Functional roles of CD26/DPP4 in lipopolysaccharide-induced lung injury.

Acute respiratory distress syndrome (ARDS) is characterized by dysregulated inflammation and increased permeability of lung microvascular cells. CD26/dipeptidyl peptidase-4 (DPP4) is a type II membrane protein that is expressed in several cell types and mediates multiple pleiotropic effects. We previously reported that DPP4 inhibition by sitagliptin attenuates lipopolysaccharide (LPS)-induced lung injury in mice. The current study characterized the functional role of CD26/DPP4 expression in LPS-induced lung injury in mice, isolated alveolar macrophages, and cultured lung endothelial cells. In LPS-induced lung injury, inflammatory responses [bronchoalveolar lavage fluid (BALF) neutrophil numbers and several proinflammatory cytokine levels] were attenuated in Dpp4 knockout (Dpp4 KO) mice. However, multiple assays of alveolar capillary permeability were similar between the Dpp4 KO and wild-type mice. TNF-α and IL-6 production was suppressed in alveolar macrophages isolated from Dpp4 KO mice. In contrast, in cultured mouse lung microvascular endothelial cells (MLMVECs), reduction in CD26/DPP4 expression by siRNA resulted in greater ICAM-1 and IL-6 expression after LPS stimulation. Moreover, the LPS-induced vascular monolayer permeability in vitro was higher in MLMVECs treated with Dpp4 siRNA, suggesting that CD26/DPP4 plays a protective role in endothelial barrier function. In summary, this study demonstrated that genetic deficiency of Dpp4 attenuates inflammatory responses but not permeability in LPS-induced lung injury in mice, potentially through differential functional roles of CD26/DPP4 expression in resident cellular components of the lung. CD26/DPP4 may be a potential therapeutic target for ARDS and warrants further exploration to precisely identify the multiple functional effects of CD26/DPP4 in ARDS pathophysiology.NEW & NOTEWORTHY We aimed to clarify the functional roles of CD26/DPP4 in ARDS pathophysiology using Dpp4-deficient mice and siRNA reduction techniques in cultured lung cells. Our results suggest that CD26/DPP4 expression plays a proinflammatory role in alveolar macrophages while also playing a protective role in the endothelial barrier. Dpp4 genetic deficiency attenuates inflammatory responses but not permeability in LPS-induced lung injury in mice, potentially through differential roles of CD26/DPP4 expression in the resident cellular components of the lung.

Magnetization Precession at Sub-Terahertz Frequencies in Polycrystalline Cu2 Sb-Type (Mn-Cr)AlGe Ultrathin Films.

A ferromagnetic metal nanolayer with a large perpendicular magnetic anisotropy, small saturation magnetization, and small magnetic damping constant is a crucial requirement for high-speed spintronic devices. Fabrication of these devices on Si/SiO2 amorphous substrates with polycrystalline structure is also strongly desired for the mass production industry. This study involves the investigation of sub-terahertz (THz) magnetization precessional motion in a newly developed material system consisting of Cu2 Sb-type MnAlGe and (Mn-Cr)AlGe films by means of an all-optical pump-probe method. These materials exhibit large perpendicular magnetic anisotropy in regions of a few nanometers in size. The pseudo-2D crystal structures are clearly observed in the high-resolution transmission electron microscopy (TEM) images for the film samples grown on thermally oxidized silicon substrates. The TEM images also show a partial substitution of Cr atoms for the Mn sites in MnAlGe. A magnetization precession frequency of 0.164 THz with a relatively small effective magnetic damping constant of 0.012 is obtained for (Mn-Cr)AlGe. Theoretical calculation infers that the modification of the total density of states by Cr substitution decreases the intrinsic magnetic damping constant of (Mn-Cr)AlGe.

The clinical characteristics, treatment, and survival of portopulmonary hypertension in Japan.

