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Abdominal aortic aneurysm (AAA) is an inflammatory vascular disease characterized by structural deterioration of the aorta caused by inflammation and oxidative stress, leading to aortic dilatation and rupture. Peroxiredoxin 2 (PRDX2), an antioxidant enzyme, has been reported as a potential negative regulator of inflammatory vascular diseases, and it has been identified as a protein that is increased in patients with ruptured AAA compared to patients with nonruptured AAA. In this study, we demonstrated that PRDX2 was a pivotal factor involved in the inhibition of AAA progression. PRDX2 levels were increased in AAA compared with those in normal aortas in both humans and mice. Ultrasound imaging revealed that the loss of PRDX2 accelerated the development of AAA in the early stages and increased AAA incidence in mice infused with angiotensin II (Ang II). Prdx2−/− mice infused with Ang II exhibited increased aortic dilatation and maximal aortic diameter without a change in blood pressure. Structural deterioration of the aortas from Prdx2−/− mice infused with Ang II was associated with increases in the degradation of elastin, oxidative stress, and intramural thrombi caused by microhemorrhages, immature neovessels, and the activation of matrix metalloproteinases compared to that observed in controls. Moreover, an increase in inflammatory responses, including the production of cell adhesion molecules and the accumulation of inflammatory cells and proinflammatory cytokines due to PRDX2 deficiency, accelerated Ang II-induced AAA progression. Our data confirm that PRDX2 plays a role as a negative regulator of the pathological process of AAA and suggest that increasing PRDX2 activity may be a novel strategy for the prevention and treatment of AAA., Abdominal aortic aneurysm: Potential enzyme biomarker identified An enzyme with antioxidant properties may provide a biomarker and therapeutic agent to help treat abdominal aortic aneurysm (AAA). AAA involves the structural deterioration of the aorta through chronic inflammation and oxidative stress, and can trigger life-threatening artery rupture. An antioxidant enzyme called peroxiredoxin 2 (PRDX2) is increased in patients with ruptures, but whether its role in AAA is beneficial or detrimental is unclear. Goo Taeg Oh at the Ewha Womans University in Seoul, Jong-Gil Park at the Korea Research Institute of Bioscience and Biotechnology, Daejeon, South Korea, and co-workers examined the effect of PRDX2 on AAA progression. PRDX2 suppressed structural damage in mice, limiting artery dilation and protein degradation. Loss of PRDX2 accelerated AAA development. Measuring levels of PRDX2 may indicate AAA severity in patients, while boosting the enzyme could repair aortic damage.

Gallbladder carcinoma (GBC) exhibits poor prognosis due to local recurrence, metastasis, and resistance to targeted therapies. Using clinicopathological analyses of GBC patients along with molecular in vitro and tumor in vivo analysis of GBC cells, we showed that reduction of Dsg2 expression was highly associated with higher T stage, more perineural, and lymphatic invasion. Dsg2-depleted GBC cells exhibited significantly enhanced proliferation, migration, and invasiveness in vitro and tumor growth and metastasis in vivo through Src-mediated signaling activation. Interestingly, Dsg2 binding inhibited Src activation, whereas its loss activated cSrc-mediated EGFR plasma membrane clearance and cytoplasmic localization, which was associated with acquired EGFR-targeted therapy resistance and decreased overall survival. Inhibition of Src activity by dasatinib enhanced therapeutic response to anti-EGFR therapy. Dsg2 status can help stratify predicted patient response to anti-EGFR therapy and Src inhibition could be a promising strategy to improve the clinical efficacy of EGFR-targeted therapy.

An efficient ultraviolet (UV) polariser based on multi-layered carbon nanotubes (CNTs) which is obtained by set of CNT films attached to substrate in series with matching orientations is demonstrat...

