Hemodynamic force dictates endothelial angiogenesis through MIEN1-ERK/MAPK-signaling axis.

It is well-recognized that blood flow at branches and bends of arteries generates disturbed shear stress, which plays a crucial in driving atherosclerosis. Flow-generated fluid shear stress (FSS), as one of the key hemodynamic factors, is appreciated for its critical involvement in regulating angiogenesis to facilitate wound healing and tissue repair. Endothelial cells can directly sense FSS but the mechanobiological mechanism by which they decode different patterns of FSS to trigger angiogenesis remains unclear. In the current study, laminar shear stress (LSS, 15 dyn/cm2) was employed to mimic physiological blood flow, while disturbed shear stress (DSS, ranging from 0.5 ± 4 dyn/cm2) was applied to simulate pathological conditions. The aim was to investigate how these distinct types of blood flow regulated endothelial angiogenesis. Initially, we observed that DSS impaired angiogenesis and downregulated endogenous vascular endothelial growth factor B (VEGFB) expression compared to LSS. We further found that the changes in membrane protein, migration and invasion enhancer 1 (MIEN1) play a role in regulating ERK/MAPK signaling, thereby contributing to endothelial angiogenesis in response to FSS. We also showed the involvement of MIEN1-directed cytoskeleton organization. These findings suggest the significance of shear stress in endothelial angiogenesis, thereby enhancing our understanding of the alterations in angiogenesis that occur during the transition from physiological to pathological blood flow.

[Mechanobiological Mechanisms Involved in the Regualation of the Blood-Brain Barrier by Fluid Shear Force]. / æµä½“å‰ªåˆ‡åŠ›è°ƒæŽ§è¡€è„‘å±éšœçš„åŠ›å­¦ç”Ÿç‰©å­¦æœºåˆ¶ç ”ç©¶.

Objective: To explore the mechanobiological mechanism of fluid shear force (FSF) on the protection, injury, and destruction of the structure and function of the blood-brain barrier (BBB) under normal physiological conditions, ischemic hypoperfusion, and postoperative hyperperfusion conditions. BBB is mainly composed of brain microvascular endothelial cells. Rat brain microvascular endothelial cells (rBMECs) were used as model cells to conduct the investigation. Methods: rBMECs were seeded at a density of 1×105 cells/cm2 and incubated for 48 h. FSF was applied to the rBMECs at 0.5, 2, and 20 dyn/cm2, respectively, simulating the stress BBB incurs under low perfusion, normal physiological conditions, and high FSF after bypass grafting when there is cerebral vascular stenosis. In addition, a rBMECs static culture group was set up as the control (no force was applied). Light microscope, scanning electron microscope (SEM), and laser confocal microscope (LSCM) were used to observe the changes in cell morphology and cytoskeleton. Transmission electron microscope (TEM) was used to observe the tight junctions. Immunofluorescence assay was performed to determine changes in the distribution of tight junction-associated proteins claudin-5, occludin, and ZO-1 and adherens junction-associated proteins VE-cadherin and PECAM-1. Western blot was performed to determine the expression levels of tight junction-associated proteins claudin-5, ZO-1, and JAM4, adherens junction-associated protein VE-cadherin, and key proteins in Rho GTPases signaling (Rac1, Cdc42, and RhoA) under FSF at different intensities. Results: Microscopic observation showed that the cytoskeleton exhibited disorderly arrangement and irregular orientation under static culture and low shear force (0.5 dyn/cm2). Under normal physiological shear force (2 dyn/cm2), the cytoskeleton was rearranged in the orientation of the FSF and an effective tight junction structure was observed between cells. Under high shear force (20 dyn/cm2), the intercellular space was enlarged and no effective tight junction structure was observed. Immunofluorescence results showed that, under low shear force, the gap between the cells decreased, but there was also decreased distribution of tight junction-associated proteins and adherens junction-associated proteins at the intercellular junctions. Under normal physiological conditions, the cells were tightly connected and most of the tight junction-associated proteins were concentrated at the intercellular junctions. Under high shear force, the gap between the cells increased significantly and the tight junction and adherens junction structures were disrupted. According to the Western blot results, under low shear force, the expression levels of claudin-5, ZO-1, and VE-cadherin were significantly up-regulated compared with those of the control group (P<0.05). Under normal physiological shear force, claudin-5, ZO-1, JAM4, and VE-cadherin were highly expressed compared with those of the control group (P<0.05). Under high shear force, the expressions of claudin-5, ZO-1, JAM4, and VE-cadherin were significantly down-regulated compared with those of the normal physiological shear force group (P<0.05). Under normal physiological shear force, intercellular expressions of Rho GTPases proteins (Rac1, Cdc42, and RhoA) were up-regulated and were higher than those of the other experimental groups (P<0.05). The expressions of Rho GTPases under low and high shear forces were down-regulated compared with that of the normal physiological shear force group (P<0.05). Conclusion: Under normal physiological conditions, FSF helps maintain the integrity of the BBB structure, while low or high shear force can damage or destroy the BBB structure. The regulation of BBB by FSF is closely related to the expression and distribution of tight junction-associated proteins and adherens junction-associated proteins.

