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Neuropathic pain is an unbearable condition caused by nervous system damage. As distinct acute pain, neuropathic pain is chronic, and it severely influences quality of life. N,N-Dimethyl-d-erythro-sphingosine (DMS), a neuropathic pain inducer, is metabolited de novo from sphingosine. In a recent study, metabolomics showed an increased concentration level of DMS in the spinal cord in mice with neuropathic pain. Nerve growth factor (NGF) is one of the peripheral nervous system targeted pain factors that interact with tropomyosin receptor kinase A (trkA). On the basis of this information, we were interested in the possibility that DMS may induce neuropathic pain-like behavior through an increase of NGF activity. In this study, we showed that DMS can enhance the binding of NGF to trkA, followed by neurite outgrowth of epidermal nerve fibers and phosphorylation of trkA. In addition, a stereoisomer, N,N-dimethyl-l-erythro-sphingosine, did not any show such biological activities. The results suggest that DMS can enhance the binding of NGF to trkA and that its stereochemistry is an essential factor for exhibiting its activity.

Strains ofRalstonia solanacearumspecies complex (RSSC), though known as the causative agent of bacterial wilt disease in plants, induce the chlamydospores of many fungi species and invade them through the spores. The lipopeptide ralstonins are the chlamydospore inducers produced by RSSC and are essential for this invasion. However, no mechanistic investigation of this interaction has been conducted. In this study, we report that quorum sensing (QS), which is bacterial cell–cell communication, is important for RSSC to invade the fungusFusarium oxysporum(Fo). ΔphcB, a deletion mutant of QS signal synthase, lost the ability to both produce ralstonins and invadeFochlamydospores. The QS signal methyl 3-hydroxymyristate rescued these disabilities. In contrast, exogenous ralstonin A, while inducingFochlamydospores, failed to rescue the invasive ability. Gene-deletion and -complementation experiments revealed that the QS-dependent production of extracellular polysaccharide (EPS I) is essential for this invasion. The RSSC cells adhered toFohyphae and formed biofilms there before inducing chlamydospores. This biofilm formation was not observed in the EPS I- or the ralstonin-deficient mutant. Microscopic analysis showed that RSSC infection resulted in the death ofFochlamydospores. Altogether, we reported that the RSSC QS system is important for this lethal endoparasitism. Among the factors regulated by the QS system, ralstonins, EPS I, and biofilm are important parasitic factors.SignificanceRSSC strains are Gram-negative bacteria that infect both plants and fungi. ThephcQS system of RSSC is important for parasitism in plants because it allows them to invade and increase within the host by causing appropriate system activation at each infection step. In this study, we confirmed not only the importance of ralstonins asFochlamydospore inducers, but also that of biofilm formation on the hyphae. In addition to ralstonins, EPS I turned out to be important for biofilm formation. The QS system comprehensively controls the production of these factors in the interaction withFo. Due to RSSC infection, the cell membranes and organelles ofFochlamydospores were destroyed, showing that RSSC cells are not endosymbionts but lethal invaders. This result advocates a new QS-dependent mechanism for the process by which a bacterium invades a fungus.

Purpose: Migration is a major cause of reintervention after endovascular aneurysm repair (EVAR). In patients with common iliac artery (CIA) dilation due to proximal migration of the iliac limb, internal iliac blood flow can be preserved by implanting an iliac branch device (IBD). Case Report: In this report, we discuss the case of a patient in whom the bilateral limbs were completely displaced into the aortic aneurysm due to proximal migration of the iliac limb after EVAR. By taking advantage of the characteristics of this migration, we formed a pull-through wire through the native terminal aorta without passing through the flow divider of the stent graft, and the IBD was deployed safely. Conclusion: The present case indicates that the preservation of at least 1 internal iliac artery is possible in patients with CIA dilation due to proximal migration of the iliac limb. However, the unique features of each case must be considered to determine the appropriate approach.

