Mg_(97)Zn_(1)Y_(2)alloys with high ignition temperatures were developed by adding Sr.The addition of Sr resulted in the formation of a uniform and thin Y_(2)O_(3)film.Mg–Zn–Y alloys containing at least 0.25 at.%Sr e...Mg_(97)Zn_(1)Y_(2)alloys with high ignition temperatures were developed by adding Sr.The addition of Sr resulted in the formation of a uniform and thin Y_(2)O_(3)film.Mg–Zn–Y alloys containing at least 0.25 at.%Sr exhibited ignition temperatures of 1270–1320 K.As a result of EDS measurement,Sr was found to be concentrated in the Y_(2)O_(3)film.In addition,a mixed film of MgO and Sr O formed on the outer layer in the 1.5 at.%Sr-containing Mg_(97)Zn_(1)Y_(2)alloy.These findings suggest that the uniform and thin Y_(2)O_(3)film that maintains high soundness at high temperatures was formed owing to valence control and the formation of a protective outer oxide film.展开更多
The fracture toughness of extruded Mg-1Zn-2Y(at.%)alloys,featuring a multimodal microstructure containing fine dynamically recrystallized(DRXed)grains with random crystallographic orientation and coarse-worked grains ...The fracture toughness of extruded Mg-1Zn-2Y(at.%)alloys,featuring a multimodal microstructure containing fine dynamically recrystallized(DRXed)grains with random crystallographic orientation and coarse-worked grains with a strong fiber texture,was investigated.The DRXed grains comprised randomly oriented equiaxedα-Mg grains.In contrast,the worked grains includedα-Mg and long-period stacking ordered(LPSO)phases that extended in the extrusion direction(ED).Both types displayed a strong texture,aligning the(10.10)direction parallel to the ED.The volume fractions of the DRXed and worked grains were controlled by adjusting the extrusion temperature.In the longitudinal-transverse(L-T)orientation,where the loading direction was aligned parallel to the ED,there was a tendency for the conditional fracture toughness,KQ,tended to increase as the volume fraction of the worked grains increased.However,the KQ values in the T-L orientation,where the loading direction was perpendicular to the ED,decreased with an increase in the volume fraction of the worked grains.This suggests strong anisotropy in the fracture toughness of the specimen with a high volume fraction of the worked grains,relative to the test direction.The worked grains,which included the LPSO phase and were elongated perpendicular to the initial crack plane,suppressed the straight crack extension,causing crack deflection,and generating secondary cracks.Thus,these worked grains significantly contributed to the fracture toughness of the extruded Mg-1Zn-2Y alloys in the L-T orientation.展开更多
The deformation mechanisms and dynamic recrystallization(DRX)behavior of specifically grown bicrystals with a symmetric 90°<1010>and 90°<1120>tilt grain boundary,respectively,were investigated un...The deformation mechanisms and dynamic recrystallization(DRX)behavior of specifically grown bicrystals with a symmetric 90°<1010>and 90°<1120>tilt grain boundary,respectively,were investigated under deformation in plane strain compression at 200℃and 400℃.The microstructures were analyzed by panoramic optical microscopy and large-area electron backscatter diffraction(EBSD)orientation mapping.The analysis employed a meticulous approach utilizing hundreds of individual,small EBSD maps with a small step size that were stitched together to provide comprehensive access to orientation and misorientation data on a macroscopic scale.Basal slip primarily governed the early stages of deformation at the two temperatures,and the resulting shear induced lattice rotation around the transverse direction(TD)of the sample.The existence of the grain boundary gave rise to dislocation pile-up in its vicinity,leading to much larger TD-lattice rotations within the boundary region compared to the bulk.With increasing temperature,the deformation was generally more uniform towards the bulk due to enhanced dislocation mobility and more uniform stress distribution.Dynamic recrystallization at 200℃was initiated in{1011}-compression twins at strains of 40%and higher.At 400℃,DRX consumed the entire grain boundary region and gradually replaced the deformed microstructure with progressing deformation.The recrystallized grains displayed characteristic orientations,such that their c-axes were perpendicular to the TD and additionally scattered between 0°and 60°from the loading axis.These recrystallized grains displayed mutual rotations of up to 30°around the c-axes of the initial grains,forming a discernible basal fiber texture component,prominently visible in the{1120}pole figure.It is noteworthy that the deformation and DRX behaviors of the two analyzed bicrystals exhibited marginal variations in response to strain and deformation temperature.展开更多
Background:Colorectal cancer(CRC)is one of the most frequently diagnosed cancers.In many cases,the poor prognosis of advanced CRC is associated with resistance to treatment with chemotherapeutic drugs such as 5-Fluoro...Background:Colorectal cancer(CRC)is one of the most frequently diagnosed cancers.In many cases,the poor prognosis of advanced CRC is associated with resistance to treatment with chemotherapeutic drugs such as 5-Fluorouracil(5-FU).The epithelial-to-mesenchymal transition(EMT)and dysregulation in protein methylation are two mechanisms associated with chemoresistance in many cancers.This study looked into the effect of 5-FU dose escalation on EMT and protein methylation in CRC.Materials and Methods:HCT-116,Caco-2,and DLD-1 CRC cell lines were exposed to dose escalation treatment of 5-FU.The motility and invasive potentials of the cells before and after treatment with 5-FU were investigated through wound healing and invasion assays.This was followed by aWestern blot which analyzed the protein expressions of the epithelial marker E-cadherin,mesenchymal marker vimentin,and the EMT transcription factor(EMTTF),the snail family transcriptional repressor 1(Snail)in the parental and desensitized cells.Western blotting was also conducted to study the protein expressions of the protein methyltransferases(PMTs),Euchromatic histone lysine methyltransferase 2(EHMT2/G9A),protein arginine methyltransferase(PRMT5),and SET domain containing 7/9(SETD7/9)along with the global lysine and arginine methylation profiles.Results:The dose escalation method generated 5-FU desensitized CRC cells with distinct morphological features and increased tolerance to high doses of 5-FU.The 5-FU desensitized cells experienced a decrease in migration and invasion when compared to the parental cells.This was reflected in the observed reduction in E-cadherin,vimentin,and Snail in the desensitized cell lines.Additionally,the protein expressions of EHMT2/G9A,PRMT5,and SETD7/9 also decreased in the desensitized cells and global protein lysine and arginine methylation became dysregulated with 5-FU treatment.Conclusion:This study showed that continuous,dose-escalation treatment of 5-FU in CRC cells generated 5-FU desensitized cancer cells that seemed to be less aggressive than parental cells.展开更多
The Mg-Y-Zn magnesium alloy system is commonly recognized for its remarkable combination of high strength and ductility,achieved even with minimal amounts of alloying elements.This exceptional performance is attribute...The Mg-Y-Zn magnesium alloy system is commonly recognized for its remarkable combination of high strength and ductility,achieved even with minimal amounts of alloying elements.This exceptional performance is attributed to its unique microstructure,which includes Long-Period Stacking Ordered(LPSO)phases or the distinctive microstructure derived from the LPSO phase,referred to as the Mille-Feuille structure(MFS).This study systematically compares the traditional ingot metallurgy method with the rapid solidification technique,coupled with diverse heat treatments and extrusion processes.Microscopic analyses reveal variations in the presence of LPSO phases,Mille-Feuille structure,and grain size,leading to divergent mechanical and corrosion properties.The rapid solidification approach stands out,ensuring superior mechanical properties alongside a reasonable corrosion rate.展开更多