Vascular smooth muscle cells in intracranial aneurysms.

Intracranial aneurysm (IA) is a severe cerebrovascular disease characterized by abnormal bulging of cerebral vessels that may rupture and cause a stroke. The expansion of the aneurysm accompanies by the remodeling of vascular matrix. It is well-known that vascular remodeling is a process of synthesis and degradation of extracellular matrix (ECM), which is highly dependent on the phenotype of vascular smooth muscle cells (VSMCs). The phenotypic switching of VSMC is considered to be bidirectional, including the physiological contractile phenotype and alternative synthetic phenotype in response to injury. There is increasing evidence indicating that VSMCs have the ability to switch to various phenotypes, including pro-inflammatory, macrophagic, osteogenic, foamy and mesenchymal phenotypes. Although the mechanisms of VSMC phenotype switching are still being explored, it is becoming clear that phenotype switching of VSMCs plays an essential role in IA formation, progression, and rupture. This review summarized the various phenotypes and functions of VSMCs associated with IA pathology. The possible influencing factors and potential molecular mechanisms of the VSMC phenotype switching were further discussed. Understanding how phenotype switching of VSMC contributed to the pathogenesis of unruptured IAs can bring new preventative and therapeutic strategies for IA.

A sensitive method to determine dopamine in the presence of uric acid based on In2O3 nanosheet arrays grown on 3D graphene.

A nonenzymatic voltammetric assay for dopamine (DA) was developed based on the combination of three-dimensional graphene (3D Gr) and indium oxide nanosheet arrays (In2O3 NSAs). 3D Gr was prepared by chemical vapor deposition (CVD), and In2O3 NSAs were grown on its surface by hydrothermal synthesis. The results show that 3D Gr maintains a good porous structure (200 µm), and the pore size of In2O3 NSAs is 0.50 µm. Differential pulse voltammetry (DPV) is mainly used to determine the electrochemical properties of In2O3 NSAs/3D Gr. It possesses a sensitivity of 2.69 µA·µM-1·cm-2 towards DA (5-60 µM) at 0.14 V, and the detection limit (LOD) is 0.10 µM (S/N = 3). The recoveries obtained for spiked samples in the real sample detection is 105 (± 8)%. Graphical abstractSchematic representation of DA sensitive detection by growing In2O3 nanosheets arrays on three-dimentional graphene modified ITO.

3-Dimensional hollow graphene balls for voltammetric sensing of levodopa in the presence of uric acid.

The development of novel nanomaterials brings new opportunity and challenge for high sensing detection of biomolecules. The authors describe the preparation of 3-dimentional hollow graphene balls (3D HGBs) using nickel nanoparticles (Ni-NPs) as the template. The Ni-NPs were synthesized by chemical reduction of nickel chloride and then graphene was coated onto their surface via carburization and carbonization. After etching Ni-NPs, 3D HGBs with few layers and a typical size of 100 nm were obtained. They were sprayed onto indium tin oxide glass to obtain a working electrode for electrochemical determination of levodopa in the presence of uric acid. Due to the unique hollow porous structure of the 3D HGBs, the electrode exhibits a sensitivity of 0.69 µA·µM-1·cm-2 and a 1 µM limit of detection. It is selective, reproducible and stable. It was applied to the determination of levodopa in spiked human plasma samples and it is of potential use in clinical research. Graphical abstract Schematic presentation of the preparation of 3-dimensional hollow graphene balls (HGBs) by using nickel nanoparticles as a template that can be removed by etching. The HGBs were sprayed onto indium tin oxide (ITO) glass to obtain a working electrode that has a sensitivity of 0.69 µA⋅µM-1·cm-2 and a 1 µM limit of detection for the determination of levodopa.