The extracellular accumulation of aggregated amyloid-β (Aβ) in the brain leads to the early pathology of Alzheimer’s disease (AD). The administration of exogenous plant-type ceramides into AD model mice can promote the release of neuronal exosomes, a subtype of extracellular vesicles, that can mediate Aβ clearance. In vitro studies showed that the length of fatty acids in mammalian-type ceramides is crucial for promoting neuronal exosome release. Therefore, investigating the structures of plant ceramides is important for evaluating the potential in releasing exosomes to remove Aβ. In this study, we assessed plant ceramide species with D-erythro-(4E,8Z)-sphingadienine and D-erythro-(8Z)-phytosphingenine as sphingoid bases that differ from mammalian-type species. Some plant ceramides were more effective than mammalian ceramides at stimulating exosome release. In addition, using deuterium chemistry-based lipidomics, most exogenous plant ceramides were confirmed to be derived from exosomes. These results suggest that the ceramide-dependent upregulation of exosome release may promote the release of exogenous ceramides from cells, and plant ceramides with long-chain fatty acids can effectively release neuronal exosomes and prevent AD pathology.

Non-invasive fatty acid (FA) metabolic imaging is crucial for the evaluation of cardiac function in the heart. Currently, single-photon emission computed tomography (SPECT) and positron emission tomography (PET) are widely employed for cardiac metabolic imaging both in pre-clinical and clinical studies. Although SPECT and PET enable highly sensitive cardiac metabolic imaging, there are several disadvantages such as the high cost of instruments and radioactive tracer synthesis. In contrast, near-infrared (NIR) optical imaging using fluorescent FAs provides a simple and useful platform for

High-molecular-weight (HMW) benzoxazines were synthesized by Mannich condensation with various combinations of bisphenols and diamines, and the mechanical and thermal properties of the polybenzoxazines derived from the HMW benzoxazines were measured by tensile tests and thermogravimetric analysis (TGA) to investigate the structure-property relationship. Free-standing precursor films were easily obtained from the solutions of HMW benzoxazines by a cast method on glass plates, and transparent and very tough polybenzoxazine films were obtained by thermally curing the precursor films at a temperature up to 240 °C. The polybenzoxazine films showed higher tensile strength and larger elongation at break than typical polybenzoxazine, i.e., PB-a obtained from low-molecular weight benzoxazine synthesized from bisphenol-A and aniline. In particular, among the HMW polybenzoxazines presented in this work, the PODP-oda film derived from 4,4′-oxydiphenol and 4,4′-oxydianiline showed remarkably good mechanical properties (E = 3.7 GPa, sb = 125 MPa, and eb = 4.5%). Moreover, the PODP-oda film revealed a higher 5 wt% weight loss temperature (Td5 = 332 °C) and char yield at 850 °C (CY850 = 58%) than PB-a (Td5 = 301 °C and CY850 = 42%), as evidenced by TGA, suggesting good thermal stability. High-molecular-weight (HMW) benzoxazines were synthesized by Mannich condensation with various combinations of bisphenols and diamines, and the mechanical and thermal properties of the polybenzoxazines derived from the HMW benzoxazines were measured by tensile tests and thermogravimetric analysis to investigate the structure-property relationship. Among the polybenzoxazines presented in this work, the PODP-oda film derived from 4,4′-oxydiphenol and 4,4′-oxydianiline showed remarkably good mechanical properties (E = 3.7 GPa, sb = 125 MPa, and eb = 4.5%) and thermal stability (Td5 = 332 °C).

Haemophilus parainfluenzae is a gram-negative coccobacillus that is a part of the normal flora in the human upper airway and sometimes causes infective endocarditis. We present a case of a 68-year-old Japanese man who had vascular graft infection caused by H. parainfluenzae 4 years after surgery for chronic aortic dissection.