Centered or striped wick structures have been used to develop ultrathin heat pipes.Differing from traditional heat pipes,the centered or striped wick structures leave noncontact container surfaces with the wick struct...Centered or striped wick structures have been used to develop ultrathin heat pipes.Differing from traditional heat pipes,the centered or striped wick structures leave noncontact container surfaces with the wick structure.In this study,experiments andnumerical analyseswere conductedtoinvestigate the influenceof thesenoncontact surfaces.In the experiments,a strip-shaped wick structure was placed vertically,the top was sandwiched between wider rods and the bottom was immersed in a working fluid.The rod width was greater than the wick width;thus,noncontact surfaces were left between the rod and the wick structure.The heat was applied from the rod to the wick structure,and the evaporation heat transfer characteristics of the working fluid from the wick structure were evaluated.Water was used as the working fluid.The experiments were conducted by varying the rod and wick widths.The experimental results were obtained when the wick structures were placed separately.In the numerical analyses,the temperature and heat flux distributions in the rod were obtained.From the experimental and numerical results,it was confirmed that the noncontact surfaces caused the heat flux in the rod near both surfaces of the wick structure to concentrate,which increased the evaporation thermal resistance of the wick structure.A reduction in the noncontact surface area by increasing the wick width was found to be effective in decreasing the evaporation thermal resistance and increasing themaximumheat transfer rate of the wick structure.The separation of the wick structure increased the evaporation surface area.However,its effectiveness was limited when the heat transfer rate was small.展开更多
Visualization experiments were conducted to clarify the operational characteristics of a polymer pulsating heat pipe(PHP).Hydrofluoroether(HFE)-7100 was used as a working fluid,and its filling ratio was 50%of the enti...Visualization experiments were conducted to clarify the operational characteristics of a polymer pulsating heat pipe(PHP).Hydrofluoroether(HFE)-7100 was used as a working fluid,and its filling ratio was 50%of the entire PHP channel.A semi-transparent PHP was fabricated using a transparent polycarbonate sheet and a plastic 3D printer,and the movements of liquid slugs and vapor plugs of the working fluid were captured with a high-speed camera.The video images were then analyzed to obtain the flow patterns in the PHP.The heat transfer characteristics of the PHPwere discussed based on the flowpatterns and temperature distributions obtainedwith thermocouples.Before starting heating,because of high wettability,large liquid slugs positioned at the evaporator section of the PHP.After starting heating,since the occurrence of boiling divided the large liquid slugs,oscillatory flowof smaller liquid slugs and vapor plugs was found in the PHP.Clear circulation flow of liquid slugs and vapor plugs was observed when the power input to the PHP was larger than 12.0 W.The flow patterns and temperature distributions confirmed that the circulation flow enhanced the heat transfer from the evaporator section to the condenser section of the PHP.In the circulation flow mode,large growth and contraction of vapor plugs were found one after another in all even-numbered PHP channels.However,the analysis of flow patterns clarified that the phase-change heat transfer rate by large growth and contraction of vapor plugs was 19%of the total heat transfer rate of the PHP.Although the generation of large vapor plugs was found in the PHP,most of the heat was transferred by the sensible heat of the working fluid.展开更多
Thermal and fluid-flow characteristics were numerically analyzed for ultra-thin heat pipes.Many studies have been conducted for ultra-thin heat pipes with a centered wick structure,but this study focused on separated ...Thermal and fluid-flow characteristics were numerically analyzed for ultra-thin heat pipes.Many studies have been conducted for ultra-thin heat pipes with a centered wick structure,but this study focused on separated wick structures to increase the evaporation/condensation surface areas within the heat pipe and to reduce the concentration of heat flux within the wick structure.A mathematical heat-pipe model was made in the threedimensional coordinate system,and the model consisted of three regions:a vapor channel,liquid-wick,and container wall regions.The conservation equations for mass,momentum,and energy were solved numerically with boundary conditions by using a code developed by one of the authors.The numerical results with the separated wick structures were compared with those with the centered,which confirmed the effectiveness of the separation of the wick structure.However,the effectiveness of the separation was affected by the position of the separated wick structure.A simple equation was presented to determine the optimum position of the separated wick structures.Numerical analyses were also conducted when the width of the heat pipe was increased with the cooled section,which clarified that the increase in the cooled-section width with the addition of wick structures wasmore effective than the increase in the cooled-section length.A 44%reduction in the total temperature difference of the heat pipe was obtained under the present numerical conditions.Furthermore,a comparison wasmade between experimental results and numerical results.展开更多
Extended experiments were conducted on the oscillation characteristics of merged liquid slugs in a horizontally oriented polymer pulsating heat pipe(PHP).The PHP’s serpentine channel comprised 14 parallel channels wi...Extended experiments were conducted on the oscillation characteristics of merged liquid slugs in a horizontally oriented polymer pulsating heat pipe(PHP).The PHP’s serpentine channel comprised 14 parallel channels with a width of 1.3 mm and a height of 1.1 mm.The evaporator and condenser sections were 25 and 50 mm long,respectively,and the adiabatic section in between was 75mmlong.Using a plastic 3D printer and semi-transparent filament made from acrylonitrile butadiene styrene,the serpentine channel was printed directly onto a thin polycarbonate sheet to form the PHP.The PHP was charged with hydrofluoroether-7100.In the experiments,the evaporator section was heated,and the condenser section was cooled using high-temperature and low-temperature thermostatic baths,respectively.Flow patterns of the working fluid were obtained with temperature distributions of the PHP.A mathematical model was developed to analyze the flow patterns.Themerged liquid slugs were observed in every two channels,and their oscillation characteristics were found to be approximately the same in time and space.It was also found that the oscillations of the merged liquid slugs became slower,but the heat transfer rate of the PHP increased with a decrease in the filling ratio of the working fluid.This is because vapor condensation was enhanced in vapor plugs as the filling ratio decreased.However,the filling ratio had a lower limit,and the heat transfer rate was maximum when the filling ratio was 40.6%in the present experimental range.展开更多
Mg-Y-Zn-Al alloys processed by rapidly solidified ribbon consolidation(RSRC)technique exhibit an exceptional mechanical performance indicating promising application potential.This material has a bimodal microstructure...Mg-Y-Zn-Al alloys processed by rapidly solidified ribbon consolidation(RSRC)technique exhibit an exceptional mechanical performance indicating promising application potential.This material has a bimodal microstructure consisting of fine recrystallized and coarse non-recrystallized grains with solute-rich stacking faults forming cluster arranged layers(CALs)and nanoplates(CANaPs),or complete long period stacking ordered(LPSO)phase.In order to reveal the deformation mechanisms,in-situ synchrotron X-ray diffraction line profile analysis was employed for a detailed study of the dislocation arrangement created during tension in Mg-0.9%Zn-2.05%Y-0.15%Al(at%)alloy.For uncovering the effect of the initial microstructure on the mechanical performance,additional samples were obtained by annealing of the as-consolidated specimen at 300 and 400℃ for 2 h.The heat treatment at 300℃ had no significant effect on the initial microstructure,its evolution during tension and,thus,the overall deformation behavior under tensile loading.On the other hand,annealing at 400℃ resulted in a significant increase of the recrystallized grains fraction and a decrease of the dislocation density,leading to only minor degradation of the mechanical strength.The maximum dislocation density at the failure of the samples corresponding to the plastic strain of 10-25% was estimated to be about 16-20×10^(14)m^(-2).The diffraction profile analysis indicated that most dislocations formed during tension were of non-basal and pyramidal types,what was also in agreement with the Schmid factor values revealed independently from orientation maps.It was also shown that the dislocation-induced Taylor hardening was much lower below the plastic strain of 3% than above this value,which was explained by a model of the interaction between prismatic dislocations and CANaPs/LPSO plates.展开更多
