The activity of Zn precursors determines the cation exchange reaction kinetics with Ag_(2)S:Zn-doped Ag_(2)S or Ag_(2)S@ZnS QDs

Cation exchange(CE)has been emerged as a promising post-synthesis strategy of colloidal nanocrystals.However,it is unclear how the cation precursor affects the CE process and the final colloidal nanocrystals.Herein,we utilized two Zn-B Lewis acidbase adduct complexes(B=oleylamine(OAM)and methanol(MeOH))as Zn precursors for CE with Ag_(2)S quantum dots(QDs).Our study revealed that the steric hindrance and complexing capabilities of Zn precursor significantly affect the CE kinetics.As a result,the Zn-doped Ag_(2)S(Zn:Ag_(2)S)and Ag_(2)S@ZnS core–shell QDs were successfully obtained with enormous enhancement of their photoluminescence(PL)intensities.Theoretical simulation showed that the Zn-OAM with higher desolvation energy and spatial hindrance tended to form doped Zn:Ag_(2)S QDs due to the inefficient cation exchange.Whereas the Zn-MeOH with lower exchange barrier promoted the conversion of Ag-S to Zn-S,thus forming Ag_(2)S@ZnS core–shell QDs.We anticipate that this finding will enrich the regulatory approaches of post-synthesis of colloidal nanocrystals with desirable properties.

Dual stimuli-activatable versatile nanoplatform for photodynamic therapy and chemotherapy of triple-negative breast cancer

Photodynamic therapy(PDT)has emerged as an efficient cancer treatment method with minimal invasiveness.However,the majority of current photosensitizers(PSs)display severe dark toxicity and low tumor specificity due to their"always-on"photoactivity in blood circulation.To address this concern,we herein report a series of acid-activatable PSs for ultrasensitive PDT of triple-negative breast tumors.These set of novel PSs are synthesized by covalently modifying tetrakis(4-carboxyphenyl)porphyrin(TCPP)with a variety of tertiary amines for acidity-activatable fluorescence imaging and reactive oxygen species(RoS)generation.The resultant TCPP derivatives are grafted with a poly(ethylene glycol)(PEG)chain via a matrix metalloproteinase-2(MMP-2)-liable peptide spacer and chelated with Mn^(2+)for magnetic resonance imaging(MRI)capability.The PEGylated TCPP derivatives are amphiphilic and self-assemble into micellar nanoparticles to elongate blood circulation and for tumor-specific PDT.We further demonstrate that the PEGylated TCPP nanoparticles could serve as a nanoplatform to deliver the anticancer drug doxorubicin(DOX)and perform fluorescence image-guided combinatorial PDT and chemotherapy,which efficiently suppress the growth of 4T1 breast tumors and lung metastases in a mouse model.These acid-activatable PS-incorporated nanoparticles might provide a versatile platform for precise PDT and combinatorial breast cancer therapy.

Transplantation of neural stem progenitor cells from different sources for severe spinal cord injury repair in rat

Neural stem progenitor cell(NSPC)transplantation has been regarded as a promising therapeutic method for spinal cord injury(SCI)repair.However,different NSPCs may have different therapeutic effects,and it is therefore important to identify the optimal NSPC type.In our study,we compared the transcriptomes of human fetal brain-derived NSPCs(BNSPCs),spinal cord-derived NSPCs(SCNSPCs)and H9 embryonic stem-cell derived NSPCs(H9-NSPCs)in vitro and subsequently we transplanted each NSPC type on a collagen scaffold into a T8-9 complete SCI rat model in vivo.In vitro data showed that SCNSPCs had more highly expressed genes involved in nerve-related functions than the other two cell types.In vivo,compared with BNSPCs and H9-NSPCs,SCNSPCs exhibited the best therapeutic effects;in fact,SCNSPCs facilitated electrophysiological and hindlimb functional recovery.This study demonstrates that SCNSPCs may be an appropriate candidate cell type for SCI repair,which is of great clinical significance.

