体,此中间体经过铑催化活化在两端分别进行羰基化反应,最终生成产物己二酸.通过质谱检测到两个推测的中间体,进一步证实该反应机理.综上,本文为己二酸、戊二酸和其他重要的二羧酸(如1,7-庚二酸和1,8-辛二酸)的有效合成提供了一种新策略,为二元羧酸的高效、绿色合成提供参考.

DIA-based proteome profiling with PRM verification reveals the involvement of ER-associated protein processing in pollen abortion in Ogura CMS cabbage

Ogura cytoplasmic male sterility(Ogura CMS)is extensively applied in hybrid seed production in cruciferous crops.However,the posttranscriptional molecular basis of Ogura CMS in cruciferous crops remains elusive.Here,a data-independent acquisition-based proteomic approach coupled with a parallel reaction monitoring-based targeted proteomic assay was used to analyze the proteome dynamics of Ogura CMS cabbage line RM and its maintainer line RF during floral bud development to obtain insights into the mechanism underlying Ogura CMS in cruciferous crops.A total of 9162 proteins corresponding to 61464 peptides were identified in RM and RF floral buds.The proteomic fluctuation of RM was weaker than that of RF.Differences in protein expression between RM and RF gradually enlarged with floral bud development.Fifteen continually up-regulated and eight continually down-regulated proteins were found in RM relative to RF throughout floral bud development.Differentially expressed proteins between RM and RF during floral bud development were implicated in the endoplasmic reticulum(ER)-associated protein processing pathway,in which most of them exhibited down-regulated expression in RM.These data suggest that ER-associated protein processing may be involved in pollen abortion in Ogura CMS cabbage by inhibiting the expression of critical factors.Our findings not only deepen the understanding of the molecular mechanisms of Ogura CMS in cruciferous crops but also provide better guidance for applying Ogura CMS in the hybrid breeding of cruciferous crops.

沉淀-焙烧法制备高振实密度四氧化三锰的研究

过渡金属氧化物四氧化三锰因其独特的结构特征和物理化学性质,在储能领域尤其是电池行业有着广泛的应用。近年来,电池行业对四氧化三锰的产品质量提出更高的要求,其中产品振实密度是影响电池材料性能的关键因素之一。因此,为提高四氧化三锰的振实密度,本研究以高纯硫酸锰为原料,以氨水为沉淀剂,采用硫酸锰溶液沉淀-焙烧法制备高振实密度四氧化三锰,探究沉淀反应参数及热工制度对四氧化三锰振实密度的影响,并对四氧化三锰产物形貌、结构和组成方面进行表征。实验结果表明,最优工艺条件为氨锰比3:1、硫酸锰浓度2.0 mol/L、焙烧温度1150℃、焙烧时间4 h、焙烧气氛强制通风,该条件下获得的四氧化三锰锰含量为71.91wt%,D_(50)为10.723μm,比表面积为1.786 m^(2)/g,形貌为类球形,微量元素含量符合要求且振实密度达到2.85 g/cm^(3),满足高纯四氧化三锰的行业标准。

Engineered stem cells by emerging biomedical stratagems

Stem cell therapy holds immense potential as a viable treatment for a widespread range of intractable disorders.As the safety of stem cell transplantation having been demonstrated in numerous clinical trials,various kinds of stem cells are currently utilized in medical applications.Despite the achievements,the therapeutic benefits of stem cells for diseases are limited,and the data of clinical researches are unstable.To optimize tthe effectiveness of stem cells,engineering approaches have been developed to enhance their inherent abilities and impart them with new functionalities,paving the way for the next generation of stem cell therapies.This review offers a detailed analysis of engineered stem cells,including their clinical applications and potential for future development.We begin by briefly introducing the recent advances in the production of stem cells(induced pluripotent stem cells(ipsCs),embryonic stem cells(ESCs),mesenchymal stem cells(MSCs)and hematopoietic stem cells(HSCs).Furthermore,we present the latest developments of engineered strategies in stem cells,including engineered methods in molecular biology and biomaterial fields,and their application in biomedical research.Finally,we summarize the current obstacles and suggest future prospects for engineered stem cells in clinical translations and biomedical applications.

