Development of a Remote Displacement Measuring Laser System for Bridge Inspection.

Measuring displacement is essential for assessing the safety of bridges. Non-contact sensors such as vision sensors can precisely measure displacement but may be expensive or incapable of micro-scale measurement at a low cost, unlike contact displacement sensors, which are economical but challenging to install. This study proposes an economical, remote non-contact sensor system. The system comprises a laser beam transmitter and a light receiver, deriving the displacement based on the position where the laser beam is irradiated to the light-receiving surface. To measure this, the light receiver was installed at the measurement point and included a wireless communicator to transmit the displacement data. A displacement experiment was conducted to evaluate the performance. The results confirmed that precise displacement measurements were possible at a resolution of 100 µm. For bridge load tests, a light receiver under a bridge was installed, laser beams irradiated to the light-receiving surface from a distance, and the displacement was measured for each test and compared with the values measured by a conventional contact sensor. The results were highly consistent with those of the existing sensor, indicating that the proposed sensor system applies to bridge loading tests and the safety diagnosis for various structures.

Particulate Matter Exacerbates the Death of Dopaminergic Neurons in Parkinson's Disease through an Inflammatory Response.

Particulate matter (PM), a component of air pollution, has been epidemiologically associated with a variety of diseases. Recent reports reveal that PM has detrimental effects on the brain. In this study, we aimed to investigate the biological effects of ambient particles on the neurodegenerative disease Parkinson's disease (PD). We exposed mice to coarse particles (PM10: 2.5-10 µm) for short (5 days) and long (8 weeks) durations via intratracheal instillation. Long-term PM10 exposure exacerbated motor impairment and dopaminergic neuron death in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse models. Short-term PM10 exposure resulted in both pulmonary and systemic inflammatory responses in mice. We further investigated the mechanism underlying PM10-induced neurotoxicity in cocultures of lung LA-4 epithelial cells and RAW264.7 macrophages. PM10 treatment elicited a dramatic increase in proinflammatory mediators in LA-4/RAW264.7 coculture. Treating BV2 microglial cells with PM10-treated conditioned medium induced microglial activation. Furthermore, 1-methyl-4-phenylpyridinium (MPP+) treatment caused notable cell death in N2A neurons cocultured with activated BV2 cells in PM10-conditioned medium. Altogether, our results demonstrated that PM10 plays a role in the neurodegeneration associated with PD. Thus, the impact of PM10 on neurodegeneration could be related to detrimental air pollution-induced systemic effects on the brain.

Correction: Fasting regulates EGR1 and protects from glucose- and dexamethasone-dependent sensitization to chemotherapy.

[This corrects the article DOI: 10.1371/journal.pbio.2001951.].

Fasting regulates EGR1 and protects from glucose- and dexamethasone-dependent sensitization to chemotherapy.

Fasting reduces glucose levels and protects mice against chemotoxicity, yet drugs that promote hyperglycemia are widely used in cancer treatment. Here, we show that dexamethasone (Dexa) and rapamycin (Rapa), commonly administered to cancer patients, elevate glucose and sensitize cardiomyocytes and mice to the cancer drug doxorubicin (DXR). Such toxicity can be reversed by reducing circulating glucose levels by fasting or insulin. Furthermore, glucose injections alone reversed the fasting-dependent protection against DXR in mice, indicating that elevated glucose mediates, at least in part, the sensitizing effects of rapamycin and dexamethasone. In yeast, glucose activates protein kinase A (PKA) to accelerate aging by inhibiting transcription factors Msn2/4. Here, we show that fasting or glucose restriction (GR) regulate PKA and AMP-activated protein kinase (AMPK) to protect against DXR in part by activating the mammalian Msn2/4 ortholog early growth response protein 1 (EGR1). Increased expression of the EGR1-regulated cardioprotective peptides atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) in heart tissue may also contribute to DXR resistance. Our findings suggest the existence of a glucose-PKA pathway that inactivates conserved zinc finger stress-resistance transcription factors to sensitize cells to toxins conserved from yeast to mammals. Our findings also describe a toxic role for drugs widely used in cancer treatment that promote hyperglycemia and identify dietary interventions that reverse these effects.

Rapidly Growing Intra-Cardiac Mass Mimicking a Local Recurrence of Lung Cancer or a Thrombus in the Left Atrium.

Cardiac myxoma typically is thought to be a slow-growing, benign primary. Atrial myxomas can lead to many complications and can also mimic mitral stenosis, infective endocarditis, and other vascular diseases associated with systemic embolization. A 75-year-old woman with a history of lung cancer (pT1cN1, adenocarcinoma), atrial fibrillation, and a cerebral infarction presented with dysarthria and visual disturbances. In our case, we had to consider some questionable issues with the left atrial mass, and whether the recurrence of cerebral events was due to the thrombotic material in the left atrium or from locally recurrent lung cancer from the stump margin of the previously resected left superior pulmonary vein. We present a case with a rapidly-growing left atrial myxoma with a growth rate of 12.60 mm/month, rather than a thrombus or local recurrence of tumor under a medication of non-VKA oral antagonists.