Transplantation of adult spinal cord grafts into spinal cord transected rats improves their locomotor function

Grafted embryonic central neural tissue pieces can recover function of hemisected spinal cord in neonatal rats and promote axonal growth in adults. However, spinal cord segments from adults have not been used as donor segments for allogeneic transplantation. Here, we utilized adult spinal cord tissue grafts(aSCGs) as donor constructs for repairing complete spinal cord injury(SCI). Moreover, to provide a favourable microenvironment for SCI treatment, a growth factor cocktail containing three growth factors(brain-derived neurotrophic factor, neurotrophin-3 and vascular endothelial growth factor), was applied to the aSCG transplants. We found that the locomotor function was significantly improved 12 weeks after transplantation of aSCGs into the spinal cord lesion site in adult rats. Transplantation of aSCGs combined with these growth factors enhanced neuron and oligodendrocyte survival and functional restoration. These encouraging results indicate that treatment of complete SCI by transplanting aSCGs, especially in the presence of growth factors, has a positive effect on motor functional recovery, and therefore could be considered as a possible therapeutic strategy for SCI.

Real-time in vivo visualization of tumor therapy by a near-infrared-II Ag2S quantum dot-based theranostic nanoplatform

治疗学的功效的实时、客观的反馈将具有为肿瘤处理的大价值。这里，我们报导聪明的 Ag <潜水艇class=“ a-plus-plus ”> 2 S 基于QD 的 theranostic nanoplatform ( DOX@PEG-Ag <潜水艇class=“ a-plus-plus ”> 2 S )由把反癌症药 doxorubicin (纪录影片)装进聚乙烯获得了乙二醇涂的银硫化物量点( PEG-Ag <潜水艇class=“ a-plus-plus “> 2 S QD )通过恐水病恐水病的相互作用，展出了装载能力的高药，到 Ag 的纪录影片的 93 wt.%<潜水艇class=” a-plus-plus “> 2 S QD )，在血的长循环( t <潜水艇class=” a-plus-plus “在指向肿瘤组织以后，从 PEG-Ag 的纪录影片 < 潜水艇 class= “ a-plus-plus ” > 2 S 货物有选择地并且很快被释放进癌症房间，产生重要肿瘤抑制。由于深织物穿入和 Ag 的高时间空间的分辨率<潜水艇class=“ a-plus-plus ”> 2 在第二扇在红外线附近的窗户( NIR-II )中的 S QD 荧光， DOX@PEG-Ag <潜水艇class=“ a-plus-plus ”> 2 在了解指向过程和治疗学的功效的药的 vivo 即时的启用的 S 。我们期望那如此的新奇 theranostic nanoplatform， DOX@PEG-Ag < 潜水艇 class= “ a-plus-plus ” > 2 与综合的药交货，治疗和评价功能， S 将为肿瘤的个性化的治疗是高度有用的。

Allotransplantation of adult spinal cord tissues after complete transected spinal cord injury: long-term survival and functional recovery in canines

Spinal cord injury(SCI), especially complete transected SCI, leads to loss of cells and extracellular matrix and functional impairments. In a previous study, we transplanted adult spinal cord tissues(aSCTs) to replace lost tissues and facilitate recovery in a rat SCI model. However, rodents display considerable differences from human patients in the scale, anatomy and functions of spinal cord systems, and responses after injury. Thus, use of a large animal SCI model is required to examine the repair efficiency of potential therapeutic approaches. In this study, we transplanted allogenic aSCTs from adult dogs to the lesion area of canines after complete transection of the thoracic spinal cord, and investigated the long-term cell survival and functional recovery. To enhance repair efficiency, a growth factor cocktail was added during aSCT transplantation, providing a favorable microenvironment. The results showed that transplantation of a SCTs, in particular with the addition of growth factors, significantly improves locomotor function restoration and increases the number of neurofilament-, microtubule-associated protein2-, 5-hydroxytryptamine-, choline acetyltransferase-and tyrosine hydroxylase-positive neurons in the lesion area at 6 months post-surgery. In addition, we demonstrated that donor neurons in a SCTs can survive for a long period after transplantation. This study showed for the first time that transplanting aSCTs combined with growth factor supplementation facilitates reconstruction of injured spinal cords, and consequently promotes long lasting motor function recovery in a large animal complete transected SCI model, and therefore could be considered as a possible therapeutic strategy in humans.