Effect of cobalt substitution for nickel on microstructural evolution and hydrogen storage properties of La_(0.66)Mg_(0.34)Ni_(3.5-x)Co_(x) alloys

Superlattice hydrogen storage alloys offer a compelling advantage with rapid hydriding rate and high storage capacity.However,its practical applications face challenges including complex structure,low dehydriding capacity,and cyclic instability.In this work,we successfully prepared La_(0.66)Mg_(0.34)Ni_(3.5-x)Co_(x) superlattice hydrogen storage alloys with enhanced dehydriding capacity and stability by partially substituting Co for Ni.X-ray diffraction(XRD)refinements analysis reveals the presence of(La,Mg)_(3)Ni_(9),(La,Mg)_5Ni_(19),and LaNi_(5) phases within the alloy.Following Co substitution in the La_(0.06)Mg_(0.34)Ni_(3.4)Co_(0.1)alloy,there is a significant increase in content of the(La,Mg)_(3)Ni_(9) phase and a reduction in the hysteresis factor,resulting in an improved reversible hydrogen storage capacity from 1.45 wt%to 1.60 wt%.The dehydriding kinetics of the alloy is controlled by diffusion model with an activation energy of 8.40 kJ/mol.Furthermore,the dehydriding enthalpy value of the Co-substituted alloy decreases from 30.84 to 29.85 kJ/mol.Impressively,the cycling performance of the alloy after Co substitution exhibits excellent stability,with a capacity retention rate of 92.3%after 100 cycles.These findings provide valuable insights for the development of cost-effective hydrogen storage materials.

Traditional Chinese Medicine Integrated Responsive Microneedles for Systemic Sclerosis Treatment

Traditional Chinese medicine,such as Tripterygium wilfordii and Paeonia lactiflora,has potential values in treating systemic sclerosis(SSc)and other autoimmune diseases,while their toxic side effect elimination and precise tropical drug delivery are still challenges.Here,we present multiple traditional Chinese medicine integrated photoresponsive black phosphorus(BP)microneedles(MNs)with the desired features for the SSc treatment.By employing a template-assisted layer-by-layer curing method,such MNs with triptolide(TP)/paeoniflorin(Pae)needle tips and BP-hydrogel needle bottoms could be well generated.The combined administration of TP and Pae can not only provide anti-inflammatory,detoxification,and immunomodulatory effects to treat skin lesions in the early stage of SSc but also remarkably reduce the toxicity of single drug delivery.Besides,the additive BPs possess good biocompatibility and near-infrared(NIR)responsiveness,imparting the MN photothermal-controlled drug release capability.Based on these features,we have demonstrated that the traditional Chinese medicine integrated responsive MNs could effectively improve skin fibrosis and telangiectasia,reduce collagen deposition,and reduce epidermal thickness in the SSc mouse models.These results indicated that the proposed Chinese medicine integrated responsive MNs had enormous potential in clinical therapy of SSc and other diseases.

Spatial tumor biopsy with fluorescence PCR microneedle array

Biopsy is the gold standard for tumor diagnosis,as this technology provides highly detailed and reliable information on tumorigenesis and progression.Resembling the discrete wettability of desert beetles,in this study,a fluorescence polymerase chain reaction(F-PCR)microneedle array(MNA)platform is developed for efficient spatial tumor biopsy.This MNA is fabricated by the coupled strategies of bottom-up self-assembly and top-down photolithography;it comprises a hydrophobic silica nanoparticle-assembled substrate and graphene aerogel-hydrogel hybrid microneedle peaks.Benefitting from the hydrophilicity and absorption capacity of its graphene hybrid microneedle peaks,MNA can easily penetrate tissue specimens and collect tumor nucleic acid biomarkers stereoscopically.In addition,because of the discrete wettability of the platform,both tissue fluids and PCR liquids can be easily removed from the substrate,and each microneedle peak is similar to an independent island for directly conducting F-PCR reactions for tumor marker discovery.Based on these advantages,the F-PCR-MNA platform is demonstrated to be ideal for detecting DNA biomarkers of lung carcinoma in standard solutions,mouse tissue samples,and clinical specimens,thus indicating its practical potential as an innovative tumor biopsy system.

