The powerful potential of amino acid menthyl esters for anti-inflammatory and anti-obesity therapies.

Our newly developed menthyl esters of valine and isoleucine exhibit anti-inflammatory properties beyond those of the well-known menthol in macrophages stimulated by lipopolysaccharide (LPS) and in a mouse model of colitis induced by sodium dextran sulfate. Unlike menthol, which acts primarily through the cold-sensitive TRPM8 channel, these menthyl esters displayed unique mechanisms that operate independently of this receptor. They readily penetrated target cells and efficiently suppressed LPS-stimulated tumour necrosis factor-alpha (Tnf) expression mediated by liver X receptor (LXR), a key nuclear receptor that regulates intracellular cholesterol and lipid balance. The menthyl esters showed affinity for LXR and enhanced the transcriptional activity through their non-competitive and potentially synergistic agonistic effect. This effect can be attributed to the crucial involvement of SCD1, an enzyme regulated by LXR, which is central to lipid metabolism and plays a key role in the anti-inflammatory response. In addition, we discovered that the menthyl esters showed remarkable efficacy in suppressing adipogenesis in 3T3-L1 adipocytes at the mitotic clonal expansion stage in an LXR-independent manner as well as in mice subjected to diet-induced obesity. These multiple capabilities of our compounds establish them as formidable allies in the fight against inflammation and obesity, paving the way for a range of potential therapeutic applications.

Spin-State Control of Shallow Single NV Centers in Hydrogen-Terminated Diamond.

The ability to control the charge and spin states of nitrogen-vacancy (NV) centers near the diamond surface is of pivotal importance for quantum applications. Hydrogen-terminated diamond is promising for long spin coherence times and ease of controlling the charge states due to the low density of surface defects. However, it has so far been challenging to create negatively charged single NV centers with controllable spin states beneath a hydrogen-terminated surface because atmospheric adsorbates that act as acceptors induce surface holes. In this study, we optically detected the magnetic resonance of shallow single NV centers in hydrogen-terminated diamond through precise control of the nitrogen implantation fluence. Furthermore, we found that the probability of detecting the resonance was enhanced by reducing the surface acceptor density through passivation of the hydrogen-terminated surface with hexagonal boron nitride without air exposure. This control method opens up new opportunities for using NV centers in quantum applications.

Metabolic engineering of betacyanin in vegetables for anti-inflammatory therapy.

Betalains, which consist of the subgroups betaxanthins and betacyanins, are hydrophilic pigments that have classically been used for food colorants. Owing to their strong antioxidant property, their usefulness for application for therapeutic use is also expected. In addition, as betalains are mainly naturally available from plants of the order Caryophyllales, including beet (Beta vulgaris), metabolic engineering for betalain production in crops such as vegetables, fruits and cereals may provide new food resources useful for healthcare. Here we conducted metabolic engineering of betacyanins in tomato fruits and potato tubers. The transgenic tomato fruits and potato tubers with coexpression of betacyanin biosynthesis genes, CYP76AD1 from B. vulgaris, DOD (DOPA 4,5-dioxygenase) and 5GT (cyclo-DOPA 5-O-glucosyltransferase) from Mirabilis jalapa, under control of suitable specific promoters, possessed dark red tissues with enriched accumulation of betacyanins (betanin and isobetanin). The anti-inflammatory activity of transgenic tomato fruit extract was superior to that of wild-type fruit extract on macrophage RAW264.7 cells stimulated with lipopolysaccharide (LPS), as a result of decreased LPS-stimulated transcript levels of proinflammatory genes. These findings were in accord with the observation that administration of the transgenic tomato fruits ameliorated dextran sulfate sodium (DSS)-induced colitis as well as body weight loss and disease activity index in mice, via suppression of DSS-stimulated transcript levels of pro-inflammatory genes, including Tnf (encoding TNF-alpha), Il6, and Ptgs2 (encoding cyclooxygenae 2). Intriguingly, given the fact that the transgenic potato tuber extract failed to enrich the anti-inflammatory activity of macrophage cells, it is likely that metabolic engineering of betacyanins will be a powerful way of increasing the anti-inflammatory property of ordinary foods such as tomato.

Stabilization of VEGF i-motif structure by CpG methylation.

