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The recent interest in microscopic autonomous systems, including microrobots, colloidal state machines, and smart dust, has created a need for microscale energy storage and harvesting. However, macroscopic materials for energy storage have noted incompatibilities with microfabrication techniques, creating substantial challenges to realizing microscale energy systems. Here, we photolithographically patterned a microscale zinc/platinum/SU-8 system to generate the highest energy density microbattery at the picoliter (10−12 liter) scale. The device scavenges ambient or solution-dissolved oxygen for a zinc oxidation reaction, achieving an energy density ranging from 760 to 1070 watt-hours per liter at scales below 100 micrometers lateral and 2 micrometers thickness in size. The parallel nature of photolithography processes allows 10,000 devices per wafer to be released into solution as colloids with energy stored on board. Within a volume of only 2 picoliters each, these primary microbatteries can deliver open circuit voltages of 1.05 ± 0.12 volts, with total energies ranging from 5.5 ± 0.3 to 7.7 ± 1.0 microjoules and a maximum power near 2.7 nanowatts. We demonstrated that such systems can reliably power a micrometer-sized memristor circuit, providing access to nonvolatile memory. We also cycled power to drive the reversible bending of microscale bimorph actuators at 0.05 hertz for mechanical functions of colloidal robots. Additional capabilities, such as powering two distinct nanosensor types and a clock circuit, were also demonstrated. The high energy density, low volume, and simple configuration promise the mass fabrication and adoption of such picoliter zinc-air batteries for micrometer-scale, colloidal robotics with autonomous functions. Editor's summary: Energy storage at the micrometer scale is an ever-growing challenge as robots are progressively downsized. Moreover, the use of wet chemistry in battery technologies limits their potential to be scaled down beyond millimeters in size. Zhang et al. have now developed a high energy density zinc-air battery at the picoliter scale in volume. Using photolithography, 10,000 batteries could be fabricated from a single 50.8-mm wafer and released into solution. Moreover, the batteries could achieve an energy density above 760 watt-hours per liter and were capable of powering micrometer-sized devices such as colloidal robots, sensors, and memristor circuits. —Amos Matsiko [ABSTRACT FROM AUTHOR]

Phenotypic switch of vascular smooth muscle cells (VSMCs) is important in vascular remodeling which causes hyperplasia and restenosis after intimal injury. Platelets are activated at injured intima and secrete platelet-derived microvesicles (PMVs). Herein, we demonstrated the role of PMVs in VSMC phenotypic switch and the potential underlying mechanisms. In vivo, platelets were locally adhered and activated at intimal injury site, while Lamtor1 was promoted and VSMCs were dedifferentiated. PMVs, collected from collagen-activated platelets in vitro which mimicked collagen exposure during intimal injury, promoted VSMC dedifferentiation, induced Lamtor1 expression, and activated mTORC1 signaling, reflected by the phosphorylation of two downstream targets, i.e., S6K and 4E-BP1. Knockdown of Lamtor1 with small interfering RNA attenuated these processes induced by PMVs. Based on the previously published proteomic data, Ingenuity Pathway Analysis revealed that Src may participate in regulating effects of PMVs. Src inhibitor significantly reversed the effects of PMVs on VSMC dedifferentiation, Lamtor1 expression and mTORC1 activation. Furthermore, in SMC-specific Lamtor1 knockout mice, intimal hyperplasia was markedly attenuated after intimal injury compared with the wild type. Our data suggested that PMVs secreted by activated platelets promoted VSMC dedifferentiation via Src/Lamtor1/mTORC1 signaling pathway. Lamtor1 may be a potential therapeutic target for intimal hyperplasia after injury.

The arterial mechanical microenvironment, including stiffness, is a crucial pathophysiological feature of vascular remodeling, such as neointimal hyperplasia after carotid endarterectomy and balloon dilatation surgeries. In this study, we examined changes in neointimal stiffness in a Sprague-Dawley rat carotid artery intimal injury model and revealed that extracellular matrix (ECM) secretion and vascular stiffness were increased. Once the endothelial layer is damaged in vivo, activated platelets adhere to the intima and may secrete platelet-derived extracellular vesicles (pEVs) and communicate with vascular smooth muscle cells (VSMCs). In vitro, pEVs stimulated VSMCs to promote collagen secretion and cell adhesion. MRNA sequencing analysis of a carotid artery intimal injury model showed that ECM factors, including col8a1, col8a2, col12a1, and elastin, were upregulated. Subsequently, ingenuity pathway analysis (IPA) was used to examine the possible signaling pathways involved in the formation of ECM, of which the Akt pathway played a central role. In vitro, pEVs activated Akt signaling through the PIP3 pathway and induced the production of Col8a1. MicroRNA (miR) sequencing of pEVs released from activated platelets revealed that 14 of the top 30 miRs in pEVs targeted PTEN, which could promote the activation of the Akt pathway. Further research showed that the most abundant miR targeting PTEN was miR-92a-3p, which promoted Col8a1 expression. Interestingly, knockdown of Col8a1 expression in vivo abrogated the increase in carotid artery stiffness and simultaneously increased the degree of neointimal hyperplasia. Our results revealed that pEVs may deliver miR-92a-3p to VSMCs to induce the production and secretion of Col8a1 via the PTEN/PIP3/Akt pathway, subsequently increasing vascular stiffness. Therefore, pEVs and key molecules may be potential therapeutic targets for treating neointimal hyperplasia.