Fluid shear stress induced-endothelial phenotypic transition contributes to cerebral ischemia-reperfusion injury and repair.

Long-term ischemia leads to insufficient cerebral microvascular perfusion and dysfunction. Reperfusion restores physiological fluid shear stress (FSS) but leads to serious injury. The mechanism underlying FSS-induced endothelial injury in ischemia-reperfusion injury (IRI) remains poorly understood. In this study, a rat model of middle cerebral artery occlusion was constructed to explore cerebrovascular endothelial function and inflammation in vivo. Additionally, the rat brain microvascular endothelial cells (rBMECs) were exposed to a laminar FSS of 0.5 dyn/cm2 for 6 h and subsequently restored to physiological fluid shear stress level (2 dyn/cm2) for 2 and 12 h, respectively. We found that reperfusion induced endothelial-to-mesenchymal transition (EndMT) in endothelial cells, leading to serious blood-brain barrier dysfunction and endothelial inflammation, accompanied by the nuclear accumulation of Yes-associated protein (YAP). During the later stage of reperfusion, cerebral endothelium was restored to the endothelial phenotype with a distinct change in mesenchymal-to-endothelial transition (MEndT), while YAP was translocated and phosphorylated in the cytoplasm. Knockdown of YAP or inhibition of actin polymerization markedly impaired the EndMT in rBMECs. These findings suggest that ischemia-reperfusion increased intensity of FSS triggered an EndMT process and, thus, led to endothelial inflammation and tissue injury, whereas continuous FSS induced a time-dependent reversal MEndT event contributing to the endothelial repair. This study provides valuable insight for therapeutic strategies targeting IRI.

Construction of hierarchical MOF-derived CoS2 microsheet arrays@NiMo2S4 nanoflakes on Ni foam as a high-performance supercapacitor electrode.

The reasonable design of electrode material composition and structure is an effective way to solve the low energy density of supercapacitors. In this paper, hierarchical MOF-derived CoS2 microsheet arrays@NiMo2S4 nanoflakes on Ni foam (CoS2@NiMo2S4/NF) was prepared by the co-precipitation, electrodeposition and sulfurization process. MOF-derived CoS2 microsheet arrays on NF are used as ideal backbones to provide fast transport channels, and NiMo2S4 nanoflakes with a network-like distribution on the CoS2 microsheet arrays can improve the accessible active sites and promote the penetration and transfer of electrolyte ions. Due to the synergistic effects between the multi components, CoS2@NiMo2S4 exhibits excellent electrochemical properties. The specific capacity of CoS2@NiMo2S4 is 802 C g-1 at 1 A g-1. Hybrid supercapacitor assembled by CoS2@NiMo2S4 and activated carbon exhibits an energy density of 32.1 Wh kg-1 at a power density of 1130.3 W kg-1 and a cycle stability of 87.2% after 10, 000 cycles. This confirms the great potential of CoS2@NiMo2S4 as a supercapacitor electrode material.

The influence of microenvironment stiffness on endothelial cell fate: Implication for occurrence and progression of atherosclerosis.

Atherosclerosis, the primary cause of cardiovascular diseases (CVDs), is characterized by phenotypic changes in fibrous proliferation, chronic inflammation and lipid accumulation mediated by vascular endothelial cells (ECs) and vascular smooth muscle cells (SMCs) which are correlated with the stiffening and ectopic remodeling of local extracellular matrix (ECM). The native residents, ECs and SMCs, are not only affected by various chemical factors including inflammatory mediators and chemokines, but also by a range of physical stimuli, such as shear stress and ECM stiffness, presented in the microenvironmental niche. Especially, ECs, as a semi-selective barrier, can sense mechanical forces, respond quickly to changes in mechanical loading and provide context-specific adaptive responses to restore homeostasis. However, blood arteries undergo stiffening and lose their elasticity with age. Reports have shown that the ECM stiffening could influence EC fate by changing the cell adhesion, spreading, proliferation, cell to cell contact, migration and even communication with SMCs. The cell behaviour changes mediated by ECM stiffening are dependent on the activation of a signaling cascade of mechanoperception and mechanotransduction. Although the substantial evidence directly indicates the importance of ECM stiffening on the native ECs, the understanding about this complex interplay is still largely limited. In this review, we systematically summarize the roles of ECM stiffening on the behaviours of endothelial cells and elucidate the underlying details in biological mechanism, aiming to provide the process of how ECs integrate ECM mechanics and the highlights for bioaffinity of tissue-specific engineered scaffolds.

