Targeted Delivery of Anesthetic Agents to Bone Tissues using Conductive Microneedles Enhanced Iontophoresis for Painless Dental Anesthesia

Pain management during dental procedures is a cornerstone for successful daily practice. In current practice, the traditional needle and syringe injection is used to administer local anesthesia. However, the appearance of long needles and the pain associated with it often leads to dental anxiety deterring timely interventions. Microneedles (MNs) have emerged as a minimally invasive alternative to hypodermic needles and shown to be effective in transdermal drug delivery applications. In this article, the potential use of MNs for local anesthesia delivery in dentistry is explored. The development of a novel conductive MN array that can be used in combination with iontophoresis technique to achieve drug penetration through the oral mucosa and the underlying bone tissue is presented. The conductive MN array plays a dual-role, creating micro-conduits and lowering the resistance of the oral mucosa. The reduced tissue resistance further enhances the application of a low-voltage current that is able to direct and accelerate the drug molecules to target the sensory nerves supplying teeth. The successful delivery of lidocaine using this new strategy in a clinically relevant rabbit incisor model is shown to be as effective as the current gold standard.     

TGFβ-1 Induced Cross-Linking of the Extracellular Matrix of Primary Human Dermal Fibroblasts

Excessive cross-linking is a major factor in the resistance to the remodelling of the extracellular matrix (ECM) during fibrotic progression. The role of TGFβ signalling in impairing ECM remodelling has been demonstrated in various fibrotic models. We hypothesised that increased ECM cross-linking by TGFβ contributes to skin fibrosis in Systemic Sclerosis (SSc). Proteomics was used to identify cross-linking enzymes in the ECM of primary human dermal fibroblasts, and to compare their levels following treatment with TGFβ-1. A significant upregulation and enrichment of lysyl-oxidase-like 1, 2 and 4 and transglutaminase 2 were found. Western blotting confirmed the upregulation of lysyl hydroxylase 2 in the ECM. Increased transglutaminase activity in TGFβ-1 treated ECM was revealed from a cell-based assay. We employed a mass spectrometry-based method to identify alterations in the ECM cross-linking pattern caused by TGFβ-1. Cross-linking sites were identified in collagens I and V, fibrinogen and fibronectin. One cross-linking site in fibrinogen alpha was found only in TGFβ-treated samples. In conclusion, we have mapped novel cross-links between ECM proteins and demonstrated that activation of TGFβ signalling in cultured dermal fibroblasts upregulates multiple cross-linking enzymes in the ECM.     

Dysprosium doped copper oxide (Cu1-xDyxO) nanoparticles enabled bifunctional electrode for overall water splitting

The production of hydrogen, a favourable alternative to an unsustainable fossil fuel remains as a significant hurdle with the pertaining challenge in the design of proficient, highly productive and sustainable electrocatalyst for both oxygen evolution reaction (OER) and hydrogen evolution reaction (HER). Herein, the dysprosium (Dy) doped copper oxide (Cu_1-xDy_xO) nanoparticles were synthesized via solution combustion technique and utilized as a non-noble metal based bi-functional electrocatalyst for overall water splitting. Due to the improved surface to volume ratio and conductivity, the optimized Cu_1-xDy_xO (x = 0.01, 0.02) electrocatalysts exhibited impressive HER and OER performance respectively in 1 M KOH delivering a current density of 10 mAcm^?2 at a potential of ?0.18 V vs RHE for HER and 1.53 V vs RHE for OER. Moreover, the Dy doped CuO electrocatalyst used as a bi-functional catalyst for overall water splitting achieved a potential of 1.56 V at a current density 10 mAcm^?2 and relatively high current density of 66 mAcm^?2 at a peak potential of 2 V. A long term stability of 24 h was achieved for a cell voltage of 2.2 V at a constant current density of 30 mAcm^?2 with only 10% of the initial current loss. This showcases the accumulative opportunity of dysprosium as a dopant in CuO nanoparticles for fabricating a highly effective and low-cost bi-functional electrocatalyst for overall water splitting.     

基于Control-mind数控系统的电液束设备控制功能开发

现有的电液束加工设备存在控制可扩展性不够、无对刀功能、加工孔的入口孔型一致性难以得到保证、人工输入及修改数控程序时易出现错误等问题.基于Control-mind数控系统,开发出具有定制界面和特定功能的新电液束加工设备,以满足新的加工工艺需求.     

