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Acute stroke management is critically time-sensitive and challenging. Blood-based biomarkers that can differentiate acute ischemic stroke (IS) from hemorrhagic stroke (HS) can greatly facilitate triage and early management. Admission blood samples obtained within 6 h of stroke symptom onset were analyzed in a derivation/validation design. GFAP, N-FL, NT-proBNP, copeptin, neutrophils (%), NLR, and platelet counts were assessed in the derivation cohort. The informative markers and the derived cutoff values were evaluated in the validation cohort. GFAP > 703 pg/mL showed a PPV of 76.9% and NPV of 95.8% for differentiating HS from IS. Multiple logistic regression analysis showed that GFAP and NT-proBNP were independent variables associated with IS and HS differentiation. Furthermore, applying a combined cutoff (GFAP > 703 pg/mL and NT-proBNP ≤ 125 pg/mL) for HS detection increased the PPV in both the derivation and validation cohorts (93.3% and 100%, respectively). GFAP and NT-proBNP levels were validated as informative blood biomarkers in the differentiation of IS and HS and using a combination of GFAP and NT-proBNP is suggested as a feasible strategy to differentiate stroke subtypes in the hyperacute phase of stroke. [ABSTRACT FROM AUTHOR]

Background: Age-related changes in the cerebrovasculature, including blood–brain barrier (BBB) disruption and vascular dementia, are emerging as potential risks for many neurodegenerative diseases. Therefore, the endothelial cells that constitute the cerebrovasculature may play key roles in preventing brain injury. Our previous study showed that CU06-1004, an endothelial cell dysfunction blocker, prevented vascular leakage, enhanced vascular integrity in ischemic reperfusion injury, and promoted the normalization of tumor vasculature. Here, we evaluated the effects of CU06-1004 on age-related cerebrovascular functional decline in the aged mouse brain. Results: In this study, we investigated the protective effects of CU06-1004 against oxidative stress–induced damage in human brain microvascular endothelial cells (HBMECs). HBMECs were treated with hydrogen peroxide (H2O2) to establish an oxidative stress–induced model of cellular injury. Compared with H2O2 treatment alone, pretreatment of HBMECs with CU06-1004 considerably reduced oxidative stress–induced cytotoxicity, reactive oxygen species generation, senescence-associated β-galactosidase activity, senescence marker expression, and the expression levels of inflammatory proteins. Based on the observed cytoprotective effects of CU06-1004 in HBMECs, we examined whether CU06-1004 displayed protective effects against cerebrovascular aging in mice. Long-term administration of CU06-1004 alleviated age-associated cerebral microvascular rarefaction and cerebrovascular senescence in the aged mouse brain. CU06-1004 supplementation also reduced the extravasation of plasma IgG by improving BBB integrity in the aged mouse brain, associated with reductions in neuronal injury. A series of behavioral tests also revealed improved motor and cognitive functions in aged mice that received long-term CU06-1004 administration. Conclusions: These findings suggest that CU06-1004 may represent a promising therapeutic approach for delaying age-related cerebrovascular impairment and improving cognitive function in old age. [ABSTRACT FROM AUTHOR]

Background: Age-related changes in the cerebrovasculature, including blood–brain barrier (BBB) disruption and vascular dementia, are emerging as potential risks for many neurodegenerative diseases. Therefore, the endothelial cells that constitute the cerebrovasculature may play key roles in preventing brain injury. Our previous study showed that CU06-1004, an endothelial cell dysfunction blocker, prevented vascular leakage, enhanced vascular integrity in ischemic reperfusion injury, and promoted the normalization of tumor vasculature. Here, we evaluated the effects of CU06-1004 on age-related cerebrovascular functional decline in the aged mouse brain. Results: In this study, we investigated the protective effects of CU06-1004 against oxidative stress–induced damage in human brain microvascular endothelial cells (HBMECs). HBMECs were treated with hydrogen peroxide (H2O2) to establish an oxidative stress–induced model of cellular injury. Compared with H2O2 treatment alone, pretreatment of HBMECs with CU06-1004 considerably reduced oxidative stress–induced cytotoxicity, reactive oxygen species generation, senescence-associated β-galactosidase activity, senescence marker expression, and the expression levels of inflammatory proteins. Based on the observed cytoprotective effects of CU06-1004 in HBMECs, we examined whether CU06-1004 displayed protective effects against cerebrovascular aging in mice. Long-term administration of CU06-1004 alleviated age-associated cerebral microvascular rarefaction and cerebrovascular senescence in the aged mouse brain. CU06-1004 supplementation also reduced the extravasation of plasma IgG by improving BBB integrity in the aged mouse brain, associated with reductions in neuronal injury. A series of behavioral tests also revealed improved motor and cognitive functions in aged mice that received long-term CU06-1004 administration. Conclusions: These findings suggest that CU06-1004 may represent a promising therapeutic approach for delaying age-related cerebrovascular impairment and improving cognitive function in old age. [ABSTRACT FROM AUTHOR]

