Transducing thermal energy into mechanical movements via molecular reconfigurations offers a cutting-edge approach to thermal actuating materials,which could be applied to sensors,energy harvesting and storage devices...Transducing thermal energy into mechanical movements via molecular reconfigurations offers a cutting-edge approach to thermal actuating materials,which could be applied to sensors,energy harvesting and storage devices[1].Thermal expansion is a pivotal aspect in solid state chemistry,intricately intertwined with various factors such as crystal structure,chemical composition,electronic configuration,microstructure,and defects.Most materials undergo isotropic and positive thermal expansion(PTE)because of the disharmonic vibrational amplitudes of their chemical bonds.Moreover,anisotropic thermal expansion(ATE)and negative thermal expansion(NTE)are fascinating physical attributes of solids,which can originate from electronic or magnetic mechanisms,as well as through a transverse phonon mechanism in insulating lattice solids.展开更多
BACKGROUND Excessive endoplasmic reticulum(ER)stress in intestinal epithelial cells can lead to damage to the intestinal mucosal barrier,activate the signal transducer and activator of transcription 3(STAT3)/nuclear f...BACKGROUND Excessive endoplasmic reticulum(ER)stress in intestinal epithelial cells can lead to damage to the intestinal mucosal barrier,activate the signal transducer and activator of transcription 3(STAT3)/nuclear factor kappa B(NF-κB)signaling pathway,and exacerbate the inflammatory response,thus participating in the pathogenesis of ulcerative colitis(UC).Mesalazine is a commonly used drug in the clinical treatment of UC.However,further studies are needed to determine whether mesalazine regulates the ER stress of intestinal epithelial cells,downregulates the STAT3/NF-κB pathway to play a role in the treatment of UC.AIM To study the therapeutic effects of mesalazine on spontaneous colitis in interleukin-10(IL-10)-/-mice.METHODS The 24-week-old IL-10-/-mice with spontaneous colitis were divided into the model group and the 5-amino salicylic acid group.Littermates of wild-type mice of the same age group served as the control.There were eight mice in each group,four males and four females.The severity of symptoms of spontaneous colitis in IL-10-/-mice was assessed using disease activity index scores.On day 15,the mice were sacrificed.The colon length was measured,and the histopathological changes and ultrastructure of colonic epithelial cells were detected.The protein expressions of STAT3,p-STAT3,NF-κB,IκB,p-IκB,and glucoseregulated protein 78 were identified using Western blotting.The STAT3 and NF-κB mRNA expressions were identified using real-time polymerase chain reaction.The glucose-regulated protein 78 and C/EBP homologous protein expressions in colon sections were detected using immunofluorescence.RESULTS Mesalazine reduced the symptoms of spontaneous colitis in IL-10 knockout mice and the histopathological damage of colonic tissues,and alleviated the ER stress in epithelial cells of colitis mice.Western blotting and quantitative real-time polymerase chain reaction results showed that the STAT3/NF-κB pathway in the colon tissue of model mice was activated,suggesting that this pathway was involved in the pathogenesis of UC and might become a potential therapeutic target.Mesalazine could down-regulate the protein expressions of p-STAT3,NF-κB and p-IκB,and down-regulate the mRNA expression of STAT3 and NF-κB.CONCLUSION Mesalazine may play a protective role in UC by reducing ER stress by regulating the STAT3/NF-κB signaling pathway.展开更多
BACKGROUND Dermatofibrosarcoma protuberans(DFSP)is a rare,low-grade,locally aggressive cutaneous sarcoma.DFSP in the periocular region is exceedingly rare,leading to diagnostic and surgical challenges due to anatomica...BACKGROUND Dermatofibrosarcoma protuberans(DFSP)is a rare,low-grade,locally aggressive cutaneous sarcoma.DFSP in the periocular region is exceedingly rare,leading to diagnostic and surgical challenges due to anatomical constraints in the periocular region.Precise diagnosis is essential to guide appropriate surgical management and prevent recurrence.CASE SUMMARY A 32-year-old female presented with a recurrent tumor in the medial canthus,previously diagnosed as a solitary fibrous tumor in an outside institution.After complete radiological and systemic workup,she was scheduled for a wide local excision followed by reconstruction after getting tumor clear margins on frozen section.Histopathology confirmed DFSP,characterized by storiform spindle cell proliferation,diffuse cluster of differentiation 34 positivity,and signal transducer and activator of transcription 6 negativity.CONCLUSION This case highlights the challenges in the diagnostic and surgical management of DFSP in periocular tumors.Comprehensive surgical excision with appropriate reconstruction is critical for achieving oncological control while preserving aesthetics and function.展开更多
Background:Gallic acid(GA),a plant-derived polyphenol,possesses diverse biological functions such as reducing inflammation and against tumors.Currently,the influence of GA on the resistance of esophageal squamous cell...Background:Gallic acid(GA),a plant-derived polyphenol,possesses diverse biological functions such as reducing inflammation and against tumors.Currently,the influence of GA on the resistance of esophageal squamous cell carcinoma(ESCC)cells to cisplatin(DDP)is not well understood.Methods:Cell counting kit-8 assay examined how GA affected KYSE30 and TE-1 cell viability.5-Ethynyl-2′-deoxyuridine and TdT-mediated dUTP Nick-End labeling staining detected cell proliferation and apoptosis.Clone formation assay,flow cytometry,Carboxyfluorescein diacetate succinimidyl ester fluorescent probes,and Transwell assay determined cell biological properties,and 2′,7′-Dichlorofluorescin diacetate(DCFH-DA)fluorescent probes detected oxidative stress levels.Signal transducer and activator of transcription 3(STAT3)/Notch pathway protein levels after GA and/or Interleukin-6(IL-6)intervention were examined through Western blot.Furthermore,a model for subcutaneous graft tumors was established in nude mice.Results:GA exerted suppressive effects on cell proliferation,and caused apoptosis of KYSE30 and TE-1 cells.IL-6 intervention activated the STAT3/Notch pathway and promoted the malignant biological properties of ESCC cells.In contrast,GA attenuated the effects of IL-6,while STAT3 or Notch inhibitor further enhanced the effects of GA,suggesting that GA inhibited the IL-6/STAT3/Notch pathway.Not only that,GA promoted oxidative stress and enhanced cell sensitivity to DDP both in vitro and in vivo.Conclusion:GA suppresses the malignant progression of ESCC and enhances cell sensitivity to DDP by hindering the IL-6/STAT3/Notch pathway.展开更多