Background: The neural representation of the body is easily altered by integrating multiple sensory signals in the brain. The “Rubber Hand Illusion” (RHI) is one of the most popular experimental paradigms to investi...Background: The neural representation of the body is easily altered by integrating multiple sensory signals in the brain. The “Rubber Hand Illusion” (RHI) is one of the most popular experimental paradigms to investigate this phenomenon. During this illusion, ownership of a rubber hand is temporarily induced. It was shown that external and continuous cooling of the palm enhanced the RHI, suggesting an association between altered the autonomic nervous system regulation and altered the sense of ownership of a specific limb. Purpose: To investigate whether artificially cooling the entire hand for a short period affects the magnitude of the illusion. Methods: Participants immersed their entire hand in cool, cold, or warm water for 1 min before the RHI procedure. Results: We found that cooling the entire hand enhanced the proprioceptive drift during the RHI but not the subjective feeling of ownership. In contrast, warming and intense cooling of the entire hand did not affect the RHI strength. Conclusion: Our results suggest that transient and moderate cooling of the entire hand was sufficient in enhancing the illusory disembodiment of one’s own hand.展开更多
Gastrointestinal(GI)cancer is a malignancy arising in the digestive system and accounts for approximately a third of increasing global cancer-related mortality,especially in the colorectum,esophagus,stomach,and liver....Gastrointestinal(GI)cancer is a malignancy arising in the digestive system and accounts for approximately a third of increasing global cancer-related mortality,especially in the colorectum,esophagus,stomach,and liver.Interleukin-1β(IL-1β)is a leukocytic pyrogen recognized as a tumor progression-related cytokine.IL-1βsecretion and maturation in inflammatory responses could be regulated by nuclear factor-kappaB-dependent expression of NLR family pyrin domain containing 3,inflammasome formation,and activation of IL-1 converting enzyme.Several studies have documented the pro-tumorigenic effects of IL-1β in tumor microenvironments,promoting proliferation and metastatic potential of cancer cells in vitro and tumorigenesis in vivo.The application of IL-1β inhibitors is also promising for targeted therapy development in some cancer types.However,as a leukocytic pro-inflammatory cytokine,IL-1β may also possess anti-tumorigenic effects and be type-specific in different cancers.This editorial discusses the up-to-date roles of IL-1β in GI cancers,including underlying mechanisms and down-stream signaling pathways.Understanding and clarifying the roles of IL-1β would significantly benefit future therapeutic targeting and help improve therapeutic outcomes in patients suffering from GI cancer.展开更多
Controlling Li ion transport in glasses at atomic and molecular levels is key to realizing all-solid-state batteries,a promising technology for electric vehicles.In this context,Li_(3)PS_(4)glass,a promising solid ele...Controlling Li ion transport in glasses at atomic and molecular levels is key to realizing all-solid-state batteries,a promising technology for electric vehicles.In this context,Li_(3)PS_(4)glass,a promising solid electrolyte candidate,exhibits dynamic coupling between the Li^(+)cation mobility and the PS_(4)^(3-)anion libration,which is commonly referred to as the paddlewheel effect.In addition,it exhibits a concerted cation diffusion effect(i.e.,a cation-cation interaction),which is regarded as the essence of high Li ion transport.However,the correlation between the Li^(+)ions within the glass structure can only be vaguely determined,due to the limited experimental information that can be obtained.Here,this study reports that the Li ions present in glasses can be classified by evaluating their valence oscillations via Bader analysis to topologically analyze the chemical bonds.It is found that three types of Li ions are present in Li_(3)PS_(4)glass,and that the more mobile Li ions(i.e.,the Li3-type ions)exhibit a characteristic correlation at relatively long distances of 4.0-5.0A.Furthermore,reverse Monte Carlo simulations combined with deep learning potentials that reproduce X-ray,neutron,and electron diffraction pair distribution functions showed an increase in the number of Li3-type ions for partially crystallized glass structures with improved Li ion transport properties.Our results show order within the disorder of the Li ion distribution in the glass by a topological analysis of their valences.Thus,considering the molecular vibrations in the glass during the evaluation of the Li ion valences is expected to lead to the development of new solid electrolytes.展开更多
Smoking habits are thought to be strongly impacted by family relationships. In this study, we looked specifically at family relationships with the aim of finding effective anti-smoking education measures. We surveyed ...Smoking habits are thought to be strongly impacted by family relationships. In this study, we looked specifically at family relationships with the aim of finding effective anti-smoking education measures. We surveyed 290 university students in order to establish their current smoking habits, along with their family relationships from primary and junior high school until now. The results showed that students with one or more smokers in their family were clearly more likely to smoke. Furthermore, a poor relationship between the student’s parents and a poor relationship with his/her father are believed to have a causal relationship with the student smoking. In the section in which students were asked how often they were told to study, we found that students who smoked had been instructed to study a significantly higher number of times. It is believed that the stress experienced by students frequently told that they must study during their elementary or junior high school years leads to a tendency to smoke. Among the group of non-smokers, we found many who ate breakfast with their parents during elementary or junior high school, along with many who regularly went on holidays with their families. The lack of these things appears to distance parents from children and may be a factor regarding why children end up smoking. In this study, while no clear correlation was found between family relationships and smoking, several types of family relationships that may lead to smoking were suggested.展开更多
Self-esteem is an important factor in the rise of depression cases among children and adolescents. In order to build self-esteem, it is important for parents to respect their children, acknowledge their value, and alw...Self-esteem is an important factor in the rise of depression cases among children and adolescents. In order to build self-esteem, it is important for parents to respect their children, acknowledge their value, and always encourage them, as well as for teachers to acknowledge their character and ability, in addition to allowing them to experience success. At the same time, voices calling for parents and teachers to rediscover their willingness and responsibility to scold children when necessary have also been growing. Therefore, the objective of the present study was to determine the association between self-esteem and the way of scolding. With 311 university students as the study subjects, self-esteem and the relevant factors thereof were evaluated. As a result, no association was observed between the way of being scolded and self-esteem. Moreover, the reasons for being scolded were also not associated with self-esteem. However, regarding the association between the degree of acceptance (convinced by the way of being scolded) and self-esteem, it was revealed that student groups with higher self-esteem had a higher degree of acceptance. This suggested that self-esteem is associated with whether or not the people being scolded are convinced, as opposed to the way of being scolded or the reason for being scolded. Therefore, it was suggested that building a good relationship with those you scold is more important than the way of scolding.展开更多