To achieve robust sEMG measurements in an EMG prosthetic system, this study proposes a surface electromyogram (sEMG) sensor with a novel electrode structure composed of two-layered conductive silicone with different carbon concentrations. We hypothesized there is an optimal carbon concentration for achieving a large sEMG amplitude with robustness to external perturbation, and we empirically determined this optimal concentration. We produced fourteen sets of electrodes, with the weight ratio of carbon to silicone ranging from 1.7% to 4.0%. Using these electrodes, the user sEMG and electrical properties of the electrodes were measured. An external perturbation was applied on one side of the electrode to introduce a condition of unbalanced contact to the sEMG sensor. We defined an index of robustness for the sEMG sensor based on the signal-to-noise ratio in the balanced and unbalanced contact conditions. Based on the results of the robustness index, two optimal carbon concentrations, at weight ratios of 2.0%–2.1% and 2.6%–2.7%, were observed. Moreover, the double-peak property was correlated to the capacitance. Our results clearly demonstrate an optimal carbon concentration for robust sEMG measurements, and suggest that the robust measurement of sEMG is supported by the capacitance component of the sensor system.

[Image: see text] The interaction between natural occurring inhibitors and targeted membrane proteins could be an alternative medicinal strategy for the treatment of metabolic syndrome, notably, obesity. In this study, we identified malabaricones A–C and E (1–4) isolated from the fruits of Myristica cinnamomea King as natural inhibitors for sphingomyelin synthase (SMS), a membrane protein responsible for sphingolipid biosynthesis. Having the most promising inhibition, oral administration of compound 3 exhibited multiple efficacies in reducing weight gain, improving glucose tolerance, and reducing hepatic steatosis in high fat diet-induced obesity mice models. Liver lipid analysis revealed a crucial link between the SMS activities of compound 3 and its lipid metabolism in vitro and in vivo. The nontoxic nature of compound 3 makes it a suitable candidate in search of drugs which can be employed in the treatment and prevention of obesity.

Plant pathogenic bacteria possess sophisticated mechanisms to detect the presence of host plants by sensing host-derived compounds. Ralstonia solanacearum, the causative agent of bacterial wilt on solanaceous plants, employs quorum sensing to control the production of the secondary metabolite ralfuranones/ralstonins, which have been suggested to be involved in virulence. Here, we report that d-galactose and d-glucose, plant sugars, activate the production of ralfuranones/ralstonins in R. solanacearum. As a result, two new derivatives, ralfuranone M (1) and ralstonin C (2), were found in the culture extracts, and their structures were elucidated by spectroscopic and chemical methods. Ralstonin C (2) is a cyclic lipopeptide containing a unique fatty acid, (2S,3S,Z)-3-amino-2-hydroxyicos-13-enoic acid, whereas ralfuranone M (1) has a common aryl-furanone structure with other ralfuranones. d-Galactose and d-glucose activated the expression of the biosynthetic ralfuranone/ralstonin genes and in part became the biosynthetic source of ralfuranones/ralstonins. Ralfuranones and ralstonins were detected from the xylem fluid of the infected tomato plants, and their production-deficient mutants exhibited reduced virulence on tomato and tobacco plants. Taken together, these results suggest that activation of ralfuranone/ralstonin production by host sugars functions in R. solanacearum virulence.

Recently, shortwave-infrared (SWIR) fluorescence imaging for the optical diagnostics of diseases has attracted much attention as a new noninvasive imaging modality. For this application, the development of SWIR molecular imaging probes with high biocompatibility is crucial. Although many types of biocompatible SWIR fluorescent probes based on organic dyes have been reported, there are no SWIR-emitting molecular imaging probes that can be used for the detection of specific biomolecules in vivo. To apply SWIR-emitting molecular imaging probes to biomedical fields, we developed a biocompatible SWIR fluorescent dye based on π-conjugation extended indocyanine green (ICG), where ICG is the only approved near-infrared dye by the US Food and Drug Administration (FDA) for use in the clinic. Using the π-conjugation extended ICG, we prepared SWIR molecular imaging probes that can be used for in vivo tumor imaging. Herein, we demonstrate noninvasive SWIR fluorescence imaging of human epidermal growth factor receptor 2 (HER2)-positive and epidermal growth factor receptor (EGFR)-positive breast tumors using π-conjugation extended ICG and monoclonal antibody conjugates. The presented π-conjugation extended ICG analog probes will be a breakthrough to apply SWIR fluorescence imaging in biomedical fields.