N-glycan maturation is crucial for cytokinin-mediated development and cellulose synthesis in Oryza sativa.

To explore the physiological significance of N-glycan maturation in the plant Golgi apparatus, gnt1, a mutant with loss of N-acetylglucosaminyltransferase I (GnTI) function, was isolated in Oryza sativa. gnt1 exhibited complete inhibition of N-glycan maturation and accumulated high-mannose N-glycans. Phenotypic analyses revealed that gnt1 shows defective post-seedling development and incomplete cell wall biosynthesis, leading to symptoms such as failure in tiller formation, brittle leaves, reduced cell wall thickness, and decreased cellulose content. The developmental defects of gnt1 ultimately resulted in early lethality without transition to the reproductive stage. However, callus induced from gnt1 seeds could be maintained for periods, although it exhibited a low proliferation rate, small size, and hypersensitivity to salt stress. Shoot regeneration and dark-induced leaf senescence assays indicated that the loss of GnTI function results in reduced sensitivity to cytokinin in rice. Reduced expression of A-type O. sativa response regulators that are rapidly induced by cytokinins in gnt1 confirmed that cytokinin signaling is impaired in the mutant. These results strongly support the proposed involvement of N-glycan maturation in transport as well as in the function of membrane proteins that are synthesized via the endomembrane system.

Socialized mitochondria: mitonuclear crosstalk in stress.

Traditionally, mitochondria are considered sites of energy production. However, recent studies have suggested that mitochondria are signaling organelles that are involved in intracellular interactions with other organelles. Remarkably, stressed mitochondria appear to induce a beneficial response that restores mitochondrial function and cellular homeostasis. These mitochondrial stress-centered signaling pathways have been rapidly elucidated in multiple organisms. In this review, we examine current perspectives on how mitochondria communicate with the rest of the cell, highlighting mitochondria-to-nucleus (mitonuclear) communication under various stresses. Our understanding of mitochondria as signaling organelles may provide new insights into disease susceptibility and lifespan extension.

Selective induction of Rab9-dependent alternative mitophagy using a synthetic derivative of isoquinoline alleviates mitochondrial dysfunction and cognitive deficits in Alzheimer's disease models.

Rationale: Promotion of mitophagy is considered a promising strategy for the treatment of neurodegenerative diseases including Alzheimer's disease (AD). The development of mitophagy-specific inducers with low toxicity and defined molecular mechanisms is essential for the clinical application of mitophagy-based therapy. The aim of this study was to investigate the potential of a novel small-molecule mitophagy inducer, ALT001, as a treatment for AD. Methods: ALT001 was developed through chemical optimization of an isoquinolium scaffold, which was identified from a chemical library screening using a mitophagy reporter system. In vitro and in vivo experiments were conducted to evaluate the potential of ALT001 as a mitophagy-targeting therapeutic agent and to investigate the molecular mechanisms underlying ALT001-induced mitophagy. The therapeutic effect of ALT001 was assessed in SH-SY5Y cells expressing mutant APP and mouse models of AD (5×FAD and PS2APP) by analyzing mitochondrial dysfunction and cognitive defects. Results: ALT001 specifically induces mitophagy both in vitro and in vivo but is nontoxic to mitochondria. Interestingly, we found that ALT001 induces mitophagy through the ULK1-Rab9-dependent alternative mitophagy pathway independent of canonical mitophagy pathway regulators such as ATG7 and PINK1. Importantly, ALT001 reverses mitochondrial dysfunction in SH-SY5Y cells expressing mutant APP in a mitophagy-dependent manner. ALT001 induces alternative mitophagy in mice and restores the decreased mitophagy level in a 5×FAD AD model mouse. In addition, ALT001 reverses mitochondrial dysfunction and cognitive defects in the PS2APP and 5×FAD AD mouse models. AAV-mediated silencing of Rab9 in the hippocampus further confirmed that ALT001 exerts its therapeutic effect through alternative mitophagy. Conclusion: Our results highlight the therapeutic potential of ALT001 for AD via alleviation of mitochondrial dysfunction and indicate the usefulness of the ULK1-Rab9 alternative mitophagy pathway as a therapeutic target.

Intranasal delivery of mitochondrial protein humanin rescues cell death and promotes mitochondrial function in Parkinson's disease.

