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Immune checkpoint inhibitors (ICIs) are effective against many advanced malignancies. However, many patients are nonresponders to immunotherapy, and overcoming this resistance to treatment is important. Boron neutron capture therapy (BNCT) is a local chemoradiation therapy with the combination of boron drugs that accumulate selectively in cancer and the neutron irradiation of the cancer site. Here, we report the first boron neutron immunotherapy (B-NIT), combining BNCT and ICI immunotherapy, which was performed on a radioresistant and immunotherapy-resistant advanced-stage B16F10 melanoma mouse model. The BNCT group showed localized tumor suppression, but the anti-PD-1 antibody immunotherapy group did not show tumor suppression. Only the B-NIT group showed strong tumor growth inhibition at both BNCT-treated and shielded distant sites. Intratumoral CD8+ T-cell infiltration and serum high mobility group box 1 (HMGB1) levels were higher in the B-NIT group. Analysis of CD8+ T cells in tumor-infiltrating lymphocytes (TILs) showed that CD62L- CD44+ effector memory T cells and CD69+ early-activated T cells were predominantly increased in the B-NIT group. Administration of CD8-depleting mAb to the B-NIT group completely suppressed the augmented therapeutic effects. This indicated that B-NIT has a potent immune-induced abscopal effect, directly destroying tumors with BNCT, inducing antigen-spreading effects, and protecting normal tissue. B-NIT, immunotherapy combined with BNCT, is the first treatment to overcome immunotherapy resistance in malignant melanoma. In the future, as its therapeutic efficacy is demonstrated not only in melanoma but also in other immunotherapy-resistant malignancies, B-NIT can become a new treatment candidate for advanced-stage cancers.
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PURPOSE: Glioblastoma is a malignant brain tumor with a poor prognosis. Genetic mutations associated with this disease are complex are not fully understood and require further elucidation for the development of new treatments. The purpose of this study was to comprehensively analyze genetic mutations in glioblastomas and evaluate the usefulness of RNA sequencing. PATIENTS AND METHODS: We analyzed 42 glioblastoma specimens that were resected in routine clinical practice and found wild-type variants of the IDH1 and IDH2 genes. RNA was extracted from frozen specimens and sequenced, and genetic analyses were performed using the CLC Genomics Workbench. RESULTS: The most common genetic alterations in the 42 glioblastoma specimens were TP53 mutation (28.6%), EGFR splicing variant (16.7%), EGFR mutation (9.5%), and FGFR3 fusion (9.5%). Novel genetic mutations were detected in 8 patients (19%). In 12 cases (28.6%), driver gene mutations were not detected, suggesting an association with PPP1R14A overexpression. Our findings suggest the transcription factors SOX10 and NKX6-2 are potential markers in glioblastoma. CONCLUSION: RNA sequencing is a promising approach for genotyping glioblastomas because it provides comprehensive information on gene expression and is relatively cost-effective.
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Neoplasias Encefálicas , Glioblastoma , Isocitrato Deshidrogenasa , Mutación , Humanos , Glioblastoma/genética , Isocitrato Deshidrogenasa/genética , Masculino , Femenino , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Persona de Mediana Edad , Anciano , Adulto , Análisis de Secuencia de ARN/métodos , Biomarcadores de Tumor/genética , Genómica/métodos , Adulto Joven , Anciano de 80 o más Años , PronósticoRESUMEN
INTRODUCTION: Diffuse hemispheric glioma, H3 G34-mutant (DHGs), is a newly categorized tumor in pediatric-type diffuse high-grade gliomas, World Health Organization grade 4, with a poor prognosis. Although prognostic factors associated with genetic abnormalities have been reported, few reports have examined the clinical presentation of DHGs, especially from the viewpoint of imaging findings. In this study, we investigated the relationship between clinical factors, including imaging findings, and prognosis in patients with DHGs. METHODS: We searched Medline through the PubMed database using two search terms: "G34" and "glioma", between 1 April 2012 and 1 July 2023. We retrieved articles that described imaging findings and overall survival (OS), and added one DHG case from our institution. We defined midline invasion (MI) as invasion to the contralateral cerebrum, brainstem, corpus callosum, thalamus, and basal ganglia on magnetic resonance imaging. The primary outcome was 12-month survival, estimated using Kaplan-Meier curves and logistic regression. RESULTS: A total of 96 patients were included in this study. The median age was 22 years, and the proportion of male patients was 48.4%. Lesions were most frequently located in the frontal lobe (52.6%). MI was positive in 39.6% of all patients. The median OS was 14.4 months. Univariate logistic regression analysis revealed that OS was significantly worse in the MI-positive group compared with the MI-negative group. Multivariate logistic regression analysis revealed that MI was an independent prognostic factor in DHGs. CONCLUSIONS: In this study, MI-positive cases had a worse prognosis compared with MI-negative cases. PREVIOUS PRESENTATIONS: No portion of this study has been presented or published previously.