An H-section steel bar that had been set against the wall fell and hit the abdomen and then both legs of a 33-year-old Chinese man. As his vital signs were stable and his chief complaint was leg pain, he was transferred to a local medical facility. After the confirmation of gross hematuria by an indwelling a bladder catheter there, he was transported to our hospital. On arrival, his vital signs were stable. His main complaint was foot pain. He had a scabbing injury at the scrotum and bilateral foot joint deformity. Whole-body computed tomography (CT) from head to toe revealed trabecular formation in the bladder and slight fluid collection in the rectovesical pouch, as well as bilateral fracture-dislocations at the ankles. The urinary tract injury and the fluid collection in the rectovesical pouch were managed conservatively, and the lower limbs were treated tentatively. Follow-up CT on day 3 revealed multiple free air pockets in the intra-abdominal cavity, which was considered to indicate perforation of the duodenal ulcer and treated conservatively. However, he showed abdominal pain on day 7, and repeated CT revealed increased fluid in the intra-abdominal cavity. Urgent laparoscopy showed intact bowels and perforation of the bladder that was closed by suturing. He ultimately obtained a survival outcome. This is the first case of transient trabecular formation in the bladder and delayed free air due to traumatic intraperitoneal bladder rupture. This unique case adds another radiological finding to the list of documented etiologies of traumatic bladder perforation.

Regional cerebral oximetry using near-infrared spectroscopy devices is commonly used for detecting cerebral ischemia during cardiopulmonary bypass, and aim to avoid poor cerebral perfusion which may result in perioperative neurological impairment. Today, several devices that can detect cerebral ischemia are commercially available. Although these devices operate on the same measurement principles, their algorithms for detecting and calculating cerebral ischemia are different and no criteria for directly comparing values measured by such different devices exist. From January 2017 to August 2017, 80 adult cardiovascular surgery patients were enrolled in the prospective study. In each patient, preoperative regional cerebral oxygen saturation values were measured by two different devices and their correlations with various preoperative factors were evaluated. Regional cerebral oxygen saturation levels were significantly higher for values of FORE-SIGHT ELITE (CAS Medical Systems, Branford, CT, USA) (F value) than those of the INVOS 5100C (Medtronic, Minneapolis, MN, USA) (I value). Scalp-cortex distance, hemoglobin concentration, and the presence or absence of hemodialysis showed significant correlations with ratios of measured values specific to each device (F/I). An appropriate device should be selected according to preoperative patient characteristics, and factors influencing regional cerebral oxygen saturation values should be considered to ensure the correct interpretation of measured values. This research was conducted with the approval of the ethics committee of our university (approval number: B16-96).

Neuroendocrine carcinoma (NEC) of the colon is very rare, and squamous cell carcinoma (SCC) of colon cancer is rare. We recently treated a patient with both NEC and SCC that initially presented as multiple unresectable liver and lung metastases. A 68-year-old Japanese man was referred to our hospital because of diarrhea with descending colon cancer obstruction. He underwent a left colectomy. Based on immunohistochemistry results, we diagnosed mixed NEC and SCC, the primary lesion location of which was probably the lung in the final pathologic examination. He began systemic palliative chemotherapy with CDDP and CPT-11. After 3 months of treatment, shown the progressive disease, we started CDDP and VP-16. The patient was not eligible for additional chemotherapy after 2 months.