Controlled synthesis of porous spinel cobalt manganese oxides as efficient oxygen reduction reaction electrocatalysts

In this article, we report a facile precursor pyrolysis method to prepare porous spinel-type cobalt manganese oxides （CoxMng-xO4） with controllable morphologies and crystalline structures. The capping agent in the reaction was found to be crucial on the formation of the porous spinel cobalt manganese oxides from cubic Co2MnO4 nanorods to tetragonal CoMn2O4 microspheres and tetragonal CoMn204 cubes, respectively. All of the prepared spinel materials exhibit brilliant oxygen reduction reaction （ORR） electrocatalysis along with high stability. In particular, the cubic Co2MnO4 nanorods show the best performance with an onset potential of 0.9 V and a half-wave potential of 0.72 V which are very close to the commercial Pt/C. Meanwhile, the cubic Co2MnO4 nanorods present superior stability with negligible degradation of their electrocatalytic activity after a continuous operation time of 10,000 seconds, which is much better than the commercial Pt/C electrocatalvst.

Facile synthesis of magnetic-plasmonic nanocomposites as T1 MRI contrast enhancing and photothermal therapeutic agents

Nanocomposites combining magnetic and plasmonic components have received widespread attention in recent years due to their potential applications in biomedical research. Herein, we describe a facile method for growing small iron oxide nanoparticles on various plasmonic core materials with different shapes and surfaces by utilizing a polypyrrole interlayer. By focusing on Au nanorod@polypyrrole@iron oxide （Au NR@PPy@FexO） nanocomposites, we show that these systems exhibit a low r2/rl ratio of 4.8, making them efficient T1 positive contrast-enhancing agents for magnetic resonance imaging （MRI）. Moreover, we show that the nanocomposites are excellent photothermal agents in the second near infrared region, with high photothermal conversion efficiency, reaching up to 46%. In addition, the Au NR@PPy@FexO nanocomposites show very low cytotoxicity. In summary, the present results highlight the great potential of the synthetic method and the nanocomposites developed in this study for T~ MRI and/or infrared thermal imaging-guided photothermal cancer therapeutic applications.

All-in-one theranostic nanoplatfbrm with controlled drug release and activated MRI tracking functions for synergistic NIR-II hyperthermiachemotherapyof tumors

Real-time tracking drug release behavior is fundamentally important for avoiding adverse effects or unsuccessful treatment in personalizemedical treatment.However,the development of a non-invasive drug reporting platform still remains challenging.Herein the design of a novelsyn thetic magnetic resonance imaging(MRI)agent for drug release tracking(SMART)is reported,which integrates photothermal core andparamagnetic ion/drug loading shell with a thermal valve in a hybrid structure.Through near-infrared(NIR)-II photothermal effect originatingfrom inner Au-Cu9S5 nanohybrid core,burst release of drugs loaded in the mesoporous silica shell is achieved.The concomitant use of aphase change material not only prevents premature drug release,but also regulates heating effect,keeping local temperature below 45℃,enabling synergistic chemotherapy and mild hyperthermia in vitro and in vivo.Furthermore,the drug release from SMART facilitates protonaccessibility to the paramagnetic ions anchored inside mesopores channels,enhancing Iongitudinal T1 relaxation rate and displaying positivesignal correlation to the amount of released drug,thus allowing norvinvasive real-time monitoring of drug release event.The current studyhighlights the potential of designed MRI nanophores such as SMART for real-time and in-situ monitoring of drug delivery for precisionthera nostic applications.

AgAuSe quantum dots with absolute photoluminescence quantum yield of 87.2%:The effect of capping ligand chain length

Surface ligands of colloidal quantum dots(QDs)have a profound influence on their surface states,which has been verified in the studies of the effect of ligand head groups on the photoluminescence(PL)properties of QDs.However,the investigation of the ligand chain length is limited.Here,we systematically explored the effect of chain length on the Ag_(2)Se QDs by selecting three ligands,1-octanethiol(OTT),1-dodecanethiol(DDT),and 1-hexadecanethiol(HDT),with diverse chain lengths.We found that the PL intensity of Ag_(2)Se QDs increased with the decrease of the ligand chain length due to the enhanced passivation of surface defects emerging from the robust QD-ligand interface binding affinity and the weaker hydrophobic chain–chain interaction.Subsequently,AgAuSe QDs terminated with OTT were obtained by alloying parent OTT-Ag_(2)Se QDs with Au precursor with a record absolute PL quantum yield(PLQY)of 87.2%at 970 nm,facilitating ultrasensitive in vivo angiography imaging in a nude mouse model.We expect that our finding of the important role of the ligand chain length on the optical properties of QDs will be suggestive to the design and synthesis of high-quality QDs,and also look forward to the clinical applications of the ultra-bright AgAuSe QDs.

