Zebrafish pancreatic ß cell clusters undergo stepwise regeneration using Neurod1-expressing cells from different cell lineages.

Pancreatic ß cell clusters produce insulin and play a central role in glucose homeostasis. The regenerative capacity of mammalian ß cells is limited and the loss of ß cells causes diabetes. In contrast, zebrafish ß cell clusters have a high regenerative capacity, making them an attractive model to study ß cell cluster regeneration. How zebrafish ß cell clusters regenerate, when the regeneration process is complete, and the identification of the cellular source of regeneration are fundamental questions that require investigation. Here, using larval and adult zebrafish, we demonstrate that pancreatic ß cell clusters undergo a two-step regeneration process, regenerating functionality and then ß cell numbers. Additionally, we found that all regenerating pancreatic ß cells arose from Neurod1-expressing cells and that cells from different lineages contribute to both functional and ß cell number recovery throughout their life. Furthermore, we found that during development and neogenesis, as well as regeneration, all ß cells undergo Neurod1expression in zebrafish. Together, these results shed light on the fundamental cellular mechanisms underlying ß cell cluster development, neogenesis, and regeneration.

Nickel particles are present in Crohn's disease tissue and exacerbate intestinal inflammation in IBD susceptible mice.

Crohn's disease is an inflammatory disease of the gut caused by a complex interplay among genetic, microbial, and environmental factors. The intestinal tract is constantly exposed to metals and other trace elements ingested as food. Synchrotron radiation-induced X-ray fluorescence spectroscopy and X-ray absorption fine structure analysis revealed the deposition of nickel particles within Crohn's disease tissue specimens. After nickel particle stimulation, THP-1 cells showed filopodia formation and autophagic vacuoles containing lipid bodies. Nickel particles precipitated colitis in mice bearing mutations of the IBD susceptibility protein A20/TNFAIP3. Nickel particles also exacerbated dextran sulfate sodium-induced colitis in mice harboring myeloid cell-specific Atg5 deficiency. These findings illustrate that nickel particle ingestion may worsen Crohn's disease by perturbing autophagic processes in the intestine, providing new insights into environmental factors in Crohn's disease pathogenesis.

Zranb1-mutant mice display abnormal colonic mucus production and exacerbation of DSS-induced colitis.

Expression of mucin MUC2, a component of the colonic mucus layer, plays a crucial role in intestinal homeostasis. Here, we describe a new regulator of MUC2 expression, the deubiquitinase ZRANB1 (Trabid). A ZRANB1 mutation changing cysteine to serine in amino acid position 443, affects ubiquitination. To analyze ZRANB1 function in the intestine, we generated Zranb1 C443S mutant knock-in (Zranb1C443S/C443S) mice using the CRISPR/Cas9 system. Zranb1C443S/C443S mice exhibited decreased mRNA expression and MUC2 production. Colonic organoids from Zranb1C443S/C443S mice displayed decreased Muc2 mRNA expression following differentiation into goblet cells. Finally, we analyzed dextran sulfate sodium-induced colitis to understand ZRANB1's role in intestinal inflammation. Zranb1C443S/C443S mice with colitis exhibited significant weight loss, reduced colon length, and worsening clinical and pathological scores, indicating that ZRANB1 contributes to intestinal homeostasis. Together, these results suggest that ZRANB1 regulates MUC2 expression and intestinal inflammation, which may help elucidating the pathogenesis of inflammatory bowel disease and developing new therapeutics targeting ZRANB1.

Disruption of the pancreatic vasculature in zebrafish affects islet architecture and function.