Endothelial progenitor cells (EPCs) play a vital role in endothelial repair following vascular injury by maintaining the integrity of endothelium. As EPCs home to endothelial injury sites, they may communicate with exposed vascular smooth muscle cells (VSMCs), which are subjected to cyclic stretch generated by blood flow. In this study, the synergistic effect of cyclic stretch and communication with neighboring VSMCs on EPC function during vascular repair was investigated. In vivo study revealed that EPCs adhered to the injury site and were contacted to VSMCs in the Sprague–Dawley (SD) rat carotid artery injury model. In vitro, EPCs were cocultured with VSMCs, which were exposed to cyclic stretch at a magnitude of 5% (which mimics physiological stretch) and a constant frequency of 1.25 Hz for 12 h. The results indicated that stretched VSMCs modulated EPC differentiation into mature endothelial cells (ECs) and promoted angiogenesis. Meanwhile, cyclic stretch upregulated the mRNA expression and secretion level of connective tissue growth factor (CTGF) in VSMCs. Recombinant CTGF (r-CTGF) treatment promoted endothelial differentiation of EPCs and angiogenesis, and increased their protein levels of FZD8 and β-catenin. CTGF knockdown in VSMCs inhibited cyclic stretch-induced EPC differentiation into ECs and attenuated EPC tube formation via modulation of the FZD8/β-catenin signaling pathway. FZD8 knockdown repressed endothelial differentiation of EPCs and their angiogenic activity. Wnt signaling inhibitor decreased the endothelial differentiation and angiogenetic ability of EPCs cocultured with stretched VSMCs. Consistently, an in vivo Matrigel plug assay demonstrated that r-CTGF-treated EPCs exhibited enhanced angiogenesis; similarly, stretched VSMCs also induced cocultured EPC differentiation toward ECs. In a rat vascular injury model, r-CTGF improved EPC reendothelialization capacity. The present results indicate that cyclic stretch induces VSMC-derived CTGF secretion, which, in turn, activates FZD8 and β-catenin to promote both differentiation of cocultured EPCs into the EC lineage and angiogenesis, suggesting that CTGF acts as a key intercellular mediator and a potential therapeutic target for vascular repair.

Micrometer‐scale robots capable of navigating enclosed spaces and remote locations are approaching reality. However, true autonomy remains an open challenge despite substantial progress made with externally supervised and manipulated systems. To accelerate the development of autonomous microrobots, alternatives to conventional top‐down lithography are sought. Such additive technologies like printing, coating, and colloidal self‐assembly allow for rapid prototyping and access to novel materials, such as polymers, bio‐ and nanomaterials. On the basis of recent experimental findings that memristive networks can be rapidly printed and lifted off as electronic microparticles, an alternative design paradigm is introduced based on arrays of two‐terminal memristive elements, which enables real‐time use of memory, sensing, and actuation in microrobots. Several memristor‐based designs are validated, each representing a key building block toward robotic autonomy: tracking elapsed time, timestamping a rare event, continuously cataloguing time‐indexed data, and accessing the collected information for a feedback‐controlled response as in a robotic glucose‐responsive insulin. The computational results establish an actionable framework for microrobotic design—tasks normally requiring complex circuits can now be achieved with self‐assembled and printed memristor arrays within microparticles. [ABSTRACT FROM AUTHOR]

The oxygen evolution reaction (OER) is involved in various renewable energy systems, such as water-splitting cells and metal-air batteries. Ni-Fe layered double hydroxides (LDHs) have been reported as promising OER electrocatalysts in alkaline electrolytes. The rational design of advanced nanostructures for Ni-Fe LDHs is highly desirable to optimize their electrocatalytic performance. Herein, we report a facile self-templated strategy for the synthesis of novel hierarchical hollow nanoprisms composed of ultrathin Ni-Fe LDH nanosheets. Tetragonal nanoprisms of nickel precursors were first synthesized as the self-sacrificing template. Afterwards, these Ni precursors were consumed during the hydrolysis of iron(II) sulfate for the simultaneous growth of a layer of Ni-Fe LDH nanosheets on the surface. The resultant Ni-Fe LDH hollow prisms with large surface areas manifest high electrocatalytic activity towards the OER with low overpotential, small Tafel slope, and remarkable stability. [ABSTRACT FROM AUTHOR]