BACKGROUND: Portopulmonary hypertension (PoPH) refers to the simultaneous presentation of pulmonary arterial and portal hypertension. However, few reports have included the characteristics and treatments for patients with PoPH of Asian population; thus, we investigated the clinical characteristics, treatment, and survival of these patients in a Japanese cohort. METHODS: Pulmonary arterial hypertension (PAH) has been included in the National Research Project on Intractable Disease in Japan; therefore, we extracted data of patients with PoPH from the forms of newly registered cases of the project from 2012 to 2013 (for 2 years), and updated cases of the project in 2013 (Study 1, n = 36 newly registered forms, n = 46 updated forms). Additionally, for Study 2, we performed a retrospective, observational cohort study at Chiba University Hospital (n = 11). We compared the characteristics between patients with PoPH and those with idiopathic/heritable PAH (I/H-PAH). RESULTS: Both studies showed higher cardiac outputs (COs) and cardiac indexes (CIs), lower pulmonary vascular resistance (PVR), and less treated with combination therapy in patients with PoPH than those with I/H-PAH. In Study 2, the overall and disease-specific survival between PoPH and I/H-PAH were similar. Conversely, many patients (45%) had to change their PAH-specific medicine because of adverse effects. CONCLUSION: As seen in western countries, Japanese patients with PoPH showed higher COs and CIs, better exercise tolerance, and lower PVRs than patients with I/H-PAH. Further studies are needed to improve PoPH treatments.

Characteristics of patients meeting the new definition of pre-capillary pulmonary hypertension (Nice 2018) in a single Japanese pulmonary hypertension center.

BACKGROUND: The 6th World Symposium on Pulmonary Hypertension (Nice 2018) proposed a new definition of pre-capillary pulmonary hypertension (PH) as a condition with mean pulmonary artery pressure (mPAP) > 20 mmHg, pulmonary artery wedge pressure ≤ 15 mmHg, and pulmonary vascular resistance (PVR) ≥ 3 Wood units (WU). The characteristics and prognosis of patients with pre-capillary PH, according to this new definition, is unclear. Therefore, we determined the characteristics and survival of patients with borderline pre-capillary PH. METHODS: We retrospectively enrolled 683 patients who underwent their first right heart catheterization at Chiba University, Japan. Among them, 489 patients met the pre-capillary PH requirement with mPAP ≥ 25 mmHg (conventional pre-capillary PH group), while 22 patients met the borderline pre-capillary PH criteria (borderline pre-capillary PH group). Additionally, 16 patients with a mean PAP of 20-25 and PVR of 2-3 WU were also examined. RESULTS: The borderline pre-capillary PH group comprised 4.3% of the total patients with pre-capillary PH, and the majority was in Group 3 (40.9%) or 4 (45.5%). The survival of the borderline pre-capillary PH group tended to be better than that of the conventional pre-capillary PH group. The prognosis of Group3 PH was the worst among the patients with borderline precapillary PH. There was no significant difference in survival between the borderline pre-capillary PH group with PVR ≥ 3 WU and that with PVR of 2-3 2WU, although none of the patients in the latter group died due to right heart failure. CONCLUSIONS: This is the first study conducted in a PH center in an Asian country to reveal the characteristics of patients with pre-capillary PH, according to the Nice 2018 definition. They comprised 4.3% of the total population with pre-capillary PH, and the majority of the pre-capillary PH cases were in either Group3 or 4. The prognosis may be affected by the patients' underlying diseases. Further prospective studies are needed to determine whether the new definition, including the PVR cut-off, is beneficial in clinical practice.

Alternative approaches for clinical clerkship during the COVID-19 pandemic: online simulated clinical practice for inpatients and outpatients-A mixed method.