A dense local vascular network is crucial for pancreatic endocrine cells to sense metabolites and secrete hormones, and understanding the interactions between the vasculature and the islets may allow for therapeutic modulation in disease conditions. Using live imaging in two models of vascular disruption in zebrafish, we identified two distinct roles for the pancreatic vasculature. At larval stages, expression of a dominant negative version of Vegfaa (dnVegfaa) in ß-cells led to vascular and endocrine cell disruption with a minor impairment in ß-cell function. In contrast, expression of a soluble isoform of Vegf receptor 1 (sFlt1) in ß-cells blocked the formation of the pancreatic vasculature and drastically stunted glucose response, although islet architecture was not affected. Notably, these effects of dnVegfaa or sFlt1 were not observed in animals lacking vegfaa, vegfab, kdrl, kdr or flt1 function, indicating that they interfere with multiple ligands and/or receptors. In adults, disrupted islet architecture persisted in dnVegfaa-expressing animals, whereas sFlt1-expressing animals displayed large sheets of ß-cells along their pancreatic ducts, accompanied by impaired glucose tolerance in both models. Thus, our study reveals novel roles for the vasculature in patterning and function of the islet.

[A Case of Solitary Desmoid Tumor after Laparoscopic Sigmoid Colon Cancer Resection].

A 71-year-old man with pathological Stage Ⅰ(pT1bN0M0)underwent laparoscopic sigmoid colon cancer resection. After 18 months postoperatively, follow-up computed tomography(CT)showed a 30 mm enhanced soft tissue tumor near the anastomotic site. Considering the magnetic resonance imaging(MRI)and positron emission tomography(PET)results, we diagnosed sigmoid colon cancer with local recurrence. Laparoscopic radical resection of the colon and intestine, including the tumor, was performed. Pathologically, the tumor comprised spindle-shaped cells with collagen fibers and was diagnosed as a desmoid tumor by immunostaining(ß-catenin+, c-kit-, CD34-, α-SMA-, and DOG-1-). We report a case of intra-abdominal desmoid tumor near the anastomotic site after laparoscopic sigmoid colon cancer resection.

[A Case of Long-Term Survival without Recurrence following Resection of Hepatic and Pulmonary Metastases of Gastric Cancer].

A 78-year-female underwent distal gastrectomy for gastric cancer. The final diagnosis was moderately differentiated tubular adenocarcinoma, T4a, N2, M0, Stage ⅢB. Four years later, S6 hepatic metastasis and S9 pulmonary metastasis were detected. After 10 courses of S-1 plus oxaliplatin therapy, she received partial hepatectomy(S6). One year after hepatectomy, she underwent partial pulmonary resection for lung metastasis in the left lung(S9). Histopathological findings revealed the lung tumor was a pulmonary metastasis from gastric cancer with a small primary lung adenocarcinoma. There has been no recurrence for 30 months since the last operation.

Nickel ions attenuate autophagy flux and induce transglutaminase 2 (TG2) mediated post-translational modification of SQSTM1/p62.

Nickel, the most frequent contact allergy cause, is widely used for various metallic materials and medical devices. Autophagy is an intracellular protein degradation system and contributes to metal recycling. However, it is unclear the functions of nickel in autophagy. We here demonstrated that NiCl2 induced microtubule-associated protein 1 light chain 3 (LC3)-II and LC3 puncta, markers of autophagosomes. Bafilomycin A1 (BafA1) treatment did not enhance LC3 puncta under NiCl2 stimulation, suggesting that NiCl2 did not induce autophagic flux. In addition, NiCl2 promotes the accumulation of SQSTM1/p62 and increased SQSTM1/p62 colocalization with lysosomal-associated membrane protein 1 (LAMP1). These data indicated that NiCl2 attenuates autophagic flux. Interestingly, NiCl2 induced the expression of the high-molecular-weight (MW) form of SQSTM1/p62. Inhibition of NiCl2-induced reactive oxygen species (ROS) reduced the high-MW SQSTM1/p62. We also showed that NiCl2-induced ROS activate transglutaminase (TG) activity. We found that transglutaminase 2 (TG2) inhibition reduced high-MW SQSTM1/p62 and SQSTM1/p62 puncta under NiCl2 stimulation, indicating that TG2 regulates SQSTM1/p62 protein homeostasis under NiCl2 stimulation. Our study demonstrated that nickel ion regulates autophagy flux and TG2 restricted nickel-dependent proteostasis.