Aims The nuclear factor-κB (NF-κB) signalling pathway plays a critical role in the pathogenesis of multiple vascular diseases. However, in endothelial cells (ECs), the molecular mechanisms responsible for the negative regulation of the NF-κB pathway are poorly understood. In this study, we investigated a novel role for protein tyrosine phosphatase type IVA1 (PTP4A1) in NF-κB signalling in ECs. Methods and results In human tissues, human umbilical artery ECs, and mouse models for loss of function and gain of function of PTP4A1, we conducted histological analysis, immunostaining, laser-captured microdissection assay, lentiviral infection, small interfering RNA transfection, quantitative real-time PCR and reverse transcription-PCR, as well as luciferase reporter gene and chromatin immunoprecipitation assays. Short hairpin RNA-mediated knockdown of PTP4A1 and overexpression of PTP4A1 in ECs indicated that PTP4A1 is critical for inhibiting the expression of cell adhesion molecules (CAMs). PTP4A1 increased the transcriptional activity of upstream stimulatory factor 1 (USF1) by dephosphorylating its S309 residue and subsequently inducing the transcription of tumour necrosis factor-alpha-induced protein 3 (TNFAIP3/A20) and the inhibition of NF-κB activity. Studies on Ptp4a1 knockout or transgenic mice demonstrated that PTP4A1 potently regulates the interleukin 1β-induced expression of CAMs in vivo. In addition, we verified that PTP4A1 deficiency in apolipoprotein E knockout mice exacerbated high-fat high-cholesterol diet-induced atherogenesis with upregulated expression of CAMs. Conclusion Our data indicate that PTP4A1 is a novel negative regulator of vascular inflammation by inducing USF1/A20 axis-mediated NF-κB inactivation. Therefore, the expression and/or activation of PTP4A1 in ECs might be useful for the treatment of vascular inflammatory diseases.

Increased oxidative stress (OS) is considered a common etiology in the pathogenesis of cardiovascular disease (CVD). Therefore, the precise regulation of reactive oxygen species (ROS) in cardiovascular cells is essential to maintain normal physiological functions. Numerous regulators of cellular homeostasis are reportedly influenced by ROS. Hydrogen peroxide (H2O2), as an endogenous ROS in aerobic cells, is a toxic substance that can induce OS. However, many studies conducted over the past two decades have provided substantial evidence that H2O2 acts as a diffusible intracellular signaling messenger. Antioxidant enzymes, including superoxide dismutases, catalase, glutathione peroxidases, and peroxiredoxins (Prdxs), maintain the balance of ROS levels against augmentation of ROS production during the pathogenesis of CVD. Especially, Prdxs are regulatory sensors of transduced intracellular signals. The intracellular abundance of Prdxs that specifically react with H2O2 act as regulatory proteins. In this review, we focus on the role of Prdxs in the regulation of ROS-induced pathological changes in the development of CVD.

High-strength carbon nanotubes (CNTs) enhance the mechanical properties in metal matrix composites; however, their extremely high aspect ratio leads to the anisotropy of mechanical properties. This underlying issue has not yet been clarified owing to the complicated multiple strengthening mechanisms. Herein, we report the anisotropic mechanical properties of a CNT-reinforced aluminum composite and strengthening mechanisms. The uniaxial alignment of CNTs and control of alignment angles were achieved via a mechanical pulling method using a vertically grown CNT forest. As a result, the modulus and strengths decreased in proportion to the misorientation angle. Owing to the superaligned CNTs, the experimental tensile strength in the iso-strain state of the Al-0.15 vol% CNT composite (improved by 20.1%) was near the theoretical value (21.8%), and the strengthening efficiency of the composite was ∼1000. On the other hand, there was a significant deviation between the experimental result and theoretical value in the iso-stress state of the composites. This unusual anisotropic tendency was demonstrated by the strengthening effect of the CNT bridges, which tied the aligned CNTs together, in line with the interconnecting model. The anisotropic mechanical properties corroborate well with our predicted model from calculation by the failure criterion theory with the interconnecting model.

