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Eosinophilic inflammation is primarily characterized by type 2 immune responses against parasitic organisms. In the contemporary human being especially in developed countries, eosinophilic inflammation is strongly associated with allergic/sterile inflammation, and constitutes an undesired immune reaction. This situation is in stark contrast to neutrophilic inflammation, which is indispensable for the host defense against bacterial infections. Among eosinophilic inflammatory disorders, massive accumulation of eosinophils within mucus is observed in certain cases, and is often linked to the distinctive clinical finding of mucus with high viscosity. Eosinophilic mucus is found in a variety of diseases, including chronic allergic keratoconjunctivitis, chronic rhinosinusitis encompassing allergic fungal sinusitis, eosinophilic otitis media, eosinophilic sialodochitis, allergic bronchopulmonary aspergillosis/mycosis, eosinophilic plastic bronchitis, and eosinophilic asthma. In these pathological conditions, chronic inflammation and tissue remodeling coupled with irreversible organ damage due to persistent adhesion of toxic substances and luminal obstruction may impose a significant burden on the body. Eosinophils aggregate in the hyperconcentrated mucus together with cell-derived crystals, macromolecules, and polymers, thereby affecting the biophysical properties of the mucus. This review focuses on the clinically significant challenges of mucus and discusses the consequences of activated eosinophils on the mucosal surface that impact mucus and persistent inflammation.

Objective: Craniocervical junction arteriovenous fistula (CCJ-AVF) is a rare disease, and preoperative imaging evaluation is important in developing treatment strategies due to the complexity of the vascular architecture, such as the feeding vessels, shunt points, and draining veins. In the present study, we report a case of hemorrhagic perimedullary CCJ-AVF with multiple feeding vessels in which the common single draining vein was dissected by craniotomy and completely treated. Case presentation: A 71-year-old woman presented with subarachnoid hemorrhage (Hunt & Kosnik, grade II). Cerebrovascular CTA showed no intracranial cerebral aneurysm and findings suggestive of shunt disease at the CCJ. Based on cerebral angiography, the patient was diagnosed with perimedullary CCJ AVF, with the right radicular and the left anterior spinal arteries as feeders which drain into a common dilated coronary vein through a shunt located on the ventral side of the spinal cord and then drain into the ascending and descending anterior spinal veins. Ventricular drainage was performed for acute hydrocephalus, and arteriovenous fistula was dissected electively by craniotomy on day 17 after onset. A clip was applied to the single draining vein, which had been evaluated using preoperative imaging diagnosis. Intraoperative digital subtraction angiography (DSA) confirmed the disappearance of shunt blood flow, and the surgery was completed. The follow-up DSA did not show shunt blood flow, and the patient was transferred to a rehabilitation hospital with a modified Rankin scale score of 2. Conclusion: CCJ-AVF cases often have a complex vascular architecture, and it is important to use various modalities to understand the vascular anatomy in detail and develop an appropriate treatment strategy.

Abstract Nanodisc technology has dramatically advanced the analysis of molecular interactions for membrane proteins. A nanodisc is designed as a vehicle for membrane proteins that provide a native-like phospholipid environment and better thermostability in a detergent-free buffer. This enables the determination of the thermodynamic and kinetic parameters of small molecule binding by surface plasmon resonance. In this study, we generated a nanodisc specific anti-MSP (membrane scaffold protein) monoclonal antibody biND5 for molecular interaction analysis of nanodiscs. The antibody, biND5 bound to various types of nanodiscs with sub-nanomolar to nanomolar affinity. Epitope mapping analysis revealed specific recognition of 8 amino acid residues in the exposed helix-4 structure of MSP. Further, we performed kinetics binding analysis between adenosine A2a receptor reconstituted nanodiscs and small molecule antagonist ZM241385 using biND5 immobilized sensor chips. These results show that biND5 facilitates the molecular interaction kinetics analysis of membrane proteins substituted in nanodiscs.