Efficacy and safety of vadadustat compared with darbepoetin alfa in Japanese anemic patients on hemodialysis: a Phase 3, multicenter, randomized, double-blind study.

BACKGROUND: Vadadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis. METHODS: The efficacy and safety of vadadustat, compared with darbepoetin alfa, was determined in a Phase 3 double-blind study in Japanese anemic patients on hemodialysis. Patients receiving erythropoiesis-stimulating agents (ESAs) were randomized and switched to either vadadustat or darbepoetin alfa for 52 weeks. Doses were adjusted to maintain a hemoglobin (Hb) level of 10.0-12.0 g/dL. The primary endpoint was average Hb level at Weeks 20 and 24. RESULTS: Of the 323 randomized patients, 120 and 135 completed the 52-week treatment period in the vadadustat and darbepoetin alfa groups, respectively. The average Hb levels at Weeks 20 and 24 [least square mean (LSM) and 95% confidence interval (CI)] were 10.61 (10.45-10.76) and 10.65 (10.50-10.80) g/dL in the vadadustat and darbepoetin alfa groups, respectively, demonstrating vadadustat's noninferiority to darbepoetin alfa (difference: -0.05 g/dL; 95% CI -0.26 to 0.17). In both groups, the mean Hb levels were maintained within the target range for 52 weeks. Furthermore, irrespective of patient backgrounds, the LSMs of Hb at Week 52 were within the target range. The most common adverse events were nasopharyngitis, diarrhea and shunt stenosis, which occurred at similar frequencies in both groups. No new safety concerns were identified. CONCLUSIONS: Vadadustat was as well-tolerated and effective as darbepoetin alfa in maintaining Hb levels within the target range. The findings suggest that vadadustat can be an alternative to ESA in the management of anemia in Japanese hemodialysis patients receiving ESA (ClinicalTrials.gov, NCT03439137).

Life history of the endangered Japanese striped loach, Cobitis kaibarai (Cypriniformes: Cobitidae), with special reference to its reproductive ecology and the influence of creek reshapings on its population density.

In recent years, the biodiversity of freshwater fishes has been markedly decreasing worldwide because of anthropogenic activities. The Japanese striped loach, Cobitis kaibarai (Cypriniformes: Cobitidae), is a primary freshwater fish endemic to northern Kyushu, Japan. This species is designated as endangered IB class in the Red List by the Japan Ministry of the Environment. Its population is decreasing, possibly because of habitat loss and degradation. To conserve C. kaibarai populations, information on its basic ecology is necessary; nonetheless, its detailed life history and reproductive ecology have yet to be clarified. In this study, the authors conducted monthly capture-mark-recapture surveys and periodical observations to investigate the life history, spawning sites and season of C. kaibarai. They also evaluated the influence of creek reshaping (concrete revetment) on the C. kaibarai population in Saga Plain, northern Kyushu. Between 2015 and 2018, more individuals were captured during winter than summer. The average body width of females peaked in early June and small immatures were confirmed from July. Some individuals were captured across 15 or more months after their initial marking. In the survey of reproductive sites, eggs and larvae of C. kaibarai were found in shallow areas in mid-June; these were temporarily submerged following the increase in water level from early June. Therefore, C. kaibarai spawns in shallow areas during this season. Based on the capture-mark-recapture surveys, the estimated population density of C. kaibarai significantly decreased in a census site that had undergone creek reshaping, which contrasted with the results in a control site, where no significant difference was detected. The standard length of C. kaibarai increased following creek reshaping, suggesting that the proportion of C. kaibarai postponing spawning had increased, possibly because of degradation of spawning environments. The results of this study provide important ecological knowledge for the conservation of C. kaibarai and emphasize the importance of shallow waters for floodplain spawners.

Antitumor activity of cyclin-dependent kinase inhibitor alsterpaullone in Epstein-Barr virus-associated lymphoproliferative disorders.