Rationale: Mitochondrial dysfunction is a key factor in the pathogenesis of Parkinson's disease (PD). Accordingly, many aspects of mitochondrial function have been studied as a putative therapeutic target. Here we present a novel strategy to promote mitochondrial function and protect against Parkinson's disease by the peptide encoded within mitochondrial genome, mitochondria-derived peptide (MDP) humanin (HN). Methods: To test humanin as a potential biomarker in PD, we measured protein levels of circulating humanin from the plasma of PD patients and transgenic or neurotoxic mouse models of PD. Next, we aimed to identify whether HN peptide treatment can regulate its activity or expression. Using mouse models of PD, we assessed HN delivery to the brain via the nasal route of administration. We further revealed a possible mechanism underlying the therapeutic effectiveness of HN peptide for PD using in vitro and ex vivo model of PD. Results: Although the expression of intracellular HN was not correlated with PD, HN treatment itself could induce intracellular HN expression and enhance mitochondrial biogenesis inducing mitochondrial gene expression. After intranasal administration, HN peptide resulted in neuroprotection and behavioral recovery in an animal model of PD. Interestingly, HN peptide following intranasal delivery was found within the brain, mainly via the trigeminal pathways. Mechanistically, HN treatment induced activation of phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) signaling pathway which led to enhanced mitochondrial biogenesis resulting in upregulation of mitochondrial gene including humanin. Conclusion: These data support a novel role of mitochondrial protein humanin in mitochondrial function and neuronal survival against Parkinson's disease, in which humanin treatment is sufficient for stimulating mitochondrial gene expression.

Mitral valve re-repair in an adolescent patient with prosthetic ring endocarditis: posterior leaflet augmentation and posterior strip annuloplasty.

Endocarditis after mitral valve (MV) annuloplasty is uncommon. The ring used in MV annuloplasty is often inadequate because it opposes the growth of the MV leaflets and annulus. We report a 15-year-old male that required redo surgery for prosthetic ring endocarditis 40 months after a previous MV annuloplasty. After the previous ring was removed, the undergrown posterior leaflet was repaired with pericardial augmentation and the posterior annulus was stabilized with a Mitra-Lift® supra-annular strip to preserve a flexible valve orifice and allow the anterior MV annulus and the commissures to grow in relation to body size.

Targeted Panel Sequencing Identifies an Intronic c.5225-3C>G Variant of the FBN1 Gene Causing Sporadic Marfan Syndrome with Annuloaortic Ectasia.

Marfan syndrome (MFS) is a hereditary connective tissue disease whose clinical severity varies widely. Mutations of the FBN1 gene encoding fibrillin-1 are the most common genetic cause of Marfanoid habitus; however, about 10% of MFS patients are unaware of their genetic defects. Herein, we report a Korean patient with MFS and annuloaortic ectasia caused by an intronic c.5225-3C>G variant of the FBN1 gene identified by targeted panel sequencing. The reverse transcription analysis of FBN1 revealed that the intron 43 sequence from positions c.5297-1516 to c.5297-1 was retained at the coding sequence as a consequence of the c.5225-3C>G variant enhancing a cryptic splice acceptor site (c.5297-1518_5297-1517AG) in intron 43. The retained sequence of the part of intron 43 caused the same effect as insertion mutation (NM_000138.5:c.5297_c.5298ins5297-1516_5297-1), resulting in a frameshift mutation resulting in p.Ile1767Trpfs*3. The patient underwent an urgent modified Bentall operation with a 29 mm mechanical valve for annuloaortic ectasia and severe aortic valve regurgitation. This report emphasizes the need for functional investigations into the diagnostic workflows of certain diseases or gene panels with suspected high rates of intronic variants and potential pathogenic effects. Hence, further descriptions of individuals with intronic variants causing alternative splicing expected to have pathogenic effects at different transcript levels are crucial for improving our understanding.

Adoptive therapy with amyloid-ß specific regulatory T cells alleviates Alzheimer's disease.