Alpha-voltaic cell is a type of micro nuclear battery that provides several decades of reliable power in the nano watt to microwatt range,supplying for special applications where traditional chemical batteries or sola...Alpha-voltaic cell is a type of micro nuclear battery that provides several decades of reliable power in the nano watt to microwatt range,supplying for special applications where traditional chemical batteries or solar cells are difficult to operate.However,the power conversion efficiency of the alpha-voltaic cells reported are still far behind the theoretical limit,making the development of alpha-voltaic cell challenging.Developing advanced semiconductor transducers with higher efficiency in converting the energy of alpha particles into electric energy is proving to be necessary for realizing high-power conversion efficiency.Herein,we propose an alpha-voltaic cell based on SiC PIN transducer that includes a sensitive region with an area of 1 cm^(2),a width of 51.2μm,and a charge collection efficiency of 95.6%at 0 V bias.We find that optimizing the unintentional doping concentration and crystal quality of the SiC epitaxial layer can significantly increase the absorption and utilization of the energy of alpha particles,resulting in a 2.4-fold enhancement in power conversion efficiency compared with that of the previous study.Electrical properties of the SiC alpha-voltaic cell are measured using an He-ion accelerator as the equivalentα-radioisotopes,with the best power conversion efficiency of 2.10%and maximum output power density of 406.66 nW cm-2 is obtained.Our research makes a big leap in SiC alpha-voltaic cell,bridging the gap between micro nuclear batteries and practical applications in micro-electromechanical systems,micro aerial vehicles,and tiny satellites.展开更多
This study explores the feasibility of electromagnetic acoustic transducers(EMATs)for ultrasonic rail inspection,focusing on bulk wave generation from the rail head and on defect detection at the central part of the r...This study explores the feasibility of electromagnetic acoustic transducers(EMATs)for ultrasonic rail inspection,focusing on bulk wave generation from the rail head and on defect detection at the central part of the rail foot.As a contactless method,EMATs could overcome some known limitations of conventional ultrasonic techniques,but require further validation.Differ-ent campaigns of experimental tests were performed,evaluating,by means of a probability of detection approach,the response of the technique to several artificial semi-elliptical flaws of increasing size and by considering two sensors characterized by different working frequencies.In contact,static tests allowed to assess the basic feasibility of the inspection technique and showed a linear response to defect size,saturating when defect width exceeded the rail web thickness.Dynamic tests allowed to introduce the effects of lift-off on signal responses.During all tests,the higher-frequency sensor outperformed the lower-frequency one.Finally,full-scale bogie tests on an indoor permanent track installation,comprehensive of defec-tive rails,confirmed the higher flaw detection rates of the higher-frequency sensor,with minimal detection failures despite occasional false alarms.EMATs showed encouraging results for in-motion rail inspection:with further technical development and optimization,this technique could enhance ultrasonic rail inspection by diagnostic trains.展开更多
As an emerging multifunctional metal with the lowest melting point except for mercury,gallium combines a wide range of metallic and non-metallic elements to form advanced semiconductors critically important in cutting...As an emerging multifunctional metal with the lowest melting point except for mercury,gallium combines a wide range of metallic and non-metallic elements to form advanced semiconductors critically important in cutting-edge technologies.However,due to its low melting point and poor machinability,it is quite difficult to simultaneously characterize gallium’s elastic properties and damping characteristics using conventional methods,which is es-sential in designing and evaluating gallium-based structures.Therefore,developing effective methods to achieve accurate and efficient measurements of Young’s modulus and corresponding internal friction of gallium is of great significance.This letter studies simultaneous measurements of the variations in Young’s modulus and internal friction of gallium at varying temperatures by employing the modified piezoelectric ultrasonic composite oscil-lator technique.Combining the explicit theoretical formulas with the measured resonance and anti-resonance frequencies,it has been discovered that Young’s modulus undergoes an approximately linear decrease as the temperature rises,declining from 83.84 GPa at -70℃ to 79.37 GPa at 20℃.Moreover,like aluminum in the same Group ⅢA of the Periodic Table of Elements and exhibits a grain-boundary internal friction peak,gallium displays a longitudinal internal friction peak at approximately-12°C,with the peak value reaching 1.77×10^(-3).This basic research on gallium’s elastic properties and damping characteristics under low-temperature condi-tions will inspire further explorations of the mechanical properties of a diverse spectrum of low-melting-point functional materials and facilitate applications of gallium-based structures under complex conditions.展开更多
We theoretically investigate the feasibility of reconstructing the transverse structures of femtosecond laser filaments in air by photoacoustic tomography.To simulate the emission and transmission of filament-induced ...We theoretically investigate the feasibility of reconstructing the transverse structures of femtosecond laser filaments in air by photoacoustic tomography.To simulate the emission and transmission of filament-induced ultrasonic signals more truly,a series of experimentally recorded cross-sectional images are used to simulate the initial pressure rise from multiple filaments(MFs).The aperture size and sensitivity of the detector was incorporated into the reconstruction algorithm.The results show that frequency of acoustic signals induced by MFs with maximum volumetric energy density~100 k J/m^(3)is about 2 MHz below.The initial spatial distribution of optical filaments can be clearly reconstructed with the back projection based algorithm.We recommend a PAT system with transducers of a lower central frequency and a stronger apodization working at a longer scanning radius can be used in photoacoustic image reconstruction of femtosecond laser multifilaments.This study demonstrates the feasibility of using photoacoustic tomography to reconstruct femtosecond multifilament images,which is helpful for studying the complex dynamic processes of multifilament and multifilament manipulation and is also valuable for the remote applications of laser filaments.展开更多