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Neoplasias Encefálicas , Glioma , Humanos , Masculino , Niño , Adulto Joven , Adulto , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Histonas/genética , Mutación , Glioma/diagnóstico por imagen , Glioma/genética , PronósticoRESUMEN
Type-A aortic dissection is an acute injury involving the delamination of the aorta at the parts of the aortic media. Aldehyde crosslinker-containing glues have been used to adhere to the media of the dissected aorta before joining an artificial graft. These glues effectively adhere to the aortic media; however, they show low biocompatibility due to the release of aldehyde compounds. In this study, we report innovative adhesives based on hydrophobically modified Alaska pollock gelatin (hm-ApGltn) with different alkyl or cholesteryl (Chol) groups that adhere to the media of the dissected aorta by combining hm-ApGltns with a biocompatible crosslinker, pentaerythritol poly(ethylene glycol) ether tetrasuccinimidyl glutarate. The modification of alkyl or Chol groups contributed to enhanced adhesion strength between porcine aortic media. The adhesion strength increased with increasing modification ratios of alkyl groups from propanoyl to dodecanoyl groups and then decreased at a modification ratio of ~20 mol %. Porcine aortic media adhered using 7.5Chol-ApGltn adhesive showed stretchability even when expanded and shrunk vertically by 25% at least five times. Hm-ApGltn adhesives subcutaneously injected into the backs of mice showed no severe inflammation and were degraded during the implantation period. These results indicated that hm-ApGltn adhesives have potential applications in type-A aortic dissection.
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Disección Aórtica , Gelatina , Glutaratos , Polietilenglicoles , Animales , Ratones , Porcinos , Gelatina/farmacología , Alaska , Aorta , Adherencias Tisulares , AldehídosRESUMEN
Although high-dose methotrexate (HD-MTX) is the standard therapy for primary central nervous system lymphoma (PCNSL), the prognosis remains poor. Because 90% of PCNSL is diffuse large B-cell lymphoma (DLBCL), chimeric antigen receptor (CAR)-T cell therapy is expected to be beneficial. However, there are limited reports on CAR-T cell therapy for PCNSL because of the concern of neurotoxicity. Here, we report a case of relapsed PCNSL treated with anti-CD19 CAR-T cell therapy. A 40-year-old woman presenting with visual disturbance in her left eye was initially diagnosed with bilateral uveitis. Her histological diagnosis was DLBCL, and she was positive for CD19. Although she received chemotherapy including HD-MTX, the tumor relapsed in her right occipital lobe. She underwent remission induction therapy and then anti-CD19 CAR-T cell therapy. Cytokine release syndrome (CRS) grade 2 occurred, but there were no complications of CAR-T cell-related encephalopathy syndrome (CRES). She has achieved complete response for more than 1 year. Anti-CD19 CAR-T cell therapy is a revolutionary immunotherapy for treating relapsed or refractory (R/R) B lineage malignancies. Although there are concerns regarding CRS and CRES in central nervous system lymphoma, the use of anti-CD19 CAR-T cells to treat R/R PCNSL is safe and feasible.
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PURPOSE: Pilocytic astrocytoma (PA) is a circumscribed low-grade astrocytic glioma, generally considered to be associated with a good prognosis. However, a subset of PA patients shows unfavorable outcomes. In this study, we retrospectively reviewed PA patients and performed further molecular analysis, such as DNA methylation profiling, to identify prognostic factors. METHODS: We analyzed 29 histologically-confirmed PA patients from a single center from 2002 to 2021 and conducted integrated molecular analyses among elderly PA patients since age was an independent prognostic factor for poor outcomes. RESULTS: The median age at diagnosis was 14 years (range 3-82 years) and 4 patients (14%) were elderly (patients ≥ 60 years old). Age over 60 was associated with poor progression-free survival and overall survival. We performed DNA methylation analysis on 2 of the 4 elderly patients. Both cases were histologically diagnosed as PA, but DNA methylation profiling revealed one as high-grade astrocytoma with piloid features (all methylation class scores were below 0.3 in both v11b4 and v12.5) and the other as glioblastoma, IDH-wildtype (score was over 0.5 in both v11b4 and v12.5), using the German Cancer Research Center methylation profiling classifiers and t-SNE analysis. CONCLUSIONS: Elderly patients with PA morphology showed unfavorable outcomes in this cohort. In those patients, further molecular analysis and DNA methylation profiling revealed the possibility of high-grade astrocytic tumors, including newly defined entities.