Humans have approximately 400 different olfactory receptors (hORs) and recognize odorants through the repertoire of hOR responses. Although the cell surface expression of hORs is critical to evaluate their response, hORs are poorly expressed on the surface of heterologous cells. To address this problem, previous studies have focused on hOR transportation to the membrane. Nevertheless, the response pattern of hORs to odorants has yet to be successfully linked, and the response sensitivity still remains to be improved. In this study, we demonstrate that increasing the transcriptional level can result in a significant increase in cell surface and functional expression of hORs. We used the TAR-Tat system, which increases the transcription efficiency through positive feedback, and found that OR1A1, OR6N2, and OR51M1 exhibited robust expression. Moreover, this system induces enhanced hOR responses to odorants, thus defining four hORs as novel n-hexanal receptors and n-hexanal is an inverse agonist to one of them. Our results suggested that using the TAR-Tat system and increasing the transcriptional level of hORs can help understanding the relationship between hORs and odorants that were previously undetectable. This finding could facilitate the understanding of the sense of smell by decoding the repertoire of hOR responses.

Food allergies are a significant health issue worldwide. In many countries, labeling of primary allergens in food products has been made mandatory to ensure consumer safety. In food manufacturing settings, the lateral flow immunoassay (LFI)—based on antigen–antibody reactions—is a rapid and accurate method for allergen testing and is widely used. Peptide arrays are tools that enable the synthesis of peptides of any sequence on a substrate and high-throughput analysis of their interactions with chemicals. This study aimed to investigate a new application of peptide arrays in the field of food technology, particularly in the development of antibodies for food allergen testing. First, monoclonal antibodies against hen egg ovalbumin, a major food allergen, were produced. Then, using a peptide array, the epitope and specificity of the antibodies were comprehensively and precisely analyzed. Finally, an LFI kit incorporating the antibodies demonstrated both high specificity and detection sensitivity for food allergen testing. These findings indicate that peptide arrays are valuable tools in the development of antibodies for food allergen testing, ensuring reliability and accuracy at the molecular level.

Background Neurofibromatosis type I is rarely associated with vascular abnormalities. Here, we report a case of rapid airway stenosis caused by a ruptured occipital artery that was treated with surgical airway management. Case Presentation A 40‐year‐old woman, with no medical history, presented with a chief complaint of a sudden neck pain on the left side. She had a prominent mass in the outer left side of the neck. After arrival at the emergency room, the patient complained of severe dyspnea and experienced a rapid drop in oxygen saturation. Supplemental ventilation was ineffective, and tracheal intubation was attempted; however, laryngeal expansion could not be observed because of the enlarged cervical mass. Therefore, to manage the surgical airway, a cricothyrotomy was first carried out, which resulted in an immediate increase in oxygen saturation. Two percutaneous embolizations and one surgical procedure were carried out, and the patient was discharged without any complications. Conclusion For a sudden onset cervical mass, airway management should be undertaken, keeping in mind the possibility of worsening rapid airway narrowing due to bleeding.

The aim of this study is to provide a new perspective on the development of masking agents by examining the application of their time-series sensory profiles. The analysis of the relationship between 14 time-intensity (TI) parameters and the beany flavor masking ability of 100 flavoring materials indicate that the values of AreaInc, DurDec, and AreaDec, TI parameters related to the flavor release in the increasing and decreasing phases, were significantly higher in the top 10 masking score materials than in the bottom 10 materials. In addition to individual analysis, machine learning analysis, which can derive complex rules from large amounts of data, was performed. Machine learning-based principal component analysis and cluster analysis of the flavoring materials presented AreaInc and AreaDec as TI parameters contributing to the classification of flavor materials and their masking ability. AreaDec was suggested to be particularly important for the beany flavor masking in the two different analyses: an effective masking can be achieved by focusing on the TI profiles of flavor materials. This study proposed that time-series profiles, which are mainly used for the understanding of the sensory characteristics of foods, can be applied to the development of masking agents.

Cellular metabolism is a key regulator of hematopoietic stem cell (HSC) maintenance. HSCs rely on anaerobic glycolysis for energy production to minimize the production of reactive oxygen species and shift toward mitochondrial oxidative phosphorylation upon differentiation. However, increasing evidence has shown that HSCs still maintain a certain level of mitochondrial activity in quiescence, and exhibit high mitochondrial membrane potential, which both support proper HSC function. Since glycolysis and the tricarboxylic acid (TCA) cycle are not directly connected in HSCs, other nutrient pathways, such as amino acid and fatty acid metabolism, generate acetyl-CoA and provide it to the TCA cycle. In this review, we discuss recent insights into the regulatory roles of cellular metabolism in HSCs. Understanding the metabolic requirements of healthy HSCs is of critical importance to the development of new therapies for hematological disorders.