This paper proposes a method to generate Bessel-like collimated beams with suppressed side lobes using the flexural vibration modes of a fixed boundary circular plate,which is excited by a longitudinally vibrating tra...This paper proposes a method to generate Bessel-like collimated beams with suppressed side lobes using the flexural vibration modes of a fixed boundary circular plate,which is excited by a longitudinally vibrating transducer in a ring excitation manner.The factors affecting the generation of Bessel-like collimated beams are investigated by theoretical analysis,numerical simulation and experimental methods.The results indicate that Bessel-like wave can be generated by a thin circular plate with fixed boundaries.The third-order mode of the circular plate can be modified to generate a collimated beam with suppressing side lobes when it is excited in a ring excitation manner and the excitation position lies between the first two nodal circles of the plate.As the excitation radius increases,the main lobe width of the resulting Bessel-like collimated beam decreases,the extent of the focusing region increases,and the amplitude of the side lobes initially increases and then decreases.Based on the simulation results,a prototype Bessel-like collimated beam generation system is made and measured experimentally.The experimental results are in good agreement with the numerical results.The Bessel-like collimated beam can be generated by the proposed system,which has potential application in the fields of long-range detection,imaging of highly attenuated materials,and airflow acceleration.展开更多
Few-layer nanosheets(NSs)of hexagonal boron nitride(h-BN)and molybdenum disulfide(MoS_(2))display notable piezoelectric properties.Yet,their integration into polymers typically yields non-piezoelectric composites due ...Few-layer nanosheets(NSs)of hexagonal boron nitride(h-BN)and molybdenum disulfide(MoS_(2))display notable piezoelectric properties.Yet,their integration into polymers typically yields non-piezoelectric composites due to NSs’random distribution.We introduce a facile method for fabricating intrinsic piezoelectric composites incorporated with NSs without electric poling.Our innovative process aligns NSs within polyvinyl alcohol polymer,leveraging ice-water interfacial tension,water crystallization thrust,and directional cross-linking during freezing.The resulting PE composites exhibit a maximum piezoelectric coefficient of up to 25.5-28.4 pC N^(-1),comparable to polyvinylidene difluoride(PVDF),with significant costefficiency,safety,and scalability advantages over conventional materials.Using this composite,we develop highly sensitive wearable pressure and strain sensors,and an ultrasound energy harvester.These sensors detect finger bending and differentiate between walking and running,while the harvester generates1.18 V/2.31μA under 1Wcm^(-2)ultrasound input underwater.This universal method offers a novel manufacturing technique for piezoelectric composites,demonstrating remarkable effectiveness in synthesizing intrinsic piezoelectric composites based on 2D materials.Moreover,its potential extends to applications in wearable electronics and energy harvesting,promising significant advancements in these fields.展开更多
In traditional meander line coil electromagnetic acoustic transducer(MLC-EMAT)structures,the bias magnetic field is usually set to be along the normal direction of plate surface.However,since the particle vibration of...In traditional meander line coil electromagnetic acoustic transducer(MLC-EMAT)structures,the bias magnetic field is usually set to be along the normal direction of plate surface.However,since the particle vibration of the antisymmetric Lamb wave is always dominated by out-of-plane components,using bias magnetic field perpendicular to plate surface is kind of inefficient.In this paper,the performance of both the normal bias magnetic field EMAT(NB-EMAT)and the parallel bias magnetic field EMAT(PB-EMAT)for transmitting and receiving A0 mode Lamb waves are thoroughly studied.The mechanisms of these two structures are elaborated.First,the finite element models of both structures are established.The magnetic fields of these two EMATs are numerically calculated and the results are compared with experiments.Then,the Lorentz force distributions excited by the two EMATs are compared to prove the feasibility of improving the excitation efficiency of MLC-EMAT by selecting the direction of bias magnetic field.Furthermore,the excitation efficiencies of NB-EMAT and PB-EMAT are quantitatively analyzed and compared in simulation software.Results show that the excitation efficiency of PB-EMAT is 108%higher than NB-EMAT.Finally,several groups of comparative experiments are conducted to verify the conclusion obtained through numerical calculation.Experimental results show that by simply replacing the tradition NB-EMAT with PB-EMAT,the excitation efficiency can be greatly increased by more than 50%.If PB-EMATs are used as both the receiver and transmitter,the excitation efficiency can be further increased by 113%.展开更多
BACKGROUND Diabetic retinopathy(DR)is the leading cause of vision loss in patients with diabetes.The vascular endothelial growth factor(VEGF)pathway plays a critical role in the pathogenesis of DR,and ranibizumab,an a...BACKGROUND Diabetic retinopathy(DR)is the leading cause of vision loss in patients with diabetes.The vascular endothelial growth factor(VEGF)pathway plays a critical role in the pathogenesis of DR,and ranibizumab,an anti-VEGF agent,has shown promise in its treatment.Signal transducer and activator of transcription 3(STAT3)is involved in inflammatory processes and cellular signaling,while glial fibrillary acidic protein(GFAP)is a marker of glial cell activation,both contributing to retinal damage in DR.However,the mechanisms by which ranibizumab affect early-stage DR through the VEGF/STAT3/GFAP pathway are not fully understood.AIM To investigate the role of ranibizumab in early DR via the VEGF/STAT3/GFAP pathway.METHODS Adult retinal pigment epithelial 19(ARPE-19)cells and human retinal microvascular endothelial cells(HRMECs)were cultured under high-glucose conditions to simulate a diabetic environment.The effects of ranibizumab on cytokine mRNA and protein expression were analyzed by quantitative polymerase chain reaction and Western blot analysis.A diabetic rat model was induced with streptozotocin(60 mg/kg).Retinal changes,including retinal ganglion cell(RGC)apoptosis,vascular alterations,and cytokine expression,were evaluated using fundus fluorescein angiography,hematoxylin and eosin and periodic acid Schiff staining,immunofluorescence,confocal imaging,and Western blot analysis.RESULTS High-glucose conditions significantly increased the mRNA and protein levels of VEGF,STAT3,GFAP,and other cytokines in ARPE-19 and HRMECs.However,these levels were partially suppressed by ranibizumab.RGC apoptosis,vascular leakage,and elevated cytokine expression were observed during early-stage DR in diabetic rats.Ranibizumab treatment in diabetic rats reduced cytokine expression,restored RGCs,and repaired vascular networks.CONCLUSION Intravitreal ranibizumab modulates the VEGF/STAT3/GFAP pathway,suppresses cytokine expression,and promotes retinal repair,effectively delaying or preventing early DR progression.展开更多
