AIM: To determine the difference in clinical outcome between ulcerative colitis (UC) patients with Mayo endoscopic subscore (MES) 0 and those with MES 1.
Immunodeficient mice engrafted with human peripheral blood cells are promising tools for in vivo analysis of human patient individual immune responses.However,when human peripheral blood mononuclear cells(PBMCs)are tr...Immunodeficient mice engrafted with human peripheral blood cells are promising tools for in vivo analysis of human patient individual immune responses.However,when human peripheral blood mononuclear cells(PBMCs)are transferred into NOG(NOD/Shi-scid,IL-2rg null)mice,severe graft versus host disease(GVHD)hinders long term detailed analysis.Administration of human PBMCs into newly developed murine MHC class I-and class II-deficient NOG(NOG-dKO;NOG-Iab,B2m-double-knockout)mice showed sufficient engraftment of human immune cells with little sign of GVHD.Immunization with influenza vaccine resulted in an increase in influenza-specific human IgG Ab,indicating induction of antigen-specific B cells in the NOG-dKO mice.Immunization with human dendritic cells pulsed with HLA-A2 restricted cytomegalovirus peptide induced specific cytotoxic T cells,indicating the induction of antigen-specific T cells in the NOG-dKO mice.Adoptive cell therapies(ACTs)using melanoma antigen recognized by T cells(MART-1)-specific TCR-transduced activated T cells showed strong tumor growth inhibition in NOG-dKO mice without any sign of GVHD accompanied by preferential expansion of the transferred MART-1-specific T cells.ACTs using cultured human melanoma infiltrating T cells also showed anti-tumor effects against autologous melanoma cells in NOG-dKO mice,in which changes in human cancer phenotypes by immune intervention,such as increased CD271 expression,could be evaluated.Therefore,NOG-dKO mice are useful tools for more detailed analysis of both the induction and effector phases of T-cell and B-cell responses for a longer period than regular NOG mice.展开更多
Bone is one of the preferred sites for the metastasis of malignant tumours,such as breast cancer,lung cancer and malignant melanoma.Tumour cells colonizing bone have the capacity to induce the expression of receptor a...Bone is one of the preferred sites for the metastasis of malignant tumours,such as breast cancer,lung cancer and malignant melanoma.Tumour cells colonizing bone have the capacity to induce the expression of receptor activator of nuclear factor-κB ligand(RANKL),which promotes osteoclast differentiation and activation.Tumour-induced osteoclastic bone resorption leads to a vicious cycle between tumours and bone cells that fuels osteolytic tumour growth,causing bone pain and hypercalcaemia.Furthermore,RANKL contributes to bone metastasis by acting as a chemoattractant to bone for tumour cells that express its receptor,RANK.Thus inhibition of the RANKL–RANK pathway is a promising treatment for bone metastasis,and a human monoclonal anti-RANKL antibody,denosumab,has been used in the clinic.However,orally available drugs targeting RANKL must be developed to increase the therapeutic benefits to patients.Here we report the efficacy of the small-molecule RANKL inhibitor AS2676293 in treating bone metastasis using mouse models.Oral administration of AS2676293 markedly inhibited bone metastasis of human breast cancer cells MDA-MB-231-5a-D-Luc2 as well as tumour-induced osteolysis.AS2676293 suppressed RANKLmediated tumour migration in the transwell assay and inhibited bone metastasis of the murine cell line B16F10,which is known not to trigger osteoclast activation.Based on the results from this study,RANKL inhibition with a small-molecule compound constitutes a promising therapeutic strategy for treating bone metastasis by inhibiting both osteoclastic bone resorption and tumour migration to bone.展开更多
Warthin’s tumor is the second most frequent neoplasm next to pleomorphic adenoma in the salivary gland. The tumor contains the epithelial oncocyte cells with the presence of rich-mitochondria and their surrounding ab...Warthin’s tumor is the second most frequent neoplasm next to pleomorphic adenoma in the salivary gland. The tumor contains the epithelial oncocyte cells with the presence of rich-mitochondria and their surrounding abundant lymphocytes. A relatively new disease entity of IgG4-related disease frequently occurs in the salivary gland. However, the coexistence of Warthin’s tumor and IgG4-related disease is scarcely observed. We have recently experienced a rare case of Warthin’s tumor with IgG4-related sialadenitis. A 51-year-old man presented to our hospital, complaining of a mass with right submandibular tenderness and spontaneous pain. A computed tomography scan of the cervical region revealed a suspicion of lymph node proliferative disease, including malignant lymphoma. Elevated serum levels of IL-2R: 1843 U/ml (reference value 122 - 496 U/ml), IgG: 3430 mg/dl (reference value 861 - 1747 mg/dl), and IgG4: 3140 mg/dl (reference value 11 - 121 mg/dl) were observed. Other laboratory data showed within normal ranges. The cervical tumor was diagnosed as Warthin’s tumor by the findings of fine-needle aspiration cytology and biopsy examination. Immunohistochemistry revealed numerous IgG4- and IgG-positive cells with fibrosis surrounding the epithelial component of Warthin’s tumor, suggesting IgG4-rerated sialadenitis. Finally, we diagnosed the cervical tumor as Warthin tumor with IgG4-related sialadenitis. This is the second report describing a case of Warthin’s tumor with possible involvement of IgG4-related sialadenitis.展开更多
Chlorella residues are currently underutilized. Therefore, in this study, we analyzed the nutritional components of Chlorella residue, and investigated its potential use as an organic fertilizer/bio-stimulant. Composi...Chlorella residues are currently underutilized. Therefore, in this study, we analyzed the nutritional components of Chlorella residue, and investigated its potential use as an organic fertilizer/bio-stimulant. Composition analyses revealed that the Chlorella residue contained a substantial amount of nitrogen (97,910 mg/kg), and significant quantities of secondary macronutrients, such as calcium (4300 mg/kg) and magnesium (9700 mg/kg), and micronutrients, such as iron (1850 mg/L) and manganese (359 mg/kg). The application of Chlorella residue to soil resulted in increased soil bacterial biomass. When Chlorella residue was added to the soil at a rate of 0.5% or 1.0% (w/w), the fresh weights of Brassica rapa and Spinacia oleracea were significantly increased. Furthermore, the application of Chlorella residue to the soil of B. rapa suppressed the reduction of the microbiome caused by clubroot disease and decreased the clubroot disease index. Therefore, Chlorella residue can be included in organic fertilizers that effectively improve soil nutrient contents, promote plant growth, and reduce the incidence of disease.展开更多
AIM:To clarify the impact of cytomegalovirus(CMV)activation and antiviral therapy based on CMV antigen status on the long-term clinical course of ulcerative colitis(UC)patients.METHODS:UC patients with flare-up were d...AIM:To clarify the impact of cytomegalovirus(CMV)activation and antiviral therapy based on CMV antigen status on the long-term clinical course of ulcerative colitis(UC)patients.METHODS:UC patients with flare-up were divided into CMV-positive and-negative groups according to the CMV antigenemia assay.The main treatment strategy provided for the patients in the CMV-positive group comprised a dose reduction of corticosteroids and administration of ganciclovir.RESULTS:The median number of days to initial remission was significantly greater for the patients in the CMV-positive group(21 d vs 16 d,P=0.009).However,the relapse rate after remission and colectomy rate during more than 30 mo of observation did not differ between the two groups.Multivariate analysis revealed that administration of ganciclovir was the only independent factor for avoiding colectomy in patients of the CMV-positive group.CONCLUSION:CMV antigen status did not significantly affect the long-term prognosis in UC patients under treatment with appropriate antiviral therapy.展开更多