肠源性腹膜透析相关性腹膜炎治疗失败的危险因素:多中心回顾性研究

目的探讨肠源性腹膜透析相关性腹膜炎(PDAP)治疗失败的危险因素。方法回顾性收集2013年至2019年吉林省4家三甲医院PDAP患者临床资料,按照PDAP的致病菌类型,将研究对象分为肠源性PDAP组(284例)和非肠源性PDAP组(519例)。采用广义估计方程(GEE)比较两组患者的临床资料、初始疗效、当次PDAP治疗结果以及肠源性PDAP治疗失败的危险因素。结果本研究共纳入803例次PDAP,其中肠源性PDAP组为284例次,大肠埃希菌最多,为100例次(35.21%)。与非肠源性PDAP组相比,肠源性PDAP组的女性占比较高(55.99%和47.21%,P=0.043),且原发病为糖尿病肾病的比例较高(16.96%和11.27%,P=0.029)。两组患者在年龄、血红蛋白、血清白蛋白水平等方面均未见明显差异(均P>0.05)。与非肠源性PDAP组相比,肠源性PDAP组初始疗效和当次治疗结果均较差(均P<0.001)。多因素GEE分析显示,长透析龄、生活在农村、低血清白蛋白,以及肺炎克雷伯杆菌、铜绿假单胞菌、真菌及混合菌感染均为肠源性PDAP治疗失败的独立危险因素(P<0.05)。结论肠源性PDAP的治疗效果比非肠源性PDAP差。长透析龄、农村生活、低血清白蛋白水平及肺炎克雷伯杆菌、铜绿假单胞菌、真菌及混合菌感染是肠源性PDAP治疗失败的独立危险因素。

Bee Sting-Inspired Inflammation-Responsive Microneedles for Periodontal Disease Treatment

Periodontal lesions are common and frustrating diseases that impact life quality.Efforts in this aspect aim at developing local drug delivery systems with better efficacy and less toxicity.Herein,inspired by the sting separation behavior of bees,we conduct novel reactive oxygen species(ROS)-responsive detachable microneedles(MNs)that carry antibiotic metronidazole(Met)for controllable periodontal drug delivery and periodontitis treatment.Benefiting from the needle-base separation ability,such MNs can penetrate through the healthy gingival to reach the gingival sulcus's bottom while offering minimal impact to oral function.Besides,as the drug-encapsulated cores were protected by poly(lactic-co-glycolic acid)(PLGA)shells in MNs,the surrounding normal gingival tissue is not affected by Met,resulting in excellent local biosafety.Additionally,with the ROS-responsive PLGA-thioketal-polyethylene glycol MN tips,they can be unlocked to release Met directly around the pathogen under the high ROS in the periodontitis sulcus,bringing about improved therapeutic effects.Based on these characteristics,the proposed bioinspired MNs show good therapeutic results in treating a rat model with periodontitis,implying their potential in periodontal disease.

Developing hierarchical microneedles for biomedical applications

As a new kind of microcarrier device,microneedles are featured by micrometer needle arrays with an overall size in the centimeter scale.Due to the needle shape and the micron size,microneedles can penetrate the skin without harming nerves and blood vessels,which causes many advantages such as minimally invasive,safe and convenient.The past few decades have witnessed a great leap in microneedles research.The main materials of microneedles have changed from metal and ceramic to polymers with more complex functions,and the optimiza-tion of materials and preparation strategies has led to a greater variety of microneedle styles.Among them,the construction or combination of smaller size structures or materials on microneedles to fabricate hierarchical mi-croneedles is a major research hotspot.Here,we present the recent research progress of hierarchical microneedles for biomedicine.We begin by discussing the fabrication strategies of hierarchical microneedles,including main-stream casting and coating methods based on microneedle molds and three dimensions(3D)printing methods.We then expand the discussion from the hierarchical microneedles with porous structure to those composited with nanomaterials.Eventually,we have a discussion about the research progress of hierarchical microneedles in the area of biomarkers detection and transdermal drug delivery,as well as its future development direction.

Christmas Tree-Shaped Microneedles as FOLFIRINOX Spatiotemporal Delivery System for Pancreatic Cancer Treatment

As an effective combination chemotherapy,FOLFIRINOX regimen(fluorouracil,leucovorin,irinotecan,and oxaliplatin)has shown definite antitumor eficacy for treating pancreatic cancer(PC)nowadays.However,the traditional systematic administration of these chemotherapeutics limits the drug targeting and causes unwanted effects.

Bio-inspired clamping microneedle arrays from flexible ferrofluid-configured moldings

Microneedle(MN)arrays have demonstrated value for cosmetics,diagnosis,transdermal drug delivery,and other biomedical areas.Much effort has been devoted to developing simple stratagem for creating versatile moldings and generating functional MN arrays.Here,inspired by the serrated microstructure of mantises’forelegs,we present a novel serration-like clamping MN array based on ferrofluidconfigured moldings.Benefiting from the flexibility and versatility of ferrofluids,negative microhole array moldings with various sizes and angles toward the midline could be created easily.The corresponding biocompatible polymer MN arrays with both isotropic and anisotropic structures could then be produced feasibly and cost-effectively by simply replicating these moldings.It was found that the resultant serrated clamping MN arrays had the ability to adhere to skin firmly,enabling them to be used over a relatively long time and while the recipient was moving.This proposed technology performed well in minimally invasive drug administration and sustained glucocorticoids release during treatment for imiquimod-induced psoriasis in mice.These features indicated that such MN arrays could play important roles in wearable transdermal drug delivery systems and in other applications.