BACKGROUND Helicobacter pylori(H.pylori)infection is widely considered to be a major risk factor for gastric cancer,contributing to its development through the Correa cascade.Yin Yang 1(YY1)is a transcription factor t...BACKGROUND Helicobacter pylori(H.pylori)infection is widely considered to be a major risk factor for gastric cancer,contributing to its development through the Correa cascade.Yin Yang 1(YY1)is a transcription factor that acts as a promoter or suppressor of cancer progression.However,the role of YY1 in the inflammatory transformation associated with H.pylori-induced gastric cancer remains unclear.AIM To explore the expression of YY1 in gastric cancer and its impact on cancer progression with H.pylori infection.METHODS H.pylori bacteria were cocultured with GSE1 cells,AGS cells,and SGC7901 cells,as well as in infected and xenograft mouse models.Expression of YY1,members of the Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)signaling pathway,and epithelial-mesenchymal transition(EMT)-related proteins in gastric cancer was examined using Western blotting,quantitative realtime polymerase chain reaction,and immunohistochemistry.Survival analysis was performed using the Kaplan-Meier method with the log-rank test.The role of YY1 in gastric cancer cell proliferation was further evaluated through in vitro and in vivo assays.RESULTS YY1 was highly expressed in gastric cancer tissues and cells.Kaplan-Meier survival curves indicated that high YY1 expression correlated with a poor prognosis.YY1 expression showed a gradually increasing trend in H.pyloriinduced gastritis and gastric tumors.In vivo and in vitro experiments demonstrated that H.pylori infection promoted phosphorylation of JAK2 and STAT3,thereby activating the EMT pathway,in which YY1 played a key role.YY1 and JAK2 interaction was validated by chromatin immunoprecipitation.YY1 knockdown or pharmacological inhibition reversed EMT and suppressed gastric cancer cell proliferation and metastasis.CONCLUSION These results suggest that YY1 plays an important role in progression of H.pylori-induced gastric cancer by activating EMT.展开更多
Mast cells(MCs)under stress conditions contribute to the development of irritable bowel syndrome(IBS),yet their precise mechanisms in IBS remain unclear.AIM To investigate the role of MC-derived thymosinβ4(Tβ4)in st...Mast cells(MCs)under stress conditions contribute to the development of irritable bowel syndrome(IBS),yet their precise mechanisms in IBS remain unclear.AIM To investigate the role of MC-derived thymosinβ4(Tβ4)in stress-induced intestinal barrier dysfunction.METHODS The colonic mucus Tβ4 levels in IBS patients were determined and their effects on the epithelial barrier were assessed in vitro and in vivo.Specifically,rats genetically deficient in Tβ4(Tβ4^(-/-))or mice deficient in MCs(Kit^(w-sh/w-sh))were used to observe the effects of reintroducing Tβ4 or wild-type peritoneal MCs(wt-PMCs)into these animals.Additionally,the regulatory mechanism underlying Tβ4 secretion in MCs was investigated.RESULTS We demonstrated that high levels of Tβ4 in IBS mucus and intestinal MCs mediate stress-associated disruptive changes to the epithelial barrier.Moreover,Tβ4 treatment of wild-type or MC-deficient Kit^(w-sh/w-sh)mice caused a reduction in tight junction proteins and the interleukin 22 receptor A1(IL22RA1)/Reg3γcascade,but an increase in myosin light chain kinase.Furthermore,Tβ4^(-/-)rats were resistant to stress,though reintroduction of Tβ4 or wt-PMCs restored stress or corticotropin-releasing hormone(CRH)-induced barrier disturbance.Consistently,Tβ4 release from MCs was dependent on the CRH receptor 1,but not degranulation.The effect of Tβ4 was accompanied by IL22RA1/Janus kinase 1(JAK1)/signal transducer and activation of transcription 3(STAT3)pathway inhibition,suggesting a mechanism for physical and immune barrier suppression.CONCLUSION Collectively,these results suggest that Tβ4,which is abundant in IBS mucus and the secretome of MCs,plays a crucial role in the pathogenesis of IBS via IL22RA1/JAK1/STAT3 signaling,with potential implications for diagnostic and therapeutic targeting.展开更多
Diabetes mellitus(DM)and its complications continue to impose a substantial burden on healthcare systems worldwide.Diabetic neuropathy(DN)is one of the most common chronic microvascular and neurodegenerative complicat...Diabetes mellitus(DM)and its complications continue to impose a substantial burden on healthcare systems worldwide.Diabetic neuropathy(DN)is one of the most common chronic microvascular and neurodegenerative complications of DM.It is clinically characterized by allodynia,hyperalgesia,and abnormal or absent nerve fiber sensation,which collectively contribute to poor quality of life,sleep disturbances,depression,and increased mortality.Although several pharmacological agents are available to alleviate DN-related symptoms,their limited long-term efficacy and adverse side effects underscore the urgent need for novel therapeutic approaches.This limitation may be attributed to an incomplete understanding of the underlying mechanisms of DN.Accumulating evidence has highlighted the contribution of glial cells including astrocytes,microglia,and oligodendrocytes to the pathogenesis of DN.However,the specific role of astrocytes remains insufficiently defined.Therefore,this review provides a comprehensive evaluation of current knowledge regarding astrocyte involvement in DN mechanisms,with the goal of clarifying their contribution to disease progression and identifying potential therapeutic targets.展开更多