Epstein-Barr virus (EBV) is a well-established tumor virus that has been implicated in a wide range of immunodeficiency-associated lymphoproliferative disorders (LPDs). Although rituximab, a CD20 mAb, has proven effective against EBV-associated LPDs, prolonged use of this drug could lead to resistance due to the selective expansion of CD20- cells. We have previously shown that cyclin-dependent kinase (CDK) inhibitors are able to specifically suppress the expression of viral late genes, particularly those encoding structural proteins; however, the therapeutic effect of CDK inhibitors against EBV-associated LPDs is not clear. In this study, we examined whether CDK inhibitors confer a therapeutic effect against LPDs in vivo. Treatment with alsterpaullone, an inhibitor of the CDK2 complex, resulted in a survival benefit and suppressed tumor invasion in a mouse model of LPDs. Inhibition of CDK efficiently induced G1 cell cycle arrest and apoptosis in EBV-positive B cells. These results suggest that alsterpaullone suppresses cell cycle progression, resulting in the antitumor effect observed in vivo.

Characterization of methyl-accepting chemotaxis proteins (MCPs) for amino acids in plant-growth-promoting rhizobacterium Pseudomonas protegens CHA0 and enhancement of amino acid chemotaxis by MCP genes overexpression.

Pseudomonas protegens CHA0, known as plant-growth-promoting rhizobacterium, showed positive chemotactic responses toward proteinaceous L-amino acids. Genomic analysis revealed that P. protegens CHA0 possesses four putative chemoreceptors for amino acids (designated CtaA, CtaB, CtaC, and CtaD, respectively). Pseudomonas aeruginosa PCT2, a mutant defective in chemotaxis to amino acids, harboring a plasmid containing each of ctaA, ctaB, ctaC, and ctaD showed chemotactic responses to 20, 4, 4, and 11 types of amino acids, respectively. To enhance chemotaxis toward amino acids, we introduced the plasmids containing ctaA, ctaB, ctaC, or ctaD into P. protegens CHA0. By overexpression of the genes, we succeeded in enhancing chemotaxis toward more than half of the tested ligands. However, unexpectedly, the P. protegens CHA0 transformants showed unchanged or decreased responses to some amino acids when compared to wild-type CHA0. We speculate that alternation of expression of a chemoreceptor may affect the abundance of other chemoreceptors. ABBREVIATIONS: cDNA: complementary DNA; LBD: ligand-binding domain; MCP: methyl-accepting chemotaxis protein; PDC: PhoQ/DcuS/CitA; PGPR: plant-growth-promoting rhizobacteria; qRT-PCR: quantitative reverse transcription PCR.

The Survival Benefit of a Novel Trauma Workflow that Includes Immediate Whole-body Computed Tomography, Surgery, and Interventional Radiology, All in One Trauma Resuscitation Room: A Retrospective Historical Control Study.

OBJECTIVE: The aim of this study was to evaluate the impact of a novel trauma workflow, using an interventional radiology (IVR)-computed tomography (CT) system in severe trauma. BACKGROUND: In August 2011, we installed an IVR-CT system in our trauma resuscitation room. We named it the Hybrid emergency room (ER), as it enabled us to perform all examinations and treatments required for trauma in a single place. METHODS: This retrospective historical control study conducted in Japan included consecutive severe (injury severity score ≥16) blunt trauma patients. Patients were divided into 2 groups: Conventional (from August 2007 to July 2011) or Hybrid ER (from August 2011 to July 2015). We set the primary endpoint as 28-day mortality. The secondary endpoints included cause of death and time course from arrival to start of CT and surgery. Multivariable logistic regression analysis adjusted for clinically important variables was performed to evaluate the clinical outcomes. RESULTS: We included 696 patients: 360 in the Conventional group and 336 in the Hybrid ER group. The Hybrid ER group was significantly associated with decreased mortality [adjusted odds ratio (OR), 0.50 (95% confidence interval, 95% CI, 0.29-0.85); P = 0.011] and reduced deaths from exsanguination [0.17 (0.06-0.47); P = 0.001]. The time to CT initiation [Conventional 26 (21 to 32) minutes vs Hybrid ER 11 (8 to 16) minutes; P < 0.0001] and emergency procedure [68 (51 to 85) minutes vs 47 (37 to 57) minutes; P < 0.0001] were both shorter in the Hybrid ER group. CONCLUSION: This novel trauma workflow, comprising immediate CT diagnosis and rapid bleeding control without patient transfer, as realized in the Hybrid ER, may improve mortality in severe trauma.