Migratory birds have evolved diverse migration strategies in response to a variety of factors, but information about the detailed migration patterns of Asian songbirds is not yet available. To understand the short-distance migration pattern of declining Yellow-throated Buntings (Emberiza elegans) in East Asia, we analyzed stable isotopes from the outermost tail feathers (rectrices) of individual buntings collected in Korea and Japan. Temporal changes in feather hydrogen (δ2Hf) and oxygen (δ18Of) isotopic values at stopover islands suggested that northern populations start migration earlier than southern populations, especially in autumn. Latitudinal gradient in δ2Hf values of three wintering populations implied that northern breeders wintered farther north than southern breeders. The migration pattern of this bunting, known as Type II chain migration, was also inferred from hydrogen isotope-based geographic assignments of feather growth origins. Our data demonstrate that stable isotope analysis may help to bridge current knowledge gaps in songbird migration despite coarsely mapped isoscapes and as-of-yet undetermined isotope calibration functions in Asia.

The disruption of the retinal pigment epithelium (RPE), for example, through oxidative damage, is a common factor underlying age-related macular degeneration (AMD). Aberrant autophagy also contributes to AMD pathology, as autophagy maintains RPE homeostasis to ensure blood–retinal barrier (BRB) integrity and protect photoreceptors. Thioredoxin-interacting protein (TXNIP) promotes cellular oxidative stress by inhibiting thioredoxin reducing capacity and is in turn inversely regulated by reactive oxygen species levels; however, its role in oxidative stress-induced RPE cell dysfunction and the mechanistic link between TXNIP and autophagy are largely unknown. Here, we observed that TXNIP expression was rapidly downregulated in RPE cells under oxidative stress and that RPE cell proliferation was decreased. TXNIP knockdown demonstrated that the suppression of proliferation resulted from TXNIP depletion-induced autophagic flux, causing increased p53 activation via nuclear localization, which in turn enhanced AMPK phosphorylation and activation. Moreover, TXNIP downregulation further negatively impacted BRB integrity by disrupting RPE cell tight junctions and enhancing cell motility by phosphorylating, and thereby activating, Src kinase. Finally, we also revealed that TXNIP knockdown upregulated HIF-1α, leading to the enhanced secretion of VEGF from RPE cells and the stimulation of angiogenesis in cocultured human retinal microvascular endothelial cells. This suggests that the exposure of RPE cells to sustained oxidative stress may promote choroidal neovascularization, another AMD pathology. Together, these findings reveal three distinct mechanisms by which TXNIP downregulation disrupts RPE cell function and thereby exacerbates AMD pathogenesis. Accordingly, reinforcing or restoring BRB integrity by targeting TXNIP may serve as an effective therapeutic strategy for preventing or attenuating photoreceptor damage in AMD., Macular degeneration: crucial protein identified A protein found in retinal cells promotes the development of age-related macular degeneration and may provide a therapeutic target. Sight loss through macular degeneration is triggered by disruption to the retinal pigment epithelium (RPE), a layer of cells that carries nutrients to the eye. RPE cells can be disrupted under oxidative stress conditions, but how this influences macular degeneration is unclear. Jeong-Ki Min and Sang-Hyun Lee at the Korea Research Institute of Bioscience and Biotechnology in Daejeon, South Korea, and co-workers found that oxidative stress reduces levels of the thioredoxin-interacting protein (TXNIP) in human RPE cell cultures. This interrupts cellular communication and disturbs the balance between cell proliferation and cell recycling. It also increases the levels of proteins that promote excess blood vessel formation, a key process contributing to macular degeneration.

Travelling from across its breeding range in northern Eurasia, Yellow-breasted Buntings (Emberiza aureola) stopover in China before migrating to their wintering areas in South-East Asia and the Indian subcontinent. This species is now considered critically endangered because its global population has declined dramatically; moreover, it is overexploited by illegal trapping at its stopover sites during the moult. Currently, two subspecies of the Yellow-breasted Bunting are recognized: aureola and ornata. However, the moult strategies of these subspecies at their stopover sites remain unknown. In the present study, we analysed the moult and plumage patterns of E. a. ornata in Korea (n = 262) between 2005 and 2018 as part of a long-term bird ringing project at a key migrant stopover site. We observed significant sexual dimorphism in the morphological characteristics of both adults and immatures: the males had longer wings, tails, and tarsi, and weighed more than the females. Moult patterns were distinct in relation to age. Adults underwent a complete post-breeding moult, entirely replacing their body and flight feathers before the onset of autumn migration over a breeding range. Remarkably, 93.4% of first-winter birds underwent an eccentric primary moult, having moulted the 3–4 outermost primaries (P6–P9 or P7–P9) before arriving at the stopover site. Males achieve full adult breeding plumage in their second summer. More than three types of median wing coverts were identified in the first-winter males, with various plumage colours and patterns. To the best of our knowledge, this is the first report on the moulting and plumage patterns in the subspecies ornata as it passes through an East Asian migratory flyway stopover site in Korea. Our results will contribute to an understanding of the migration behaviour and subspecies populations that are at risk in their specific environments. This is essential for ecological monitoring to facilitate the conservation of this critically endangered species.