BACKGROUND: The COVID-19 pandemic has created a need for educational materials and methods that can replace clinical clerkships (CCs) for online simulated clinical practice (online-sCP). This study evaluates the impact of using simulated electronic health records (sEHR) for inpatients, and electronic problem-based learning (e-PBL) and online virtual medical interviews (online-VMI) for outpatients, for an online-sCP using a learning management system (LMS) and online meeting system facilitated by a supervising physician. METHODS: The sEHR was reviewed by medical students and subsequently discussed with a supervising physician using an online meeting system. In the e-PBL, medical students reviewed the simulated patients and discussed on the LMS. For the online-VMI, a faculty member acted as an outpatient and a student acted as the doctor. Small groups of students discussed the clinical reasoning process using the online meeting system. A mixed-method design was implemented. Medical students self-assessed their clinical competence before and after the online-sCP. They answered questionnaires and participated in semi-structured focus group interviews (FGIs) regarding the advantages and disadvantages of the practice. RESULTS: Forty-three students completed the online-sCP during May and June 2020. All students indicated significant improvement in all aspects of self-evaluation of clinical performance after the online-sCP. Students using sEHR reported significant improvement in writing daily medical records and medical summaries. Students using e-PBL and online-VMI reported significant improvement in medical interviews and counseling. Students also indicated CCs as more useful for learning associated with medical interviews, physical examinations, and humanistic qualities like professionalism than the online-sCP. Eight FGIs were conducted (n = 42). The advantages of online-sCP were segregated into five categories (learning environment, efficiency, accessibility, self-paced learning, and interactivity); meanwhile, the disadvantages of online-sCP were classified into seven categories (clinical practice experience, learning environment, interactivity, motivation, memory retention, accessibility, and extraneous cognitive load). CONCLUSIONS: Online-sCP with sEHR, e-PBL, and online-VMI could be useful in learning some of the clinical skills acquired through CC. These methods can be implemented with limited preparation and resources.

The positive effect of student-oriented clinical clerkship rounds employing role-play and peer review on the clinical performance and professionalism of clerkship students.

Background: Role-play (RP) and peer review (PR) are occasionally used in training and evaluating communication skills in clinical clerkship (CC). Thus, we evaluated the effect of combining RP and PR during student-oriented CC rounds.Methods: Clerkship students conducted medical interviews with and performed physical examinations on their patients, which were reviewed by five peer students who observed their performance while role-playing as senior physicians or patients' families. The peer reviewers then provided feedback to the students. The performance of the students was evaluated based on a mini-clinical evaluation exercise (Mini-CEX) and a professionalism mini-evaluation exercise (P-MEX) before and after the rounds by two attending physicians. After the CC, the students responded to questionnaires about the rounds.Results: Seventy-five students completed the rounds, and the duration of each round was 41.7 ± 7.1 min. Their communication skills and professionalism abilities on Mini-CEX and P-MEX showed significant improvement after the rounds. Improvements in medical interviewing and physical examinations were also noted. Additionally, the students recognized the importance of multiple viewpoints in patient care through experiences of the rounds.Conclusions: Combining RP and PR with CC rounds improves the students' clinical performance and professionalism and promotes their awareness of the importance of multiple viewpoints in patient care.

[Efficacy and Safety of Gefitinib as First-Line Chemotherapy for Elderly Patients with Advanced Non-Small Cell Lung Cancer(NSCLC)].

Epidermalgrowth factor receptor tyrosine kinase inhibitor(EGFR-TKI)is the first choice for the treatment of EGFR mutation- positive advanced non-small cell lung cancer(NSCLC). There have been few reports on the efficacy and safety of gefitinib in elderly patients with EGFR mutation-positive advanced NSCLC. We retrospectively assessed the efficacy and safety of gefitinib as first-line chemotherapy in 22 patients with advanced NSCLC aged 75 years or older and who were treated with gefitinib. The response rate was 81.8%, and the disease controlrate was 95.5%. The median progression-free survivaltime was 14.2 months, and the median survivaltime was 30.7 months. The common adverse events were skin toxicities(50.0%), liver dysfunction(18.2%), and diarrhea(18.2%). The dose of gefitinib was reduced in 36.3% of the patients, and the treatment of gefitinib was discontinued in 18.2% of the patients. Gefitinib is effective and safe for elderly patients with advanced NSCLC.

Magnetic Switching in Granular FePt Layers Promoted by Near-Field Laser Enhancement.