A 54-year-old woman complained about a headache. Six days later, she developed subcortical hemorrhage (4 × 4 × 5 cm) due to reversible cerebral vasoconstriction syndrome (RCVS). She underwent a craniotomy procedure and maintained oral administration of verapamil. She suffered from higher brain dysfunction, was transferred to convalescent rehabilitation hospital at mRS3 stage, and recovered to mRS0 stage in three months. However, because there was cognitive decline such as inability to calculate and because there was a ventricular enlargement on the image, we performed an LP shunt procedure under the judgment of secondary hydrocephalus. Her cognitive function has improved, and the postoperative course is going smoothly.

Chalcone synthase is the first committed enzyme in the plant flavonoid biosynthesis pathway, yet shows low product specificity in vitro. Here Waki et al. show that chalcone isomerase-like proteins bind to and reduce the catalytic promiscuity of chalcone synthase, ensuring efficient flavonoid production in planta.

To improve the accuracy of the calculation analysis of crank journal bearings in motorcycle engines and accurately understand lubrication conditions, the oil film conditions of actual crankshafts and journal bearings should be measured. This research study focuses on the oil film pressure generated in the main bearing, and by using an original thin-film pressure sensor with improved durability achieved through the use of DLC (Diamond-like Carbon), it was possible to perform experiments at a maximum of 13,000 rpm and full load, which was not possible before. This established a method for measuring the oil film pressure generated in the main bearing of a high-speed motorcycle engine during operation without changing the surrounding environment. The maximum oil film pressure was 140 MPa, and the oil film pressure generated by each main bearing was successfully measured under different experimental conditions. The timing of pressure onset agreed well between the calculation and experiment stages, but the peak oil film pressure values were different. By varying the temperature of the engine in the calculation model, the calculated values approached the measured values. In the future, we plan to investigate ways to improve the accuracy of the current analytical model.

Advances in intravital microscopy (IVM) have enabled the studies of cellular organization and dynamics in the native microenvironment of intact organisms with minimal perturbation. The abilities to track specific cell populations and monitor their interactions have opened up new horizons for visualizing cell biology in vivo, yet the success of standard fluorescence cell labeling approaches for IVM comes with a “dark side” in that unlabeled cells are invisible, leaving labeled cells or structures to appear isolated in space, devoid of their surroundings and lacking proper biological context. Here we describe a novel method for “filling in the void” by harnessing the ubiquity of extracellular (interstitial) fluid and its ease of fluorescence labelling by commonly used vascular and lymphatic tracers. We show that during routine labeling of the vasculature and lymphatics for IVM, commonly used fluorescent tracers readily perfuse the interstitial spaces of the bone marrow (BM) and the lymph node (LN), outlining the unlabeled cells and forming negative contrast images that complement standard (positive) cell labeling approaches. The method is simple yet powerful, offering a comprehensive view of the cellular landscape such as cell density and spatial distribution, as well as dynamic processes such as cell motility and transmigration across the vascular endothelium. The extracellular localization of the dye and the interstitial flow provide favorable conditions for prolonged Intravital time lapse imaging with minimal toxicity and photobleaching.

Objective: Sacroiliac joint pain is one of several causes of lower limb and lower back pain not originating from the spine, spinal cord, or nerve roots. The authors examined outcomes of treating sacroiliac joint pain using radiofrequency neurotomy (RFN), as described in several previous studies by Murakami et al. between 2007 and 2018. The RFN treatment in the present study was performed on 67 patients (31 male, 36 female; median age 61.8 years) who experienced re-flares of pain despite ≥2 injections of local anesthetics into the sacroiliac joint. Patients and Methods: RFN treatment was considered to be effective when pain was reduced by ≤50% after treatment. Additional RFN treatment(s) was administered to patients who experienced pain re-flares. Results: Of the 67 patients, 57 (85.1%) achieved sustained pain relief, 30 (44.8%) of whom experienced immediate pain relief after the first treatment and no longer required therapy. The other 27 patients who experienced subsequent re-flares underwent additional RFN treatment(s) and successfully achieved sustainable pain relief sufficient to end therapy. Conclusion: RFN resulted in no complications and was safe and minimally invasive, and should be considered a conservative treatment option in advance of sacroiliac joint fusion surgery.