A Cascade Targeted and Activatable NIR-ⅡNanoprobe for Highly Sensitive Detection of Acute Myeloid Leukemia in an Orthotopic Model

Acute myeloid leukemia(AML)remains a significant concern in modern medicine.Early diagnosis is the key to improving the therapeutic effects of AML.In the present work,a cascade-targeted and activatable NIR-Ⅱ nanoprobe(Ald&A1094@Ag_(2)S)was developed for early detection of AML in an orthotopic model.Upon intravenous injection,Ald&A1094@Ag_(2)S effectively accumulated in bone tissue due to its high affinity for alendronate(Ald)to the bone.Thereafter,the AML microenvironment allowed for the membrane-penetrating peptide TAT(cell‐penetrating peptide(CGRRRQRRKKRG))to be exposed via pH-sensitive hydrazone bond-mediated detaching of bone-targeted ligands,resulting in efficient internalization of nanoprobes in HL60 cells.Endogenous peroxynitrite(ONOO–)in HL60 cells further activated NIR-Ⅱ fluorescence of Ag_(2)S QDs via A1094 oxidation,thereby inhibiting fluorescence resonance energy transfer(FRET).Such a unique cascade-targeted and activatable strategy enables the nanoprobes to only light up the AML lesion region in the bone marrow with negligible background effects,which holds great potential for clinical applications in the future.

Microvascular endothelial cells derived from spinal cord promote spinal cord injury repair

Neural regeneration after spinal cord injury (SCI) closely relates to the microvascular endothelial cell (MEC)- mediated neurovascular unit formation. However, the effects of central nerve system-derived MECs on neovascularization and neurogenesis, and potential signaling involved therein, are unclear. Here, we established a primary spinal cord-derived MECs (SCMECs) isolation with high cell yield and purity to describe the differences with brain-derived MECs (BMECs) and their therapeutic effects on SCI. Transcriptomics and proteomics revealed differentially expressed genes and proteins in SCMECs were involved in angiogenesis, immunity, metabolism, and cell adhesion molecular signaling was the only signaling pathway enriched of top 10 in differentially expressed genes and proteins KEGG analysis. SCMECs and BMECs could be induced angiogenesis by different stiffness stimulation of PEG hydrogels with elastic modulus 50-1650 Pa for SCMECs and 50-300 Pa for BMECs, respectively. Moreover, SCMECs and BMECs promoted spinal cord or brain-derived NSC (SNSC/BNSC) proliferation, migration, and differentiation at different levels. At certain dose, SCMECs in combination with the NeuroRegen scaffold, showed higher effectiveness in the promotion of vascular reconstruction. The potential underlying mechanism of this phenomenon may through VEGF/AKT/eNOS- signaling pathway, and consequently accelerated neuronal regeneration and functional recovery of SCI rats compared to BMECs. Our findings suggested a promising role of SCMECs in restoring vascularization and neural regeneration.

用于伤口修复的无二次损伤的保水可撕断粘附水凝胶

作为新型伤口敷料,粘附性水凝胶已被广泛研究.然而,由于易失水和敷料更换时二次损伤的问题,粘附水凝胶敷料的临床应用仍然是一个重大挑战.本文中,我们设计了一种基于双键化丝素蛋白、单宁酸和聚氨酯二丙烯酸酯的具有保水性能和可撕断性能的粘附水凝胶敷料.通过复合具有大量儿茶酚基团的单宁酸,使得水凝胶具有增强的机械性能、良好的组织粘附性能、止血性能以及生物相容性能.随后将疏水性的聚氨酯二丙烯酸酯涂层聚合在水凝胶表面,该涂层的存在可以使水凝胶长时间保持高含水量.此外,由于该水凝胶的粘附能高于断裂能,其在剥离时可以被撕断,并最大程度减小对伤口部位的影响.动物实验结果表明,这种具有粘附止血性能的水凝胶可以通过提供长久的湿性愈合环境和无二次损伤的换料来加速伤口愈合.这些结果表明这种多功能水凝胶是一种具有临床应用前景的伤口敷料.