Self-templated flower-like NiCoZn-carbonate hydroxide hollow nanospheres for asymmetric supercapacitors with high performance.

With the increasing demand for energy resources, it is crucial to explore electrode materials with high specific capacitance and cycling stability for supercapacitors. Herein, flower-like NiCoZn-carbonate hydroxide (NiCoZn-CH) hollow nanospheres are prepared using self-templated NiCoZn-glycerate solid nanospheres through the Kirkendall effect in a solvothermal reaction. Benefiting from a flower-like morphology, NiCoZn-CH not only provides large contact areas on the electrolyte-electrode and an abundant number of active sites but also shortens the ion transportation pathway. Meanwhile, the hollow structure also improves cycling stability by relieving stresses. Furthermore, Zn2+ can accelerate the ion transfer and improve the electrochemical activity. Therefore, the Ni1Co1Zn0.25-CH electrode shows an attractive specific capacitance of 1585.2 F g-1 at 1 A g-1 and excellent cycling stability. Additionally, the asymmetric supercapacitor Ni1Co1Zn0.25-CH//AC delivers a superior cycling stability of 99.9% after 15 000 cycles at 10 A g-1 and an energy density of 33.7 W h kg-1 at a power density of 400 W kg-1. This work provides a simple and efficient route for the fabrication of various carbonate hydroxides.

Two Birds with One Stone: Prelithiated Two-Dimensional Nanohybrids as High-Performance Anode Materials for Lithium-Ion Batteries.

As an inexpensive and naturally abundant two-dimensional (2D) material, molybdenum disulfide (MoS2) exhibits a high Li-ion storage capacity along with a low volume expansion upon lithiation, rendering it an alternative anode material for lithium-ion batteries (LIBs). However, the challenge of using MoS2-based anodes is their intrinsically low electrical conductivity and unsatisfied cycle stability. To address the above issues, we have exploited a wet chemical technique and integrated MoS2 with highly conductive titanium carbide (Ti3C2) MXene to form a 2D nanohybrid. The binary hybrids were then subjected to an n-butyllithium (n-Buli) treatment to induce both MoS2 deep phase transition and MXene surface functionality modulation simultaneously. We observed a substantial increase in 1T-phase MoS2 content and a clear suppression of -F-containing functional groups in MXene due to the prelithiation process enabled by the n-Buli treatment. Such an approach not only increases the overall network conductivity but also improves Li-ion diffusion kinetics. As a result, the MoS2/Ti3C2 composite with n-Buli treatment delivered a high Li-ion storage capacity (540 mA h g-1 at 100 mA g-1), outstanding cycle stability (up to 300 cycles), and excellent rate capability. This work provides an effective strategy for the structure-property engineering of 2D materials and sheds light on the rational design of high-performance LIBs using 2D-based anode materials.

Recognition at chiral interfaces: From molecules to cells.

As a ubiquitous phenomenon in nature, chirality plays a pivotal role in a variety of biological and physiological processes. The construction of chiral interfaces and exploration of their effect on the behavior of various substances, especially biomolecules such as DNA, proteins and cells, are effective ways to fully understand the chirality in nature and to further develop their applications. In order to accelerate the research process of chiral mechanism and provide new ideas for the interpretation of chiral phenomena in nature, thus further promoting the applications of chiral effect in biology, medicine and other related fields, various types of chiral interfaces were prepared and their effects on drug molecules, biomolecules and cells have also been investigated. This review covers the preparation of various chiral interfaces with different geometrical structures and the stereoselective interaction between biological or related systems and the chiral interface materials. Moreover, some challenges and perspectives are also presented.