Functional inhibitory peptides of human dipeptidyl peptidase 4 (hDPP4) have been highly anticipated as the active ingredient of functional food for type II diabetes; however, the molecular mechanism of hDPP4 inhibition remains unclear. In this study, we focused on dipeptides and tripeptides, which display structure-function correlations that are relatively easy to analyze, and examined their interactions with hDPP4 on an atomic level using a combination of docking studies and an hDPP4 inhibition assay. First, we performed comprehensive binding mode analysis of the dipeptide library and demonstrated that the formation of a tight interaction with the S1 subsite composing part of the substrate pocket is essential for dipeptides to compete with the substrate and strongly inhibit hDPP4. Next, we synthesized tripeptides by adding various amino acids to the C-terminus of Ile-Pro and Val-Pro, which have especially high inhibitory activity among compounds in the dipeptide library, and measured the hDPP4 inhibitory activity of the tripeptides. When hydrophobic amino acids (Ile, Met, Val, Trp) were added, the inhibitory activity increased several-fold. This phenomenon could be explained as follows: the C-terminal amino acid of the tripeptide formed hydrophobic interactions with Tyr547 and Trp629, which compose the S1′ subsite located relatively outside the substrate pocket, thereby stabilizing the hDPP4-peptide binding. The structural information on the interaction between hDPP4 and peptide inhibitors attained in this study is anticipated to be useful in the development of a more potent hDPP4 competitive inhibitor.

Because transient receptor potential ankyrin 1 (TRPA1) is involved in various physiological functions, TRPA1-targeting drugs have been energetically developed. Although TRPA1 is considered a multimodal receptor, the structural diversity of TRPA1 agonists is not fully elucidated. We hypothesized that collecting a wider variation of TRPA1–compound interaction data would aid the understanding of its complex mechanism and aimed to challenge such data collection using an “image-based TRPA1 assay system combined with an in silico chemical space clustering concept.” Our library was clustered with 27 physicochemical molecular descriptors in silico, and structurally diverse compounds from each cluster were selected for a detailed kinetic assay to investigate variations of agonist structural rules. Through two sets of assays evaluating various compounds in parallel with validating effects of the previously established structural rules, we discovered that different chemical groups contribute to agonist activity, indicating that there are multiple agonist design concepts. A novel core structure for a TRPA1 agonist has been also proposed. Our new approach, “collection of TRPA1 activity data on compounds with physicochemical diversity,” will not only facilitate the understanding of the structural diversity of TRPA1 agonists but also contribute to the development of a new type of TRPA1-targeting drug.

Persistence of resistant leukemic cells after therapy is the main cause of relapse. Here, the authors show that mesenchymal stem cells-derived PML is involved in the maintenance of leukemia cells through Cxcl1 and IL6 and that PML inhibition enhances sensitivity to chemotherapy.

Abstract Transplantation of a single hematopoietic stem cell is an important method for its functional characterization, but the standard transplantation protocol relies on cell homing to the bone marrow after intravenous injection. Here, we present a method to transplant single cells directly into the bone marrow of live mice. We developed an optical platform that integrates a multiphoton microscope with a laser ablation unit for microsurgery and an optical tweezer for cell micromanipulation. These tools allow image-guided single cell transplantation with high spatial control. The platform was used to deliver single hematopoietic stem cells. The engraftment of transplants was tracked over time, illustrating that the technique can be useful for studying both normal and malignant stem cells in vivo.

Objectives: Demonstration of flat electroencephalogram (EEG) both at low- and high-sensitivity is required to legally determine brain death. Critically brain-injured patients frequently undergo decompressive craniectomy (DC) to relieve the raised intracranial pressure before being considered as candidates for legal brain death determination. The main objective of this study was to evaluate influence of DC on the interpretation of EEG at high-sensitivity. Methods: A retrospective study was conducted in 23 critically brain-injured patients with flat EEGs at low-sensitivity. An experienced EEG technician determined whether each high-sensitivity EEG was interpretable as flat in a blinded manner. DC had been performed in 13 patients (57%). Results: There was no significant difference in the demographics between the DC and non-DC group. The frequency of flat EEG at high-sensitivity was 62% in DC and 100% in the non-DC group, and the difference was statistically significant (p = 0.045). Determination of flat EEG at high-sensitivity was unable to be made in five DC patients (38%). All five patients died within 4 days of the initial EEG. Conclusions: In DC patients, EEG amplitudes at high-sensitivity may be exaggerated on the side of DC due to the absence of the skull. The findings of this study are: (1) 38% of DC patients showed some electrical activity at high-sensitivity on the side of DC; and (2) the electrical activity disappeared within several days and did not predict resuscitability. These findings may be useful to physicians who treat critically brain injured patients.