Ubiquitin ligase HMG-CoA reductase degradation 1 (HRD1) prevents cell death in a cellular model of Parkinson's disease.

Endoplasmic reticulum (ER) stress may play a role in the etiology of Parkinson's disease (PD). We have previously reported that ubiquitin ligase 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase degradation 1 (HRD1) involved in ER stress degrades unfolded protein that accumulates in the ER due to loss of function of Parkin, which is a causative factor in familial PD. We have also demonstrated that cell death is suppressed by the degradation of unfolded proteins. These findings indicate that HRD1 may serve as a compensatory mechanism for the loss of function of Parkin in familial PD patients. However, the role of HRD1 in sporadic PD has not yet been identified. This study aimed to reveal the roles of HRD1 and associated molecules in a cellular model of PD. We demonstrated that expressions of HRD1 and Suppressor/Enhancer Lin12 1-like (SEL1L: a HRD1 stabilizer) increased in SH-SY5Y human neuroblastoma cells upon exposure to 6-hydroxydopamine (6-OHDA). The 6-OHDA-induced cell death was suppressed in cells overexpressing wt-HRD1, whereas cell death was enhanced in cells with knockdown of HRD1 expression. These results suggest that HRD1 is a key molecule involved in 6-OHDA-induced cell death. By contrast, suppression of SEL1L expression decreased the amount of HRD1 protein. As a result, 6-OHDA-induced cell death was enhanced in cells suppressing SEL1L expression, and this cell death was much more evident than that in cells with suppression of HRD1 expression. These findings strongly indicate that SEL1L is necessary for maintaining and stabilizing the amount of HRD1 protein, and stabilizing the amount of HRD1 protein through SEL1L may serve to protect against 6-OHDA-induced cell death. Furthermore, the expression of Parkin was reinforced when HRD1 mRNA had been suppressed in cells, but was not observed when SEL1L mRNA had been restrained. It is possible that Parkin expression is induced as a compensatory mechanism when HRD1 mRNA decreases. This intracellular transduction may suppress the enhancement of 6-OHDA-induced cell death caused by the loss of HRD1. Taken together with these results, it is suggested that HRD1 and its stabilizer (SEL1L) are key molecules for elucidating the pathogenesis and treatment of PD.

Zebrafish as a model for studying functional pancreatic ß cells development and regeneration.

Pancreatic ß cells produce insulin and play a central role in glucose homeostasis. The regenerative capacity of mammalian ß cells is limited, so that loss and dysfunction of ß cells causes diabetes. Zebrafish have a pancreas which is functionally and morphologically conserved with human pancreas. Zebrafish have high regenerative capacity of islets. In the present review, development of zebrafish pancreas was described in comparison to that of mammals, and the regenerative process of zebrafish pancreas was also described. This review will give information on understanding islet and pancreatic ß cell development and regeneration and provide possibilities of zebrafish research for developing new diabetic therapies and regenerative medicines.

Successful multimodal therapy for the metastasis of ascending colon after curative resection of esophageal cancer: a case report with long-term survival.

Solitary colonic metastasis from esophageal cancer is rare. The prognosis of patients with distant metastases from esophageal cancer is extremely poor. A case of long-term survival with colonic metastasis from esophageal cancer treated by multimodal therapy is reported. A 67-year-old man was diagnosed with middle thoracic esophageal squamous cell carcinoma. The patient received neoadjuvant chemotherapy and then underwent subtotal esophagectomy. Approximately 1 year after esophagectomy, an asymptomatic, solitary colonic mass was detected on the follow-up computed tomography for esophageal cancer. Preoperative colonoscopy showed a 5-cm type 3 tumor at the ascending colon, and histological findings of the biopsy specimen indicated possible metastasis from primary esophageal squamous cell carcinoma. The patient underwent laparoscopic ileocolic resection with D3 lymph noddle dissection. Histologically, the colonic tumor was confirmed to be a metastasis from the esophageal squamous cell carcinoma. To the best of our knowledge, only eight cases with resected solitary colonic metastasis, including the present case, have been reported, and the present patient achieved greater than 3-year survival after esophagectomy. Resection of an asymptomatic solitary organ metastasis from primary esophageal cancer appears to be a good therapeutic option, even following esophagectomy.

