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This study presents an approach to better characterize the P‐wave and S‐wave velocity structure of the seafloor sediment layer using ocean bottom seismometers. The presence of low‐velocity seafloor sediment layers influences the observed seismic record at the seafloor over a broad frequency range, such that detailed knowledge of this sediment structure is essential to predict its effect on teleseismic records. We use the radial component of teleseismic P waves and autocorrelation functions of the radial, vertical, and pressure components of teleseismic P and S waves to obtain sediment layer models using the Markov chain Monte Carlo approach with parallel tempering. Synthetic tests show that the body waves constrain the P‐ and S‐wave impedances and travel times and the P‐ to S‐wave velocity ratio of the sediment layers. The proposed method resolves thin layers at a high resolution, including the uppermost thin (∼50 m to a few hundred meters) low S‐wave velocity layer. Real data applications at sites across the Pacific Ocean that are coincident with previous in situ studies demonstrate the effectiveness of this method in characterizing the seafloor sediment unit. The sediment models characterized by this new approach will allow us to more accurately predict and correct the effects of sediment layers in generating P‐ and S‐wave reverberations. Plain Language Summary: Ocean bottom seismometers are powerful tools for investigating the detailed structure of the oceanic mantle. However, most ocean bottom seismometers are placed above the low‐velocity water‐saturated sediment layer, such that their seismic records are inevitably affected by this seafloor sediment layer. Detailed constraints on the structure of the seafloor sediment layer allow us to accurately predict its effects on the observed seismic records. The seafloor sediment layer may consist of multiple discontinuities and vary regionally. This study proposes a new approach for characterizing the seismic properties of the seafloor sediment layer using teleseismic body waves recorded at ocean bottom seismometers. Synthetic tests show that the method can resolve thin sublayers within the sediment layer, such as a very thin low shear‐wave velocity layer and sharp seismic velocity jumps. Real data applications show that the sediment models obtained using this approach are in good agreement with those obtained from direct measurements and previous body‐wave analyses. Our proposed method will enable more detailed prediction and correction of the influence of the sediment layer on ocean bottom seismometer records, thereby providing more accurate constraints on deeper Earth structures. Key Points: The seismic properties of the seafloor sediment layer are characterized using ocean bottom seismometer teleseismic body‐wave recordsThe P‐ and S‐wave impedances and travel times and the VP/VS values of each sublayer within the sediment layer are resolvedIn situ seafloor sediment structure constraints will enable accurate correction and prediction of shallow structure effects [ABSTRACT FROM AUTHOR]

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]

Indoor air quality, especially in terms of particulate matter (PM), is a critical public health concern. Although various methods for removing indoor PM have been suggested, the effects of various influential factors on PM deposition have not been clearly understood. Here, the effect of the flow structure inside a test chamber on PM deposition was quantitatively investigated using flow visualization techniques. To elucidate the flow parameters that influence the PM deposition, the efficiency of PM removal and deposition constant were examined for different flow directions, flow velocities, and distances between the fan and the surface of the test chamber. The spatial distributions of the mean velocity and turbulence intensity inside the test chamber were obtained experimentally using a particle image velocimetry technique to understand the mechanism associated with PM deposition. The overall mean velocity, recirculating flow region, and turbulent intensity in the near-wall regions may partially explain the difference in the PM deposition under various flow conditions. [ABSTRACT FROM AUTHOR]

This study presents reflectivity images of the northeast (NE) Japan subduction zone continuous across the ocean and land. As nearly half of its forearc region is under the ocean, data from ocean bottom seismometers (OBSs) must be utilized to fully image the region by passive seismic analysis. The use of OBS data has been a challenge due to inherent characters of the ocean bottom observations: high noise level and effects of seafloor sediment. Now, decent imaging is possible in NE Japan overcoming the high level noise due to the accumulated data set of the OBSs. The low‐velocity of seafloor sediment significantly delays and amplifies S waves passing through them, and thus complicates teleseismic waveforms. We identify and correct these effects to produce coherent receiver function images throughout the amphibious subduction zone. Our images provide a potential for discussing new structural features and will help better understanding of the dynamics of the NE Japan subduction zone. Plain Language Summary: In northeast Japan, the Pacific plate is subducting beneath the Japanese arc, and delineating how the actual subduction is taking place at depths has been the target of many seismological studies. This study presents our effort of continuous imaging of subsurface interfaces across the ocean and land employing an amphibious data set. On the land side, there are dense seismic networks that have been used to reveal the seismic interfaces using converted phases of distant earthquakes. On the ocean side, the accumulation of data from temporary ocean bottom seismometers in the last decade and the recently installed ocean bottom cable network has made it possible to use a similar approach as on the land. However, the low‐velocity sediment beneath the seafloor causes systematic slower arrivals and larger amplitudes of the seismic phases of interest that result in highly disturbed images if we analyze them in the same way as the land. Here, we identify and correct the effects of the seafloor sediment to analyze the seismic interfaces across the ocean and land. As a result, we succeed in imaging the interfaces of the subducting oceanic crust throughout the region, as well as previously unidentified features under the ocean that may deserve future investigation. Key Points: The northeast Japan subduction zone is imaged using receiver functions (RFs) of an amphibious data setWe identify significant amplitude and time delay effects on RFs from seafloor sedimentCorrections of the sediment effects significantly improve images across an amphibious region [ABSTRACT FROM AUTHOR]