The microstructural factors contributing to the high strength of additive-manufactured Al-Si alloys us-ing laser-beam powder bed fusion(PBF-LB)were identified by in-situ synchrotron X-ray diffraction in tensile deform...The microstructural factors contributing to the high strength of additive-manufactured Al-Si alloys us-ing laser-beam powder bed fusion(PBF-LB)were identified by in-situ synchrotron X-ray diffraction in tensile deformation and transmission electron microscopy.PBF-LB and heat treatment were employed to manufacture Al-12%Si binary alloy specimens with different microstructures.At an early stage of de-formation prior to macroscopic yielding,stress was dominantly partitioned into the α-Al matrix,rather than the Si phase in all specimens.Highly concentrated Si solute(~3%)in the α-Al matrix promoted the dynamic precipitation of nanoscale Si phase during loading,thereby increasing the yield strength.After macroscopic yielding,the partitioned stress in the Si phase monotonically increased in the strain-hardening regime with an increase in the dislocation density in the α-Al matrix.At a later stage of strain hardening,the flow curves of the partitioned stress in the Si phase yielded stress relaxation owing to plastic deformation.Therefore,Si-phase particles localized along the cell walls in the cellular-solidified microstructure play a significant role in dislocation obstacles for strain hardening.Compared with the results of the heat-treated specimens with different microstructural factors,the dominant strengthening factors of PBF-LB manufactured Al-Si alloys were discussed.展开更多
BACKGROUND Most species of aconite contain highly toxic aconitines,the oral ingestion of which can be fatal,primarily because they cause ventricular arrhythmias.We describe a case of severe aconite poisoning that was ...BACKGROUND Most species of aconite contain highly toxic aconitines,the oral ingestion of which can be fatal,primarily because they cause ventricular arrhythmias.We describe a case of severe aconite poisoning that was successfully treated through venoarterial extracorporeal membrane oxygenation(VA-ECMO)and in which detailed toxicological analyses of the aconite roots and biological samples were performed using liquid chromatography-tandem mass spectrometry(LC-MS/MS).CASE SUMMARY A 23-year-old male presented to the emergency room with circulatory collapse and ventricular arrhythmia after ingesting approximately half of a root labeled,“Aconitum japonicum Thunb”.Two hours after arrival,VA-ECMO was initiated as circulatory collapse became refractory to antiarrhythmics and vasopressors.Nine hours after arrival,an electrocardiogram revealed a return to sinus rhythm.The patient was weaned off VA-ECMO and the ventilator on hospital days 3 and 5,respectively.On hospital day 15,he was transferred to a psychiatric hospital.The other half of the root and his biological samples were toxicologically analyzed using LC-MS/MS,revealing 244.3 mg/kg of aconitine and 24.7 mg/kg of mesaconitine in the root.Serum on admission contained 1.50 ng/mL of aconitine.Beyond hospital day 2,neither were detected.Urine on admission showed 149.09 ng/mL of aconitine and 3.59 ng/mL of mesaconitine,but these rapidly decreased after hospital day 3.CONCLUSION The key to saving the life of a patient with severe aconite poisoning is to introduce VA-ECMO as soon as possible.展开更多
BACKGROUND Pancreaticoduodenectomy(PD)for advanced gastric cancer is rarely performed because of the high morbidity and mortality rates and low survival rate.However,neoadjuvant chemotherapy for advanced gastric cance...BACKGROUND Pancreaticoduodenectomy(PD)for advanced gastric cancer is rarely performed because of the high morbidity and mortality rates and low survival rate.However,neoadjuvant chemotherapy for advanced gastric cancer has improved,and chemotherapy combined with trastuzumab may have a preoperative tumorreducing effect,especially for human epidermal growth factor receptor 2(HER2)-positive cases.CASE SUMMARY We report a case of successful radical resection with PD after neoadjuvant S-1 plus oxaliplatin(SOX)and trastuzumab in a patient(66-year-old male)with advanced gastric cancer invading the pancreatic head.Initial esophagogastroduodenoscopy detected a type 3 advanced lesion located on the lower part of the stomach obstructing the pyloric ring.Computed tomography detected lymph node metastasis and tumor invasion to the pancreatic head without distant metastasis.Pathological findings revealed adenocarcinoma and HER2 positivity(immunohistochemical score of 3+).We performed staging laparoscopy and confirmed no liver metastasis,no dissemination,negative lavage cytological findings,and immobility of the distal side of the stomach due to invasion to the pancreas.Laparoscopic gastrojejunostomy was performed at that time.One course of SOX and three courses of SOX plus trastuzumab were administered.Preoperative computed tomography showed partial response;therefore,PD was performed after neoadjuvant chemotherapy,and pathological radical resection was achieved.CONCLUSION We suggest that radical resection with PD after neoadjuvant chemotherapy plus trastuzumab is an option for locally advanced HER2-positive gastric cancer invading the pancreatic head in the absence of non-curative factors.展开更多
To identify the microstructural features of the lattice structures of Al alloys built via the selective laser melting(SLM)process,AlSil OMg alloy with a body-centered cubic(BCC)-type lattice structure was prepared.Cha...To identify the microstructural features of the lattice structures of Al alloys built via the selective laser melting(SLM)process,AlSil OMg alloy with a body-centered cubic(BCC)-type lattice structure was prepared.Characteristic microstructures comprising melt pools with several columnarα-Al phases with<001>orientations along the elongation direction and surrounded by eutectic Si particles were observed at all portions of the built lattice structure.In the node portions of the lattice structure,a gradient microstructure(continuous change in microstructure)was observed.The columnarα-Al phases were observed near the top surface of the node portion,whereas they became coarser and more equiaxed near the bottom surface,resulting in softening localized near the bottom surface.In the strut portions of the lattice structure,the columnarα-Al phases were elongated along the inclined direction of struts.This trend was more prevalent near the bottom surface.Theα-Al phases became coarser and more equiaxed near the bottom surface as well.The aforementioned results were the basis of a discussion of the development of the gradient microstructure in lattice-structured Al alloys during the SLM process in terms of thermal conductivities at the boundaries between the manufactured(locally melted and rapidly solidified)portions and adjacent(unmelted)alloy powder.展开更多