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Astrocitoma , Neoplasias Encefálicas , Humanos , Anciano , Preescolar , Niño , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano de 80 o más Años , Metilación de ADN , Estudios Retrospectivos , Neoplasias Encefálicas/patología , Mutación , Astrocitoma/patología , Isocitrato Deshidrogenasa/genéticaRESUMEN
We developed a new cranioplasty method that utilizes artificial bone made of ultra-high-molecular-weight polyethylene, with a wedge-shaped edge (UHMWPE Wing). This study shows the methods and data of case series and finite element analyses with the UHMWPE Wing. A circumferential wing was preoperatively designed for a custom-made artificial bone made of UHMWPE to achieve high fixed power and to minimize the usage of cranial implants. Here, we present 4 years of follow-up data and finite element analyses for patients treated with the UHMWPE Wing between February 2015 and February 2019. Eighteen consecutive patients underwent cranioplasty using our UHMWPE Wing design. There were no postoperative adverse events in 17 of the patients for at least 18 months. One case of hydrocephalus experienced screw loosening and graft uplift due to shunt malfunction. Placement of a ventriculo-peritoneal shunt immediately returned the artificial bone to normal position. Finite element analyses revealed that a model using the UHMWPE Wing had the highest withstand load and lowest deformation. This is the first report on the UHMWPE Wing method. This method may enable clinicians to minimize dead space and achieve high strength in cranioplasty.
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Polietilenos , Prótesis e Implantes , Animales , Análisis de Elementos Finitos , HumanosRESUMEN
Postoperative adhesion can lead to an increase in the number of surgeries required, longer operation times, and high medical costs, resulting in the quality of life of the patient being lowered. To address these clinical problems, we developed a surgical sealant with anti-adhesion properties for the prevention of postoperative adhesion following application to the large intestine surface. The developed sealant was composed of octyl (C8) group-modified Alaska pollock-derived gelatin (C8-ApGltn) and a poly(ethylene)glycol-based 4-armed crosslinker (4S-PEG) (C8-ApGltn/4S-PEG sealant). Hydrophobic modification of the ApGltn molecule with C8 groups effectively enhanced both the burst strength on the large intestine surface and the bulk modulus. An in vitro anti-adhesion test indicated that cured C8-ApGltn/4S-PEG sealant adhered to the large intestine surface showed low adhesive strength compared with commercial anti-adhesion film. Besides, cured C8-ApGltn/4S-PEG sealant effectively inhibited albumin permeation and penetration of L929 fibroblasts. In vivo experiments using a rat peritoneal anti-adhesion model showed that C8-ApGltn/4S-PEG sealant acted as a sealing barrier on the target cecum surface and also provided an anti-adhesion barrier to prevent postoperative adhesion between the peritoneum and cecum. C8-ApGltn/4S-PEG sealant showed sufficient cytocompatibility and biodegradability and therefore has potential for use in gastroenterological surgery.
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Gelatina , Adhesivos Tisulares , Alaska , Animales , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Calidad de Vida , Ratas , Adhesivos Tisulares/farmacologíaRESUMEN
We find that the use of Au substrate allows fast, self-limited WS2 monolayer growth using a simple sequential exposure pattern of low cost, low toxicity precursors, namely tungsten hexacarbonyl and dimethylsulfide (DMS). We use this model reaction system to fingerprint the technologically important metal organic chemical vapour deposition process by operando X-ray photoelectron spectroscopy (XPS) to address the current lack of understanding of the underlying fundamental growth mechanisms for WS2 and related transition metal dichalcogenides. Au effectively promotes the sulfidation of W with simple organosulfides, enabling WS2 growth with low DMS pressure (<1 mbar) and a suppression of carbon contamination of as-grown WS2, which to date has been a major challenge with this precursor chemistry. Full WS2 coverage can be achieved by one exposure cycle of 10 minutes at 700 °C. We discuss our findings in the wider context of previous literature on heterogeneous catalysis, 2D crystal growth, and overlapping process technologies such as atomic layer deposition (ALD) and direct metal conversion, linking to future integrated manufacturing processes for transition metal dichalcogenide layers.