The intercalated motif (i-motif) is a non-canonical nucleic acid structure formed by intercalated hemi-protonated cytosine base pairs (C-C+) under acidic conditions. The i-motif structure formation is involved in biological processes such as transcription regulation. Therefore, the identification of factors controlling i-motif formation is important in elucidating the cellular functions it controls. We previously reported that the VEGF G-quadruplex structure is stabilized by CpG methylation. In this study, the effect of CpG methylation on the stability of the VEGF i-motif structure was investigated. The VEGF i-motif-forming oligonucleotide contains four cytosines on CpG sites, and three of the four cytosines (C4, C15, and C20) are involved in C-C+ formation in the i-motif structure. Circular dichroism (CD) spectra analysis demonstrated that full CpG methylation increased the pH of mid transition (pHT) of the i-motif structure by 0.1, and the melting temperature (Tm) by 5.1 °C in 25 mM sodium cacodylate buffer at pH 5.0. Moreover, single methylation at C4, C15, and C20 increased Tm by 0.5, 1.7, and 2.0 °C in the buffer, respectively. These results demonstrated that CpG methylation stabilized the VEGF i-motif structure.

Electron tomography imaging methods with diffraction contrast for materials research.

Transmission electron microscopy (TEM) and scanning transmission electron microscopy (STEM) enable the visualization of three-dimensional (3D) microstructures ranging from atomic to micrometer scales using 3D reconstruction techniques based on computed tomography algorithms. This 3D microscopy method is called electron tomography (ET) and has been utilized in the fields of materials science and engineering for more than two decades. Although atomic resolution is one of the current topics in ET research, the development and deployment of intermediate-resolution (non-atomic-resolution) ET imaging methods have garnered considerable attention from researchers. This research trend is probably not irrelevant due to the fact that the spatial resolution and functionality of 3D imaging methods of scanning electron microscopy (SEM) and X-ray microscopy have come to overlap with those of ET. In other words, there may be multiple ways to carry out 3D visualization using different microscopy methods for nanometer-scale objects in materials. From the above standpoint, this review paper aims to (i) describe the current status and issues of intermediate-resolution ET with regard to enhancing the effectiveness of TEM/STEM imaging and (ii) discuss promising applications of state-of-the-art intermediate-resolution ET for materials research with a particular focus on diffraction contrast ET for crystalline microstructures (superlattice domains and dislocations) including a demonstration of in situ dislocation tomography.

Single-channel 15.3 Tbit/s, 64 QAM coherent Nyquist pulse transmission over 150†km with a spectral efficiency of 8.3 bit/s/Hz.

We report the first single-channel 15.3 Tbit/s, 1.28 Tbaud, 64 QAM transmission using 670 fs coherent Nyquist pulses. We newly constructed an optical gate to improve the signal-to-noise ratio (SNR) of the homodyne detection signal, a coherent spectral expansion technique, and an optical phase-locked loop (OPLL) circuit with a 0.6 deg. phase noise. We also constructed an active 70 fs timing stabilization circuit between the OTDM signal and Nyquist LO pulse to realize precise homodyne detection. With these new techniques, we successfully achieved a record speed of 15.3 Tbit/s in a single channel transmission over 150 km with a spectral efficiency of 8.3 bit/s/Hz.

Single-channel 7.68 Tbit/s, 64 QAM coherent Nyquist pulse transmission over 150 km with a spectral efficiency of 9.7 bit/s/Hz.

We achieved a record capacity of 7.68 Tbit/s in a single-channel OTDM transmission with a 9.7 bit/s/Hz spectral efficiency, where a polarization-multiplexed 640 Gbaud, 64 QAM coherent Nyquist pulse has been transmitted over 150 km. In this scheme, a 1.39 ps optical Nyquist pulse with an OSNR of 53 dB at a 0.1 nm resolution was generated by combining a mode-locked laser and a highly nonlinear fiber and used at both the transmitter and receiver. Phase synchronization was achieved between these pulse sources with an advanced optical phase-locked loop based on the higher harmonics of the mode-locked laser mode. In addition, we suppressed a nonlinear phase rotation at an EDFA in the transmitter by broadening the pulse width with second-order dispersion and recompressed it to the original pulse width before a 150 km transmission link. We succeeded in a bit error rate below 2 x 10-2 for all tributaries.

Hypersensitivity Pneumonitis Caused by a Home Ultrasonic Humidifier Contaminated with Candida guilliermondii.