AIM: To assess the risk of relapse in ulcerative colitis (UC) patients in clinical remission using mucosal status and fecal immunochemical test (FIT) results.METHODS: The clinical outcomes of 194 UC patients in clinic...AIM: To assess the risk of relapse in ulcerative colitis (UC) patients in clinical remission using mucosal status and fecal immunochemical test (FIT) results.METHODS: The clinical outcomes of 194 UC patients in clinical remission who underwent colonoscopy were based on evaluations of Mayo endoscopic subscores (MESs) and FIT results.RESULTS: Patients with an MES of 0 (n = 94, 48%) showed a ten-fold lower risk of relapse than those with an MES of 1-3 (n = 100, 52%) (HR = 0.10, 95%CI: 0.05-0.19). A negative FIT result (fecal hemoglobin concentrations ≤ 100 ng/mL) was predictive of patients with an MES of 0, with a sensitivity of 0.94 and a specific of 0.76. Moreover, patients with a negative FIT score had a six-fold lower risk of clinical relapse than those with a positive score (HR = 0.17, 95%CI: 0.10-0.28). Inclusion of the distinguishing parameter, sustaining clinical remission > 12 mo, resulted in an even stronger correlation between negative FIT results and an MES of 0 with respect to the risk of clinical relapse (HR = 0.11, 95%CI: 0.04-0.23).CONCLUSION: Negative FIT results one year or more after remission induction correlate with complete mucosal healing (MES 0) and better prognosis. Performing FIT one year after remission induction may be useful for evaluating relapse risk.展开更多
Many psychogenic issues trigger issues in children, such as refusal to attend school or bullying. That is to say, there are risks of serious problems occurring, such as suicide or mental illness, when such stress is a...Many psychogenic issues trigger issues in children, such as refusal to attend school or bullying. That is to say, there are risks of serious problems occurring, such as suicide or mental illness, when such stress is a relatively large factor in that person’s life and they are unable to adapt thereto. Therefore, with this research, we sought to clarify the relationship between lifestyle habits and the seven stress responses of depression, anxiety, anger, emotional responses, seclusion, physical fatigue, and hyperactivity of the autonomous nervous system, and based on our results, we investigated the ways in which school nurses can support younger students who experience such psychogenic issues. The subjects of our investigation included 341 university students (123 males and 218 females). We had the subjects complete a measurement of their degrees of stress and a survey about their lifestyle habits. The results indicated that the higher the stress level, lifestyle rhythms were disturbed, especially with regards to diet, and that there were differences between males and females as well. The results also suggested that the higher the stress level, the less amount of rest. This research revealed that increased stress leads to disturbances in lifestyle habits. Some examples of ways in which school nurses can support students include creating an environment in which it is easier for younger students to talk to school nurses, conducting health consultation activities in coordination with teachers and relevant organizations, and ascertaining information regarding the circumstances of younger students. Thus, it is thought that building better lifestyle habits will make it easier to cope with stress, thereby leading to better balance in mental and physical health.展开更多
AIM:To investigate serum PC-594 fatty acid levels as a potential biomarker in North American pancreatic cancer(PaC) patients,and to compare its performance to CA19-9.METHODS:Using tandem mass spectrometry,we evaluated...AIM:To investigate serum PC-594 fatty acid levels as a potential biomarker in North American pancreatic cancer(PaC) patients,and to compare its performance to CA19-9.METHODS:Using tandem mass spectrometry,we evaluated serum PC-594 levels from 84 North American patients with confirmed PaC and 99 cancer-free control subjects.We determined CA19-9 levels by ELISA.Significance between Pa C patients and controls,and association with clinical variables was determined by analysis of variance and t-tests.Diagnostic performance was evaluated by receiver-operator characteristic(ROC)curve analysis,and PC-594 correlation with age and CA19-9 determined by regression analysis.RESULTS:Mean PC-594 levels were 3.7 times lower in Pa C patients compared to controls(P < 0.0001).The mean level in PaC patient serum was 0.76 ± 0.07 μmol/L,and the mean level in control subjects was 2.79 ± 0.15 μmol/L.There was no correlation between PC-594 and age,disease stage or gender(P > 0.05).Using 1.25 μmol/L as a PC-594 threshold produced a relative risk(RR) of 9.4(P < 0.0001,95%CI:5.0-17.7).The area under the receiver-operator characteristic curve(ROCAUC) was 0.93(95%CI:0.91-0.95) for PC-594 and 0.85(95%CI:0.82-0.88) for CA19-9.Sensitivity at 90% specificity was 87% for PC-594 and 71% for CA19-9.Six Pa C patients with CA19-9 above 35 U/m L showed normal PC-594 levels,while 24 Pa C patients with normal CA19-9 showed low PC-594 levels.Eighty-five of the 99 control subjects(86%) showed normal levels of both markers.CONCLUSION:PC-594 biomarker levels are significantly reduced in North American Pa C patients,and showed superior diagnostic performance compared to CA19-9.展开更多
Atypical polypoid adenomyoma (APAM) is a rare polypoid tumor that generally occurs in women of reproductive age who have abnormal genital bleeding. The tumor was reported as a new disease concept by Mazur in 1981. Pat...Atypical polypoid adenomyoma (APAM) is a rare polypoid tumor that generally occurs in women of reproductive age who have abnormal genital bleeding. The tumor was reported as a new disease concept by Mazur in 1981. Pathologically, APAM consist of irregularly proliferated endometrial gland cells and interlacing bundles of smooth muscle cells within the stroma, and have a similar form to adenocarcinoma, adenofibroma, adenosarcoma, and carcinosarcoma. Therefore, differential diagnosis is required in many cases. APAM is pathologically classified as a benign lesion and clinically has a comparatively favorable outcome. However, treatment and follow-up observation should be performed carefully because recurrence and residual lesions occur in many patients after conservative treatment. Concomitant development of endometrial adenocarcinoma also occurs in many cases and it is difficult to differentiate this disease from APAM. Thus, diagnosis of APAM should be made carefully, particularly since the number of cases of endometrial adenocarcinoma has increased in recent years. Furthermore, APAM tends to develop during a woman’s reproductive years, and fertility sparing treatment should be considered. Here, we review the clinicopathological characteristics of APAM, including the difficulty of diagnosis as a benign or malignant uterine tumor, and we examine the relationship between APAM and endometrial cancer.展开更多
We experienced a case of small, round-cell malignant neoplasm diagnosed by touch smear cytology and histopathology when an open biopsy was performed in a 50-year-old Japanese woman. She was suspected of having a cervi...We experienced a case of small, round-cell malignant neoplasm diagnosed by touch smear cytology and histopathology when an open biopsy was performed in a 50-year-old Japanese woman. She was suspected of having a cervical spine tumor after surgery for cervical spine foraminal stenosis. After consent, the cervical spine tumor histologically diagnosed by an open biopsy was confirmed to be Ewing sarcoma (EWS) by genetic testing. EWS belongs to a group of small, round-cell tumors that are morphologically similar and often difficult to differentiate. After the open biopsy, the present patient received radiotherapy, and her plasma level of Pro-Gastrin-Releasing-Peptide was decreased (217.2 pg/ml before surgery to 30.3 pg/ml;reference value: 0 - 80 pg/ml). We herein report the process for making the final diagnosis by focusing on the intraoperative cytology, histopathology, and immunohistochemical findings. Our diagnosis was validated by karyotyping and a fluorescence <em>in-situ</em> hybridization analysis.展开更多