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The mitogen-activated protein kinase (MAPK) pathways are involved in many cellular processes, including the development of fibrosis. Here, we examined the role of Sprouty-related EVH-1-domain-containing protein (Spred) 2, a negative regulator of the MAPK-ERK pathway, in the development of bleomycin (BLM)-induced pulmonary fibrosis (PF). Compared to WT mice, Spred2-/- mice developed milder PF with increased proliferation of bronchial epithelial cells. Spred2-/- lung epithelial cells or MLE-12 cells treated with spred2 siRNA proliferated faster than control cells in vitro. Spred2-/- and WT macrophages produced similar levels of TNFα and MCP-1 in response to BLM or lipopolysaccharide and myeloid cell-specific deletion of Spred2 in mice had no effect. Spred2-/- fibroblasts proliferated faster and produced similar levels of MCP-1 compared to WT fibroblasts. Spred2 mRNA was almost exclusively detected in bronchial epithelial cells of naïve WT mice and it accumulated in approximately 50% of cells with a characteristic of Clara cells, 14 days after BLM treatment. These results suggest that Spred2 is involved in the regulation of tissue repair after BLM-induced lung injury and increased proliferation of lung bronchial cells in Spred2-/- mice may contribute to faster tissue repair. Thus, Spred2 may present a new therapeutic target for the treatment of PF.
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Bleomicina/farmacología , Proliferación Celular/fisiología , Células Epiteliales/metabolismo , Pulmón/metabolismo , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/metabolismo , Proteínas Represoras/metabolismo , Animales , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Células Epiteliales/efectos de los fármacos , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Lipopolisacáridos/metabolismo , Pulmón/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/fisiología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratones , Ratones Endogámicos C57BL , Células Mieloides/efectos de los fármacos , Células Mieloides/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Future changes in tropical cyclone properties are an important component of climate change impacts and risk for many tropical and midlatitude countries. In this study we assess the performance of a multimodel ensemble of climate models, at resolutions ranging from 250 to 25 km. We use a common experimental design including both atmosphere-only and coupled simulations run over the period 1950-2050, with two tracking algorithms applied uniformly across the models. There are overall improvements in tropical cyclone frequency, spatial distribution, and intensity in models at 25 km resolution, with several of them able to represent very intense storms. Projected tropical cyclone activity by 2050 generally declines in the South Indian Ocean, while changes in other ocean basins are more uncertain and sensitive to both tracking algorithm and imposed forcings. Coupled models with smaller biases suggest a slight increase in average TC 10 m wind speeds by 2050.
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The locally accumulated damage by tropical cyclones (TCs) can intensify substantially when these cyclones move more slowly. While some observational evidence suggests that TC motion might have slowed significantly since the mid-20th century (1), the robustness of the observed trend and its relation to anthropogenic warming have not been firmly established (2-4). Using large-ensemble simulations that directly simulate TC activity, we show that future anthropogenic warming can lead to a robust slowing of TC motion, particularly in the midlatitudes. The slowdown there is related to a poleward shift of the midlatitude westerlies, which has been projected by various climate models. Although the model's simulation of historical TC motion trends suggests that the attribution of the observed trends of TC motion to anthropogenic forcings remains uncertain, our findings suggest that 21st-century anthropogenic warming could decelerate TC motion near populated midlatitude regions in Asia and North America, potentially compounding future TC-related damages.
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Slow-moving tropical cyclones (TCs) can cause heavy rain because of their duration of influence. Combined with expected increase in rain rates associated with TCs in a warmer climate, there is growing interest in TC translation speed in the past and future. Here we present that a slowdown trend of the translation speed is not simulated for the period 1951-2011 based on historical model simulations. We also find that the annual-mean translation speed could increase under global warming. Although previous studies show large uncertainties in the future projections of TC characteristics, our model simulations show that the average TC translation speed at higher latitudes becomes smaller in a warmer climate, but the relative frequency of TCs at higher latitudes increases. Since the translation speed is much larger in the extratropics, the increase in the relative frequency of TCs at higher latitudes compensates the reduction of the translation speed there, leading to a global mean increase in TC translation speed.