Background:This investigation aimed to evaluate the therapeutic impact of the Yigan Xiaozheng formula on liver cirrhosis in rats,particularly induced by diethylnitrosamine(DEN).The study focused on analyzing liver str...Background:This investigation aimed to evaluate the therapeutic impact of the Yigan Xiaozheng formula on liver cirrhosis in rats,particularly induced by diethylnitrosamine(DEN).The study focused on analyzing liver structure,cell apoptosis,and the modulation of the Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)signaling pathway,employing a combination of network pharmacology and experimental approaches.Methods:A DEN-induced rat model of liver cirrhosis was established to assess the formula’s effectiveness.Parameters such as overall health,liver morphology,and survival were monitored.Network pharmacology was employed to decipher the active compounds and key targets of the formula in addressing liver cirrhosis.Predictions made via network pharmacology were substantiated through experimental validation in the animal model.Results:Administration of the Yigan Xiaozheng formula led to noticeable improvements in clinical symptoms of liver cirrhosis in rats,marked by enhanced body weight,lessened liver pathology,and higher survival rates.Network pharmacological analysis unveiled intricate interactions between active ingredients of the formula and cirrhosis-related targets.Protein-protein interaction(PPI)networks pinpointed crucial proteins and regulatory modules.Enrichment analysis underscored a significant involvement of the JAK2/STAT3 signaling pathway.On a molecular scale,the formula was observed to reduce the expression of BCL-2 associated X protein(Bax)and cytochrome C(Cyt-C),diminish the Bax/B-cell lymphoma 2(Bcl-2)ratio,and impede JAK2/STAT3 pathway activation,thereby curtailing liver fibrosis and cellular apoptosis.Conclusion:The study demonstrates the Yigan Xiaozheng formula’s capacity to ameliorate liver cirrhosis in a DEN-induced model,primarily through its active ingredients’interactions with cirrhosis targets and modulation of the JAK2/STAT3 pathway.These findings endorse the potential of this traditional Chinese medicinal formula as a viable treatment option for liver cirrhosis.展开更多
BACKGROUND Inflammatory bowel disease(IBD)is a chronic,progressive inflammatory condition of the intestine.Mesenchymal stem cell(MSC)therapy for IBD has made significant progress in recent years.To better exploit the ...BACKGROUND Inflammatory bowel disease(IBD)is a chronic,progressive inflammatory condition of the intestine.Mesenchymal stem cell(MSC)therapy for IBD has made significant progress in recent years.To better exploit the therapeutic potential of MSCs,pretreatment strategies are employed to enhance their therapeutic capabilities.As a compound with diverse pharmacological effects,quercetin(QUR)is applied to pretreat human umbilical cord-derived MSCs(hUCMSCs)in this study,thereby augmenting their immunotherapeutic potential.AIM To evaluate the therapeutic efficacy of QUR-pretreated hUCMSCs.METHODS We induced colitis in a mouse model using a 2,4,6-trinitrobenzenesulfonic acid solution.Intraperitoneal injection of QUR-pretreated hUCMSCs significantly improved clinical and pathological manifestations of colitis compared to the model group.Interestingly,the therapeutic effect was superior to that of untreated hUCMSCs.Mice exhibited significantly reduced weight loss,diminished infiltration of inflammatory cells observed in hematoxylin and eosin staining,improved Disease Activity Index and Histological Activity Index scores.Furthermore,colonic tissue analysis revealed a significant upregulation of the anti-inflammatory cytokine interleukin 10(IL-10),accompanied by a downregulation of the pro-inflammatory cytokine IL-6.Further tests also suggested that QUR pretreatment led to inhibition of Janus kinase/signal transducer and activator of transcription(STAT)phosphorylation.RESULTS Our study demonstrated that QUR pretreatment of hUCMSCs significantly enhanced their immune-regulatory capacity.This approach effectively mitigated colonic inflammation in a mouse colitis model by modulating the IL-10/Janus kinase/STAT signaling pathway.CONCLUSION These findings suggest that QUR pretreatment acts synergistically to augment the inherent anti-inflammatory and immune-regulatory properties of hUCMSCs,resulting in enhanced therapeutic efficacy for IBD treatment.展开更多
This article comments on the study by Zhang et al,which proposed that exosomes derived from hypoxia-injured endometrial epithelial cells promote human umbilical cord mesenchymal stem cell migration and differentiation...This article comments on the study by Zhang et al,which proposed that exosomes derived from hypoxia-injured endometrial epithelial cells promote human umbilical cord mesenchymal stem cell migration and differentiation into endo-metrial epithelial cells via exosomal miR-137-3p.The authors demonstrated that miR-137-3p targets ubiquitin protein ligase E3C and activates signal transducer and activator of transcription 3 signaling,thereby driving epithelial lineage transition.While this study expands our understanding of exosome-mediated intercellular communication in endometrial repair,several key gaps remain.Notably,microRNA(miRNA)profiling was performed in human umbilical cord mesenchymal stem cells post-exosome treatment,not in the exosomes derived from hypoxia-injured endometrial epithelial cell themselves,leaving open whether miR-137-3p is directly transferred or indirectly induced.In addition,data on exosome characterization were unavailable,and the rationale for selecting miR-137-3p over other differentially expressed miRNAs was not well justified.Future studies should include direct exosomal miRNA content analysis,in vivo validation,and deeper mechanistic exploration of the ubiquitin protein ligase E3C-signal transducer and activator of transcription 3 ubiquitination axis to establish the clinical and biological relevance of this pathway.展开更多
The canonical signaling of interferon gamma(IFN-γ)through the Janus kinase 1 and 2–signal transducer and activator of transcription 1(STAT1)axis leads to the expression of several interferon-stimulated genes(ISGs),w...The canonical signaling of interferon gamma(IFN-γ)through the Janus kinase 1 and 2–signal transducer and activator of transcription 1(STAT1)axis leads to the expression of several interferon-stimulated genes(ISGs),which have diverse effects depending on the cellular context.In glioblastoma,a highly aggressive primary brain tumor in adults,elements of IFN-γcanonical signaling are deregulated,resulting in the overexpression of STAT1-target ISGs associated with tumor progression.This mini-review highlights key ISGs,including STAT1,interferon regulatory factor 1,programmed death-ligand 1,indoleamine 2,3-dioxygenase 1,and interferon-stimulated gene 15,involved in the pathology of glioblastoma.These genes may serve as valuable biomarkers and have therapeutic potential for targeting IFN-γsignaling in this malignancy.展开更多