Metal-organic frameworks (MOFs) have been intensively used as the templates/precursors to synthesize complex hollow structures for various energy-related applications. Herein we report a facile two-step diffusion-controlled strategy to generate novel MOFs derived hierarchical hollow prisms composed of Nanosized CoS2 bubble-like subunits. Uniform zeolitic imidazolate framework-67 (ZIF-67) hollow prisms assembled by interconnected nanopolyhedra are first synthesized via a transformation process. Afterwards, these ZIF-67 building blocks are converted into CoS2 bubble-like hollow particles to form the complex hollow prisms through a sulfidation reaction with an additional annealing treatment. When evaluated as an electrode material for lithium-ion batteries, the as-obtained CoS2 nanobubble hollow prisms show remarkable electrochemical performance with good rate capability and long cycle life. [ABSTRACT FROM AUTHOR]

Vascular intimal injury initiates various cardiovascular disease processes. Exposure to subendothelial collagen can cause platelet activation, leading to collagen-activated platelet-derived microvesicles (aPMVs) secretion. In addition, vascular smooth muscle cells (VSMCs) exposed to large amounts of aPMVs undergo abnormal energy metabolism; they proliferate excessively and migrate after the loss of endothelium, eventually contributing to neointimal hyperplasia. However, the roles of aPMVs in VSMC energy metabolism are still unknown. Our carotid artery intimal injury model indicated that platelets adhered to injured blood vessels. In vitro, phosphorylated Pka (cAMP-dependent protein kinase) content was increased in aPMVs. We also found that aPMVs significantly reduced VSMC glycolysis and increased oxidative phosphorylation, and promoted VSMC migration and proliferation by upregulating phosphorylated PRKAA (a catalytic subunit of AMP-activated protein kinase) and phosphorylated FoxO1. Compound C, an inhibitor of PRKAA, effectively reversed the enhancement of cellular function and energy metabolism triggered by aPMVs in vitro and neointimal formation in vivo. We show that aPMVs can affect VSMC energy metabolism through the Pka-PRKAA-FoxO1 signaling pathway and this ultimately affects VSMC function, indicating that the shift in VSMC metabolic phenotype by aPMVs can be considered a potential target for the inhibition of hyperplasia. This provides a new perspective for regulating the abnormal activity of VSMCs after injury. [ABSTRACT FROM AUTHOR]

Objective To explore the value of arthroscopy in the diagnosis and treatment of traumatic patella dislocation. Method We retrospectively analyzed the data of 31 patients with traumatic patellar dislocation admitted to our hospital during 2009-2013, including 9 males and 22 females with mean age of (17±3.4) years. All patients had a clear history of knee sprains and a good follow-up. Arthroscopy was used to explore articular injury at the initial outset of the procedure, and then sutured medial patellar retinaculum through a small incision. The average follow-up time was 6-24 months, and knee function recovering was observed. The differences of preoperative and postoperative Lysholm scores were compared. Results Lysholm score was improved from 56.6 ± 6.3 preoperatively to 96.4 ±5.2 (P < 0.01). All patients' retinaculumhad varying degree tear, and the lower edge of the patella and femoral condyle had contusion, of which 15 patients had osteochondral fracture of the lower edge of the patella and formed loose body. Conclusion Arthroscopy assisted small incision has good effect on treating traumatic patellar dislocation. Arthroscopy can not only clear the tear range, but also probe handle osteochondral fracture and prevent traumatic arthritis caused by loose body. Arthroscopy has a practical and important clinical value in the diagnosis and treatment of traumatic patellar dislocation. [ABSTRACT FROM AUTHOR]

Chinese patent medicine constitutes a vital segment of the traditional Chinese medicine(TCM) industry and stands as a significant emblem of TCM modernization. At present, the quality stability between batches of Chinese patent medicine preparations has become a pivotal factor directly restricting the high-quality development of the TCM industry. Consequently, addressing the homogeneity of Chinese patent medicines, this paper proposes a research scheme of homogenization feeding. It systematically elaborates on the object and pretreatment of homogenization, operational procedures of homogenization feeding, selection of homogenization evaluation indices, homogenization feeding algorithm, and homogenization feeding process. With the key quality control indicators as the homogenization target, the homogenization feeding process and its quality analysis were discussed. Finally, a demonstration strategy for homogenization feeding of Chinese patent medicine was formed, providing the scientific basis for advancing the research of quality consistency across batches of Chinese patent medicine preparations.

Metal-organic frameworks (MOFs) have been intensively used as the templates/precursors to synthesize complex hollow structures for various energy-related applications. Herein we report a facile two-step diffusion-controlled strategy to generate novel MOFs derived hierarchical hollow prisms composed of Nanosized CoS 2 bubble-like subunits. Uniform zeolitic imidazolate framework-67 (ZIF-67) hollow prisms assembled by interconnected nanopolyhedra are first synthesized via a transformation process. Afterwards, these ZIF-67 building blocks are converted into CoS 2 bubble-like hollow particles to form the complex hollow prisms through a sulfidation reaction with an additional annealing treatment. When evaluated as an electrode material for lithium-ion batteries, the as-obtained CoS 2 nanobubble hollow prisms show remarkable electrochemical performance with good rate capability and long cycle life., (© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)