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Hexagonal boron nitride (h-BN) is a 2D, wide band gap semiconductor that has recently been shown to display bright room-temperature emission in the visible region, sparking immense interest in the material for use in quantum applications. In this work, we study highly crystalline, single atomic layers of chemical vapor deposition grown h-BN and find predominantly one type of emissive state. Using a multidimensional super-resolution fluorescence microscopy technique we simultaneously measure spatial position, intensity, and spectral properties of the emitters, as they are exposed to continuous wave illumination over minutes. As well as low emitter heterogeneity, we observe inhomogeneous broadening of emitter line-widths and power law dependency in fluorescence intermittency; this is strikingly similar to previous work on quantum dots. These results show that high control over h-BN growth and treatment can produce a narrow distribution of emitter type and that surface interactions heavily influence the photodynamics. Furthermore, we highlight the utility of spectrally resolved wide-field microscopy in the study of optically active excitations in atomically thin two-dimensional materials.
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To fabricate a soft-tissue adhesion surface by nanostructural control and functional modification, we prepared bio-inspired adhesive surfaces composed of hexanoyl group-modified gelatin (HxGltn) and silicon nanowire (SiNW). We synthesized the HxGltn with different modification ratios of 27 mol% (27HxGltn), 37 mol% (37HxGltn), and 50 mol% (50HxGltn) and processed two different types of SiNW plates (800 pitch and 1500 pitch) with 1400 nm in height and 400 nm in diameter (800/1400 SiNW and 1500/1400 SiNW, respectively. To enhance the adhesion to the intestine surface, we covalently immobilized HxGltn on the surface of SiNW plates. A significant increase in bonding strength was not observed when Gltn-, 27HxGltn-immobilized 800/1400 SiNW, and Gltn-, 27HxGltn, 37HxGltn, 50HxGltn-immobilized 1500/1400 SiNW were used. Furthermore, 37HxGltn- and 50HxGltn-immobilized 800/1400 SiNW only showed 5-fold higher bonding strength to intestine tissue compared with other samples. These 37HxGltn- and 50HxGltn-immobilized 800/1400 SiNW surfaces had potential for the application of soft tissue adhesion.
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Gelatina/química , Nanocables/química , Silicio/química , Adhesivos Tisulares/químicaRESUMEN
Hemorrhaging often occurs during cardiac surgery, and postoperative bleeding is associated with medical complications or even death. Medical complications resulting from hemorrhaging can lead to longer hospital stays, thus increasing costs. Hemostatic agents are the main treatment for bleeding. In the present study, hemostatic agents composed of aldehyde groups and hydrophobically modified with hyaluronic acid (ald-hm-HyA) and hydrophobically modified gelatin (hm-ApGltn) were developed and their hemostatic effects were evaluated. These modified hemostatic agents formed more stable blood clots compared with the nonhydrophobically modified HyA-based hemostatic agent. The bulk strength of the whole blood clot using the aldehyde and stearoyl group-modified hyaluronic acid (ald-C18-HyA)/hm-ApGltn-based hemostatic agent was higher than that of the aldehyde group only modified HyA (ald-HyA)/hm-ApGltn-based hemostatic agent. Rheological experiments using α-cyclodextrin showed that hydrophobic modification of HyA with C18 groups effectively enhanced anchoring to the red blood cell surface. Therefore, the ald-hm-HyA/hm-ApGltn-based hemostatic agent has potential applications in cardiac surgery.
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Gelatina/química , Geles/química , Hemostáticos/química , Ácido Hialurónico/análogos & derivados , Gelatina/síntesis química , Gelatina/farmacología , Geles/síntesis química , Geles/farmacología , Hemostasis/efectos de los fármacos , Hemostáticos/síntesis química , Hemostáticos/farmacología , Humanos , Ácido Hialurónico/síntesis química , Ácido Hialurónico/farmacología , Interacciones Hidrofóbicas e Hidrofílicas , Ensayo de Materiales , ReologíaRESUMEN
Although many ecological properties of species respond to climate change, their evolutionary responses are poorly understood. Here, we use data from long-term demographic studies to predict evolutionary responses of three herbaceous perennial orchid species, Cypripedium parviflorum, C. candidum and Ophrys sphegodes, to predicted climate changes in the habitats they occupy. We focus on the evolution of sprouting probability, because all three species exhibit long-term vegetative dormancy, i.e. individual plants may not emerge above-ground, potentially for several consecutive years. The drivers of all major vital rates for populations of the species were analysed with general linear mixed models (GLMMs). High-dimensionality function-based matrix projection models were then developed to serve as core elements of deterministic and stochastic adaptive dynamics models used to analyse the adaptive context of sprouting in all populations. We then used regional climate forecasts, derived from high-resolution general atmospheric circulation models, of increased mean annual temperatures and spring precipitation at the occupied sites, to predict evolutionary trends in sprouting. The models predicted that C. parviflorum and O. sphegodes will evolve higher and lower probabilities of sprouting, respectively, by the end of the twenty-first century, whereas, after considerable variation, the probability of sprouting in C. candidum will return to its current level. These trends appear to be driven by relationships between mortality and size: in C. parviflorum and C. candidum, mortality is negatively related to size in the current year but positively related to growth since the previous year, whereas in O. sphegodes, mortality is positively related to size.