Presenteeism refers to impaired performance attributed to attending work with health problems. There has been no study examining the state of presenteeism with objective measures. We compared cerebral hemodynamic chan...Presenteeism refers to impaired performance attributed to attending work with health problems. There has been no study examining the state of presenteeism with objective measures. We compared cerebral hemodynamic changes, measured by near-infrared spectroscopy (NIRS), during neuropsychological tests conducted by university students with presenteeism and healthy controls. Twenty-two university students participated in the study;11 of them with impaired performance caused by mental health problem were allocated to the presenteeism group and 11 without health problems to the control group. Presenteeism was assessed by the Presenteeism Scale for Students. To evoke hemodynamics changes, the participants completed a Word Fluency Test (WFT) and a Trail Making Test (TMT). The NIRS probes were located over the bilateral prefrontal area. Students with presenteeism had significantly higher incidences of depression than controls. However, there was no significant difference in behavioral performance examinations between the two groups. With regard to hemodynamics changes, the repeated measures analysis of covariance of the NIRS signals revealed significant interactions between group and task activation. Although we observed a significant increase in oxygenated hemoglobin concentration during the WFT among controls (simple main effect;left channel, F(1, 19) = 27.34, P F(1, 19) = 22.05, P < 0.001), no changes were found in students with presenteeism during either the WFT (simple main effect;left channel, F(1, 19) = 0.12, P F(1, 19) = 0.08, P t = ﹣0.94, P with Bonferroni correction = 0.745;right channel, t = ﹣2.19, P with Bonferroni correction < 0.113). This is the first study to reveal differences in activity in the cerebral cortex associated with presenteeism. The fact that students with presenteeism have prefrontal dysfunction might reinforce the concept of presenteeism.展开更多
Coronavirus disease 2019(COVID-19)caused by the novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has become a major global public health event,resulting in a significant social and economic burden.Alth...Coronavirus disease 2019(COVID-19)caused by the novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has become a major global public health event,resulting in a significant social and economic burden.Although COVID-19 was initially characterized as an upper respiratory and pulmonary infection,recent evidence suggests that it is a complex disease including gastrointestinal symptoms,such as diarrhea,nausea,and vomiting.Moreover,it remains unclear whether the gastrointestinal symptoms are caused by direct infection of the gastrointestinal tract by SARS-CoV-2 or are the result of systemic immune activation and subsequent dysregulation of homeostatic mechanisms.This review provides a brief overview of the mechanisms by which SARS-CoV-2 disrupts the integrity of the gastrointestinal barrier including the mechanical barrier,chemical barrier,microbial barrier,and immune barrier.展开更多
The relationship between IgA nephropathy(IgAN)and Crohn’s disease was reported.IgAN is the most common primary glomerulonephritis and one of the leading causes of chronic kidney disease and end-stage renal failure,an...The relationship between IgA nephropathy(IgAN)and Crohn’s disease was reported.IgAN is the most common primary glomerulonephritis and one of the leading causes of chronic kidney disease and end-stage renal failure,and up to 50%of cases progressed to end-stage renal disease within 25 years after IgAN diagnosis.However,specific and effective therapeutic strategies are still lacking.In this review,we discuss the possibility of the mechanism involved in IgAN associated with Crohn’s disease based on the findings of basic and clinical studies.Although the etiology of IgAN associated with Crohn’s disease is not permanent and various factors are thought to be involved,the stabilization of the disease condition of Crohn’s disease is believed to help treat IgAN.展开更多
BACKGROUND The association between diabetes mellitus(DM)and the increased risk and progression of cholangiocarcinoma(CCA)has been reported with unclear underlying mechanisms.Previous studies showed thatγ-aminobutyric...BACKGROUND The association between diabetes mellitus(DM)and the increased risk and progression of cholangiocarcinoma(CCA)has been reported with unclear underlying mechanisms.Previous studies showed thatγ-aminobutyric acid(GABA)B2 receptor(GABBR2)was upregulated in CCA cells cultured in high glucose(HG)conditions.Roles of GABA receptors in CCA progression have also been studied,but their association with DM and hyperglycemia in CCA remains unclarified.AIM To investigate the effects of hyperglycemia on GABBR2 expression and the potential use of GABBR2 as a CCA therapeutic target.METHODS CCA cells,KKU-055 and KKU-213A,were cultured in Dulbecco Modified Eagle’s Medium supplemented with 5.6 mmol/L(normal glucose,NG)or 25 mmol/L(HG)glucose and assigned as NG and HG cells,respectively.GABBR2 expression in NG and HG cells was investigated using real-time quantitative polymerase chain reaction and western blot.Expression and localization of GABBR2 in CCA cells were determined using immunocytofluorescence.GABBR2 expression in tumor tissues from CCA patients with and without DM was studied using immunohistochemistry,and the correlations of GABBR2 with the clinicopathological characteristics of patients were analyzed using univariate analysis.Effects of baclofen,a GABA-B receptor agonist,on CCA cell proliferation and clonogenicity were tested using the MTT and clonogenic assays.Phospho-kinases arrays were used to screen the affected signaling pathways after baclofen treatment,and the candidate signaling molecules were validated using the public transcriptomic data and western blot.RESULTS GABBR2 expression in CCA cells was induced by HG in a dose-and time-dependent manner.CCA tissues from patients with DM and hyperglycemia also showed a significantly higher GABBR2 expression compared with tumor tissues from those with euglycemia(P<0.01).High GABBR2 expression was significantly associated with a poorer non-papillary histological subtype but with smaller sizes of CCA tumors(P<0.05).HG cells of both tested CCA cell lines were more sensitive to baclofen treatment.Baclofen significantly suppressed the proliferation and clonogenicity of CCA cells in both NG and HG conditions(P<0.05).Phospho-kinase arrays suggested glycogen synthase kinase 3(GSK3),β-catenin,and the signal transducer and activator of transcription 3(STAT3)as candidate signaling molecules under the regulation of GABBR2,which were verified in NG and HG cells of the individual CCA cell lines.Cyclin D1 and c-Myc,the common downstream targets of GSK3/β-catenin and STAT3 involving cell proliferation,were accordingly downregulated after baclofen treatment.CONCLUSION GABBR2 is upregulated by HG and holds a promising role as a therapeutic target for CCA regardless of the glucose condition.展开更多
基金supported by Grants-in-Aid for Scientific Research C(JP21K04693)from JSPS,Japan。
文摘Mg_(97)Zn_(1)Y_(2)alloys with high ignition temperatures were developed by adding Sr.The addition of Sr resulted in the formation of a uniform and thin Y_(2)O_(3)film.Mg–Zn–Y alloys containing at least 0.25 at.%Sr exhibited ignition temperatures of 1270–1320 K.As a result of EDS measurement,Sr was found to be concentrated in the Y_(2)O_(3)film.In addition,a mixed film of MgO and Sr O formed on the outer layer in the 1.5 at.%Sr-containing Mg_(97)Zn_(1)Y_(2)alloy.These findings suggest that the uniform and thin Y_(2)O_(3)film that maintains high soundness at high temperatures was formed owing to valence control and the formation of a protective outer oxide film.