The role of mitochondria in the fate determination of hematopoietic stem and progenitor cells (HSPCs) is not solely limited to the switch from glycolysis to oxidative phosphorylation, but also involves alterations in mitochondrial features and properties, including mitochondrial membrane potential (ΔΨmt). HSPCs have a high ΔΨmt even when the rates of respiration and phosphorylation are low, and we have previously shown that the minimum proton flow through ATP synthesis (or complex V) enables high ΔΨmt in HSPCs. Here we show that HSPCs sustain a unique equilibrium between electron transport chain (ETC) complexes and ATP production. HSPCs exhibit high expression of ETC complex II, which sustains complex III in proton pumping, although the expression levels of complex I or V are relatively low. Complex II inhibition by TTFA caused a substantial decrease of ΔΨmt, particularly in HSPCs, while the inhibition of complex I by Rotenone mainly affected mature populations. Functionally, pharmacological inhibition of complex II reduced in vitro colony-replating capacity but this was not observed when complex I was inhibited, which supports the distinct roles of complex I and II in HSPCs. Taken together, these data highlight complex II as a key regulator of ΔΨmt in HSPCs and open new and interesting questions regarding the precise mechanisms that regulate mitochondrial control to maintain hematopoietic stem cell self-renewal. Keywords: Mitochondrial membrane potential, TMRM, HSC, SDHA, Electron transport chain, ATP synthase

Summary: The Ten-eleven translocation (TET) enzymes regulate gene expression by promoting DNA demethylation and partnering with chromatin modifiers. TET2, a member of this family, is frequently mutated in hematological disorders. The contributions of TET2 in hematopoiesis have been attributed to its DNA demethylase activity, and the significance of its nonenzymatic functions has remained undefined. To dissect the catalytic and non-catalytic requirements of Tet2, we engineered catalytically inactive Tet2 mutant mice and conducted comparative analyses of Tet2 mutant and Tet2 knockout animals. Tet2 knockout mice exhibited expansion of hematopoietic stem and progenitor cells (HSPCs) and developed myeloid and lymphoid disorders, while Tet2 mutant mice predominantly developed myeloid malignancies reminiscent of human myelodysplastic syndromes. HSPCs from Tet2 knockout mice exhibited distinct gene expression profiles, including downregulation of Gata2. Overexpression of Gata2 in Tet2 knockout bone marrow cells ameliorated disease phenotypes. Our results reveal the non-catalytic roles of TET2 in HSPC homeostasis. : The DNA demethylase TET2 is commonly mutated in hematological disorders, but the significance of its enzymatic versus nonenzymatic roles in hematopoiesis remains undefined. Using Tet2 catalytic-mutant and knockout mice, Ito et al. find that Tet2 enzymatic activity is critical for myelopoiesis, while aberrant lymphopoiesis is mainly associated with complete loss of Tet2. Keywords: Tet2, 5-hydroxymethylcytosine, 5hmC, hematopoietic stem cells, HSCs, myelodysplastic syndrome, MDS, chronic lymphocytic leukemia, CLL

The quantitation of pungency is difficult to achieve using sensory tests because of persistence, accumulation, and desensitization to the perception of pungency. Transient receptor vanilloid 1 (TRPV1), which is a chemosensory receptor, plays a pivotal role in the perception of many pungent compounds, suggesting that the activity of this receptor might be useful as an index for pungency evaluation. Although Ca2+-sensitive fluorescence dyes are commonly used for measuring human TRPV1 (hTRPV1) activity, their application is limited, as foods often contain fluorescent substances that interfere with the fluorescent signals. This study aims to design a new pungency evaluation system using hTRPV1. Instead of employing a fluorescent probe as the Ca2+ indicator, this assay system uses the luminescent protein aequorin. The luminescence assay successfully evaluated the hTRPV1 activity in foods without purification, even for those containing fluorescent substances. The hTRPV1 activity in food samples correlated strongly with the pungency intensity obtained by the human sensory test. This luminescence-based hTRPV1 assay system will be a powerful tool for objectively quantifying the pungency of spicy foods in both laboratory and industrial settings.