Understanding CO2 migration and distribution in fault systems is essential to evaluate long-term secure CO2 storage and prevent hazardous effects caused by CO2 leakage. To elucidate the role of the fault system on subsurface CO2 migration and leakage processes, a two-dimensional multi-phase transport model was constructed to represent Little Grand Wash (LGW) and Salt Wash (SW) faults, where naturally originating CO2 is being leaked to the surface. According to simulation results, buoyant CO2 leaked through various pathways including the faults themselves, fault offsets, and damaged caprock. Because of both fault systems and caprocks serving as barriers, multiple trapped CO2 plumes were developed in this region. Presence of trapped CO2 plumes in the subsurface is supported by multiple field-observations (e.g., elevated soil CO2 fluxes, travertines, and CO2-driven cold-water geysers/CO2 springs) adjacent to both LGW and SW faults. Sensitivity studies were conducted with different permeabilities for faults and caprock, various CO2 source locations, and differing fault parameters (e.g., fault throw and cutoff angle), which affected subsurface CO2 distribution including size, shape, and location of trapped CO2 plumes. Finally, such trapped CO2 plumes have played a key role in the development of CO2-driven cold-water geysers in these regions.

We sequenced the complete mitochondrial (mt) genome of Chloris sinica ussuriensis. The circular mt genome is 16,813 bp long and encodes 13 proteins, 22 transfer RNAs, and 2 ribosomal RNAs. Phylogenetic analysis based on full mt genome sequences confirmed that the C. s. ussuriensis is monophyletic group of the Chloris sinica. The complete mitochondrial genome of C. s. ussuriensis can provide a valuable data for resolving geographical distribution of evolutionary subdivision within the C. sinica species in East Asia.

Molt strategies have received relatively little attention in current ornithology, and knowledge concerning the evolution, variability and extent of molt is sparse in many bird species. This is especially true for East Asian Locustella species where assumptions on molt patterns are based on incomplete information. We provide evidence indicating a complex postbreeding molt strategy and variable molt extent among the Pallas's Grasshopper Warbler Locustella certhiola, based on data from six ringing sites situated along its flyway from the breeding grounds to the wintering areas. Detailed study revealed for the first time that in most individuals wing feather molt proceeds from the center both toward the body and the wing‐tip, a molt pattern known as divergent molt (which is rare among Palearctic passerines). In the Russian Far East, where both breeding birds and passage migrants occur, a third of the adult birds were molting in late summer. In Central Siberia, at the northwestern limit of its distribution, adult individuals commenced their primary molt partly divergently and partly with unknown sequence. During migration in Mongolia, only descendantly (i.e., from the body toward the wing‐tip) molting birds were observed, while further south in Korea, Hong Kong, and Thailand the proportion of potential eccentric and divergent feather renewal was not identifiable since the renewed feathers were already fully grown as expected. We found an increase in the mean number of molted primaries during the progress of the autumn migration. Moderate body mass levels and low‐fat and muscle scores were observed in molting adult birds, without any remarkable increase in the later season. According to optimality models, we suggest that an extremely short season of high food abundance in tall grass habitats and a largely overland route allow autumn migration with low fuel loads combined with molt migration in at least a part of the population. This study highlights the importance of further studying molt strategy as well as stopover behavior decisions and the trade‐offs among migratory birds that are now facing a panoply of anthropogenic threats along their flyways., We analyze molt patterns in a little‐known passerine, the Pallas's Grasshopper Warbler Locustella certhiola, by using data from multiple sources and sites. We found complex and variable partial postbreeding molt strategies, including evidence for the rarely described divergent primary molt.