基金supported by the JST CREST for Research Area“Nanomechanics”[JPMJCR2094]the JSPS KAKENHI for Scientific Research B[JP21H01673]the AMADA Foundation[AF-2023044-C2].
文摘The fracture toughness of extruded Mg-1Zn-2Y(at.%)alloys,featuring a multimodal microstructure containing fine dynamically recrystallized(DRXed)grains with random crystallographic orientation and coarse-worked grains with a strong fiber texture,was investigated.The DRXed grains comprised randomly oriented equiaxedα-Mg grains.In contrast,the worked grains includedα-Mg and long-period stacking ordered(LPSO)phases that extended in the extrusion direction(ED).Both types displayed a strong texture,aligning the(10.10)direction parallel to the ED.The volume fractions of the DRXed and worked grains were controlled by adjusting the extrusion temperature.In the longitudinal-transverse(L-T)orientation,where the loading direction was aligned parallel to the ED,there was a tendency for the conditional fracture toughness,KQ,tended to increase as the volume fraction of the worked grains increased.However,the KQ values in the T-L orientation,where the loading direction was perpendicular to the ED,decreased with an increase in the volume fraction of the worked grains.This suggests strong anisotropy in the fracture toughness of the specimen with a high volume fraction of the worked grains,relative to the test direction.The worked grains,which included the LPSO phase and were elongated perpendicular to the initial crack plane,suppressed the straight crack extension,causing crack deflection,and generating secondary cracks.Thus,these worked grains significantly contributed to the fracture toughness of the extruded Mg-1Zn-2Y alloys in the L-T orientation.
基金the Deutsche Forschungsgemeinschaft(DFG)for financial support(MO 848/18-2)。
文摘The deformation mechanisms and dynamic recrystallization(DRX)behavior of specifically grown bicrystals with a symmetric 90°<1010>and 90°<1120>tilt grain boundary,respectively,were investigated under deformation in plane strain compression at 200℃and 400℃.The microstructures were analyzed by panoramic optical microscopy and large-area electron backscatter diffraction(EBSD)orientation mapping.The analysis employed a meticulous approach utilizing hundreds of individual,small EBSD maps with a small step size that were stitched together to provide comprehensive access to orientation and misorientation data on a macroscopic scale.Basal slip primarily governed the early stages of deformation at the two temperatures,and the resulting shear induced lattice rotation around the transverse direction(TD)of the sample.The existence of the grain boundary gave rise to dislocation pile-up in its vicinity,leading to much larger TD-lattice rotations within the boundary region compared to the bulk.With increasing temperature,the deformation was generally more uniform towards the bulk due to enhanced dislocation mobility and more uniform stress distribution.Dynamic recrystallization at 200℃was initiated in{1011}-compression twins at strains of 40%and higher.At 400℃,DRX consumed the entire grain boundary region and gradually replaced the deformed microstructure with progressing deformation.The recrystallized grains displayed characteristic orientations,such that their c-axes were perpendicular to the TD and additionally scattered between 0°and 60°from the loading axis.These recrystallized grains displayed mutual rotations of up to 30°around the c-axes of the initial grains,forming a discernible basal fiber texture component,prominently visible in the{1120}pole figure.It is noteworthy that the deformation and DRX behaviors of the two analyzed bicrystals exhibited marginal variations in response to strain and deformation temperature.
基金supported through the Faculty of Medicine and Surgery Award 2021 University of Malta(awarded to K.F).
文摘Background:Colorectal cancer(CRC)is one of the most frequently diagnosed cancers.In many cases,the poor prognosis of advanced CRC is associated with resistance to treatment with chemotherapeutic drugs such as 5-Fluorouracil(5-FU).The epithelial-to-mesenchymal transition(EMT)and dysregulation in protein methylation are two mechanisms associated with chemoresistance in many cancers.This study looked into the effect of 5-FU dose escalation on EMT and protein methylation in CRC.Materials and Methods:HCT-116,Caco-2,and DLD-1 CRC cell lines were exposed to dose escalation treatment of 5-FU.The motility and invasive potentials of the cells before and after treatment with 5-FU were investigated through wound healing and invasion assays.This was followed by aWestern blot which analyzed the protein expressions of the epithelial marker E-cadherin,mesenchymal marker vimentin,and the EMT transcription factor(EMTTF),the snail family transcriptional repressor 1(Snail)in the parental and desensitized cells.Western blotting was also conducted to study the protein expressions of the protein methyltransferases(PMTs),Euchromatic histone lysine methyltransferase 2(EHMT2/G9A),protein arginine methyltransferase(PRMT5),and SET domain containing 7/9(SETD7/9)along with the global lysine and arginine methylation profiles.Results:The dose escalation method generated 5-FU desensitized CRC cells with distinct morphological features and increased tolerance to high doses of 5-FU.The 5-FU desensitized cells experienced a decrease in migration and invasion when compared to the parental cells.This was reflected in the observed reduction in E-cadherin,vimentin,and Snail in the desensitized cell lines.Additionally,the protein expressions of EHMT2/G9A,PRMT5,and SETD7/9 also decreased in the desensitized cells and global protein lysine and arginine methylation became dysregulated with 5-FU treatment.Conclusion:This study showed that continuous,dose-escalation treatment of 5-FU in CRC cells generated 5-FU desensitized cancer cells that seemed to be less aggressive than parental cells.