Human DDX17 Unwinds Rift Valley Fever Virus Non-Coding RNAs

Rift Valley fever virus (RVFV) is a mosquito-transmitted virus from the Bunyaviridae family that causes high rates of mortality and morbidity in humans and ruminant animals. Previous studies indicated that DEAD-box helicase 17 (DDX17) restricts RVFV replication by recognizing two primary non-coding RNAs in the S-segment of the genome: the intergenic region (IGR) and 5′ non-coding region (NCR). However, we lack molecular insights into the direct binding of DDX17 with RVFV non-coding RNAs and information on the unwinding of both non-coding RNAs by DDX17. Therefore, we performed an extensive biophysical analysis of the DDX17 helicase domain (DDX17_135–555) and RVFV non-coding RNAs, IGR and 5’ NCR. The homogeneity studies using analytical ultracentrifugation indicated that DDX17_135–555, IGR, and 5’ NCR are pure. Next, we performed small-angle X-ray scattering (SAXS) experiments, which suggested that DDX17 and both RNAs are homogenous as well. SAXS analysis also demonstrated that DDX17 is globular to an extent, whereas the RNAs adopt an extended conformation in solution. Subsequently, microscale thermophoresis (MST) experiments were performed to investigate the direct binding of DDX17 to the non-coding RNAs. The MST experiments demonstrated that DDX17 binds with the IGR and 5’ NCR with a dissociation constant of 5.77 ± 0.15 µM and 9.85 ± 0.11 µM, respectively. As DDX17_135–555 is an RNA helicase, we next determined if it could unwind IGR and NCR. We developed a helicase assay using MST and fluorescently-labeled oligos, which suggested DDX17_135–555 can unwind both RNAs. Overall, our study provides direct evidence of DDX17_135–555 interacting with and unwinding RVFV non-coding regions.     

等离子弧异质异构增材制造构件的组织与力学性能分析

采用等离子弧增材系统实现了不锈钢/高强钢异质异构增材构件制备，等离子弧增材构件具有良好的沉积形貌及优异的力学性能.为揭示叠合方式对等离子弧异质增材构件的宏微观组织和力学性能特征影响，研究采用了体视显微镜、金相显微镜、拉伸及硬度等测试方法.结果表明，不锈钢/高强钢异质异构增材构件中存在两种过渡形式，即以奥氏体枝晶过渡和马氏体组织过渡.增材构件横截面硬度波动较大，主要是混合过渡区域的高合金元素导致的组织变化引起的.叠合方式的改变能够显著影响材料性能，在强度下降不多的情况下，提高材料的冲击韧性.     

不同煤阶煤孔隙特征及其吸附能力响应

我国是煤炭资源大国，煤层气储量规模相当可观，但煤储层又具有低孔、低渗的不足，照搬国外或常规石油天然气的开采程序和方法已被证实是走不通的。应结合实际，根据不同地质条件、不同煤阶的开采程序，进行孔隙特征研究。煤孔隙特征、连通性和吸附能力对煤层气开采影响尤为重要，为研究煤孔隙结构特征随煤变质程度的变化关系及其吸附能力的响应特点，采取不同地区不同变质程度煤样，进行压汞测试和等温吸附实验。实验结果表明，煤孔隙度和平均孔径均随变质程度增加呈现降低—升高—降低的趋势；煤中孔隙连通性随煤变质程度增加逐渐变差；随煤变质程度增加，其最大吸附能力也呈现降低—升高—降低的总体趋势。     

Cell-free Stem Cell-Derived Extract Formulation for Regenerative Medicine Applications

Stem cells for regenerative medicine purposes offer therapeutic benefits, but disadvantages are still ill defined. The benefit of stem cells may be attributed to their secretion of growth factors (GFs), cytokines (CKs), and extracellular vesicles (EVs), including exosomes. We present a novel cell-free stem cell-derived extract (CCM), formulated from human progenitor endothelial stem cells (hPESCs), characterized for biologically active factors using ELISA, nanoparticle tracking analysis and single particle interferometric reflectance imaging sensing. The effect on fibroblast proliferation and ability to induce stem cell migration was analyzed using Alamar Blue proliferation and Transwell migration assays, respectively. GFs including IGFBP 1, 2, 3, and 6, insulin, growth hormone, PDGF-AA, TGF-α, TGF-β1, VEGF, and the anti-inflammatory cytokine, IL-1RA were detected. Membrane enclosed particles within exosome size range and expressing exosome tetraspanins CD81 and CD9 were identified. CCM significantly increased cell proliferation and induced stem cell migration. Analysis of CCM revealed presence of GFs, CKs, and EVs, including exosomes. The presence of multiple factors including exosomes within one formulation, the ability to promote cell proliferation and induce stem cell migration may reduce inflammation and pain, and augment tissue repair.     

Chemotherapy drugs derived nanoparticles encapsulating mRNA encoding tumor suppressor proteins to treat triple-negative breast cancer

Triple-negative breast cancer (TNBC) is one type of the most aggressive breast cancers with poor prognosis. It is of great urgency to develop new therapeutics for treating TNBC. Based on current treatment guideline and genetic information of TNBC, a combinational therapy platform integrating chemotherapy drugs and mRNA encoding tumor suppressor proteins may become an efficacious strategy. In this study, we developed paclitaxel amino lipid (PAL) derived nanoparticles (NPs) to incorporate both chemotherapy drugs and P53 mRNA. The PAL P53 mRNA NPs showed superior properties compared to Abraxane^® and Lipusu^® used in the clinic including high paclitaxel loading capacity (24 wt.%, calculated by paclitaxel in PAL), PAL encapsulation efficiency (94.7% ± 6.8%) and mRNA encapsulation efficiency (88.7% ± 0.7%). Meanwhile, these NPs displayed synergetic cytotoxicity of paclitaxel and P53 mRNA in cultured TNBC cells. More importantly, we demonstrated in vivo anti-tumor efficacy of PAL P53 mRNA NPs in an orthotopic TNBC mouse model. Overall, these chemotherapy drugs derived mRNA NPs provide a new platform to integrate chemotherapy and personalized medicine using tumor genetic information, and therefore represent a promising approach for TNBC treatment.