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Pulmonary air leaks are medical complications of thoracic surgery for which fibrin sealant is the main treatment. In this study, innovative sealants based on hydrophobically modified Alaska pollock-derived gelatin (hm-ApGltn) and a poly(ethylene)glycol-based 4-armed cross-linker (4S-PEG) have been developed and their burst strengths have been evaluated using fresh rat lung. The developed sealants show higher lung burst strength compared with the nonmodified original ApGltn (Org-ApGltn)-based sealant and a commercial fibrin sealant. The maximum burst strength of the hm-ApGltn-based sealant is 1.6-fold higher than the Org-ApGltn-based sealant (n = 5, p < 0.05), and 2.1-fold higher than the commercial fibrin sealant (n = 5, p < 0.05). Cell culture experiments show that modification of ApGltn with cholesteryl or stearoyl groups effectively enhances anchoring to the cell surface. In addition, binding constants between hm-ApGltn and extracellular matrix proteins such as fibronectin and fibrillin are increased. Therefore, the new hm-ApGltn/4S-PEG-based sealant has the potential for applications in thoracic surgery.
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Gelatina/uso terapéutico , Interacciones Hidrofóbicas e Hidrofílicas , Enfermedades Pulmonares/tratamiento farmacológico , Adhesivos Tisulares/uso terapéutico , Animales , Línea Celular , Módulo de Elasticidad , Peces , Gelatina/síntesis química , Gelatina/química , Humanos , Ensayo de Materiales , Ratones , Polietilenglicoles/química , Espectroscopía de Protones por Resonancia Magnética , Ratas , Reología , Espectroscopía Infrarroja por Transformada de Fourier , Adhesivos Tisulares/químicaRESUMEN
Atmosphere-ocean coupling effect on the frequency distribution of tropical cyclones (TCs) and its future change is studied using an atmosphere and ocean coupled general circulation model (AOGCM). In the present climate simulation, the atmosphere-ocean coupling in the AOGCM improves biases in the AGCM such as the poleward shift of the maximum of intense TC distribution in the Northern Hemisphere and too many intense TCs in the Southern Hemisphere. Particularly, subsurface cold water plays a key role to reduce these AGCM biases of intense TC distribution. Besides, the future change of intense TC distribution is significantly different between AOGCM and AGCM despite the same monthly SST. In the north Atlantic, subsurface warming causes larger increase in frequency of intense TCs in AOGCM than that in AGCM. Such subsurface warming in AOGCM also acts to alter large decrease of intense TC in AGCM to no significant change in AOGCM over the southwestern Indian Ocean. These results suggest that atmosphere-ocean coupling characterized by subsurface oceanic structure is responsible for more realistic intense TC distribution in the current climate simulation and gives significant impacts on its future projection.
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Surgical sealants are widely used clinically. Fibrin sealant is a commonly used sealant, but is ineffective under wet conditions during surgery. In this study, we developed surgical sealants composed of hydrophobically modified Alaska-pollock-derived gelatins (hm-ApGltns) with different alkyl chain lengths from C3 to C18 and a poly(ethylene)glycol-based 4-armed crosslinker (4S-PEG). The burst strength of the hm-ApGltns-based sealant was evaluated using a fresh porcine blood vessel and was found to increase with increasing alkyl chain length from 167±22 to 299±43mmHg when the substitution ratio of amino groups of ApGltn was around 10mol%. The maximum burst strength was observed when stearoyl-group modified ApGltn (Ste-ApGltn)/4S-PEG-based sealant was used, displaying 3-fold higher burst strength than the original ApGltn (Org-ApGltn)/4S-PEG sealant, and 10-fold higher than the commercial fibrin sealant. Ste-ApGltn/4S-PEG-based sealant was biodegraded in rat subcutaneous tissue within 8 weeks without severe inflammation. By molecular interaction analysis using surface plasmon resonance, the binding constant of Ste-ApGltn to fibronectin was found to be 9-fold higher than that of Org-ApGltn. Therefore, the developed sealant, in particular the Ste-ApGltn/4S-PEG-based sealant, has potential applications in the field of cardiovascular surgery as well as thoracic surgery.