In recent years, advances in next-generation sequencing (NGS) technology have provided the opportunity to detect putative genetic drivers of disease, particularly cancers, with very high sensitivity. This knowledge has substantially improved our understanding of tumor pathogenesis. In hematological malignancies such as acute myeloid leukemia and myelodysplastic syndromes, pioneering work combining multi-parameter flow cytometry and targeted resequencing in leukemia have clearly shown that different classes of mutations appear to be acquired in particular sequences along the hematopoietic differentiation hierarchy. Moreover, as these mutations can be found in normal cells recovered during remission and can be detected at relapse, there is strong evidence for the existence of pre-leukemic stem cells (pre-LSC). These cells, while phenotypically normal by flow cytometry, morphology, and functional studies, are speculated to be molecularly poised to transform owing to a limited number of predisposing mutations. Identifying these pre-leukemic mutations and how they propagate a pre-malignant state has important implications for understanding the etiology of these disorders and for the development of novel therapeutics. NGS studies have found a substantial enrichment for mutations in epigenetic/chromatin remodeling regulators in pre-LSC, and elegant genetic models have confirmed that these mutations can predispose to a variety of hematological malignancies. In this review, we will discuss the current understanding of pre-leukemic biology in myeloid malignancies and how mutations in two key epigenetic regulators, DNMT3A and TET2, may contribute to disease pathogenesis.

In 1999, a 50-year-old woman underwent ventriculoperitoneal (VP) shunt surgery for hydrocephalus after subarachnoid hemorrhage. She was hospitalized for fever and recurrent systemic seizures in November 2006. Head computed tomography (CT) showed only old changes. The seizures and fever were controlled by medicinal therapy. However, in December, her consciousness level suddenly decreased, and she showed progressive lower abdominal distension. Head CT showed marked ventriculomegaly, and abdominal CT showed a giant cystic mass at the shunt-tube tip in the lower abdominal cavity. Because thick pus was aspirated from the intra-abdominal mass, we diagnosed the patient with acute obstructive hydrocephalus due to an infected abdominal pseudocyst. Laparotomy and direct cyst drainage were performed, and antibiotic therapy against Streptococcus, the causative pathogen, was administered. The VP shunt tube was replaced. The postoperative course was uneventful, and postoperative CT showed hydrocephalus improvement and no pseudocyst recurrence. Abdominal pseudocysts, which are rare after VP shunt surgeries, usually occur after the subacute postoperative course in younger cerebral hemorrhagic cases. Our case was quite rare because the cyst developed in the chronic phase in an older patient and was caused by streptococcal infection. The cyst components should be examined before cyst drainage when choosing surgical strategies.

A 54-year-old woman presented to our hospital with progressive motor weakness of the right arm. She had a medical history of systemic lupus erythematosus (SLE) and hypothyroidism. Magnetic resonance imaging indicated a watershed infarction of the left hemisphere. Cervical echogram indicated severe stenosis of the internal carotid artery (ICA) without wall thickening. Cerebral angiography indicated left ICA occlusion, development of unilateral moyamoya vessels, and leptomeningeal anastomosis. Encephaloduroarteriosynangiosis (EDAS) was performed after cerebral 99mTechnetium-ethyl-cysteinate-dimer single-photon emission computed tomography indicated a decreased cerebral blood flow, diminished cerebrovascular perfusion reserve. Motor weakness finally disappeared 6 months after surgery. Moyamoya syndrome is a rare complication of both SLE and hypothyroidism, and the surgical indication remains controversial. By evaluating the decreased cerebral perfusion reserve capacity and the existence of leptomeningeal anastomosis, EDAS could be an efficient method for the treatment of moyamoya syndrome associated with SLE and hypothyroidism.

A 14-year-old was girl admitted to our hospital with a subcutaneous mass of the occipital head. The mass had grown for 6 years, after she had sustained a head injury at the age of 6, and was located directly under a previous wound. Skull X-ray Photograph (xp), computed tomography (CT), and magnetic resonance imaging (MRI) showed a bony defect and cystic changes in the skull corresponding to a subcutaneous mass. Bone scintigraphy revealed partial accumulation. The patient underwent total removal of the skull mass, and the diagnosis from the pathological findings of the cyst wall was fibrous dysplasia (FD). The radiographic findings for cystic cranial FD can be various. Progressive skull disease has been reported to be associated with head trauma, but the relationship between cranial FD and head trauma has not been previously reported. Previous studies have suggested that c-fos gene expression is a key mechanism in injury-induced FD.