IgE multiple myeloma is a rare subtype of myeloma, accounting for <0.1% of all myeloma cases. Difficulties in diagnosing and monitoring this rare myeloma type are recognized, including the need of heightened awareness for initial diagnosis, performing a reflex immunofixation test using an anti-IgE antisera, and recognizing the possibility of the prozone phenomenon. Here, we report a rare case of IgE multiple myeloma with the prozone phenomenon. This case was characterized by a paradoxical increase in IgE levels with a progressive increase in the dilution factor. Moreover, serial monitoring of IgE levels correlated with the trend in the serum free light chain ratio, especially when the monoclonal protein was no longer detectable. This case highlights the need for laboratory professionals to be vigilant about the occurrence of the prozone phenomenon in IgE multiple myeloma. [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]

• Utilizing the Exdia analyzer, we have developed a highly sensitive time-resolved fluorescence lateral flow immunoassay (TRF-LFIA) • Detecting both the glial fibrillary acidic protein (GFAP) and the N-terminal fragment of B-type natriuretic peptide precursor (NT-proBNP) in a single test for the first time. • Achieved highly sensitive results within a brief 15-minute time frame. • Design an algorithm utilizing TRF-LFIA to differentiate between patients with Ischemic stroke (IS) and Hemorrhagic stroke (HS). • The implementation of this algorithm significantly reduces the diagnosis time for Ischemic Stroke (IS) and Hemorrhagic Stroke (HS). The suggested algorithm not only mitigates delays in treatment but also reduces medical costs for patients. The goal of this study is to create a highly sensitive time-resolved fluorescence lateral flow immunoassay (TRF-LFIA) capable of concurrently measuring glial fibrillary acidic protein (GFAP) and the N-terminal fragment of B-type natriuretic peptide precursor (NT-proBNP). This assay is designed as a diagnostic tool and aims to provide an algorithm for stroke management, specifically for distinguishing between Ischemic stroke (IS) and Hemorrhagic stroke (HS). However, LFIA to quantify simultaneous serum NT-proBNP and GFAP are not yet available. We have developed and validated a novel TRF-LFIA for the simultaneous quantitative detection of NT-proBNP and GFAP. The sensitivity and reproducibility of the immunoassay were significantly improved by employing specific monoclonal antibodies linked to europium nanoparticles (EuNPs) that specifically target NT-proBNP and GFAP. The detection area on the nitrocellulose membrane featured sandwich-style complexes containing two test lines for NT-proBNP and GFAP, and one Control line. The fluorescence intensity of these test lines and control line was measured using an in-house developed Exdia TRF-Plus analyzer. As proof-of-concept, we enrolled patients suspected of having a stroke who were admitted within a specific time frame (6 h). A small amount of clinical specimen (serum) was used. To optimize the LFIA, an EuNPs conjugated antibodies were investigated to improve the detection sensitivity and decrease the background signal as well shorten the detection time. The Exdia TRF-LFIA cartridge offers a wide linear dynamic detection range, rapid detection, high sensitivity, and specificity. The limit of detection was determined to be 98 pg/mL for NT-proBNP and 68 pg/mL for GFAP, with minimal cross-reactivity. There were 200 clinical human serum samples that were used to evaluate this platform with high correlation. By combining the results of NT-proBNP and GFAP, we formulated an algorithm for the clinical assessment of Ischemic Stroke (IS) and Hemorrhagic Stroke (HS). According to our proposed algorithm, the combination of GFAP and NT-proBNP emerged as the most effective biomarker combination for distinguishing between IS and HS. Exdia TRF-LFIA shows great potential as a supplemental method for in vitro diagnostics in the laboratory or in other point-of-care testing (POCT) applications. Its development substantially decreases the diagnosis time for IS and HS. The proposed algorithm not only minimizes treatment delays but also lowers medical costs for patients. [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]

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]

[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]

[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]

Retinal vascular diseases are the leading cause of blindness worldwide. These diseases have common disease mechanisms including vascular endothelial growth factor (VEGF) signaling, hypoxia, and inflammation. Treatment of these diseases with laser therapy, anti-VEGF injections and/or steroids has significantly improved clinical outcomes. However, these strategies do not address the underlying cause of the pathology and may have harmful side effects. Pathological processes that damage retinal vessels result in vascular occlusion and impairment of the barrier properties of retinal endothelial cells, leading to excessive vascular leakage. Therefore, a new therapeutic approach is needed for the treatment of retinal vascular disease. We were able to confirm that oral administration of CU06-1004, an endothelial dysfunction blocker, inhibited retinal vascular leakage induced by vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang2). Interestingly, oral administration of CU06-1004 prevented excessive vascular leakage in the diabetic retinopathy model. In addition, CU06-1004 inhibited angiogenesis and confirmed vascular stabilization in the oxygen-induced retinopathy model and laser-induced CNV model. Taken together, CU06-1004 could be a potential therapeutic agent for the treatment of retinal vascular diseases. [Display omitted] [ABSTRACT FROM AUTHOR]