Sphingoid bases, which have a 2-amino-1,3-diol common functional group, are the structural backbone units of all sphingolipids. Recently, much attention has been focused on sphingoid bases because of their potentially beneficial bioactivities toward various cancer cells as well as their dietary interest. However, low abundance and the handling complexity caused by their amphiphilic character led to very limited research on them. Glutaraldehyde has two aldehyde groups, and it reacts rapidly with the 2-amino-1,3-diol functional group of sphingosine to give a tricyclic product. Immobilization of glutaraldehyde on a resin was successfully performed by organic synthesis, starting from trans-p-coumaric acid via eight steps. This approach suppresses the self-polymerization of glutaraldehyde, and addition of water to the developed resin causes the formation of cyclic double hemiacetal function, which avoids oxidation like a reducing sugar in nature and makes it stable even for up to 1 year incubation. The resin was applied to the solid-phase extracting experiment of free sphingosine from human serum at a concentration of 280 nM. Another extraction study of edible golden oyster mushrooms showed that the sphingoid base was selectively captured from complex natural extracts. These results demonstrate that the developed glutaraldehyde resin method is a highly selective method, and hence, the combination of it with the o-phthaldialdehyde HPLC method was confirmed as an efficient and sensitive method for analysis of sphingoid bases in biological samples.

Ralstonia solanacearum has an orphan hybrid polyketide synthase-nonribosomal peptide synthetase gene cluster. We herein isolate its products (named ralstonins A and B) from R. solanacearum and elucidate their structures and biological activities. Ralstonins are unusual lipodepsipeptides composed of 11 amino acids (containing unique amino acids such as β-hydroxytyrosine and dehydroalanine) and a 3-amino-2-hydroxyoctadecanoic acid, and their production is controlled by quorum sensing, a mechanism of bacterial cell-cell communication. Ralstonins exhibited chlamydospore-inducing activity and phytotoxicity.

Konjac ceramide (kCer) is a plant-type ceramide composed of various long-chain bases and a-hydroxyl fatty acids. The presence of d4t,8t-sphingadienine is essential for semaphorin 3A (Sema3A)-like activity. Herein, we examined the three neuropilin 1 (Nrp1) domains (a1a2, b1b2, or c), and found that a1a2 binds to d4t,8t-kCer and possesses Sema3A-like activity. kCer binds to Nrp1 with a weak affinity of mM dissociation constant (Kd). We wondered whether bovine serum albumin could influence the ligand&ndash, receptor interaction that a1a2 has with a single high affinity binding site for kCer (Kd in nM range). In the present study we demonstrated the influence of bovine serum albumin. Thermal denaturation indicates that the a1a2 domain may include intrinsically disordered region (IDR)-like flexibility. A potential interaction site on the a1 module was explored by molecular docking, which revealed a possible Nrp1 activation mechanism, in which kCer binds to Site A close to the Sema3A-binding region of the a1a2 domain. The a1 module then accesses a2 as the IDR-like flexibility becomes ordered via kCer-induced protein rigidity of a1a2. This induces intramolecular interaction between a1 and a2 through a slight change in protein secondary structure.

Species of the genus Rhododendron have been used in traditional Chinese medicine, with the medicinal herb &ldquo, Manshanfong&rdquo, used as an expectorant and for the treatment of acute bronchitis. Daurichromenic acid (DCA), a constituent of Rhododendron dauricum, is a meroterpenoid with antibacterial, anti-HIV, and anti-inflammatory activities. However, the mechanisms underlying these pharmacologic activities are poorly understood. To develop new drugs based on DCA, more information is required regarding its interactions with biomolecules. The present study showed that DCA inhibits the activity of the enzyme sphingomyelin synthase, with an IC50 of 4 &micro, M. The structure&ndash, activity relationships between DCA and sphingomyelin synthase were evaluated using derivatives and cyclized hongoquercin A. In addition, DCA was found to inhibit amyloid &beta, aggregation. These results may help in the design of effective drugs based on DCA.