BACKGROUND At present,the incidence of diabetic nephropathy is increasing year by year,and there are many studies on the pathogenesis of diabetic nephropathy,but it is still not completely clear.The final pathological...BACKGROUND At present,the incidence of diabetic nephropathy is increasing year by year,and there are many studies on the pathogenesis of diabetic nephropathy,but it is still not completely clear.The final pathological result of diabetic nephropathy is mainly glomerular cell fibrosis,and the roles of micro-RNA(miRNA)-29 and DNA methyl transferase(DNMTs)in cell fibrosis have been confirmed in other studies,but there is a lack of relevant research in the kidney at present.AIM To study the potential involvement of miRNA-29a-3p in fibrosis related to diabetic kidney disease(DKD).METHODS The expression of miR-29a-3p,DNMT3A/3B,fibrosis-related molecules,Wnt3a,β-catenin,Janus kinase 2,and signal transducer and activator of transcription 3 was assessed in SV40MES13 cells and diabetic mice using quantitative real-time PCR and western blotting.Furthermore,the expression changes of fibrosis-related molecules were further analyzed using immunofluorescence and immunohistochemical blotting.The renal pathological changes of DKD in each group were also studied using hematoxylin-eosin and periodate-Schiff reaction staining.RESULTS In both the in vivo and in vitro experiments,it was observed that high glucose induction significantly decreased miR-29a-3p expression.As a result of this downregulation,DKD-related fibrosis was found to be promoted,as confirmed by elevated expression levels ofα-smooth muscle actin,collagen type I,and fibronectin.MiR-29a-3p targets the 3’non-coding regions of DNMT3A and DNMT3B and inhibits their expression.Inhibition of DNMT3A and DNMT3B can reverse the effect of miR-29a-3p downregulation on DKD-related fibrosis.CONCLUSION MiR-29a-3p can regulate Wnt/β-catenin and Janus kinase/signal transducer and activator of transcription signal pathways by regulating and inhibiting the expression of DNMT3A/3B and thus participate in the inhibition of DKD-related fibrosis.展开更多
基金supported by the National Natural Science Foundation of China(22171155)Natural Science Foundation of Shandong Province(ZR2022YQ07)Taishan Scholar Program(tsqn202306166).
文摘Transducing thermal energy into mechanical movements via molecular reconfigurations offers a cutting-edge approach to thermal actuating materials,which could be applied to sensors,energy harvesting and storage devices[1].Thermal expansion is a pivotal aspect in solid state chemistry,intricately intertwined with various factors such as crystal structure,chemical composition,electronic configuration,microstructure,and defects.Most materials undergo isotropic and positive thermal expansion(PTE)because of the disharmonic vibrational amplitudes of their chemical bonds.Moreover,anisotropic thermal expansion(ATE)and negative thermal expansion(NTE)are fascinating physical attributes of solids,which can originate from electronic or magnetic mechanisms,as well as through a transverse phonon mechanism in insulating lattice solids.
基金Supported by Xi’an Science and Technology Plan Project,No.23YXYJ0162Shaanxi Province Traditional Chinese Medicine Research and Innovation Talent Plan Project,No.TZKN-CXRC-16+2 种基金Project of Shaanxi Administration of Traditional Chinese Medicine,No.SZYKJCYC-2025-JC-010Shaanxi Province Key Research and Development Plan Project-Social Development Field,No.S2025-YF-YBSF-0391the Science and Technology Innovation Cultivation Program of Longhua Hospital affiliated to Shanghai University of Chinese Medicine,No.YD202220。
文摘BACKGROUND Excessive endoplasmic reticulum(ER)stress in intestinal epithelial cells can lead to damage to the intestinal mucosal barrier,activate the signal transducer and activator of transcription 3(STAT3)/nuclear factor kappa B(NF-κB)signaling pathway,and exacerbate the inflammatory response,thus participating in the pathogenesis of ulcerative colitis(UC).Mesalazine is a commonly used drug in the clinical treatment of UC.However,further studies are needed to determine whether mesalazine regulates the ER stress of intestinal epithelial cells,downregulates the STAT3/NF-κB pathway to play a role in the treatment of UC.AIM To study the therapeutic effects of mesalazine on spontaneous colitis in interleukin-10(IL-10)-/-mice.METHODS The 24-week-old IL-10-/-mice with spontaneous colitis were divided into the model group and the 5-amino salicylic acid group.Littermates of wild-type mice of the same age group served as the control.There were eight mice in each group,four males and four females.The severity of symptoms of spontaneous colitis in IL-10-/-mice was assessed using disease activity index scores.On day 15,the mice were sacrificed.The colon length was measured,and the histopathological changes and ultrastructure of colonic epithelial cells were detected.The protein expressions of STAT3,p-STAT3,NF-κB,IκB,p-IκB,and glucoseregulated protein 78 were identified using Western blotting.The STAT3 and NF-κB mRNA expressions were identified using real-time polymerase chain reaction.The glucose-regulated protein 78 and C/EBP homologous protein expressions in colon sections were detected using immunofluorescence.RESULTS Mesalazine reduced the symptoms of spontaneous colitis in IL-10 knockout mice and the histopathological damage of colonic tissues,and alleviated the ER stress in epithelial cells of colitis mice.Western blotting and quantitative real-time polymerase chain reaction results showed that the STAT3/NF-κB pathway in the colon tissue of model mice was activated,suggesting that this pathway was involved in the pathogenesis of UC and might become a potential therapeutic target.Mesalazine could down-regulate the protein expressions of p-STAT3,NF-κB and p-IκB,and down-regulate the mRNA expression of STAT3 and NF-κB.CONCLUSION Mesalazine may play a protective role in UC by reducing ER stress by regulating the STAT3/NF-κB signaling pathway.
文摘BACKGROUND Dermatofibrosarcoma protuberans(DFSP)is a rare,low-grade,locally aggressive cutaneous sarcoma.DFSP in the periocular region is exceedingly rare,leading to diagnostic and surgical challenges due to anatomical constraints in the periocular region.Precise diagnosis is essential to guide appropriate surgical management and prevent recurrence.CASE SUMMARY A 32-year-old female presented with a recurrent tumor in the medial canthus,previously diagnosed as a solitary fibrous tumor in an outside institution.After complete radiological and systemic workup,she was scheduled for a wide local excision followed by reconstruction after getting tumor clear margins on frozen section.Histopathology confirmed DFSP,characterized by storiform spindle cell proliferation,diffuse cluster of differentiation 34 positivity,and signal transducer and activator of transcription 6 negativity.CONCLUSION This case highlights the challenges in the diagnostic and surgical management of DFSP in periocular tumors.Comprehensive surgical excision with appropriate reconstruction is critical for achieving oncological control while preserving aesthetics and function.