Engineered human spinal cord-like tissues with dorsal and ventral neuronal progenitors for spinal cord injury repair in rats and monkeys

Transplanting human neural progenitor cells is a promising method of replenishing the lost neurons after spinal cord injury (SCI), but differentiating neural progenitor cells into the diverse types of mature functional spinal cord neurons in vivo is challenging. In this study, engineered human embryonic spinal cord-like tissues with dorsal and ventral neuronal characters (DV-SC) were generated by inducing human neural progenitor cells (hscNPCs) to differentiate into various types of dorsal and ventral neuronal cells on collagen scaffold in vitro. Transplantation of DV-SC into complete SCI models in rats and monkeys showed better therapeutic effects than undifferentiated hscNPCs, including pronounced cell survival and maturation. DV-SC formed a targeted connection with the host’s ascending and descending axons, partially restored interrupted neural circuits, and improved motor evoked potentials and the hindlimb function of animals with SCI. This suggests that the transplantation of pre-differentiated hscNPCs with spinal cord dorsal and ventral neuronal characteristics could be a promising strategy for SCI repair.

Collagen scaffolds modified with collagen-binding bFGF promotes the neural regeneration in a rat hemisected spinal cord injury model

Nerve conduit is one of strategies for spine cord injury(SCI)treatment.Recently,studies showed that biomaterials could guide the neurite growth and promote axon regeneration at the injury site.However,the scaffold by itself was difficult to meet the need of SCI functional recovery.The basic fibroblast growth factor(bFGF)administration significantly promotes functional recovery after organ injuries.Here,using a rat model of T9 hemisected SCI,we aimed at assessing the repair capacity of implantation of collagen scaffold(CS)modified by collagen binding bFGF(CBD-bFGF).The results showed that CS combined with CBD-bFGF treatment improved survival rates after the lateral hemisection SCI.The CS/CBD-bFGF group showed more significant improvements in motor than the simply CS-implanted and untreated control group,when evaluated by the 21-point Basso-Beattie-Bresnahan(BBB)score and footprint analysis.Both hematoxylin and eosin(H&E)and immunohistochemical staining of neurofilament(NF)and glial fibrillary acidic protein(GFAP)demonstrated that fibers were guided to grow through the implants.These findings indicated that administration of CS modified with CBD-bFGF could promote spinal cord regeneration and functional recovery.

Human placenta-derived mesenchymal stem cells loaded on linear ordered collagen scaffold improves functional recovery after completely transected spinal cord injury in canine

Traumatic spinal cord injury(SCI) is a major challenge in the clinic. In this study, we sought to examine the synergistic effects of linear ordered collagen scaffold(LOCS) and human placenta-derived mesenchymal stem cells(hPMSCs) when transplanted into completely transected beagle dogs. After 36 weeks observation, we found that LOCS+hPMSCs implants promoted better hindlimb locomotor recovery than was observed in the non-treatment(control) group and LOCS group. Histological analysis showed that the regenerated tissue after treatment was well integrated with the host tissue, and dramatically reduced the volume of cystic and chondroitin sulfate proteoglycans(CSPGs) expression. Furthermore, the LOCS+hPMSCs group also showed more neuron-specific βIII-tubulin(Tuj-1)-and NeuN-positive neurons in the lesion area, as well as axonal regeneration, remyelination and synapse formation in the lesion site. Additionally, dogs in the LOCS+hPMSCs group experienced enhanced sprouting of both ascending(CGRP-positive) sensory fibers and descending(5-HT-and TH-positive) motor fibers at the lesion area. All these data together suggested that the combined treatment had beneficial effects on neuronal regeneration and functional improvement in a canine complete transection model. Therefore, LOCS+hPMSCs implantation holds a great promise for bridging the nerve defect and may be clinically useful in the near future.