RNA recombination in positive-strand RNA viruses is a molecular-genetic process, which permits the greatest evolution of the genome and may be essential to stabilizing the genome from the deleterious consequences of accumulated mutations. Enteroviruses represent a useful system to elucidate the details of this process. On the biochemical level, it is known that RNA recombination is catalyzed by the viral RNA-dependent RNA polymerase using a template-switching mechanism. For this mechanism to function in cells, the recombining genomes must be located in the same subcellular compartment. How a viral genome is trafficked to the site of genome replication and recombination, which is membrane associated and isolated from the cytoplasm, is not known. We hypothesized that genome translation was essential for colocalization of genomes for recombination. We show that complete inactivation of internal ribosome entry site (IRES)-mediated translation of a donor enteroviral genome enhanced recombination instead of impairing it. Recombination did not occur by a nonreplicative mechanism. Rather, sufficient translation of the nonstructural region of the genome occurred to support subsequent steps required for recombination. The noncanonical translation initiation factors, eIF2A and eIF2D, were required for IRES-independent translation. Our results support an eIF2A/eIF2D-dependent mechanism under conditions in which the eIF2-dependent mechanism is inactive. Detection of an IRES-independent mechanism for translation of the enterovirus genome provides an explanation for a variety of debated observations, including nonreplicative recombination and persistence of enteroviral RNA lacking an IRES. The existence of an eIF2A/eIF2D-dependent mechanism in enteroviruses predicts the existence of similar mechanisms in other viruses. This study of enterovirus presents evidence for a cap-independent strategy of translation initiation that functions when eIF2α has been inactivated, identifying an RNA element upstream of the initiation codon that enables translation initiation using the non-canonical initiation factors eIF2A or eIF2D. [ABSTRACT FROM AUTHOR]

Metastasising cells express the intermediate filament protein vimentin, which is used to diagnose invasive tumours in the clinic. We aimed to clarify how vimentin regulates the motility of metastasising fibroblasts. STED super-resolution microscopy, live-cell imaging and quantitative proteomics revealed that oncogene-expressing and metastasising fibroblasts show a less-elongated cell shape, reduced cell spreading, increased cell migration speed, reduced directionality, and stronger coupling between these migration parameters compared to normal control cells. In total, we identified and compared 555 proteins in the vimentin interactome. In metastasising cells, the levels of keratin 18 and Rab5C were increased, while those of actin and collagen were decreased. Inhibition of HDAC6 reversed the shape, spreading and migration phenotypes of metastasising cells back to normal. Inhibition of HDAC6 also decreased the levels of talin 1, tropomyosin, Rab GDI β, collagen and emilin 1 in the vimentin interactome, and partially reversed the nanoscale vimentin organisation in oncogene-expressing cells. These findings describe the changes in the vimentin interactome and nanoscale distribution that accompany the defective cell shape, spreading and migration of metastasising cells. These results support the hypothesis that oncogenes can act through HDAC6 to regulate the vimentin binding of the cytoskeletal and cell–extracellular matrix adhesion components that contribute to the defective motility of metastasising cells. [ABSTRACT FROM AUTHOR]

Using the RNA-dependent RNA polymerase (RdRp) from poliovirus (PV) as our model system, we have shown that Lys-359 in motif-D functions as a general acid in the mechanism of nucleotidyl transfer. A K359H (KH) RdRp derivative is slow and faithful relative to wild-type enzyme. In the context of the KH virus, RdRp-coding sequence evolves, selecting for the following substitutions: I331F (IF, motif-C) and P356S (PS, motif-D). We have evaluated IF-KH, PS-KH, and IF-PS-KH viruses and enzymes. The speed and fidelity of each double mutant are equivalent. Each exhibits a unique recombination phenotype, with IF-KH being competent for copy-choice recombination and PS-KH being competent for forced-copy-choice recombination. Although the IF-PS-KH RdRp exhibits biochemical properties within twofold of wild type, the virus is impaired substantially for recombination in cells. We conclude that there are biochemical properties of the RdRp in addition to speed and fidelity that determine the mechanism and efficiency of recombination. The interwoven nature of speed, fidelity, the undefined property suggested here, and recombination makes it impossible to attribute a single property of the RdRp to fitness. However, the derivatives described here may permit elucidation of the importance of recombination on the fitness of the viral population in a background of constant polymerase speed and fidelity. [ABSTRACT FROM AUTHOR]