基金supported by Japan Society for the Promotion of Science(KAKENHI Grant-in-Aid for Scientific Research18H05475,18H05476 and JP20H00312)+2 种基金MRC International Collaborative Research Grant.The authors would like to thank the Czech Science Foundation(Project No.22-22248S)specific university research(A1_FCHT_2024_007)for financial supportthe assistance provided by the Ferroic Multifunctionalities project,supported by the Ministry of Education,Youth,and Sports of the Czech Republic.Project No.CZ.02.01.01/00/22_008/0004591,co-funded by the European Union.CzechNanoLab project LM2023051 funded by MEYS CR is gratefully acknowledged for the financial support of the measurements/sample fabrication at LNSM Research Infrastructure.
文摘The Mg-Y-Zn magnesium alloy system is commonly recognized for its remarkable combination of high strength and ductility,achieved even with minimal amounts of alloying elements.This exceptional performance is attributed to its unique microstructure,which includes Long-Period Stacking Ordered(LPSO)phases or the distinctive microstructure derived from the LPSO phase,referred to as the Mille-Feuille structure(MFS).This study systematically compares the traditional ingot metallurgy method with the rapid solidification technique,coupled with diverse heat treatments and extrusion processes.Microscopic analyses reveal variations in the presence of LPSO phases,Mille-Feuille structure,and grain size,leading to divergent mechanical and corrosion properties.The rapid solidification approach stands out,ensuring superior mechanical properties alongside a reasonable corrosion rate.
文摘Centered or striped wick structures have been used to develop ultrathin heat pipes.Differing from traditional heat pipes,the centered or striped wick structures leave noncontact container surfaces with the wick structure.In this study,experiments andnumerical analyseswere conductedtoinvestigate the influenceof thesenoncontact surfaces.In the experiments,a strip-shaped wick structure was placed vertically,the top was sandwiched between wider rods and the bottom was immersed in a working fluid.The rod width was greater than the wick width;thus,noncontact surfaces were left between the rod and the wick structure.The heat was applied from the rod to the wick structure,and the evaporation heat transfer characteristics of the working fluid from the wick structure were evaluated.Water was used as the working fluid.The experiments were conducted by varying the rod and wick widths.The experimental results were obtained when the wick structures were placed separately.In the numerical analyses,the temperature and heat flux distributions in the rod were obtained.From the experimental and numerical results,it was confirmed that the noncontact surfaces caused the heat flux in the rod near both surfaces of the wick structure to concentrate,which increased the evaporation thermal resistance of the wick structure.A reduction in the noncontact surface area by increasing the wick width was found to be effective in decreasing the evaporation thermal resistance and increasing themaximumheat transfer rate of the wick structure.The separation of the wick structure increased the evaporation surface area.However,its effectiveness was limited when the heat transfer rate was small.
基金supported by JSPS KAKENHI Grant Number 22K03947.
文摘Visualization experiments were conducted to clarify the operational characteristics of a polymer pulsating heat pipe(PHP).Hydrofluoroether(HFE)-7100 was used as a working fluid,and its filling ratio was 50%of the entire PHP channel.A semi-transparent PHP was fabricated using a transparent polycarbonate sheet and a plastic 3D printer,and the movements of liquid slugs and vapor plugs of the working fluid were captured with a high-speed camera.The video images were then analyzed to obtain the flow patterns in the PHP.The heat transfer characteristics of the PHPwere discussed based on the flowpatterns and temperature distributions obtainedwith thermocouples.Before starting heating,because of high wettability,large liquid slugs positioned at the evaporator section of the PHP.After starting heating,since the occurrence of boiling divided the large liquid slugs,oscillatory flowof smaller liquid slugs and vapor plugs was found in the PHP.Clear circulation flow of liquid slugs and vapor plugs was observed when the power input to the PHP was larger than 12.0 W.The flow patterns and temperature distributions confirmed that the circulation flow enhanced the heat transfer from the evaporator section to the condenser section of the PHP.In the circulation flow mode,large growth and contraction of vapor plugs were found one after another in all even-numbered PHP channels.However,the analysis of flow patterns clarified that the phase-change heat transfer rate by large growth and contraction of vapor plugs was 19%of the total heat transfer rate of the PHP.Although the generation of large vapor plugs was found in the PHP,most of the heat was transferred by the sensible heat of the working fluid.
文摘Thermal and fluid-flow characteristics were numerically analyzed for ultra-thin heat pipes.Many studies have been conducted for ultra-thin heat pipes with a centered wick structure,but this study focused on separated wick structures to increase the evaporation/condensation surface areas within the heat pipe and to reduce the concentration of heat flux within the wick structure.A mathematical heat-pipe model was made in the threedimensional coordinate system,and the model consisted of three regions:a vapor channel,liquid-wick,and container wall regions.The conservation equations for mass,momentum,and energy were solved numerically with boundary conditions by using a code developed by one of the authors.The numerical results with the separated wick structures were compared with those with the centered,which confirmed the effectiveness of the separation of the wick structure.However,the effectiveness of the separation was affected by the position of the separated wick structure.A simple equation was presented to determine the optimum position of the separated wick structures.Numerical analyses were also conducted when the width of the heat pipe was increased with the cooled section,which clarified that the increase in the cooled-section width with the addition of wick structures wasmore effective than the increase in the cooled-section length.A 44%reduction in the total temperature difference of the heat pipe was obtained under the present numerical conditions.Furthermore,a comparison wasmade between experimental results and numerical results.
基金supported by JSPS KAKENHI Grant Number 22K03947.
文摘Extended experiments were conducted on the oscillation characteristics of merged liquid slugs in a horizontally oriented polymer pulsating heat pipe(PHP).The PHP’s serpentine channel comprised 14 parallel channels with a width of 1.3 mm and a height of 1.1 mm.The evaporator and condenser sections were 25 and 50 mm long,respectively,and the adiabatic section in between was 75mmlong.Using a plastic 3D printer and semi-transparent filament made from acrylonitrile butadiene styrene,the serpentine channel was printed directly onto a thin polycarbonate sheet to form the PHP.The PHP was charged with hydrofluoroether-7100.In the experiments,the evaporator section was heated,and the condenser section was cooled using high-temperature and low-temperature thermostatic baths,respectively.Flow patterns of the working fluid were obtained with temperature distributions of the PHP.A mathematical model was developed to analyze the flow patterns.Themerged liquid slugs were observed in every two channels,and their oscillation characteristics were found to be approximately the same in time and space.It was also found that the oscillations of the merged liquid slugs became slower,but the heat transfer rate of the PHP increased with a decrease in the filling ratio of the working fluid.This is because vapor condensation was enhanced in vapor plugs as the filling ratio decreased.However,the filling ratio had a lower limit,and the heat transfer rate was maximum when the filling ratio was 40.6%in the present experimental range.