We herein report the first documented case of acute hypersensitivity pneumonitis in which Candida guilliermondii was the possible causative organism. A young Japanese woman presented to our hospital with relapsing respiratory symptoms accompanied by high fever. A detailed interview revealed that the onset of the symptoms occurred shortly after using a humidifier in her home. Her symptoms showed spontaneous improvement soon after admission, and an examination of her bronchoalveolar lavage fluid revealed the specific infiltration of inflammatory cells, which predominantly consisted of lymphocytes. Precipitin testing showed a positive reaction to C. guilliermondii, which was isolated from the home humidifier. Repeated history taking is essential for diagnosing occult respiratory disorders.

Single-channel 3.84 Tbit/s, 64 QAM coherent Nyquist pulse transmission over 150 km with a spectral efficiency of 10.6 bit/s/Hz.

We report a polarization-multiplexed 320 Gbaud, 64 QAM coherent Nyquist pulse transmission with a frequency-stabilized mode-locked laser and a modified digital back-propagation method for pulse transmission. Using a combination consisting of a mode-locked laser and a pulse shaper, we obtained a Nyquist pulse with a high OSNR of 51 dB. We achieved error free operation under a back-to-back condition with the OSNR improvement. By developing a new digital back-propagation method for pulse propagation, we achieved a bit error rate below the 7% forward error correction limit of 2x10-3 for all the tributaries of the OTDM signal data after a 150 km transmission. As a result, single-channel 3.84 Tbit/s data were successfully transmitted over 150 km with a spectral efficiency of 10.6 bit/s/Hz.

The Clinical and Hormonal Characteristics of Primary Adrenal Lymphomas: The Necessity of Early Detection of Adrenal Insufficiency.

Objective To analyze the clinical and endocrine characteristics of patients with primary adrenal lymphoma. Patients We retrospectively reviewed the cases of five patients with primary adrenal lymphoma who were treated in our hospital between April 2004 and March 2015. We investigated the characteristics of the clinical and pathological findings, treatment, prognosis and complications of adrenal insufficiency. Results Adrenal insufficiency, which was confirmed by the laboratory data at the initial presentation, was observed in two cases. One case was complicated by relative adrenal insufficiency during a course of chemotherapy. The plasma adrenaline and urinary adrenaline levels were decreased in four cases and three cases, respectively. Diffusion MRI was radiologically diagnostic. In all of the cases, the patients were pathologically diagnosed with diffuse large-B cell lymphoma and were treated with rituximab and CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone)-like chemotherapy. Two patients received central nervous system prophylaxis with high-dose methotrexate. Four of the patients survived and one patient died during the follow-up period. Conclusion The early detection of adrenal insufficiency and the administration of an appropriate dose of hydrocortisone are necessary during the course of chemotherapy as well as at the initial manifestation. The exclusion of adrenal dysfunction prior to invasive diagnostic procedures, such as CT-guided needle biopsy, is also critical.

Lanthanum Deposition in the Stomach: Usefulness of Scanning Electron Microscopy for Its Detection.

After having been treated with lanthanum carbonate administration for 4 years for hyperphosphatemia, a 75-year-old Japanese woman undergoing hemodialysis was diagnosed with lanthanum phosphate deposition in the stomach. The deposition, seen as white microgranules, was observed using esophagogastroduodenoscopy with magnifying observation. To the best of our knowledge, these are the minutest endoscopy images of lanthanum phosphate deposition in the gastric mucosa. Scanning electron microscopy (SEM) observation enabled easier identification of the deposited material, which was visible as bright areas. The present case suggests the usefulness of SEM observation in the detection of lanthanum phosphate deposition in the gastrointestinal tract.

Combined Effects of Androgen and Growth Hormone on Osteoblast Marker Expression in Mouse C2C12 and MC3T3-E1 Cells Induced by Bone Morphogenetic Protein.