The excitation process of rare-earth ions in oxide semiconductors for optical emission is thought to be related to defect levels within the band-gap of the host material. In order to improve understanding of the role ...The excitation process of rare-earth ions in oxide semiconductors for optical emission is thought to be related to defect levels within the band-gap of the host material. In order to improve understanding of the role defect levels play in the energy transfer process, junction spectroscopy techniques can be used to investigate the electrically active emission centres. It has been reported that TiO<sub>2</sub> is sensitive to humidity at low temperatures, such as those employed when conducting junction spectroscopy measurements. However, there are not many discussions how to prevent this effect and to improve the quality of measurements. After optimization of samples such as fabrication of flat surface and encupsulant for preventing external effect, temperature dependent-capacitance measurements (C-T) were carried out to characterise shallow traps formed within TiO<sub>2</sub> band-gap. TiO<sub>2</sub> and Sm-doped TiO<sub>2</sub> thin films were deposited on SrTiO<sub>3</sub> (100) templates by laser ablaton and rectifying Ruthenium Oxide Schottky diodes deposited on the TiO<sub>2</sub> surface by laser ablation. A Sm or Sm-related shallow trap was observed in the Arrhenius plot of TiO<sub>2</sub>:Sm. In this paper, we show the optimized sample fabrication/preparation process that stabilizes the junction spectroscopy measurements, even in the presence of humidity and we present initial results obtained on samples using these optimized processing techniques.展开更多
BACKGROUND Inguinal hernia repair is one of the most common general surgical operations worldwide.We present a case of indirect inguinal hernia containing an expanded portosystemic shunt vessel.CASE SUMMARY We report ...BACKGROUND Inguinal hernia repair is one of the most common general surgical operations worldwide.We present a case of indirect inguinal hernia containing an expanded portosystemic shunt vessel.CASE SUMMARY We report a 72-year-old man who had a 4 cm×4 cm swelling in the right inguinal region,which disappeared with light manual pressure.Abdominal-pelvic computed tomography(CT)revealed a right inguinal hernia containing an expanded portosystemic shunt vessel,which had been noted for 7 years due to liver cirrhosis.We performed Lichtenstein’s herniorrhaphy and identified the hernia sac as being indirect and the shunt vessel existing in the extraperitoneal cavity through the internal inguinal ring.Then,we found two short branches between the expanded shunt vessel and testicular vein in the middle part of the inguinal canal and cut these branches to allow the shunt vessel to return to the extraperitoneal cavity of the abdomen.The hernia sac was returned as well.We encountered no intraoperative complications.After discharge,groin seroma requiring puncture at the outpatient clinic was observed.CONCLUSION If an inguinal hernia patient has portal hypertension,ultrasound should be used to determine the contents of the hernia.When atypical vessels are visualized,they may be shunt vessels and additional CT is recommended to ensure the selection of an adequate approach for safe hernia repair.展开更多
Chest CT frequently reveals small pulmonary lesions. If there is no associated hilar or mediastinal lymphadenopathy, small-cell lung cancer (SCLC) is considered to be very early-stage. Few studies, however, have descr...Chest CT frequently reveals small pulmonary lesions. If there is no associated hilar or mediastinal lymphadenopathy, small-cell lung cancer (SCLC) is considered to be very early-stage. Few studies, however, have described the characteristic CT findings of very early-stage SCLC. Clarifying these findings would reduce diagnostic delay. The purpose of this study was to determine the characteristic CT findings of very earlystage SCLC. Computed tomography images obtained from 547 consecutive patients with lung cancer between 2003 and 2012 at Tokyo Dental College Ichikawa General Hospital were reviewed retrospectively. One hundred of these patients had SCLC and 447 had non-SCLC (NSCLC). These CT images, along with any that had also been obtained prior to the one on which the final diagnosis was based, were reviewed. In 5 of the cases reviewed, specific findings and a characteristic spreading pattern were identified on CT images that might have allowed a diagnosis of SCLC to have been made sooner. The findings included a sub-pleural, small nodule accompanied by daughter nodules spreading longitudinally along the bronchovascular bundle, no air bronchogram or cavitation, and background emphysematous change. These were not identified on CT images of very earlystage NCSLC, however (n = 22). Awareness of the relevance of these findings would help physicians and radiologists arrive at a differential diagnosis of small pulmonary nodules.展开更多
Corncobs could serve as a substrate for citric acid production using solid state fermentation technique. The culture optimization concerning substrate concentration, culture duration, pH, temperature and substrate hyd...Corncobs could serve as a substrate for citric acid production using solid state fermentation technique. The culture optimization concerning substrate concentration, culture duration, pH, temperature and substrate hydrolysis was carried out for maximum productivity of citric acid. Under the optimized conditions, 48.4 g of citric acid was produced from 1 kg dry corncobs. Biological evaluation was carried out for citric acid such as melanin synthesis inhibitory, anti-allergy, anti-bacterial, and hyaluronic acid production activities. The results showed that citric acid has potent melanin inhibitory activity, good inhibition for β-hexosaminidase release and potent stimulatory effect for the production of hyaluronic acid. These activities (melanin synthesis inhibitory, anti-allergy and hyaluronic acid productive activities) of citric acid have been reported for the first time.展开更多
Dear Editor,Beige adipocytes,which increase energy expenditure by dissipating energy as heat,have gained attention as a therapeutic target for combating obesity.1 Adipocytes express many types of G-protein-coupled rec...Dear Editor,Beige adipocytes,which increase energy expenditure by dissipating energy as heat,have gained attention as a therapeutic target for combating obesity.1 Adipocytes express many types of G-protein-coupled receptors(GPCRs),each of which has a unique preference for the Gs,Gi,Gq,and G12 subfamilies.While the function of Gs-coupledβ-adrenergic receptors in beige adipocyte induction is well established,2 little is known about the function of G12-coupled GPCRs beyond its suppressive roles in white adipocyte maturation.3 In this study,we generated transgenic mice conditionally expressing a G12-coupled designer GPCR using a Cre-loxP system and investigated the potential effects of G12 signaling on adipocyte biology.展开更多
文摘AIM: To determine the difference in clinical outcome between ulcerative colitis (UC) patients with Mayo endoscopic subscore (MES) 0 and those with MES 1.