Antibacterial and angiogenic chitosan microneedle array patch for promoting wound healing

A patch with the capability of avoiding wound infection and promoting tissue remolding is of great value for wound healing.In this paper,we develop a biomass chitosan microneedle array(CSMNA)patch integrated with smart responsive drug delivery for promoting wound healing.Chitosan possesses many outstanding features such as the natural antibacterial property and has been widely utilized for wound healing.Besides,the microstructure of microneedles enables the effective delivery of loaded drugs into the target area and avoids the excessive adhesion between the skin and the patch.Also,vascular endothelial growth factor(VEGF)is encapsulated in the micropores of CSMNA by temperature sensitive hydrogel.Therefore,the smart release of the drugs can be controllably realized via the temperature rising induced by the inflammation response at the site of wounds.It is demonstrated that the biomass CSMNA patch can promote inflammatory inhibition,collagen deposition,angiogenesis,and tissue regeneration during the wound closure.Thus,this versatile CSMNA patch is potentially valuable for wound healing in clinical applications.

Biomimetic intestinal barrier based on microfluidic encapsulated sucralfate microcapsules

Intestinal barriers play an important role in preventing intestinally derived diseases,and maintaining their function is a promising approach to prevent and treat those diseases.Here,inspired by the protection effect of intestinal barriers in live organisms and the mucosa adhesive property of sucralfate,we present a biomimetic intestinal barrier based on microfluidic encapsulated sucralfate microcapsules.Benefiting from the flexible selectivity and precise control of microfluidic electrospray flows,the generated microcapsules were imparted with stomach-tolerant dietary-fibre shells and controllable released sucralfate cores,both of which could contribute to forming a continuous biomimetic intestinal barrier on the intestine.Through in vitro adhesive study,in vivo computed tomography(CT)imaging and in vivo imaging system(IVIS)methods,we have demonstrated that the microcapsule-derived biomimetic intestinal barrier can effectively block food fermentation in the gut,reduce generation of fat,decrease disease risk indexes,and prevent obesity.These features make the microfluidic encapsulated sucralfate microcapsules and their resultant biomimetic intestinal barrier an approach for treating obesity and other intestinal diseases.

Bio-inspired angle-independent structural color films with anisotropic I colloidal crystal array domains

Structural color materials with the property of angle-independence have attracted increasing interest in recent years because of their applications in various research fields.In this paper,inspired by the anisotropic lattice microstructure of the Parides sesostris butterfly,we i present a novel angle-independent structural material by simply doping spinous pollen particles into the colloidal crystal arrays to interfere their self-assembling process.The resultant composited materials have anisotropic dose-packed colloidal crystal domains around the spikes of the pollens.These differently oriented domains could reflect the light to a wide range of viewing angles,and thus imparted the composite materials with the same wide angle of structural colors.Attractively,the materials were endowed with light-controlled reversible structural color changing behavior by incorporating photothermal responsive graphene-tagged hydrogels.These features of the bioinspired angle-independent structural color materials showed their potential values in constructing intelligent sensors,anti-counterfeiting barcode labels,and so on.

Bioinspired Adhesive and Antibacterial Microneedles for Versatile Transdermal Drug Delivery

Microneedles have attracted increasing interest among various medical fields due to their painless,noninvasive,and efficient way of drug delivery.However,practical applications of these microneedles in different epidermal locations and environments are still restricted by their low adhesion and poor antimicrobial activity.Here,inspired by the antibacterial strategy of Paenibacillus polymyxa and adhesion mechanisms of mussel byssi and octopus tentacles,we develop hierarchical microneedles with multifunctional adhesive and antibacterial abilities.With polydopamine hydrogel as the microneedle base and a loop of suctioncup-structured concave chambers encircling each microneedle,the generated microneedles can fit the skin well;keep strong adhesion in dry,moist,and wet environments;and realize self-repair after being split into two parts.Besides,as polymyxin is loaded into both the hydrogel tips and the polydopamine base,the microneedles are endowed with excellent ability to resist common bacteria during storage and usage.We have demonstrated that these microneedles not only showed excellent adhesion when applied to knuckles and ideal antibacterial activity but also performed well in drug-sustained release and treatment for the osteoarthritis rat model.These results indicate that bioinspired multifunctional microneedles will break through the limitation of traditional methods and be ideal candidates for versatile transdermal drug delivery systems.