Light-matter interaction at the nanoscale in magnetic materials is a topic of intense research in view of potential applications in next-generation high-density magnetic recording. Laser-assisted switching provides a pathway for overcoming the material constraints of high-anisotropy and high-packing density media, though much about the dynamics of the switching process remains unexplored. We use ultrafast small-angle X-ray scattering at an X-ray free-electron laser to probe the magnetic switching dynamics of FePt nanoparticles embedded in a carbon matrix following excitation by an optical femtosecond laser pulse. We observe that the combination of laser excitation and applied static magnetic field, 1 order of magnitude smaller than the coercive field, can overcome the magnetic anisotropy barrier between "up" and "down" magnetization, enabling magnetization switching. This magnetic switching is found to be inhomogeneous throughout the material with some individual FePt nanoparticles neither switching nor demagnetizing. The origin of this behavior is identified as the near-field modification of the incident laser radiation around FePt nanoparticles. The fraction of not-switching nanoparticles is influenced by the heat flow between FePt and a heat-sink layer.

Effect of terfenadine and pentamidine on the HERG channel and its intracellular trafficking: combined analysis with automated voltage clamp and confocal microscopy.

The effects of terfenadine and pentamidine on the human ether-a-go-go related gene (hERG) channel current and its intracellular trafficking were evaluated. Green fluorescent protein (GFP)-linked hERG channels were expressed in HEK293 cells, and the membrane current was measured by an automated whole cell voltage clamp system. To evaluate drug effects on channel trafficking to the cell membrane, the fraction of channel present on the cell membrane was quantified by current measurement after drug washout and confocal microscopy. Terfenadine directly blocked the hERG channel current but had no effect on trafficking of hERG channels to the cell membrane after application in culture medium for 2 d. In contrast, pentamidine had no direct effect on the hERG channel current but reduced trafficking of hERG channels. The two drugs inhibited hERG channel function through different mechanisms: terfenadine through direct channel blockade and pentamidine through inhibition of channel trafficking to the cell membrane. Combined use of automated voltage clamp and confocal microscopic analyses would provide insights into the mechanisms of drug-induced QT-prolongation and arrhythmogenesis.

[Continuous hemodiafiltration during graft repair for a ruptured thoracoabdominal aortic aneurysm was useful in a patient with chronic renal failure].

A 74-year-old man with ruptured thoracoabdominal aortic aneurysm was scheduled for open surgical repair under partial cardiopulmonary bypass. He had a history of diabetes mellitus and a concomitant renal dysfunction, requiring regular intermittent hemodialysis. To maintain electrolytes, acid base as well as water balance within adequate ranges, we planned to use continuous hemodiafiltration (CHDF) during the surgery because there was a high incidence of bolus transfusion to deal with massive bleeding in these surgeries. We increased fluid removal speed of ultrafiltration when blood components had to be infused rapidly. With these considerations, the patient did not develop fluid overload, hyperkalemia, or aggravation of acidosis. We did not administer anticoagulants into CHDF circuit because activated coagulation time was prolonged probably due to massive bleeding prior to the surgery. Heparin was administered just before the partial car diopulmonary bypass. There was no evidence for thromboembolic complications due to CHDF use. In conclusion, we successfully managed electrolytes as well as acid base balance, and hydration of a patient with chronic renal failure by using CHDF during open graft repair of ruptured thoracoabdominal aortic aneurysm.

Accumulation of gamma-aminobutyrate (GABA) caused by heat-drying and expression of related genes in immature vegetable soybean (edamame).

We studied the effects of drying of immature seeds of vegetable soybean (Glycine max L. Merrill) on the accumulation of gamma-aminobutyrate (GABA) in the seeds. GABA accumulated after heat-drying, with the maximum at 40°C. The GABA content (447.5 mg/100 g DW) increased to more than 5 times the value in untreated seeds (79.6 mg/100 g DW). In contrast, the glutamate content decreased rapidly to 1/3 the level in the untreated seeds. The GABA content increased early in the heat-drying treatment: after 30 min, it had increased to 1.5 times the value in the untreated seeds. GABA did not accumulate in the vacuum-drying treatment. Among genes related to the GABA shunt, the gene for glutamate decarboxylase (EC 4.1.1.15), which catalyzes the decarboxylation of glutamate to produce GABA, showed relatively high expression, decreasing to only 70% of the value in untreated seeds even after 4 h of treatment. In contrast, expression of the genes for two catabolic mitochondrial enzymes, GABA transaminase (GABA-T; EC 2.6.1.19) and succinate semialdehyde dehydrogenase (SSADH; EC 1.2.1.16), decreased rapidly during heat-drying. These results suggest that the accumulated GABA was not metabolized rapidly by GABA-T and SSADH and therefore remained at high levels.