基金This work was supported by Grants-in-aid for Scientific Research from the Ministry of Education,Culture,Sports,Science and Technology(MEXT)of Japan(22220007,26221005 and 15K09783)the Project for Development of Innovative Research on Cancer Therapeutics(P-DIRECT)and the Project for Cancer Research And Therapeutic Evolution(P-CREATE)from Japan Agency for Medical Research and Development(AMED)+2 种基金a grant from Tokyo Biochemical Research Foundationa Keio University Grant-in-Aid for Encouragement of Young Medical Scientistsa Grant-in-Aid from the Keio Medical Association.
文摘Immunodeficient mice engrafted with human peripheral blood cells are promising tools for in vivo analysis of human patient individual immune responses.However,when human peripheral blood mononuclear cells(PBMCs)are transferred into NOG(NOD/Shi-scid,IL-2rg null)mice,severe graft versus host disease(GVHD)hinders long term detailed analysis.Administration of human PBMCs into newly developed murine MHC class I-and class II-deficient NOG(NOG-dKO;NOG-Iab,B2m-double-knockout)mice showed sufficient engraftment of human immune cells with little sign of GVHD.Immunization with influenza vaccine resulted in an increase in influenza-specific human IgG Ab,indicating induction of antigen-specific B cells in the NOG-dKO mice.Immunization with human dendritic cells pulsed with HLA-A2 restricted cytomegalovirus peptide induced specific cytotoxic T cells,indicating the induction of antigen-specific T cells in the NOG-dKO mice.Adoptive cell therapies(ACTs)using melanoma antigen recognized by T cells(MART-1)-specific TCR-transduced activated T cells showed strong tumor growth inhibition in NOG-dKO mice without any sign of GVHD accompanied by preferential expansion of the transferred MART-1-specific T cells.ACTs using cultured human melanoma infiltrating T cells also showed anti-tumor effects against autologous melanoma cells in NOG-dKO mice,in which changes in human cancer phenotypes by immune intervention,such as increased CD271 expression,could be evaluated.Therefore,NOG-dKO mice are useful tools for more detailed analysis of both the induction and effector phases of T-cell and B-cell responses for a longer period than regular NOG mice.
基金partially supported by a grant for Practical Research Project for Rare/Intractable Diseases (JP17ek0109106) from the Japan Agency for Medical Research and Development a Grant-in-Aid for Specially Promoted Research from the Japan Society for Promotion of Science (JSPS) (15H05703)+3 种基金a Grant-in-Aid for Young Scientists A from JSPS (15H05653)a Grantin-Aid for Scientific Research (B) from JSPS (18H02919)a Grant-in-Aid for Challenging Research (Pioneering) from JSPS (17K19582)grants from Mitsui Life Social Welfare Foundation and Kobayashi Foundation for Cancer Research
文摘Bone is one of the preferred sites for the metastasis of malignant tumours,such as breast cancer,lung cancer and malignant melanoma.Tumour cells colonizing bone have the capacity to induce the expression of receptor activator of nuclear factor-κB ligand(RANKL),which promotes osteoclast differentiation and activation.Tumour-induced osteoclastic bone resorption leads to a vicious cycle between tumours and bone cells that fuels osteolytic tumour growth,causing bone pain and hypercalcaemia.Furthermore,RANKL contributes to bone metastasis by acting as a chemoattractant to bone for tumour cells that express its receptor,RANK.Thus inhibition of the RANKL–RANK pathway is a promising treatment for bone metastasis,and a human monoclonal anti-RANKL antibody,denosumab,has been used in the clinic.However,orally available drugs targeting RANKL must be developed to increase the therapeutic benefits to patients.Here we report the efficacy of the small-molecule RANKL inhibitor AS2676293 in treating bone metastasis using mouse models.Oral administration of AS2676293 markedly inhibited bone metastasis of human breast cancer cells MDA-MB-231-5a-D-Luc2 as well as tumour-induced osteolysis.AS2676293 suppressed RANKLmediated tumour migration in the transwell assay and inhibited bone metastasis of the murine cell line B16F10,which is known not to trigger osteoclast activation.Based on the results from this study,RANKL inhibition with a small-molecule compound constitutes a promising therapeutic strategy for treating bone metastasis by inhibiting both osteoclastic bone resorption and tumour migration to bone.
文摘Warthin’s tumor is the second most frequent neoplasm next to pleomorphic adenoma in the salivary gland. The tumor contains the epithelial oncocyte cells with the presence of rich-mitochondria and their surrounding abundant lymphocytes. A relatively new disease entity of IgG4-related disease frequently occurs in the salivary gland. However, the coexistence of Warthin’s tumor and IgG4-related disease is scarcely observed. We have recently experienced a rare case of Warthin’s tumor with IgG4-related sialadenitis. A 51-year-old man presented to our hospital, complaining of a mass with right submandibular tenderness and spontaneous pain. A computed tomography scan of the cervical region revealed a suspicion of lymph node proliferative disease, including malignant lymphoma. Elevated serum levels of IL-2R: 1843 U/ml (reference value 122 - 496 U/ml), IgG: 3430 mg/dl (reference value 861 - 1747 mg/dl), and IgG4: 3140 mg/dl (reference value 11 - 121 mg/dl) were observed. Other laboratory data showed within normal ranges. The cervical tumor was diagnosed as Warthin’s tumor by the findings of fine-needle aspiration cytology and biopsy examination. Immunohistochemistry revealed numerous IgG4- and IgG-positive cells with fibrosis surrounding the epithelial component of Warthin’s tumor, suggesting IgG4-rerated sialadenitis. Finally, we diagnosed the cervical tumor as Warthin tumor with IgG4-related sialadenitis. This is the second report describing a case of Warthin’s tumor with possible involvement of IgG4-related sialadenitis.