Neoculin occurring in the tropical fruit of Curculigo latifolia is currently the only protein that possesses both a sweet taste and a taste-modifying activity of converting sourness into sweetness. Structurally, this protein is a heterodimer consisting of a neoculin acidic subunit (NAS) and a neoculin basic subunit (NBS). Recently, we found that a neoculin variant in which all five histidine residues are replaced with alanine elicits intense sweetness at both neutral and acidic pH but has no taste-modifying activity. To identify the critical histidine residue(s) responsible for this activity, we produced a series of His-to-Ala neoculin variants and evaluated their sweetness levels using cell-based calcium imaging and a human sensory test. Our results suggest that NBS His11 functions as a primary pH sensor for neoculin to elicit taste modification. Neoculin variants with substitutions other than His-to-Ala were further analyzed to clarify the role of the NBS position 11 in the taste-modifying activity. We found that the aromatic character of the amino acid side chain is necessary to elicit the pH-dependent sweetness. Interestingly, since the His-to-Tyr variant is a novel taste-modifying protein with alternative pH sensitivity, the position 11 in NBS can be critical to modulate the pH-dependent activity of neoculin. These findings are important for understanding the pH-sensitive functional changes in proteinaceous ligands in general and the interaction of taste receptor-taste substance in particular.

Cadmium is a known contributing factor for cardiovascular diseases, such as atherosclerosis and hypertension. Although zinc protects against cadmium cytotoxicity in vascular endothelial cells, the detailed mechanisms, especially the differences in the roles of a metal transporter Zrt- and Irt-like protein 8 (ZIP8) and metallothionein (MT), remain unclear. ZIP8 is involved in the uptake of cadmium, whereas MT is induced by and sequesters it. Zinc protects bovine aortic endothelial cells from cadmium cytotoxicity in a culture system in a concentration-dependent manner. Zinc significantly decreased intracellular cadmium accumulation. Cadmium elevated the expression of ZIP8 mRNA, and zinc significantly suppressed this increase in a concentration-dependent manner. However, the expression of MT was not induced by zinc alone but by cadmium; the induction of MT by cadmium was suppressed by zinc at lower concentrations, but intensified by zinc at higher concentrations. However, even when MT induction was strongly suppressed by siRNA-mediated knockdown, cadmium cytotoxicity was reduced by zinc at both lower and higher concentrations. In the absence of zinc, cadmium cytotoxicity was increased by metal response element-binding transcription factor-1 (MTF-1) siRNA-mediated knockdown of MT-1/2. Consequently, it has been suggested that zinc protects the vascular endothelial cells through a concentration-dependent mechanism. Specifically, the decrease in ZIP8 expression is crucially important for the protective effect of zinc at low concentrations against cadmium cytotoxicity in vascular endothelial cells, whereas both the decrease in ZIP8 and the induction of MT contribute to the protection by zinc at high concentrations. [ABSTRACT FROM AUTHOR]

Background and study aims: Although deep vein thrombosis (DVT) and pulmonary embolism (PE) are major postoperative complications, risk of DVT/PE after endoscopic procedures remains unknown. This study aimed to identify risks of DVT/PE after colorectal endoscopic submucosal dissection (ESD) and double-balloon endoscopy (DBE). Patients and methods: Patients who were scheduled to undergo DBE and colorectal ESD were prospectively enrolled in this study. Before enrollment, all patients were confirmed to have no DVT on whole-leg ultrasonography (US) or contrast-enhanced computed tomography (CECT). All patients routinely underwent whole-leg US after ESD or DBE. The primary endpoint was incidence of DVT after colorectal ESD and DBE. The preplanned sample size was 170 patients in the colorectal ESD group and 75 in the DBE group. Results: Between September 2020 and June 2022, 170 patients who had colorectal ESD and 75 who had DBE were recruited for this study; however, 238 patients (ESD, n = 167; DBE, n = 71) were analyzed. Of these 238 patients, DVT occurred in only one patient after colorectal ESD and incidence of DVT was 0.4% (95% confidence interval [CI] 0-1.2) in total, including 0.6% (95% CI 0-1.8) after colorectal ESD and 0% after DBE. Conversely, no PE occurred in the entire cohort. Conclusions: This prospective study demonstrated that risk of DVT/PE following highly invasive endoscopic procedures including colorectal ESD and DBE is very low.