Development of a dye nanoparticle-loaded test strip for the Zn(II) determination in metal plating wastes.

Zincon/Latex-NR3+ nanocomposite-loaded dye nanoparticle coated test strip (Zincon/Latex-NR3+ DNTS) was fabricated to detect Zn(II) in plating wastewater by a unique color change from red-purple to deep blue and evaluated its detection performance in actual plating samples. The 5 × 5 mm square-cut DNTS attached sticks were immersed into 10 mL aliquots of aqueous solutions containing Zn(II) ion and 0.01 M TAPS buffer at pH 8.4 with stirring at 250 rpm for 60 min. The calibration curve for Zn(II) was prepared based on the integrated area intensity of reflectance by TLC at 620 nm with the 3σ detection limit was 48.61 ppb, and the quantitative range was approximately up to 1000 ppb. Although Cu(II), Mn(II), Ni(II), and Co(II) showed competitive interference due to complex formation with Zincon, a mixture of masking reagent including thiourea, 2-aminoethanthiol, and o-phenanthroline was effective in removing the contamination. To eliminate Cr(III) interference based on the incorporation of Zn(II) into Cr(III) hydrolyzed polymer, adding KBrO3 and H2SO4 under boiling for several minutes was required. With appropriate pretreatment, all results of actual plating water samples by Zincon/LatexNR3+ DNTS were close to those of ICP-OES.

Analytical chemistry toward on-site diagnostics.

Analytical Chemistry, through quantitative and/or qualitative analysis (identification), is a discipline that involves the development of methodologies and the exploration of new principles to obtain answers to given problems. In situ analysis techniques have attracted attention for its ability to elucidate phenomena occurring and to evaluate amount of a certain component in substances at real time and biological samples as applications of such analysis technology. Lots of techniques have been performed to understand the fundamental phenomena in varied fields such as X-ray, vibrational, and electrochemical impedance spectroscopies and also analytical reagents that enable to semi-quantitative analysis just observation. In fact, applying various in situ techniques in analytical chemistry expands to the medical diagnosis, which leads to be able to detect early diseases. Here, we describe some of previous researches in many fields such as electrochemical device for energy storage, biology, environment, and pathology and briefly introduce our recent challenges to analytical chemistry toward the on-site diagnosis.

Functional roles of CD26/DPP4 in bleomycin-induced pulmonary fibrosis.

The pathogenesis of pulmonary fibrosis involves complex interplay between cell types and signaling pathways. Recurrent alveolar epithelial injury can occur during pulmonary inflammation, causing dysregulation of epithelial repair. Dysregulated repair interacts with mesenchymal, inflammatory, and endothelial cells to trigger fibroblast-to-myofibroblast activation. CD26/dipeptidyl peptidase-4 (DPP4) is a type II membrane protein mediating pleiotropic effect. However, the mechanistic role of CD26/DPP4 in pulmonary fibrosis remains unclear. In this study, we aimed to characterize Dpp4 deficiency in a mouse bleomycin (BLM)-induced pulmonary fibrosis model and in cell culture systems of human lung fibroblasts (HLFs). Dpp4 knockout (Dpp4 KO) mouse lungs exhibited lower Ashcroft scale indices, collagen content, and numbers of fibroblasts and myofibroblasts compared with those in C57BL/6 wild-type (WT) mice. Upregulation of Tgfb1 and Tgfb2 mRNA levels in the lungs after BLM treatment was lower in Dpp4 KO mice compared with those in WT mice. Although TGF-ß-driven endothelial-to-mesenchymal transition (EndMT) has been implicated as one of the mechanisms of pulmonary fibrosis, a number of partial EndMT cells in lungs did not differ between Dpp4 KO mice and WT mice. The proliferation capacity and mRNA levels of COL1A1, a collagen deposition-related gene, in cultured HLFs were suppressed in DPP4 small interfering RNA-treated cells. This study indicates that the genetic deficiency of DPP4 has protective effects against BLM-induced pulmonary fibrosis, partly through the reduction in TGF-ß expression and inhibition of fibroblast activation in the lung. Our study suggests that CD26/DPP4 inhibition is a potential therapeutic strategy for pulmonary fibrosis.