文摘Chlorella residues are currently underutilized. Therefore, in this study, we analyzed the nutritional components of Chlorella residue, and investigated its potential use as an organic fertilizer/bio-stimulant. Composition analyses revealed that the Chlorella residue contained a substantial amount of nitrogen (97,910 mg/kg), and significant quantities of secondary macronutrients, such as calcium (4300 mg/kg) and magnesium (9700 mg/kg), and micronutrients, such as iron (1850 mg/L) and manganese (359 mg/kg). The application of Chlorella residue to soil resulted in increased soil bacterial biomass. When Chlorella residue was added to the soil at a rate of 0.5% or 1.0% (w/w), the fresh weights of Brassica rapa and Spinacia oleracea were significantly increased. Furthermore, the application of Chlorella residue to the soil of B. rapa suppressed the reduction of the microbiome caused by clubroot disease and decreased the clubroot disease index. Therefore, Chlorella residue can be included in organic fertilizers that effectively improve soil nutrient contents, promote plant growth, and reduce the incidence of disease.
文摘AIM:To clarify the impact of cytomegalovirus(CMV)activation and antiviral therapy based on CMV antigen status on the long-term clinical course of ulcerative colitis(UC)patients.METHODS:UC patients with flare-up were divided into CMV-positive and-negative groups according to the CMV antigenemia assay.The main treatment strategy provided for the patients in the CMV-positive group comprised a dose reduction of corticosteroids and administration of ganciclovir.RESULTS:The median number of days to initial remission was significantly greater for the patients in the CMV-positive group(21 d vs 16 d,P=0.009).However,the relapse rate after remission and colectomy rate during more than 30 mo of observation did not differ between the two groups.Multivariate analysis revealed that administration of ganciclovir was the only independent factor for avoiding colectomy in patients of the CMV-positive group.CONCLUSION:CMV antigen status did not significantly affect the long-term prognosis in UC patients under treatment with appropriate antiviral therapy.
基金JST PRESTO(grant number JPMJPR22Q4)(Japan)The Light Metal Educational Foundation,Inc.(Japan),and“Knowledge Hub Aichi”Aichi Prefectural Government(Japan)The synchrotron radiation experiments were performed at BL46XUof SPring-8with the approval of the Japan Synchrotron Radiation Research Institute(JASRI)(Proposal No.2021A1663,2022A1001and 2022A1798).
文摘The microstructural factors contributing to the high strength of additive-manufactured Al-Si alloys us-ing laser-beam powder bed fusion(PBF-LB)were identified by in-situ synchrotron X-ray diffraction in tensile deformation and transmission electron microscopy.PBF-LB and heat treatment were employed to manufacture Al-12%Si binary alloy specimens with different microstructures.At an early stage of de-formation prior to macroscopic yielding,stress was dominantly partitioned into the α-Al matrix,rather than the Si phase in all specimens.Highly concentrated Si solute(~3%)in the α-Al matrix promoted the dynamic precipitation of nanoscale Si phase during loading,thereby increasing the yield strength.After macroscopic yielding,the partitioned stress in the Si phase monotonically increased in the strain-hardening regime with an increase in the dislocation density in the α-Al matrix.At a later stage of strain hardening,the flow curves of the partitioned stress in the Si phase yielded stress relaxation owing to plastic deformation.Therefore,Si-phase particles localized along the cell walls in the cellular-solidified microstructure play a significant role in dislocation obstacles for strain hardening.Compared with the results of the heat-treated specimens with different microstructural factors,the dominant strengthening factors of PBF-LB manufactured Al-Si alloys were discussed.
文摘BACKGROUND Most species of aconite contain highly toxic aconitines,the oral ingestion of which can be fatal,primarily because they cause ventricular arrhythmias.We describe a case of severe aconite poisoning that was successfully treated through venoarterial extracorporeal membrane oxygenation(VA-ECMO)and in which detailed toxicological analyses of the aconite roots and biological samples were performed using liquid chromatography-tandem mass spectrometry(LC-MS/MS).CASE SUMMARY A 23-year-old male presented to the emergency room with circulatory collapse and ventricular arrhythmia after ingesting approximately half of a root labeled,“Aconitum japonicum Thunb”.Two hours after arrival,VA-ECMO was initiated as circulatory collapse became refractory to antiarrhythmics and vasopressors.Nine hours after arrival,an electrocardiogram revealed a return to sinus rhythm.The patient was weaned off VA-ECMO and the ventilator on hospital days 3 and 5,respectively.On hospital day 15,he was transferred to a psychiatric hospital.The other half of the root and his biological samples were toxicologically analyzed using LC-MS/MS,revealing 244.3 mg/kg of aconitine and 24.7 mg/kg of mesaconitine in the root.Serum on admission contained 1.50 ng/mL of aconitine.Beyond hospital day 2,neither were detected.Urine on admission showed 149.09 ng/mL of aconitine and 3.59 ng/mL of mesaconitine,but these rapidly decreased after hospital day 3.CONCLUSION The key to saving the life of a patient with severe aconite poisoning is to introduce VA-ECMO as soon as possible.
文摘BACKGROUND Pancreaticoduodenectomy(PD)for advanced gastric cancer is rarely performed because of the high morbidity and mortality rates and low survival rate.However,neoadjuvant chemotherapy for advanced gastric cancer has improved,and chemotherapy combined with trastuzumab may have a preoperative tumorreducing effect,especially for human epidermal growth factor receptor 2(HER2)-positive cases.CASE SUMMARY We report a case of successful radical resection with PD after neoadjuvant S-1 plus oxaliplatin(SOX)and trastuzumab in a patient(66-year-old male)with advanced gastric cancer invading the pancreatic head.Initial esophagogastroduodenoscopy detected a type 3 advanced lesion located on the lower part of the stomach obstructing the pyloric ring.Computed tomography detected lymph node metastasis and tumor invasion to the pancreatic head without distant metastasis.Pathological findings revealed adenocarcinoma and HER2 positivity(immunohistochemical score of 3+).We performed staging laparoscopy and confirmed no liver metastasis,no dissemination,negative lavage cytological findings,and immobility of the distal side of the stomach due to invasion to the pancreas.Laparoscopic gastrojejunostomy was performed at that time.One course of SOX and three courses of SOX plus trastuzumab were administered.Preoperative computed tomography showed partial response;therefore,PD was performed after neoadjuvant chemotherapy,and pathological radical resection was achieved.CONCLUSION We suggest that radical resection with PD after neoadjuvant chemotherapy plus trastuzumab is an option for locally advanced HER2-positive gastric cancer invading the pancreatic head in the absence of non-curative factors.
基金support of the“Knowledge Hub Aichi”a Priority Research Project of Aichi Prefectural Government,Japan。
文摘To identify the microstructural features of the lattice structures of Al alloys built via the selective laser melting(SLM)process,AlSil OMg alloy with a body-centered cubic(BCC)-type lattice structure was prepared.Characteristic microstructures comprising melt pools with several columnarα-Al phases with<001>orientations along the elongation direction and surrounded by eutectic Si particles were observed at all portions of the built lattice structure.In the node portions of the lattice structure,a gradient microstructure(continuous change in microstructure)was observed.The columnarα-Al phases were observed near the top surface of the node portion,whereas they became coarser and more equiaxed near the bottom surface,resulting in softening localized near the bottom surface.In the strut portions of the lattice structure,the columnarα-Al phases were elongated along the inclined direction of struts.This trend was more prevalent near the bottom surface.Theα-Al phases became coarser and more equiaxed near the bottom surface as well.The aforementioned results were the basis of a discussion of the development of the gradient microstructure in lattice-structured Al alloys during the SLM process in terms of thermal conductivities at the boundaries between the manufactured(locally melted and rapidly solidified)portions and adjacent(unmelted)alloy powder.