Microfluidic Generation of Microsprings with Ionic Liquid Encapsulation for Flexible Electronics

Inspired by helical or spiral veins,which endow plants with excellent fexibility and elasticity to withstand storms,we present novel hollow microsprings with ionic liquid encapsulation for fexible and stretchable electronics.Te microsprings were generated by using a coaxial capillary microfuidic device to consecutively spin poly(vinylidene fuoride)(PVDF)presolution and an ionic liquid,which formed laminar fows in the coaxial injection microfuidic channels.Te fast phase inversion of PVDF helps to form the core-shell structure of a microfber and guarantees the in situ encapsulation of ionic liquid.Te hybrid microfber can then spiral and be further solidifed to maintain the helical structure with increasing fow rates of the injection fuids.Because of the feasible and precise control of the injection fuids during the microfuidic spinning,the resultant microsprings have controlled core-shell structures,helical pitches,and corresponding electromechanical properties.By further embedding them into stretchable flms,the simple paradigm of a fexible device shows great conductive performance in tensile tests and even motion cycles,which could be explored as a promising candidate in stretchable sensors,fexible electronics,and electronic skins.

Preparation and characterization of biomimetic adsorbent from poly-3-hydroxybutyrate

Biomimetic adsorbent named as PHBBMA was prepared from lipophilic poly-3-hydroxybutyrate （PHB） by a modified double emulsion solvent evaporation method. PHBBMA, characterized by using scanning electron microscope and nitrogen adsorption/desorption measurements, is porous spherical particles. The characterization with the thermal gravimetric analysis and differential scanning calorimetry, 1 H nuclear magnetic resonance and Fourier transform infrared spectroscopy showed that PHBBMA preparation was a physical process without chemical reaction. The adsorption of PHBBMA for o-nitrochlorobenzene （o-NCB） was fitted better by Langmuir model than by Freundlich model, while the pseudo second-order model fitting was better than the pseudo first-order model fitting. The maximal adsorption capacity of PHBBMA for o-NCB was 57.83 mg/g at 30°C, although its specific surface area （S BET ） was only 8.45 m 2 /g. PHBBMA is a safe and environmental friendly adsorbent with high adsorption capacity because its component is innocuous and biodegradable PHB produced reusing wastes and contaminants, no byproduct can produced, and its ester and hydrocarbyl groups have strong affinity with organochlorine compounds. The further work will focus on the modification and improvement of PHBBMA in order to increase its S BET and adsorption capacity.

Smart Microneedles for Therapy and Diagnosis

Microneedles represent a cutting-edge and idea-inspiring technology in biomedical engineering,which have attracted increasing attention of scientific researchers and medical staffs.Over the past decades,numerous great achievements have been made.The fabrication process of microneedles has been simplified and becomes more precise,easy-to-operate,and reusable.Besides,microneedles with various features have been developed and the microneedle materials have greatly expanded.In recent years,efforts have been focused on generating smart microneedles by endowing them with intriguing functions such as adhesion ability,responsiveness,and controllable drug release.Such improvements enable the microneedles to take an important step in practical applications including household drug delivery devices,wearable biosensors,biomedical assays,cell culture,and microfluidic chip analysis.In this review,the fabrication strategies,distinctive properties,and typical applications of the smart microneedles are discussed.Recent accomplishments,remaining challenges,and future prospects are also presented.

Wearable droplet microfluidics

Point-of-care (POC) diagnostics, which aims at continuously measuring and screening dynamic chemical signals in human body, is attracting increasing attention among disease treatment,diagnosis, drug discovery and other biomedical fields (1,2)Recent years have witnessed the booming development of miniaturized,minimal-invasive POC technologies, such as implanted electrochemicalsensors [3,4], paper chips [5,6] and microfluidic devices[7–9]. Among them, microfluidics is one of the most promisingstrategy due to the accurate and user-friendly properties. However,most of the microfluidic POC devices are manually intensive andhighly rely on bulky laboratory equipment such as syringe pumps,external valves and microscopes, which not only limit their applicationsin wearable devices, but also hinder their moving out oflaboratory and into practical use [10,11]. These problems remainunsolved until now.