Impact of Pretreatment Systemic Inflammatory Markers on Treatment Persistence with Biologics and Conventional Systemic Therapy: A Retrospective Study of Patients with Psoriasis Vulgaris and Psoriatic Arthritis.

Systemic inflammation plays a central role in the pathophysiology of psoriasis. This study examined accessible systemic inflammatory markers in patients with psoriasis vulgaris and psoriatic arthritis. We aimed to evaluate their association with psoriasis severity, the presence of arthritis, and drug continuation rates. The findings revealed that neutrophil, monocyte, and platelet count, neutrophil/lymphocyte ratio, monocyte/lymphocyte ratio, systemic inflammation response index, systemic immune/inflammation index (SII), and CRP were positively correlated with Psoriasis Area and Severity Index scores. Patients presenting with higher platelet/lymphocyte ratio (PLR) or CRP values were more likely to be diagnosed with psoriatic arthritis than with psoriasis vulgaris in the multivariate regression analysis. Importantly, patients with higher pretreatment neutrophil or platelet count, PLR, and SII were associated with lower treatment continuation rates of conventional systemic agents. Higher pretreatment scores of systemic inflammatory markers did not affect treatment retention rates of biologics. These findings suggest that several accessible systemic inflammatory markers may effectively assess underlying systemic inflammation and may provide an indication for a therapeutic approach in patients with psoriasis vulgaris and psoriatic arthritis.

Dietary habits in Japanese patients with bullous pemphigoid: low intake of retinol.

BACKGROUND: Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease. Dietary habits may modulate the pathogenesis of BP. OBJECTIVES: We evaluated dietary habits in Japanese patients with BP and compared their results to those of age- and sex-matched healthy controls. We also examined the relationship between dietary habits versus IgG anti-BP180NC16A antibody or parameters of BP disease area index (BPDAI); cutaneous blisters/erosions, cutaneous urticaria/erythema, and mucosal blisters/erosions. MATERIALS & METHODS: Dietary habits were assessed by the validated, Brief-type self-administered Diet History Questionnaire. Severity of disease was assessed with BPDAI. RESULTS: Patients with BP showed a lower intake of retinol (vitamin A1) and beverages, and a higher intake of seasoning/spices, compared to controls. The bivariate and multivariable logistic regression analysis showed that BP was associated with a low intake of retinol and beverages. There were no significant correlations between IgG anti-BP180NC16A antibody levels and intake of nutrients/foods. The BPDAI score for cutaneous blisters/erosions significantly positively correlated with intake of carbohydrate and negatively with intake of retinol, vitamin A, animal fat, cholesterol, phosphorus, and vitamin B2. The BPDAI score for cutaneous urticaria/erythema significantly negatively correlated with intake of vitamin A. BP patients with mucosal blisters/erosions had a higher intake of cholesterol, n-6 polyunsaturated fatty acid, and eggs, and lower intake of seasoning/spices, compared to patients without BP. CONCLUSION: The supplementation of vitamin A might have prophylactic and/or therapeutic effects on BP.

Heme protein identified from scaly-foot gastropod can synthesize pyrite (FeS2) nanoparticles.