文摘AIM: To assess the risk of relapse in ulcerative colitis (UC) patients in clinical remission using mucosal status and fecal immunochemical test (FIT) results.METHODS: The clinical outcomes of 194 UC patients in clinical remission who underwent colonoscopy were based on evaluations of Mayo endoscopic subscores (MESs) and FIT results.RESULTS: Patients with an MES of 0 (n = 94, 48%) showed a ten-fold lower risk of relapse than those with an MES of 1-3 (n = 100, 52%) (HR = 0.10, 95%CI: 0.05-0.19). A negative FIT result (fecal hemoglobin concentrations ≤ 100 ng/mL) was predictive of patients with an MES of 0, with a sensitivity of 0.94 and a specific of 0.76. Moreover, patients with a negative FIT score had a six-fold lower risk of clinical relapse than those with a positive score (HR = 0.17, 95%CI: 0.10-0.28). Inclusion of the distinguishing parameter, sustaining clinical remission > 12 mo, resulted in an even stronger correlation between negative FIT results and an MES of 0 with respect to the risk of clinical relapse (HR = 0.11, 95%CI: 0.04-0.23).CONCLUSION: Negative FIT results one year or more after remission induction correlate with complete mucosal healing (MES 0) and better prognosis. Performing FIT one year after remission induction may be useful for evaluating relapse risk.
文摘Many psychogenic issues trigger issues in children, such as refusal to attend school or bullying. That is to say, there are risks of serious problems occurring, such as suicide or mental illness, when such stress is a relatively large factor in that person’s life and they are unable to adapt thereto. Therefore, with this research, we sought to clarify the relationship between lifestyle habits and the seven stress responses of depression, anxiety, anger, emotional responses, seclusion, physical fatigue, and hyperactivity of the autonomous nervous system, and based on our results, we investigated the ways in which school nurses can support younger students who experience such psychogenic issues. The subjects of our investigation included 341 university students (123 males and 218 females). We had the subjects complete a measurement of their degrees of stress and a survey about their lifestyle habits. The results indicated that the higher the stress level, lifestyle rhythms were disturbed, especially with regards to diet, and that there were differences between males and females as well. The results also suggested that the higher the stress level, the less amount of rest. This research revealed that increased stress leads to disturbances in lifestyle habits. Some examples of ways in which school nurses can support students include creating an environment in which it is easier for younger students to talk to school nurses, conducting health consultation activities in coordination with teachers and relevant organizations, and ascertaining information regarding the circumstances of younger students. Thus, it is thought that building better lifestyle habits will make it easier to cope with stress, thereby leading to better balance in mental and physical health.
文摘AIM:To investigate serum PC-594 fatty acid levels as a potential biomarker in North American pancreatic cancer(PaC) patients,and to compare its performance to CA19-9.METHODS:Using tandem mass spectrometry,we evaluated serum PC-594 levels from 84 North American patients with confirmed PaC and 99 cancer-free control subjects.We determined CA19-9 levels by ELISA.Significance between Pa C patients and controls,and association with clinical variables was determined by analysis of variance and t-tests.Diagnostic performance was evaluated by receiver-operator characteristic(ROC)curve analysis,and PC-594 correlation with age and CA19-9 determined by regression analysis.RESULTS:Mean PC-594 levels were 3.7 times lower in Pa C patients compared to controls(P < 0.0001).The mean level in PaC patient serum was 0.76 ± 0.07 μmol/L,and the mean level in control subjects was 2.79 ± 0.15 μmol/L.There was no correlation between PC-594 and age,disease stage or gender(P > 0.05).Using 1.25 μmol/L as a PC-594 threshold produced a relative risk(RR) of 9.4(P < 0.0001,95%CI:5.0-17.7).The area under the receiver-operator characteristic curve(ROCAUC) was 0.93(95%CI:0.91-0.95) for PC-594 and 0.85(95%CI:0.82-0.88) for CA19-9.Sensitivity at 90% specificity was 87% for PC-594 and 71% for CA19-9.Six Pa C patients with CA19-9 above 35 U/m L showed normal PC-594 levels,while 24 Pa C patients with normal CA19-9 showed low PC-594 levels.Eighty-five of the 99 control subjects(86%) showed normal levels of both markers.CONCLUSION:PC-594 biomarker levels are significantly reduced in North American Pa C patients,and showed superior diagnostic performance compared to CA19-9.
文摘Atypical polypoid adenomyoma (APAM) is a rare polypoid tumor that generally occurs in women of reproductive age who have abnormal genital bleeding. The tumor was reported as a new disease concept by Mazur in 1981. Pathologically, APAM consist of irregularly proliferated endometrial gland cells and interlacing bundles of smooth muscle cells within the stroma, and have a similar form to adenocarcinoma, adenofibroma, adenosarcoma, and carcinosarcoma. Therefore, differential diagnosis is required in many cases. APAM is pathologically classified as a benign lesion and clinically has a comparatively favorable outcome. However, treatment and follow-up observation should be performed carefully because recurrence and residual lesions occur in many patients after conservative treatment. Concomitant development of endometrial adenocarcinoma also occurs in many cases and it is difficult to differentiate this disease from APAM. Thus, diagnosis of APAM should be made carefully, particularly since the number of cases of endometrial adenocarcinoma has increased in recent years. Furthermore, APAM tends to develop during a woman’s reproductive years, and fertility sparing treatment should be considered. Here, we review the clinicopathological characteristics of APAM, including the difficulty of diagnosis as a benign or malignant uterine tumor, and we examine the relationship between APAM and endometrial cancer.
文摘We experienced a case of small, round-cell malignant neoplasm diagnosed by touch smear cytology and histopathology when an open biopsy was performed in a 50-year-old Japanese woman. She was suspected of having a cervical spine tumor after surgery for cervical spine foraminal stenosis. After consent, the cervical spine tumor histologically diagnosed by an open biopsy was confirmed to be Ewing sarcoma (EWS) by genetic testing. EWS belongs to a group of small, round-cell tumors that are morphologically similar and often difficult to differentiate. After the open biopsy, the present patient received radiotherapy, and her plasma level of Pro-Gastrin-Releasing-Peptide was decreased (217.2 pg/ml before surgery to 30.3 pg/ml;reference value: 0 - 80 pg/ml). We herein report the process for making the final diagnosis by focusing on the intraoperative cytology, histopathology, and immunohistochemical findings. Our diagnosis was validated by karyotyping and a fluorescence <em>in-situ</em> hybridization analysis.