Anaplastic thyroid cancer (ATC) is a rapidly growing, highly metastatic cancer with limited therapeutic alternatives, thus targeted therapies need to be developed. This study aimed to examine desmoglein 2 (Dsg2) expression in ATC and its biological role and potential as a therapeutic target in ATC. Consequently, Dsg2 was downregulated or aberrantly expressed in ATC tissues. ATC patients with low Dsg2 expression levels also presented with distant metastasis. Dsg2 depletion significantly increased cell migration and invasion, with a relatively limited effect on ATC cell proliferation in vitro and increased distant metastasis in vivo. Dsg2 knockdown induced cell motility through the hepatocyte growth factor receptor (HGFR, c-Met)/Src/Rac1 signaling axis, with no alterations in the expression of EMT-related molecules. Further, specific targeting of c-Met significantly inhibited the motility of shDsg2-depleted ATC cells. Decreased membrane Dsg2 expression increased the metastatic potential of ATC cells. These results indicate that Dsg2 plays an important role in ATC cell migration and invasiveness. Therapies targeting c-Met might be effective among ATC patients with low membrane Dsg2 expression levels, indicating that the analysis of Dsg2 expression potentially provides novel insights into treatment strategies for ATC.

We report a method for constructing an active optical polarizer using an aligned carbon nanotube (CNT) sheet that is flexible, bendable, transparent, conductive, and also serves to anchor liquid-crystal (LC) molecules. A horizontally aligned CNT sheet was obtained by mechanical stretching from a vertically grown CNT forest, which was then transferred onto a substrate. A liquid polymer was infiltrated into the CNT sheet followed by UV curing, while a part of the CNT sheet was still exposed on the film surface without polymer coating. The polymer-embedded CNT sheet (P-ECS) film with 10 layers of CNT sheets exhibited a good polarization efficiency of 87%, a sheet resistance of 340 Ω□-1, and excellent ability to align LC molecules. The high stability of the P-ECS film was confirmed from the very low variation of sheet resistance (2%) and transmittance (10%) observed during a bending test of 1000 cycles. In addition, a twisted nematic LC device constructed using the P-ECS films shows a good bright-dark switching performance. The P-ECS film functions simultaneously as a transparent electrode, a film-type polarizer, and a LC alignment layer, demonstrating the multi-functionality of the active CNT film. This study thus highlights a wide range of possible applications for active polarizers and flexible displays.

The self-renewal properties of human pluripotent stem cells (hPSCs) contribute to their efficacy in tissue regeneration applications yet increase the likelihood of teratoma formation, thereby limiting their clinical utility. To address this issue, we developed a tool to specifically target and neutralize undifferentiated hPSCs, thereby minimizing tumorigenicity risk without negatively affecting regenerated and somatic tissues. Specifically, we conjugated a monoclonal antibody (K6-1) previously generated in our laboratory against desmoglein 2 (Dsg2), which is highly differentially expressed in undifferentiated hPSCs versus somatic tissues, to the chemotherapeutic agent doxorubicin (DOX). The K6-1-DOX conjugates were selectively targeted and incorporated into Dsg2-positive hPSCs, leading to pH-dependent endosomal release and nuclear localization of DOX with subsequent cytotoxicity via an apoptotic caspase cascade. Conversely, Dsg2-negative fibroblasts showed minimal conjugate uptake or cytotoxicity, suggesting that K6-1-DOX treatment would yield few side effects owing to off-target effects. Selective removal of undifferentiated stem cells was also supported by in vivo studies using a mouse xenograft model, wherein hIgG-DOX- but not K6-1-DOX-pretreated-hPSC injection led to teratoma development. Together, these results validated the ability of the Dsg2-targeted antibody-anticancer drug conjugate to facilitate the safety of stem cell therapies.