Time-domain observation of the spinmotive force in permalloy nanowires.

The spinmotive force associated with a moving domain wall is observed directly in Permalloy nanowires using real time voltage measurements with proper subtraction of the electromotive force. Whereas the wall velocity exhibits nonlinear dependence on magnetic field, the generated voltage increases linearly with the field. We show that the sign of the voltage reverses when the wall propagation direction is altered. Numerical simulations explain quantitatively these features of spinmotive force and indicate that it scales with the field even in a field range where the wall motion is no longer associated with periodic angular rotation of the wall magnetization.

Nonequilibrium sub-10 nm spin-wave soliton formation in FePt nanoparticles.

Magnetic nanoparticles such as FePt in the L10 phase are the bedrock of our current data storage technology. As the grains become smaller to keep up with technological demands, the superparamagnetic limit calls for materials with higher magnetocrystalline anisotropy. This, in turn, reduces the magnetic exchange length to just a few nanometers, enabling magnetic structures to be induced within the nanoparticles. Here, we describe the existence of spin-wave solitons, dynamic localized bound states of spin-wave excitations, in FePt nanoparticles. We show with time-resolved x-ray diffraction and micromagnetic modeling that spin-wave solitons of sub-10 nm sizes form out of the demagnetized state following femtosecond laser excitation. The measured soliton spin precession frequency of 0.1 THz positions this system as a platform to develop novel miniature devices.

Association of lymphocyte crossmatch and the outcome of intestinal transplantation in swine.

BACKGROUND: The effect of preformed antidonor antibodies have been demonstrated in various types of solid organ transplantation. However, the significance of anti-donor antibodies in intestinal transplantation remains unclear. The aim of this study is to evaluate the impact that the extent of T cell crossmatch has on the outcome of swine intestinal transplantation. MATERIALS AND METHODS: All studies were performed on outbred domestic male pigs weighing from 15 to 20 kg. Intestinal transplantation was performed orthotopically with an exchange of grafts between white and black pigs. FK506 was administered intravenously (0.1 mg/kg per day, POD 0-7) for immunosuppression. A lymphocyte crossmatch test was performed using the direct CDC crossmatch. The results were considered positive when more than 10% of the donor lymphocytes were killed by the recipient's serum. In addition, 0-10, 11-20, 21-30, 31-80 and 81-100% of the killed lymphocytes were classified as grade 1, 2, 4, 6 and 8, respectively. RESULT: A total of 34 intestinal transplantations were performed. All but one case had positive donor specific T cell crossmatches. The number of grade 2, 4, 6 and 8 cases was 11, 14, 6 and 2, respectively. Although there was a tendency towards a decreased survival according to the grade, the survival rate was not statistically different among each different grade. Moreover, the rates of acute cellular rejection and vascular complications were not significantly different among the four grades. CONCLUSION: These results suggest that the extent of positive T cell crossmatch is not associated with the outcome of swine intestinal transplantation.

Dependence of the Growth Mode in Epitaxial FePt Films on Surface Free Energy.