基金Mechanistic Investigation into the Extraction,Purification,and Anti-Esophageal Cancer Effects of Gallic Acid Derived from Rhodiola crenulata(YLUKLM2023001).
文摘Background:Gallic acid(GA),a plant-derived polyphenol,possesses diverse biological functions such as reducing inflammation and against tumors.Currently,the influence of GA on the resistance of esophageal squamous cell carcinoma(ESCC)cells to cisplatin(DDP)is not well understood.Methods:Cell counting kit-8 assay examined how GA affected KYSE30 and TE-1 cell viability.5-Ethynyl-2′-deoxyuridine and TdT-mediated dUTP Nick-End labeling staining detected cell proliferation and apoptosis.Clone formation assay,flow cytometry,Carboxyfluorescein diacetate succinimidyl ester fluorescent probes,and Transwell assay determined cell biological properties,and 2′,7′-Dichlorofluorescin diacetate(DCFH-DA)fluorescent probes detected oxidative stress levels.Signal transducer and activator of transcription 3(STAT3)/Notch pathway protein levels after GA and/or Interleukin-6(IL-6)intervention were examined through Western blot.Furthermore,a model for subcutaneous graft tumors was established in nude mice.Results:GA exerted suppressive effects on cell proliferation,and caused apoptosis of KYSE30 and TE-1 cells.IL-6 intervention activated the STAT3/Notch pathway and promoted the malignant biological properties of ESCC cells.In contrast,GA attenuated the effects of IL-6,while STAT3 or Notch inhibitor further enhanced the effects of GA,suggesting that GA inhibited the IL-6/STAT3/Notch pathway.Not only that,GA promoted oxidative stress and enhanced cell sensitivity to DDP both in vitro and in vivo.Conclusion:GA suppresses the malignant progression of ESCC and enhances cell sensitivity to DDP by hindering the IL-6/STAT3/Notch pathway.
基金financially supported by the National Natural Science Foundation of China(Nos.12050005,11922507,and 12205016)supported by Major State Basic Research Development Program of China(No.2021YFB3201000)。
文摘Alpha-voltaic cell is a type of micro nuclear battery that provides several decades of reliable power in the nano watt to microwatt range,supplying for special applications where traditional chemical batteries or solar cells are difficult to operate.However,the power conversion efficiency of the alpha-voltaic cells reported are still far behind the theoretical limit,making the development of alpha-voltaic cell challenging.Developing advanced semiconductor transducers with higher efficiency in converting the energy of alpha particles into electric energy is proving to be necessary for realizing high-power conversion efficiency.Herein,we propose an alpha-voltaic cell based on SiC PIN transducer that includes a sensitive region with an area of 1 cm^(2),a width of 51.2μm,and a charge collection efficiency of 95.6%at 0 V bias.We find that optimizing the unintentional doping concentration and crystal quality of the SiC epitaxial layer can significantly increase the absorption and utilization of the energy of alpha particles,resulting in a 2.4-fold enhancement in power conversion efficiency compared with that of the previous study.Electrical properties of the SiC alpha-voltaic cell are measured using an He-ion accelerator as the equivalentα-radioisotopes,with the best power conversion efficiency of 2.10%and maximum output power density of 406.66 nW cm-2 is obtained.Our research makes a big leap in SiC alpha-voltaic cell,bridging the gap between micro nuclear batteries and practical applications in micro-electromechanical systems,micro aerial vehicles,and tiny satellites.
基金funded in the frame of the Joint Research Centre (JRC) Trasporti, established at Fondazione Politecnico di Milano, through contract C40/2019 “JRC Trasporti-Metodologie per l’ispezione delle rotaie nei riguardi della formazione di cricche”
文摘This study explores the feasibility of electromagnetic acoustic transducers(EMATs)for ultrasonic rail inspection,focusing on bulk wave generation from the rail head and on defect detection at the central part of the rail foot.As a contactless method,EMATs could overcome some known limitations of conventional ultrasonic techniques,but require further validation.Differ-ent campaigns of experimental tests were performed,evaluating,by means of a probability of detection approach,the response of the technique to several artificial semi-elliptical flaws of increasing size and by considering two sensors characterized by different working frequencies.In contact,static tests allowed to assess the basic feasibility of the inspection technique and showed a linear response to defect size,saturating when defect width exceeded the rail web thickness.Dynamic tests allowed to introduce the effects of lift-off on signal responses.During all tests,the higher-frequency sensor outperformed the lower-frequency one.Finally,full-scale bogie tests on an indoor permanent track installation,comprehensive of defec-tive rails,confirmed the higher flaw detection rates of the higher-frequency sensor,with minimal detection failures despite occasional false alarms.EMATs showed encouraging results for in-motion rail inspection:with further technical development and optimization,this technique could enhance ultrasonic rail inspection by diagnostic trains.
基金financially supported by the National Key R&D Program of China(Grant No.2023YFF0716800)the National Natural Science Foundation of China(Grant No.12074160)the Natural Science Foundation of Liaoning Province of China(Grant No.2024-MS-181).
文摘As an emerging multifunctional metal with the lowest melting point except for mercury,gallium combines a wide range of metallic and non-metallic elements to form advanced semiconductors critically important in cutting-edge technologies.However,due to its low melting point and poor machinability,it is quite difficult to simultaneously characterize gallium’s elastic properties and damping characteristics using conventional methods,which is es-sential in designing and evaluating gallium-based structures.Therefore,developing effective methods to achieve accurate and efficient measurements of Young’s modulus and corresponding internal friction of gallium is of great significance.This letter studies simultaneous measurements of the variations in Young’s modulus and internal friction of gallium at varying temperatures by employing the modified piezoelectric ultrasonic composite oscil-lator technique.Combining the explicit theoretical formulas with the measured resonance and anti-resonance frequencies,it has been discovered that Young’s modulus undergoes an approximately linear decrease as the temperature rises,declining from 83.84 GPa at -70℃ to 79.37 GPa at 20℃.Moreover,like aluminum in the same Group ⅢA of the Periodic Table of Elements and exhibits a grain-boundary internal friction peak,gallium displays a longitudinal internal friction peak at approximately-12°C,with the peak value reaching 1.77×10^(-3).This basic research on gallium’s elastic properties and damping characteristics under low-temperature condi-tions will inspire further explorations of the mechanical properties of a diverse spectrum of low-melting-point functional materials and facilitate applications of gallium-based structures under complex conditions.