基金financially supported by the International Visegrad Fund(project V4-Japan Joint Research Program,Ref.JP3936)the National Research,Development and Innovation Office(Contract No.:2019-2.1.7-ERANET-2021-00030)+1 种基金Support by the Ministry of Education,Youth and Sports of Czech Republic in the framework of Visegrad Group(V4)-Japan Joint Research Program-Advanced Materials under grant No.8F21011supported by JST SICORP Grant Number JPMJSC2109,Japan。
文摘Mg-Y-Zn-Al alloys processed by rapidly solidified ribbon consolidation(RSRC)technique exhibit an exceptional mechanical performance indicating promising application potential.This material has a bimodal microstructure consisting of fine recrystallized and coarse non-recrystallized grains with solute-rich stacking faults forming cluster arranged layers(CALs)and nanoplates(CANaPs),or complete long period stacking ordered(LPSO)phase.In order to reveal the deformation mechanisms,in-situ synchrotron X-ray diffraction line profile analysis was employed for a detailed study of the dislocation arrangement created during tension in Mg-0.9%Zn-2.05%Y-0.15%Al(at%)alloy.For uncovering the effect of the initial microstructure on the mechanical performance,additional samples were obtained by annealing of the as-consolidated specimen at 300 and 400℃ for 2 h.The heat treatment at 300℃ had no significant effect on the initial microstructure,its evolution during tension and,thus,the overall deformation behavior under tensile loading.On the other hand,annealing at 400℃ resulted in a significant increase of the recrystallized grains fraction and a decrease of the dislocation density,leading to only minor degradation of the mechanical strength.The maximum dislocation density at the failure of the samples corresponding to the plastic strain of 10-25% was estimated to be about 16-20×10^(14)m^(-2).The diffraction profile analysis indicated that most dislocations formed during tension were of non-basal and pyramidal types,what was also in agreement with the Schmid factor values revealed independently from orientation maps.It was also shown that the dislocation-induced Taylor hardening was much lower below the plastic strain of 3% than above this value,which was explained by a model of the interaction between prismatic dislocations and CANaPs/LPSO plates.
文摘Background: The neural representation of the body is easily altered by integrating multiple sensory signals in the brain. The “Rubber Hand Illusion” (RHI) is one of the most popular experimental paradigms to investigate this phenomenon. During this illusion, ownership of a rubber hand is temporarily induced. It was shown that external and continuous cooling of the palm enhanced the RHI, suggesting an association between altered the autonomic nervous system regulation and altered the sense of ownership of a specific limb. Purpose: To investigate whether artificially cooling the entire hand for a short period affects the magnitude of the illusion. Methods: Participants immersed their entire hand in cool, cold, or warm water for 1 min before the RHI procedure. Results: We found that cooling the entire hand enhanced the proprioceptive drift during the RHI but not the subjective feeling of ownership. In contrast, warming and intense cooling of the entire hand did not affect the RHI strength. Conclusion: Our results suggest that transient and moderate cooling of the entire hand was sufficient in enhancing the illusory disembodiment of one’s own hand.
基金Supported by National Research Council of Thailand,No.N41A640108Mekong-Lancang Cooperation Special Fund+1 种基金The Development and Promotion of Science and Technology Talents ProjectMinistry of Education,Science,Sports,and Culture of Japan,No.22K16327 and No.22K08482.
文摘Gastrointestinal(GI)cancer is a malignancy arising in the digestive system and accounts for approximately a third of increasing global cancer-related mortality,especially in the colorectum,esophagus,stomach,and liver.Interleukin-1β(IL-1β)is a leukocytic pyrogen recognized as a tumor progression-related cytokine.IL-1βsecretion and maturation in inflammatory responses could be regulated by nuclear factor-kappaB-dependent expression of NLR family pyrin domain containing 3,inflammasome formation,and activation of IL-1 converting enzyme.Several studies have documented the pro-tumorigenic effects of IL-1β in tumor microenvironments,promoting proliferation and metastatic potential of cancer cells in vitro and tumorigenesis in vivo.The application of IL-1β inhibitors is also promising for targeted therapy development in some cancer types.However,as a leukocytic pro-inflammatory cytokine,IL-1β may also possess anti-tumorigenic effects and be type-specific in different cancers.This editorial discusses the up-to-date roles of IL-1β in GI cancers,including underlying mechanisms and down-stream signaling pathways.Understanding and clarifying the roles of IL-1β would significantly benefit future therapeutic targeting and help improve therapeutic outcomes in patients suffering from GI cancer.
基金partially supported by JSPS KAKENHI(Grant Numbers 19 K05025,19H05814,19H05815,19H05816,20H02430,21H02038,and 21H05549)
文摘Controlling Li ion transport in glasses at atomic and molecular levels is key to realizing all-solid-state batteries,a promising technology for electric vehicles.In this context,Li_(3)PS_(4)glass,a promising solid electrolyte candidate,exhibits dynamic coupling between the Li^(+)cation mobility and the PS_(4)^(3-)anion libration,which is commonly referred to as the paddlewheel effect.In addition,it exhibits a concerted cation diffusion effect(i.e.,a cation-cation interaction),which is regarded as the essence of high Li ion transport.However,the correlation between the Li^(+)ions within the glass structure can only be vaguely determined,due to the limited experimental information that can be obtained.Here,this study reports that the Li ions present in glasses can be classified by evaluating their valence oscillations via Bader analysis to topologically analyze the chemical bonds.It is found that three types of Li ions are present in Li_(3)PS_(4)glass,and that the more mobile Li ions(i.e.,the Li3-type ions)exhibit a characteristic correlation at relatively long distances of 4.0-5.0A.Furthermore,reverse Monte Carlo simulations combined with deep learning potentials that reproduce X-ray,neutron,and electron diffraction pair distribution functions showed an increase in the number of Li3-type ions for partially crystallized glass structures with improved Li ion transport properties.Our results show order within the disorder of the Li ion distribution in the glass by a topological analysis of their valences.Thus,considering the molecular vibrations in the glass during the evaluation of the Li ion valences is expected to lead to the development of new solid electrolytes.
文摘Smoking habits are thought to be strongly impacted by family relationships. In this study, we looked specifically at family relationships with the aim of finding effective anti-smoking education measures. We surveyed 290 university students in order to establish their current smoking habits, along with their family relationships from primary and junior high school until now. The results showed that students with one or more smokers in their family were clearly more likely to smoke. Furthermore, a poor relationship between the student’s parents and a poor relationship with his/her father are believed to have a causal relationship with the student smoking. In the section in which students were asked how often they were told to study, we found that students who smoked had been instructed to study a significantly higher number of times. It is believed that the stress experienced by students frequently told that they must study during their elementary or junior high school years leads to a tendency to smoke. Among the group of non-smokers, we found many who ate breakfast with their parents during elementary or junior high school, along with many who regularly went on holidays with their families. The lack of these things appears to distance parents from children and may be a factor regarding why children end up smoking. In this study, while no clear correlation was found between family relationships and smoking, several types of family relationships that may lead to smoking were suggested.