Osteoblasts undergo differentiation in response to various factors, including growth factors and steroids. Bone mass is diminished in androgen- and/or growth hormone (GH)-deficient patients. However the functional relationship between androgen and GH, and their combined effects on bone metabolism, remains unclear. Here we investigated the mutual effects of androgen and GH on osteoblastic marker expression using mouse myoblastic C2C12 and osteoblast-like MC3T3-E1 cells. Combined treatment with dihydrotestosterone (DHT) and GH enhanced BMP-2-induced expression of Runx2, ALP, and osteocalcin mRNA, compared with the individual treatments in C2C12 cells. Co-treatment with DHT and GH activated Smad1/5/8 phosphorylation, Id-1 transcription, and ALP activity induced by BMP-2 in C2C12 cells but not in MC3T3-E1 cells. The insulin-like growth factor (IGF-I) mRNA level was amplified by GH and BMP-2 treatment and was restored by co-treatment with DHT in C2C12 cells. The mRNA level of the IGF-I receptor was not significantly altered by GH or DHT, while it was increased by IGF-I. In addition, IGF-I treatment increased collagen-1 mRNA expression, whereas blockage of endogenous IGF-I activity using an anti-IGF-I antibody failed to suppress the effect of GH and DHT on BMP-2-induced Runx2 expression in C2C12 cells, suggesting that endogenous IGF-I was not substantially involved in the underlying GH actions. On the other hand, androgen receptor and GH receptor mRNA expression was suppressed by BMP-2 in both cell lines, implying the existence of a feedback action. Collectively the results showed that the combined effects of androgen and GH facilitated BMP-2-induced osteoblast differentiation at an early stage by upregulating BMP receptor signaling.

A Rare Case of Diffuse Large B-cell Lymphoma in a Patient with IgG4-Related Autoimmune Pancreatitis.

A 61-year-old Japanese man with IgG4-related autoimmune pancreatitis was referred to our hospital because of perspiration during food intake. Abdominal computed tomography (CT) with contrast media revealed multiple mesenteric lymphadenopathies. An open surgical abdominal biopsy and subsequent histopathological analysis revealed abnormally large lymphoid cells that were negative for CD3, CD5, and c-myc and positive for CD20 and bcl-2, leading to a diagnosis of diffuse large B-cell lymphoma. Here, we discuss the risk of malignancies, particularly malignant lymphoma in patients with IgG4-related disease. The importance of pathological analysis to reach the appropriate diagnosis in such cases should be emphasized.

Increased Serum KL-6 Levels Induced by Pulmonary Mycobacterium Avium Complex Infection in a Patient with RA-associated Lung Disease.

KL-6 is a glycoprotein found predominantly on type II pneumocytes and alveolar macrophages, and often shows increased serum levels in patients with interstitial pneumonia. We report a case of mycobacterium avium complex (MAC) infection whose disease activity was correlated with KL-6 levels in serum. During treatment of rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) with prednisolone, chest image findings improved in association with decreased KL-6 levels. Following tapering of prednisolone, chest image findings deteriorated again as levels of KL-6 increased, suggesting recurrence of RA-ILD. Bronchoscopic examination revealed active MAC infection. Treatment of MAC infection not only improved chest image findings but also decreased KL-6 levels in serum, suggesting that KL-6 was increased by active MAC infection by itself, not by recurrence of RA-ILD. To the best of our knowledge, this is the first documentation of KL-6 elevation in serum in association with active MAC infection.

Endoscopic detection of the gastric lesions of peripheral T-cell lymphoma.

An 82-year-old Japanese man presented with a gastric involvement of peripheral T-cell lymphoma, not otherwise specified. Although gastrointestinal lesions were not detected on computed tomography, oesophagogastroduodenoscopy revealed a slight elevation of the gastric mucosa, with changes in mucosal colour and the presence of abnormal microvessels. This led to the prompt detection of gastric involvement in lymphoma. This case highlights the usefulness of detailed observation of the gastric mucosa for the endoscopic detection of gastric involvement of peripheral T-cell lymphoma.

Actinomyces turicensis Bacteremia Secondary to Pyometra.

We herein present a rare case of Actinomyces turicensis bacteremia that was caused by pyometra. The patient was successfully treated with transvaginal drainage and antibiotic therapy. A literature review in MEDLINE showed that there have been only 8 previously reported cases of A. turicensis bacteremia. This infection frequently occurs in patients with visceral abscesses, and blood culture examinations usually reveal a polymicrobial pattern. However, the prognosis of such patients has been reported to generally be benign. Due to difficulties in performing bacterial identification and the wide-spectrum clinical pictures associated with this bacteremia, no comprehensive understanding of the clinical features of each Actinomyces species has yet been established.