Objective: To investigate the anti-cancer efficacy of ENB101-LNP, an ionizable lipid nanoparticles (LNPs) encapsulating siRNA against E6/E7 of HPV 16, in combination therapy with cisplatin in cervical cancer in vitro and in vivo. Methods: CaSki cells were treated with ENB101-LNP, cisplatin, or combination. Cell viability assessed the cytotoxicity of the treatment. HPV16 E6/E7 gene knockdown was verified with RT-PCR both in vitro and in vivo. HLA class I and PD-L1 were checked by flow cytometry. A xenograft model was made using CaSki cells in BALB/c nude mice. To evaluate anticancer efficacy, mice were grouped. ENB101-LNP was given three times weekly for 3 weeks intravenously, and cisplatin was given once weekly intraperitoneally. Tumor growth was monitored. On day 25, mice were euthanized; tumors were collected, weighed, and imaged. Tumor samples were analyzed through histopathology, immunostaining, and western blot. Results: ENB101-LNP and cisplatin synergistically inhibit CaSki cell growth. The combination reduces HPV 16 E6/E7 mRNA and boosts p21 mRNA, p53, p21, and HLA class I proteins. In mice, the treatment significantly blocked tumor growth and promoted apoptosis. Tumor inhibition rates were 29.7% (1 mpk ENB101-LNP), 29.6% (3 mpk), 34.0% (cisplatin), 47.0% (1 mpk ENB101-LNP-cisplatin), and 68.8% (3 mpk ENB101-LNP-cisplatin). RT-PCR confirmed up to 80% knockdown of HPV16 E6/E7 in the ENB101-LNP groups. Immunohistochemistry revealed increased p53, p21, and HLA-A expression with ENB101-LNP treatments, alone or combined. Conclusion: The combination of ENB101-LNP, which inhibits E6/E7 of HPV 16, with cisplatin, demonstrated significant anticancer activity in the xenograft mouse model of cervical cancer. [ABSTRACT FROM AUTHOR]

Polypyrrole (PPy) is a promising conductive polymer (CP) with electrical versatility, easy synthesis and functionalization, stability, and biocompatibility. Diverse architectures have been adopted to improve PPy performance, but the direct and precise patterning of various architectures remains challenging. Here, the unique formation of a PPy membrane on the air/water interface of a droplet solution containing ammonium persulfate and phytic acid is investigated. When a PPy thin film forms on the air/water interface, the top of the droplet rapidly flattens. The formation procedure and final structure of the PPy thin film are visualized and quantitatively investigated. Unlike the typical globular structure of PPy, the self‐assembled PPy film surface fabricated in this study is very organized and regularly shaped. This well‐ordered membrane may have a very high buckling strength greater than the surface tension of the solution. The proposed precise fabrication method is simple and inexpensive for fabricating patterned functional membranes. These results provide new insight into the fabrication of CP and their applications in various practical electromaterial engineering fields. The unique formation of polypyrrole (PPy) thin film on the air/water interface of a droplet solution containing ammonium persulfate and phytic acid is investigated. The self‐assembled PPy film surface is very organized and regularly shaped. Considering that the precise patterning of various architectures hinders the design of conductive polymers, the proposed method is inexpensive and simple for fabricating patterned functional membranes. [ABSTRACT FROM AUTHOR]

Front Cover: The unique formation of a poly(pyrrole) (PPy) membrane, on the air/water interface of a droplet solution containing ammonium persulfate and phytic acid, is investigated in article number 1800707 by Sang Joon Lee and co‐workers. As polymerization occurs at the air/water interface, a blue‐black PPy clearly forms, and the top of the droplet becomes rapidly flattened. The surface of the fabricated PPy thin film has a well‐organized structure of a pretzel shape. [ABSTRACT FROM AUTHOR]