High-performance supercapacitors based on polyaniline nanowire arrays grown on three-dimensional graphene with small pore sizes.

Three-dimensional graphene (3D GR)-based hybrids have received significant attention due to their unique structures and promising applications in supercapacitors. In this paper, 3D GR with small pore sizes has been prepared by chemical vapor deposition using commercial nickel nanowires as the template. After nitric acid treatment, the hydrophilicity of 3D GR improved. Polyaniline nanowire arrays (PANI NWAs) have been successfully grown on its surface by in situ polymerization to obtain hybrid PANI NWA/3D GR. The results show that PANI NWAs with a length of ∼300 nm vertically grow on 3D GR with a pore diameter of ∼2 µm. The small pore size of 3D GR not only improves the mechanical properties of 3D GR, but also provides numerous sites for the growth of PANI NWAs. Meanwhile, PANI NWAs provide a shorter ion diffusion path and larger contact area with the electrolyte. Due to the unique structure, the hybrid exhibits a high specific capacitance of 789.9 F g-1 at 10 mV s-1. When it is assembled into a symmetric supercapacitor, it exhibits an energy density of 32.2 W h kg-1 at a power density of 793.3 W kg-1 and maintains a good cycle stability of 90% after 5000 cycles at 1.0 A g-1.

Preparation of g-C3N4/Graphene Composite for Detecting NO2 at Room Temperature.

Graphitic carbon nitride (g-C3N4) nanosheets were exfoliated from bulk g-C3N4 and utilized to improve the sensing performance of a pure graphene sensor for the first time. The role of hydrochloric acid treatment on the exfoliation result was carefully examined. The exfoliated products were characterized by X-ray diffraction (XRD) patterns, scanning electron microscopy (SEM), atomic force microscopy (AFM), and UV-Vis spectroscopy. The exfoliated g-C3N4 nanosheets exhibited a uniform thickness of about 3-5 nm and a lateral size of about 1-2 µm. A g-C3N4/graphene nanocomposite was prepared via a self-assembly process and was demonstrated to be a promising sensing material for detecting nitrogen dioxide gas at room temperature. The nanocomposite sensor exhibited better recovery as well as two-times the response compared to pure graphene sensor. The detailed sensing mechanism was then proposed.

Liquid-Phase Co-Exfoliated Graphene/MoS2 Nanocomposite for Methanol Gas Sensing.

We developed an efficient method to co-exfoliate graphite and MoS2 to fabricate graphene/MoS2 nanocomposite. The size, morphology, and crystal structure of the graphene/MoS2 nanocomposite were carefully examined. The as-prepared graphene/MoS2 nanocomposite was fabricated into thin film sensor by a facile drop casting method and tested with methanol gas in various concentrations. The sensitivity, response time, and repeatability of the graphene/MoS2 nanocomposite sensor towards methanol gas were systematically investigated. A pure MoS2 based thin film sensor was also prepared and compared with the nanocomposite sensor to better understand the synergetic effect in the sensing performance. Our research demonstrated that compositing MoS2 with graphene could overcome the shortcoming of MoS2 as a sensor material and bring in a promising gas-sensing performance with a quicker response/recovery time and an enhanced sensitivity. Moreover, this composited material with a distinct structure and an excellent electronic property is expected to have potential application in various fields, such as optoelectronic.

Hollow carbon nanospheres/silicon/alumina core-shell film as an anode for lithium-ion batteries.

Hollow carbon nanospheres/silicon/alumina (CNS/Si/Al2O3) core-shell films obtained by the deposition of Si and Al2O3 on hollow CNS interconnected films are used as the anode materials for lithium-ion batteries. The hollow CNS film acts as a three dimensional conductive substrate and provides void space for silicon volume expansion during electrochemical cycling. The Al2O3 thin layer is beneficial to the reduction of solid-electrolyte interphase (SEI) formation. Moreover, as-designed structure holds the robust surface-to-surface contact between Si and CNSs, which facilitates the fast electron transport. As a consequence, the electrode exhibits high specific capacity and remarkable capacity retention simultaneously: 1560 mA h g(-1) after 100 cycles at a current density of 1 A g(-1) with the capacity retention of 85% and an average decay rate of 0.16% per cycle. The superior battery properties are further confirmed by cyclic voltammetry (CV) and impedance measurement.