Epitaxial thin films of L10-ordered FePt alloys are one of the most important materials in magnetic recording and spintronics applications due to their large perpendicular magnetic anisotropy (PMA). The key to the production of these required superior properties lies in the control of the growth mode of the films. Further, it is necessary to distinguish between the effect of lattice mismatch and surface free energy on the growth mode because of their strong correlation. In this study, the effect of surface free energy on the growth mode of FePt epitaxial films was investigated using MgO, NiO, and MgON surfaces with almost the same lattice constant to exclude the effect of lattice mismatch. It was found that the growth mode can be tuned from a three-dimensional (3D) island mode on MgO to a more two-dimensional (2D)-like mode on MgON and NiO. Contact angle measurements revealed that MgON and NiO show larger surface free energy than MgO, indicating that the difference in the growth mode is due to their larger surface free energy. In addition, MgON was found to induce not only a flat surface as FePt grown on SrTiO3 (STO), which has a small lattice mismatch, but also a larger PMA than that of STO/FePt. As larger lattice mismatch is favored to induce a higher PMA into the FePt films, MgO substrates are exclusively used, but 3D island growth is indispensable. This work demonstrates that tuning the surface free energy enables us to achieve a large PMA and flat film surface in FePt epitaxial films on MgO. The results also indicate that modifying the surface free energy is pertinent for the flexible functional design of thin films.

Magneto-optical design of anomalous Nernst thermopile.

The introduction of spin caloritronics into thermoelectric conversion has paved a new path for versatile energy harvesting and heat sensing technologies. In particular, thermoelectric generation based on the anomalous Nernst effect (ANE) is an appealing approach as it shows considerable potential to realize efficient, large-area, and flexible use of heat energy. To make ANE applications viable, not only the improvement of thermoelectric performance but also the simplification of device structures is essential. Here, we demonstrate the construction of an anomalous Nernst thermopile with a substantially enhanced thermoelectric output and simple structure comprising a single ferromagnetic material. These improvements are achieved by combining the ANE with the magneto-optical recording technique called all-optical helicity-dependent switching of magnetization. Our thermopile consists only of Co/Pt multilayer wires arranged in a zigzag configuration, which simplifies microfabrication processes. When the out-of-plane magnetization of the neighboring wires is reversed alternately by local illumination with circularly polarized light, the ANE-induced voltage in the thermopile shows an order of magnitude enhancement, confirming the concept of a magneto-optically designed anomalous Nernst thermopile. The sign of the enhanced ANE-induced voltage can be controlled reversibly by changing the light polarization. The engineering concept demonstrated here promotes effective utilization of the characteristics of the ANE and will contribute to realizing its thermoelectric applications.

Functional Roles for CD26/DPP4 in Mediating Inflammatory Responses of Pulmonary Vascular Endothelial Cells.

Excessive inflammation in the lung is a primary cause of acute respiratory distress syndrome (ARDS). CD26/dipeptidyl peptidase-4 (DPP4) is a transmembrane protein that is expressed in various cell types and exerts multiple pleiotropic effects. We recently reported that pharmacological CD26/DPP4 inhibition ameliorated lipopolysaccharide (LPS)-induced lung injury in mice and exerted anti-inflammatory effects on human lung microvascular endothelial cells (HLMVECs), in vitro. However, the mechanistic roles of CD26/DPP4 in lung injury and its effects on HLMVECs remain unclear. In this study, transcriptome analysis, followed by various confirmation experiments using siRNA in cultured HLMVECs, are performed to evaluate the role of CD26/DPP4 in response to the pro-inflammatory involved in inflammation, barrier function, and regenerative processes in HLMVECs after pro-inflammatory stimulation. These are all functions that are closely related to the pathophysiology and repair process of lung injury. Confirmatory experiments using flow cytometry; enzyme-linked immunosorbent assay; quantitative polymerase chain reaction; dextran permeability assay; WST-8 assay; wound healing assay; and tube formation assay, reveal that the reduction of CD26/DPP4 via siRNA is associated with altered parameters of inflammation, barrier function, and the regenerative processes in HLMVECs. Thus, CD26/DPP4 can play a pathological role in mediating injury in pulmonary endothelial cells. CD26/DPP4 inhibition can be a new therapeutic strategy for inflammatory lung diseases, involving pulmonary vascular damage.