The reuse of waste papers by conversion into valuable carbon materials has received considerable attention for diverse applications such as energy storage and water purification. However, traditional methods for converting waste papers into materials with suitable properties for specific applications are often complex and ineffective, involving consecutive carbonization and activation steps. Herein, we propose a simple one-step microwave (MW)-assisted synthesis for preparing waste paper-derived porous carbons (WPCs) for energy storage and water purification. Through a 30-min synthesis, WPCs with graphitic structure and high specific surface area were successfully produced. The fabricated WPCs exhibited outstanding charge storage capability with a maximum specific capacitance of 237.7 F g−1. Additionally, the WPC demonstrates a high removal efficiency for various dyes, achieving a maximum removal efficiency of 95.0% for methylene blue. The developed one-step MW synthesis not only enables the production of porous carbon from waste paper, but also offers a viable approach to address solid waste management challenges while simultaneously yielding valuable materials. [Display omitted] • Waste paper-derived porous carbons were synthesized by one-step microwave synthesis. • Within 30-min MW synthesis, graphitic and high-surface area WPCs were produced. • WPC exhibits outstanding electrochemical capacitance of 237.7 F g−1. • WPC exhibits high removal of various dyes, with maximum of 95.0% for methylene blue. [ABSTRACT FROM AUTHOR]

Abstract: This study investigated how 20 university students described their collective and individual learning experiences using social media technologies (SMTs). Data consisted of transcribed focus group discussions, which were analysed for students' use of first person singular and plural pronouns as well as for the kinds of verbs they used to describe their learning. Findings indicate that none of the participants used first person plural pronouns more frequently than first person singular pronouns to describe their learning experiences. Students also used possessive, stative and passive verbs in addition to verbs denoting more traditional learning behaviours associated with cognitive, psychomotor, affective and conative activities when discussing their learning. We conclude that, although evidence of a clearly definable ‘collective intelligence’ was lacking, co-occurrences of both group-oriented and self-oriented utterances were evident. Students' use of verb types highlighted issues of ownership, identity and control as additional features of their SMT enabled learning experiences. [Copyright &y& Elsevier]

[Display omitted] • The effect of Coriolis force and herringbone grooves on mixing performance in rotating microchannels was investigated. • The Coriolis force balanced appropriately with centrifugal force achieved efficient mixing. • Two strategies of the Coriolis force and herringbone induced multiple local vortices, improving mixing efficiency. • A two-sided herringbone mixer required the shortest channel length for 90% mixing in this study. Mixing is a critical process in reagent reactions used in biomedical applications. Nevertheless, achieving rapid mixing in microfluidics is challenging because of the low-Reynolds region. This study numerically investigated the mixing performance of a rotating channel based on the Coriolis force with herringbone grooves. In the absence of grooves, the mixing was maximized when the Coriolis force was appropriately balanced with the centrifugal force. As the aspect ratio increased from 0.5 to 2.0, rapid mixing was achieved owing to the decreased transverse distance between the rotating flows. Mixing improved with the herringbone grooves, achieving up to >90% for the shortest channel length (20 mm) among the various microchannels. This enhancement resulted from the flow split and recombination induced by the combination of the Coriolis force and grooves. This study will help create and design microchannels for disk chip miniaturization, automation, and integration into lab-on-a-disk-based biomedical procedures, such as point-of-care diagnosis. [ABSTRACT FROM AUTHOR]

Background: Ischemic stroke is a main cause of mortality. Blood-brain barrier (BBB) breakdown appears to play a critical role in inflammation in patients with ischemic stroke and acceleration of brain injury. The BBB has a protective function and is composed of endothelial cells, pericytes, and astrocytes. In ischemic stroke treatments, regulation of vascular endothelial growth factor (VEGF)-A and vascular endothelial growth factor receptor (VEGFR)-2 is a crucial target despite adverse effects. Our previous study found that loss of C-type lectin family 14 member A (CLEC14A) activated VEGF-A/VEGFR-2 signaling in developmental and tumoral angiogenesis. Here, we evaluate the effects of BBB impairment caused by CLEC14A deficiency in ischemia-reperfusion injury.Methods: In vitro fluorescein isothiocyanate (FITC)-dextran permeability, transendothelial electrical resistance (TEER) assay, and immunostaining were used to evaluate endothelial integrity. BBB permeability was assessed using Evans blue dye and FITC-dextran injection in Clec14a-/- (CLEC14A-KO) mice and wild-type mice. Middle cerebral artery occlusion surgery and behavioral assessments were performed to evaluate the neurologic damage. The change of tight junctional proteins, adhesion molecules, pro-inflammatory cytokines, and microglial were confirmed by immunofluorescence staining, Western blotting, and quantitative reverse transcription polymerase chain reaction of brain samples.Results: In endothelial cells, knockdown of CLEC14A increased FITC-dextran permeability and decreased transendothelial electrical resistance; the severity of this effect increased with VEGF treatment. Immunofluorescence staining revealed that tight junctional proteins were attenuated in the CLEC14A knockdown endothelial cells. Consistent with the in vitro results, CLEC14A-KO mice that were injected with Evans blue dye had cerebral vascular leakage at postnatal day 8; wild-type mice had no leakage. We used a middle cerebral artery occlusion model and found that CLEC14A-KO mice had severe infarcted brain and neurological deficits with upregulated VEGFR-2 expression. FITC-dextran leakage was present in CLEC14A-KO mice after ischemia-reperfusion, and the numbers of tight junctional molecules were significantly decreased. Loss of CLEC14A increased the pro-inflammatory response through adhesion molecule expression, and glial cells were activated.Conclusions: These results suggest that activation of VEGFR-2 in CLEC14A-KO mice aggravates ischemic stroke by exacerbating cerebral vascular leakage and increasing neuronal inflammation after ischemia-reperfusion injury. [ABSTRACT FROM AUTHOR]