Since the Chernobyl and the Fukushima Daiichi disasters, contamination caused by radioactive accidents has attracted increasing attention. The present study evaluated immediate cleanup of

Many inland waters exhibit complete or partial desiccation, or have vanished due to global change, exposing sediments to the atmosphere. Yet, data on carbon dioxide (CO2) emissions from these sediments are too scarce to upscale emissions for global estimates or to understand their fundamental drivers. Here, we present the results of a global survey covering 196 dry inland waters across diverse ecosystem types and climate zones. We show that their CO2 emissions share fundamental drivers and constitute a substantial fraction of the carbon cycled by inland waters. CO2 emissions were consistent across ecosystem types and climate zones, with local characteristics explaining much of the variability. Accounting for such emissions increases global estimates of carbon emissions from inland waters by 6% (~0.12 Pg C y−1). Our results indicate that emissions from dry inland waters represent a significant and likely increasing component of the inland waters carbon cycle., Many inland waters seasonally or permanently dry up, thus exposing sediments to the atmosphere. Here the authors show that a substantial amount of CO2 is emitted from these dry sediments, increasing current inland water carbon flux estimates by 6%.

Oxidative stress activates macroautophagy/autophagy and contributes to atherogenesis via lipophagic flux, a form of lipid removal by autophagy. However, it is not known exactly how endogenous antioxidant enzymes are involved in lipophagic flux. Here, we demonstrate that the antioxidant PRDX1 (peroxiredoxin 1) has a crucial role in the maintenance of lipophagic flux in macrophages. PRDX1 is more highly expressed than other antioxidant enzymes in monocytes and macrophages. We determined that Prdx1 deficiency induced excessive oxidative stress and impaired maintenance of autophagic flux in macrophages. Prdx1-deficient macrophages had higher intracellular cholesterol mass and lower cholesterol efflux compared with wild type. This perturbation in cholesterol homeostasis was due to impaired lipophagic cholesterol hydrolysis caused by excessive oxidative stress, resulting in the inhibition of free cholesterol formation and the reduction of NR1H3 (nuclear receptor subfamily 1, group H, member 3) activity. Notably, impairment of both lipophagic flux and cholesterol efflux was restored by the 2-Cys PRDX-mimics ebselen and gliotoxin. Consistent with this observation, apoe −/− mice transplanted with bone marrow from prdx1−/−apoe−/− mice had increased plaque formation compared with apoe−/− BM-transplanted recipients. This study reveals that PRDX1 is crucial to regulating lipophagic flux and maintaining macrophage cholesterol homeostasis against oxidative stress. We suggest that PRDX1-dependent control of oxidative stress may provide a strategy for treating atherosclerosis and autophagy-related human diseases.

Endothelial progenitor cells (EPCs) promote neovascularization and tissue repair by migrating to vascular injury sites; therefore, factors that enhance EPC homing to damaged tissues are of interest. Here, we provide evidence of the prominent role of the Netrin-4 (NTN4)-Unc-5 Netrin receptor B (UNC5B) axis in EPC-specific promotion of ischemic neovascularization. Our results showed that NTN4 promoted the proliferation, chemotactic migration, and paracrine effects of small EPCs (SEPCs) and significantly increased the incorporation of large EPCs (LEPCs) into tubule networks. Additionally, NTN4 prominently augmented neovascularization in mice with hindlimb ischemia by increasing the homing of exogenously transplanted EPCs to the ischemic limb and incorporating EPCs into vessels. Moreover, silencing of UNC5B, an NTN4 receptor, abrogated the NTN4-induced cellular activities of SEPCs in vitro and blood-flow recovery and neovascularization in vivo in ischemic muscle by reducing EPC homing and incorporation. These findings suggest NTN4 as an EPC-based therapy for treating angiogenesis-dependent diseases.

Table S1. List of 34 genes that were commonly downregulated in livers of PPARα−/−, CREB3L3−/−, and PPARα/CREB3L3−/− mice in the fasted state. Table S2. Specific functions of the genes connected to cell cycle illustrated in Figs. 10b and c. Figure S1. PPARα and CREB3L3 regulate distinct pathways in liver during fasting. Figure S2. Similar effects of PPARα and combined PPARα/CREB3L3 ablation on hepatic gene expression. (PDF 1161 kb)