The scaly-foot gastropod (Chrysomallon squamiferum), which lives in the deep-sea zone of oceans around thermal vents, has a black shell and scales on the foot. Both the black shell and scales contain iron sulfide minerals such as greigite (Fe3S4) and pyrite (FeS2). Although pyrite nanoparticles can be used as materials for solar panels, it is difficult to synthesize stable and spherical nanoparticles in vitro. In this study, we extracted organic molecules that interact with nano-pyrite from the shell of the scaly-foot gastropod to develop a low-cost, eco-friendly method for pyrite nanoparticles synthesis. Myoglobin (csMG), a heme protein, was identified in the iron sulfide layer of the shell. We purified recombinant csMG (r-csMG) and demonstrated that r-csMG helped in the conversion of ferric ions, sulfide ions and sulfur into spherical shaped pyrite nanoparticles at 80°C. To reduce the effort and cost of production, we showed that commercially available myoglobin from Equus caballus (ecMG) also induced the in vitro synthesis of pyrite nanoparticles. Using structure-function experiments with digested peptides, we highlighted that the amino acid sequence of r-csMG peptides controlled the spherical shape of the nanoparticle while the hemin molecules, which the peptides interacted with, maintained the size of nanoparticles. Synthesized pyrite nanoparticles exhibited strong photoluminescence in the visible wavelength region, suggesting its potential application as a photovoltaic solar cell material. These results suggest that materials for solar cells can be produced at low cost and energy under eco-friendly conditions. STATEMENT OF SIGNIFICANCE: Pyrite is a highly promising material for photovoltaic devices because of its excellent optical, electrical, magnetic, and transport properties and high optical absorption coefficient. Almost all current pyrite synthesis methods use organic solvents at high temperature and pressure under reducing conditions. Synthesized pyrite nanoparticles are unstable and are difficult to use in devices. The scaly-foot gastropod can synthesize pyrite nanoparticles in vivo, meaning that pyrite nanoparticles can be generated in an aqueous environment at low temperature. In this study, we demonstrated the synthesis of pyrite nanoparticles using a heme protein identified in the iron sulfide layer of the scaly-foot gastropod shell. These results exemplify how natural products in organisms can inspire the innovation of new technology.

Terrestrial arthropods broadly possess endogenous phytohormones auxin and cytokinins.

Some herbivorous insects possess the ability to synthesize phytohormones and are considered to use them for manipulating their host plants, but how these insects acquired the ability remains unclear. We investigated endogenous levels of auxin (IAA) and cytokinins (iP and tZ), including their ribosides (iPR and tZR), in various terrestrial arthropod taxa. Surprisingly, IAA was detected in all arthropods analysed. In contrast, tZ and/or tZR was detected only in some taxa. Endogenous levels of IAA were not significantly different among groups with different feeding habits, but gall inducers possessed significantly higher levels of iPR, tZ and tZR. Ancestral state reconstruction of the ability to synthesize tZ and tZR revealed that the trait has only been acquired in taxa containing gall inducers. Our results strongly suggest critical role of the cytokinin synthetic ability in the evolution of gall-inducing habit and IAA has some function in arthropods.

A giant esophageal liposarcoma radically resected by the cervical approach: a case report.

Primary esophageal liposarcoma is an extremely rare malignancy, whereas liposarcoma is one of the most common soft tissue sarcomas, which develop mainly in the soft tissues of the extremities and retroperitoneum. A rare case of giant esophageal liposarcoma that originated from the cervical esophagus that was successfully excised by a cervical approach is reported. A 72-year-old woman presented with difficulty swallowing for 6 months. Esophagogastroduodenoscopy showed a pedunculated esophageal submucosal tumor arising just below the pyriform fossa in the esophagus. Contrast-enhanced computed tomography showed a giant, heterogeneous, intraluminal esophageal tumor from the cervical esophagus to the upper thoracic esophagus for approximately 17 cm. Based on the imaging findings, an esophageal liposarcoma was suspected. Since the symptom of dysphagia was gradually worsening, surgical treatment was planned. The giant esophageal tumor was successful resected through a cervical approach without either thoracotomy or laparotomy. The patient's postoperative course was uneventful, and she was discharged on day 15 after surgery. The histopathological and immunohistological findings showed well-differentiated esophageal liposarcoma, 15 × 7 × 5 cm in size. A cervical approach is an appropriate option for a tumor that developed at the cervical esophagus as a minimally invasive surgical technique.