[Display omitted] • 3D printed parallelized and multiplexed microfluidic device effectively produces functional Janus particles. • The Janus particles can form stable Pickering emulsions from oil pollutants present in water. • This approach is effective remediation method regardless of the oil viscosity, water pH or its salinity. • Over 99.7% of unconventional heavy crude oils can be recovered from water. • The Janus particles can be reusable and are environmentally friendly. The growing global energy demand and declining conventional oil supply have accelerated the use of unconventional heavy crude oils (UHCOs). However, high viscosities of UHCOs make conventional remediation methods ineffective for removing them from water. To address this challenge, we propose Pickering emulsification using amphiphilic magnetic Janus particles (AMJPs) as an efficient remediation method for UHCOs. AMJPs are produced using a multiplexed 3D-printed microfluidic droplet generator. The design of the generator is carefully optimized through a combination of experimental and numerical studies to achieve mass production of the monodisperse particles. These AMJPs have the remarkable ability to emulsify oil pollutants, with viscosities ranging from as low as 0.31 mPa∙s to as high as 97,100 mPa∙s. The Pickering emulsification using AMJPs results in rapid and highly efficient (>99.7%) recovery of UHCOs from water in a recyclable manner. We realize the first ever mass production of AMJPs via 3D-printed droplet generators. The use of these AMJPs in the Pickering emulsification approach has potential applications beyond UHCO remediation, including food, cosmetics, and pharmaceutical industries. [ABSTRACT FROM AUTHOR]

Stimuli-sensitive hydrogels have been intensively studied because of their potential applications in drug delivery, cell culture, and actuator design. Although hydrogels with directed unidirectional response, i.e. capable of bending actuated by different chemical components reaction in response to several stimuli including water and electric fields, these hydrogels are capable of being actuated in one direction only by the stimulus. By contrast the challenge of building a device that is capable of responding to the same cue (in this case a temperature gradient) to bend in either direction remains unmet. Here, inspired by the structure of pine cone scales, we design a temperature-sensitive hydrogel with bending directed an imposed fishing line. The layers with same PNIPAAm always shrinks in response to the heat. Even the layers made with different chemical property, bends away from a warm surface, whether the warm surface is applied at its upper or lower boundary. To design the bending hydrogel we exploited the coupled responses of the hydrogel; a fishing line intercalating structure and change its construction. In addition to revealing a new capability of stimulus sensitive hydrogels, our study gives insight into the structural features of pine cone bending. [ABSTRACT FROM AUTHOR]

Pine cones fold their scales when it rains to prevent seeds from short-distance dispersal. Given that the scales of pine cones consist of nothing but dead cells, this folding motion is evidently related to structural changes. In this study, the structural characteristics of pine cones are studied on micro-/macro-scale using various imaging instruments. Raindrops fall along the outer scales to the three layers (bract scales, fibers and innermost lignified structure) of inner pine cones. However, not all the layers but only the bract scales get wet and then, most raindrops move to the inner scales. These systems reduce the amount of water used and minimize the time spent on structural changes. The result shows that the pine cones have structural advantages that could influence the efficient motion of pine cones. This study provides new insights to understand the motion of pine cones and would be used to design a novel water transport system. [ABSTRACT FROM AUTHOR]