MoSe2 porous microspheres comprising monolayer flakes with high electrocatalytic activity

综合的一条灵巧的胶体的线路 MoSe < 潜水艇 class= “ a-plus-plus ” > 2 有由 MoSe 组成的 400600 nm 的直径的多孔的 microspheres < 潜水艇 class= “ a-plus-plus ” > 2 个 单层薄片在厚度的 0.7 nm 被报导。溶剂 trioctylamine TOA 和 oleylamine 操作维护管理被发现在 MoSe 的形成起重要作用 < 潜水艇 class= “ a-plus-plus ” > 2 microspheres， TOA 由此决定三维的 3D microspherical 形态学和操作维护管理，指导 MoSe 的形成 < 潜水艇 class= “ a-plus-plus ” > 2 个 单层薄片。柔韧的 3D MoSe <潜水艇class=“ a-plus-plus ”> 2 microspheres 展览为 electrocatalytic 氢进化反应的显著活动和耐久性她在酸，维持 77 mV 的小发作过电位并且为 5 妈/厘米的当前的密度保留 100 mV 的小过电位<啜class=“ a-plus-plus ”>在 1,000 以后的 2 骑车。另外，类似的 3D WSe < 潜水艇 class= “ a-plus-plus ” > 2 microspheres 能被使用这个方法也准备。我们期望这条灵巧的胶体的线路能进一步被扩展综合将在域例如里发现应用的另外的多孔的结构在精力存储，催化作用，并且察觉到。

室温绿色合成镍铁层状双氢氧化物/泡沫镍及其高效的电催化析氧反应性能（英文）

绿色能源技术如电解水和燃料电池等由于其无污染的特点,近年来一直受到人们的广泛关注.然而,在合成其催化剂的过程中多会消耗化石能源,从而造成环境污染,形成恶性循环.因此,在无额外能量输入的条件下合成高效的电催化剂是非常必要的,但同时又充满挑战.本文通过简单的一步合成法在室温下制备了一种具有高效析氧催化性能的镍铁层状双氢氧化物/泡沫镍(NiFe LDH/NF)催化剂. NiFe LDH的形成遵循溶解-沉淀机理:Fe^(3+)水解产生的酸性环境联合NO_3^-,刻蚀泡沫镍表面,形成Ni^(2+),随后, Ni^(2+)与水解的Fe物种原位共沉淀于泡沫镍表面,生成NiFe LDH.所得到的NiFe LDH/NF在碱性环境下,表现出高效的电催化析氧反应性能.在1 mol L^(-1)的氢氧化钾溶液中,当电流密度为10 mA cm^(-2)时,其电位低至1.411 V vs. RHE,相应的塔菲尔斜率仅为42.3 mV dec^(-1),而在电流密度为100 mA cm^(-2)时,所需电位也仅为1.452 V vs. RHE.此外,该材料还表现出卓越的结构稳定性.这种绿色制备NiFe LDH/NF的合成方法有望在OER催化中得到广泛的应用.

原子级Pt团簇修饰的α相氢氧化镍纳米线作为高效析氢反应催化剂（英文）

合成原子级别的催化剂是一项颇具前景但又充满挑战的课题.本文通过简单的室温反应成功制备了一种原子级别的Pt团簇修饰的多孔α相氢氧化镍纳米线(Pt_c/Ni(OH)_2)复合材料.所得到的Pt_c/Ni(OH)_2在碱性环境下表现出高效的电催化析氢反应性能.在氢气饱和的0.1 mol L^(-1)氢氧化钾溶液中,Pt_c/Ni(OH)_2的起始过电势很小,接近于0,当电流密度为10 mA cm^(-2)时,其过电势低至32 mV.此过电位低于同等条件下商业化20% Pt/C的过电势(58 mV).通过质量电流密度数据显示,在过电势为50 mV时,Pt_c/Ni(OH)_2的质量电流密度高达6.34 Amg_(Pt)^(-1),在同样的过电势条件下,这一电流是商业化Pt/C(0.223 Amg_(Pt)^(-1))的28倍,表明我们所制得的Pt_c/Ni(OH)_2在碱性环境下具有高效的电催化析氢反应性能.