文摘Self-esteem is an important factor in the rise of depression cases among children and adolescents. In order to build self-esteem, it is important for parents to respect their children, acknowledge their value, and always encourage them, as well as for teachers to acknowledge their character and ability, in addition to allowing them to experience success. At the same time, voices calling for parents and teachers to rediscover their willingness and responsibility to scold children when necessary have also been growing. Therefore, the objective of the present study was to determine the association between self-esteem and the way of scolding. With 311 university students as the study subjects, self-esteem and the relevant factors thereof were evaluated. As a result, no association was observed between the way of being scolded and self-esteem. Moreover, the reasons for being scolded were also not associated with self-esteem. However, regarding the association between the degree of acceptance (convinced by the way of being scolded) and self-esteem, it was revealed that student groups with higher self-esteem had a higher degree of acceptance. This suggested that self-esteem is associated with whether or not the people being scolded are convinced, as opposed to the way of being scolded or the reason for being scolded. Therefore, it was suggested that building a good relationship with those you scold is more important than the way of scolding.
文摘Presenteeism refers to impaired performance attributed to attending work with health problems. There has been no study examining the state of presenteeism with objective measures. We compared cerebral hemodynamic changes, measured by near-infrared spectroscopy (NIRS), during neuropsychological tests conducted by university students with presenteeism and healthy controls. Twenty-two university students participated in the study;11 of them with impaired performance caused by mental health problem were allocated to the presenteeism group and 11 without health problems to the control group. Presenteeism was assessed by the Presenteeism Scale for Students. To evoke hemodynamics changes, the participants completed a Word Fluency Test (WFT) and a Trail Making Test (TMT). The NIRS probes were located over the bilateral prefrontal area. Students with presenteeism had significantly higher incidences of depression than controls. However, there was no significant difference in behavioral performance examinations between the two groups. With regard to hemodynamics changes, the repeated measures analysis of covariance of the NIRS signals revealed significant interactions between group and task activation. Although we observed a significant increase in oxygenated hemoglobin concentration during the WFT among controls (simple main effect;left channel, F(1, 19) = 27.34, P F(1, 19) = 22.05, P < 0.001), no changes were found in students with presenteeism during either the WFT (simple main effect;left channel, F(1, 19) = 0.12, P F(1, 19) = 0.08, P t = ﹣0.94, P with Bonferroni correction = 0.745;right channel, t = ﹣2.19, P with Bonferroni correction < 0.113). This is the first study to reveal differences in activity in the cerebral cortex associated with presenteeism. The fact that students with presenteeism have prefrontal dysfunction might reinforce the concept of presenteeism.
文摘Coronavirus disease 2019(COVID-19)caused by the novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has become a major global public health event,resulting in a significant social and economic burden.Although COVID-19 was initially characterized as an upper respiratory and pulmonary infection,recent evidence suggests that it is a complex disease including gastrointestinal symptoms,such as diarrhea,nausea,and vomiting.Moreover,it remains unclear whether the gastrointestinal symptoms are caused by direct infection of the gastrointestinal tract by SARS-CoV-2 or are the result of systemic immune activation and subsequent dysregulation of homeostatic mechanisms.This review provides a brief overview of the mechanisms by which SARS-CoV-2 disrupts the integrity of the gastrointestinal barrier including the mechanical barrier,chemical barrier,microbial barrier,and immune barrier.
文摘The relationship between IgA nephropathy(IgAN)and Crohn’s disease was reported.IgAN is the most common primary glomerulonephritis and one of the leading causes of chronic kidney disease and end-stage renal failure,and up to 50%of cases progressed to end-stage renal disease within 25 years after IgAN diagnosis.However,specific and effective therapeutic strategies are still lacking.In this review,we discuss the possibility of the mechanism involved in IgAN associated with Crohn’s disease based on the findings of basic and clinical studies.Although the etiology of IgAN associated with Crohn’s disease is not permanent and various factors are thought to be involved,the stabilization of the disease condition of Crohn’s disease is believed to help treat IgAN.
基金the Research Grant for Young Talented Scholars,National Research Council of Thailand,No.N41A640108.
文摘BACKGROUND The association between diabetes mellitus(DM)and the increased risk and progression of cholangiocarcinoma(CCA)has been reported with unclear underlying mechanisms.Previous studies showed thatγ-aminobutyric acid(GABA)B2 receptor(GABBR2)was upregulated in CCA cells cultured in high glucose(HG)conditions.Roles of GABA receptors in CCA progression have also been studied,but their association with DM and hyperglycemia in CCA remains unclarified.AIM To investigate the effects of hyperglycemia on GABBR2 expression and the potential use of GABBR2 as a CCA therapeutic target.METHODS CCA cells,KKU-055 and KKU-213A,were cultured in Dulbecco Modified Eagle’s Medium supplemented with 5.6 mmol/L(normal glucose,NG)or 25 mmol/L(HG)glucose and assigned as NG and HG cells,respectively.GABBR2 expression in NG and HG cells was investigated using real-time quantitative polymerase chain reaction and western blot.Expression and localization of GABBR2 in CCA cells were determined using immunocytofluorescence.GABBR2 expression in tumor tissues from CCA patients with and without DM was studied using immunohistochemistry,and the correlations of GABBR2 with the clinicopathological characteristics of patients were analyzed using univariate analysis.Effects of baclofen,a GABA-B receptor agonist,on CCA cell proliferation and clonogenicity were tested using the MTT and clonogenic assays.Phospho-kinases arrays were used to screen the affected signaling pathways after baclofen treatment,and the candidate signaling molecules were validated using the public transcriptomic data and western blot.RESULTS GABBR2 expression in CCA cells was induced by HG in a dose-and time-dependent manner.CCA tissues from patients with DM and hyperglycemia also showed a significantly higher GABBR2 expression compared with tumor tissues from those with euglycemia(P<0.01).High GABBR2 expression was significantly associated with a poorer non-papillary histological subtype but with smaller sizes of CCA tumors(P<0.05).HG cells of both tested CCA cell lines were more sensitive to baclofen treatment.Baclofen significantly suppressed the proliferation and clonogenicity of CCA cells in both NG and HG conditions(P<0.05).Phospho-kinase arrays suggested glycogen synthase kinase 3(GSK3),β-catenin,and the signal transducer and activator of transcription 3(STAT3)as candidate signaling molecules under the regulation of GABBR2,which were verified in NG and HG cells of the individual CCA cell lines.Cyclin D1 and c-Myc,the common downstream targets of GSK3/β-catenin and STAT3 involving cell proliferation,were accordingly downregulated after baclofen treatment.CONCLUSION GABBR2 is upregulated by HG and holds a promising role as a therapeutic target for CCA regardless of the glucose condition.