Rationale: Neuroinflammation is a primary feature of Alzheimer's disease (AD), for which an increasing number of drugs have been specifically developed. The present study aimed to define the therapeutic impact of a specific subpopulation of T cells that can suppress excessive inflammation in various immune and inflammatory disorders, namely, CD4+CD25+Foxp3+ regulatory T cells (Tregs). Methods: To generate Aß antigen-specific Tregs (Aß+ Tregs), Aß 1-42 peptide was applied in vivo and subsequent in vitro splenocyte culture. After isolating Tregs by magnetic bead based purification method, Aß+ Tregs were adoptively transferred into 3xTg-AD mice via tail vein injection. Therapeutic efficacy was confirmed with behavior test, Western blot, quantitative real-time PCR (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), and immunohistochemistry staining (IHC). In vitro suppression assay was performed to evaluate the suppressive activity of Aß+ Tregs using flow cytometry. Thy1.1+ Treg trafficking and distribution was analyzed to explore the infused Tregs migration into specific organs in an antigen-driven manner in AD mice. We further assessed cerebral glucose metabolism using 18F-FDG-PET, an imaging approach for AD biological definition. Subsequently, we evaluated the migration of Aß+ Tregs toward Aß activated microglia using live cell imaging, chemotaxis, antibody blocking and migration assay. Results: We showed that Aß-stimulated Tregs inhibited microglial proinflammatory activity and modulated the microglial phenotype via bystander suppression. Single adoptive transfer of Aß+ Tregs was enough to induce amelioration of cognitive impairments, Aß accumulation, hyper-phosphorylation of tau, and neuroinflammation during AD pathology. Moreover, Aß-specific Tregs effectively inhibited inflammation in primary microglia induced by Aß exposure. It may indicate bystander suppression in which Aß-specific Tregs promote immune tolerance by secreting cytokines to modulate immune responses during neurodegeneration. Conclusions: The administration of Aß antigen-specific regulatory T cells may represent a new cellular therapeutic strategy for AD that acts by modulating the inflammatory status in AD.

Electrochemical fabrication of Pt-Au-WO3 electrodes for direct methanol fuel cell.

Pt-Au-WO3 ternary electrodes with various compositions were synthesized by electrochemical method from a mixture of H2PtCl6 aqueous solution, HAuCl4 aqueous solution, and W-peroxo complex. Their electrocatalytic activities for methanol oxidation were investigated. Film composition was controlled by varying the concentration of each component in electrolytes. Morphology and compositional analyses of the synthesized films were performed by scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). The catalytic activity and initial behavior of current density for methanol oxidation of the synthesized films were measured using cyclic voltammetry (CV) and chronoamperometry (CA) in a mixture of 0.5 M H2SO4 and 0.5 M CH3OH solution. Electrocatalytic activity for CO oxidation was also evaluated in 0.5 M H2SO4 solution. The activities of various electrodes for methanol oxidation were found to be strongly dependent on film composition. Pt-Au-WO3 electrodes exhibited higher activity for CO oxidation than pure Pt. The addition of proper amount of Au and WO3 significantly improved catalytic activity for methanol oxidation.

Fabrication of mesoporous cobalt oxide (Co3O4) film by electrochemical method for electrochemical capacitor.

Mesoporous cobalt oxide (Co3O4) films were deposited on ITO coated glass substrates by electrodeposition from an aqueous CoSO4 solution using CTAB (cetyltrimethylammonium bromide) as the templating agent. The structures of the synthesized films were characterized by X-ray diffraction, and X-ray photoelectron spectroscopy. The presence of mesoporosity was confirmed by transmission electron microscopy and small angle X-ray diffraction analyses. The mesoporous structures of the synthesized films were found to be strongly dependent on the deposition conditions, such as deposition voltage, deposition time, temperature and concentration of templating agent. Cyclic voltammetry and discharging curves were used to examine the electrochemical properties as a capacitor. The mesoporous films prepared with CTAB templating showed a much higher specific capacitance and current density than the nonporous electrode prepared without CTAB templating.

Dual inflow without circulatory arrest for hemiarch replacement.

BACKGROUND: Open distal graft to proximal aortic arch anastomosis is central to a hemiarch replacement. Even if the ischemic tolerance time of several organs during circulatory arrest (CA) at normothermia is much longer than that of the brain, very little is known about the safety and clinical efficacy of moderate hypothermia for organ protection during the average duration of CA needed for aortic arch replacement. Hemiarch replacement using the standard techniques of deep hypothermia and antegrade perfusion has often ignored the effects of prolonged distal body CA. Maintenance of distal organ, especially the liver and kidney, perfusion reduces the risk of postoperative renal dysfunction and coagulopathy. CASE PRESENTATION: A 72-year-old female patient was referred to our institute due to chest discomfort. Radiologic investigations revealed a giant aneurysm of the ascending aorta extending but confined to the proximal aortic arch. We performed an alternative technique for hemiarch replacement using a dual inflow source. CONCLUSIONS: Although this technique cannot apply to all aneurysmal aortic diseases, our basic technique involving the use of dual inflow may be well suited for standard hemiarch replacement that is confined to the proximal aortic arch, given the shortening of the bypass and ischemic times.

Successful repair of coronary sinus rupture presenting as cardiac tamponade following blunt chest trauma.

The isolated coronary sinus (CS) rupture causing cardiac tamponade following blunt chest trauma is a very rare and very unique traumatic form of cardiac tamponade. Prompt recognition of this injury is crucial for patient survival. CS injuries are frequently difficult to repair and are potentially lethal. A meticulous repair carried out on an arrested, empty and well-protected heart is recommended to achieve secure haemostasis and CS patency. To our knowledge, this is the first report on the successful repair of isolated CS rupture following blunt chest trauma.