文摘The excitation process of rare-earth ions in oxide semiconductors for optical emission is thought to be related to defect levels within the band-gap of the host material. In order to improve understanding of the role defect levels play in the energy transfer process, junction spectroscopy techniques can be used to investigate the electrically active emission centres. It has been reported that TiO<sub>2</sub> is sensitive to humidity at low temperatures, such as those employed when conducting junction spectroscopy measurements. However, there are not many discussions how to prevent this effect and to improve the quality of measurements. After optimization of samples such as fabrication of flat surface and encupsulant for preventing external effect, temperature dependent-capacitance measurements (C-T) were carried out to characterise shallow traps formed within TiO<sub>2</sub> band-gap. TiO<sub>2</sub> and Sm-doped TiO<sub>2</sub> thin films were deposited on SrTiO<sub>3</sub> (100) templates by laser ablaton and rectifying Ruthenium Oxide Schottky diodes deposited on the TiO<sub>2</sub> surface by laser ablation. A Sm or Sm-related shallow trap was observed in the Arrhenius plot of TiO<sub>2</sub>:Sm. In this paper, we show the optimized sample fabrication/preparation process that stabilizes the junction spectroscopy measurements, even in the presence of humidity and we present initial results obtained on samples using these optimized processing techniques.
文摘BACKGROUND Inguinal hernia repair is one of the most common general surgical operations worldwide.We present a case of indirect inguinal hernia containing an expanded portosystemic shunt vessel.CASE SUMMARY We report a 72-year-old man who had a 4 cm×4 cm swelling in the right inguinal region,which disappeared with light manual pressure.Abdominal-pelvic computed tomography(CT)revealed a right inguinal hernia containing an expanded portosystemic shunt vessel,which had been noted for 7 years due to liver cirrhosis.We performed Lichtenstein’s herniorrhaphy and identified the hernia sac as being indirect and the shunt vessel existing in the extraperitoneal cavity through the internal inguinal ring.Then,we found two short branches between the expanded shunt vessel and testicular vein in the middle part of the inguinal canal and cut these branches to allow the shunt vessel to return to the extraperitoneal cavity of the abdomen.The hernia sac was returned as well.We encountered no intraoperative complications.After discharge,groin seroma requiring puncture at the outpatient clinic was observed.CONCLUSION If an inguinal hernia patient has portal hypertension,ultrasound should be used to determine the contents of the hernia.When atypical vessels are visualized,they may be shunt vessels and additional CT is recommended to ensure the selection of an adequate approach for safe hernia repair.
文摘Chest CT frequently reveals small pulmonary lesions. If there is no associated hilar or mediastinal lymphadenopathy, small-cell lung cancer (SCLC) is considered to be very early-stage. Few studies, however, have described the characteristic CT findings of very early-stage SCLC. Clarifying these findings would reduce diagnostic delay. The purpose of this study was to determine the characteristic CT findings of very earlystage SCLC. Computed tomography images obtained from 547 consecutive patients with lung cancer between 2003 and 2012 at Tokyo Dental College Ichikawa General Hospital were reviewed retrospectively. One hundred of these patients had SCLC and 447 had non-SCLC (NSCLC). These CT images, along with any that had also been obtained prior to the one on which the final diagnosis was based, were reviewed. In 5 of the cases reviewed, specific findings and a characteristic spreading pattern were identified on CT images that might have allowed a diagnosis of SCLC to have been made sooner. The findings included a sub-pleural, small nodule accompanied by daughter nodules spreading longitudinally along the bronchovascular bundle, no air bronchogram or cavitation, and background emphysematous change. These were not identified on CT images of very earlystage NCSLC, however (n = 22). Awareness of the relevance of these findings would help physicians and radiologists arrive at a differential diagnosis of small pulmonary nodules.
文摘Corncobs could serve as a substrate for citric acid production using solid state fermentation technique. The culture optimization concerning substrate concentration, culture duration, pH, temperature and substrate hydrolysis was carried out for maximum productivity of citric acid. Under the optimized conditions, 48.4 g of citric acid was produced from 1 kg dry corncobs. Biological evaluation was carried out for citric acid such as melanin synthesis inhibitory, anti-allergy, anti-bacterial, and hyaluronic acid production activities. The results showed that citric acid has potent melanin inhibitory activity, good inhibition for β-hexosaminidase release and potent stimulatory effect for the production of hyaluronic acid. These activities (melanin synthesis inhibitory, anti-allergy and hyaluronic acid productive activities) of citric acid have been reported for the first time.
基金This work is supported by JP20J20669(Y.O.),JP21H04791(A.I.),JP21H05113(A.I.),JPJSBP120213501(A.I.)JPJSBP120218801(A.I.),and JP21H05115(T.S.)from The Japan Society for the Promotion of Science(JSPS)JPMJPR1331(A.I.),JPMJFR215T(A.I.),JPMJMS2023(A.I.)from the Japan Science and Technology Agency(JST)+4 种基金JP19gm5910013(A.I.),JP19gm0010004(A.I.and J.A.),JP20am0101095(A.I.),JP22ama121038(A.I.)and JP22zf0127007(A.I.)from the Japan Agency for Medical Research and Development(AMED)Takeda Science Foundation(A.I.)The Uehara Memorial Foundation(A.I.)Tokyo Biochemical Research Foundation(A.I.)and Daiichi Sankyo Foundation of Life Science(A.I.).F.R.was supported by the Italian Ministry of University and Research through the Department of excellence“Faculty of Sciences”of Scuola Normale Superiore.The research leading to these results also received funding from the Italian Association for Cancer Research(AIRC)under My First AIRC Grant(MFAG)2020-ID.24317 project-P.I.Raimondi Francesco.G.S.and R.B.R.were funded by BMBF-funded de.NBI HD-HuB network,number#031A537C.
文摘Dear Editor,Beige adipocytes,which increase energy expenditure by dissipating energy as heat,have gained attention as a therapeutic target for combating obesity.1 Adipocytes express many types of G-protein-coupled receptors(GPCRs),each of which has a unique preference for the Gs,Gi,Gq,and G12 subfamilies.While the function of Gs-coupledβ-adrenergic receptors in beige adipocyte induction is well established,2 little is known about the function of G12-coupled GPCRs beyond its suppressive roles in white adipocyte maturation.3 In this study,we generated transgenic mice conditionally expressing a G12-coupled designer GPCR using a Cre-loxP system and investigated the potential effects of G12 signaling on adipocyte biology.