基金Project supported by the National Natural Science Foundation of China(Grant No.42105176)the National University of Defense Technology Independent Research Project(Grant No.ZK21-40)。
文摘We theoretically investigate the feasibility of reconstructing the transverse structures of femtosecond laser filaments in air by photoacoustic tomography.To simulate the emission and transmission of filament-induced ultrasonic signals more truly,a series of experimentally recorded cross-sectional images are used to simulate the initial pressure rise from multiple filaments(MFs).The aperture size and sensitivity of the detector was incorporated into the reconstruction algorithm.The results show that frequency of acoustic signals induced by MFs with maximum volumetric energy density~100 k J/m^(3)is about 2 MHz below.The initial spatial distribution of optical filaments can be clearly reconstructed with the back projection based algorithm.We recommend a PAT system with transducers of a lower central frequency and a stronger apodization working at a longer scanning radius can be used in photoacoustic image reconstruction of femtosecond laser multifilaments.This study demonstrates the feasibility of using photoacoustic tomography to reconstruct femtosecond multifilament images,which is helpful for studying the complex dynamic processes of multifilament and multifilament manipulation and is also valuable for the remote applications of laser filaments.
基金Project supported by the National Natural Science Foundation of China(Grant No.12474440).
文摘This paper proposes a method to generate Bessel-like collimated beams with suppressed side lobes using the flexural vibration modes of a fixed boundary circular plate,which is excited by a longitudinally vibrating transducer in a ring excitation manner.The factors affecting the generation of Bessel-like collimated beams are investigated by theoretical analysis,numerical simulation and experimental methods.The results indicate that Bessel-like wave can be generated by a thin circular plate with fixed boundaries.The third-order mode of the circular plate can be modified to generate a collimated beam with suppressing side lobes when it is excited in a ring excitation manner and the excitation position lies between the first two nodal circles of the plate.As the excitation radius increases,the main lobe width of the resulting Bessel-like collimated beam decreases,the extent of the focusing region increases,and the amplitude of the side lobes initially increases and then decreases.Based on the simulation results,a prototype Bessel-like collimated beam generation system is made and measured experimentally.The experimental results are in good agreement with the numerical results.The Bessel-like collimated beam can be generated by the proposed system,which has potential application in the fields of long-range detection,imaging of highly attenuated materials,and airflow acceleration.
基金funded by the Key Research Project of Zhejiang(LD22E030007)the“Leading Goose”R&D Program of Zhejiang Province(No.2022C01136)+2 种基金National Science Foundation of China(NSFC No.61974037,No.61904042,No.62274049)Zhejiang University Education Foundation Global Partnership Fund(No.100000-11320)the support of the Micro-nano Fabrication Center of International campus of Zhejiang University.
文摘Few-layer nanosheets(NSs)of hexagonal boron nitride(h-BN)and molybdenum disulfide(MoS_(2))display notable piezoelectric properties.Yet,their integration into polymers typically yields non-piezoelectric composites due to NSs’random distribution.We introduce a facile method for fabricating intrinsic piezoelectric composites incorporated with NSs without electric poling.Our innovative process aligns NSs within polyvinyl alcohol polymer,leveraging ice-water interfacial tension,water crystallization thrust,and directional cross-linking during freezing.The resulting PE composites exhibit a maximum piezoelectric coefficient of up to 25.5-28.4 pC N^(-1),comparable to polyvinylidene difluoride(PVDF),with significant costefficiency,safety,and scalability advantages over conventional materials.Using this composite,we develop highly sensitive wearable pressure and strain sensors,and an ultrasound energy harvester.These sensors detect finger bending and differentiate between walking and running,while the harvester generates1.18 V/2.31μA under 1Wcm^(-2)ultrasound input underwater.This universal method offers a novel manufacturing technique for piezoelectric composites,demonstrating remarkable effectiveness in synthesizing intrinsic piezoelectric composites based on 2D materials.Moreover,its potential extends to applications in wearable electronics and energy harvesting,promising significant advancements in these fields.
基金supported by the Foundation of Guangxi Key Laboratory of Manufacturing System and Advanced Manufacturing Technology(No.17-259-05-005Z)Innovation Project of GUET Graduate Education(No.2025YCXS016)。
文摘In traditional meander line coil electromagnetic acoustic transducer(MLC-EMAT)structures,the bias magnetic field is usually set to be along the normal direction of plate surface.However,since the particle vibration of the antisymmetric Lamb wave is always dominated by out-of-plane components,using bias magnetic field perpendicular to plate surface is kind of inefficient.In this paper,the performance of both the normal bias magnetic field EMAT(NB-EMAT)and the parallel bias magnetic field EMAT(PB-EMAT)for transmitting and receiving A0 mode Lamb waves are thoroughly studied.The mechanisms of these two structures are elaborated.First,the finite element models of both structures are established.The magnetic fields of these two EMATs are numerically calculated and the results are compared with experiments.Then,the Lorentz force distributions excited by the two EMATs are compared to prove the feasibility of improving the excitation efficiency of MLC-EMAT by selecting the direction of bias magnetic field.Furthermore,the excitation efficiencies of NB-EMAT and PB-EMAT are quantitatively analyzed and compared in simulation software.Results show that the excitation efficiency of PB-EMAT is 108%higher than NB-EMAT.Finally,several groups of comparative experiments are conducted to verify the conclusion obtained through numerical calculation.Experimental results show that by simply replacing the tradition NB-EMAT with PB-EMAT,the excitation efficiency can be greatly increased by more than 50%.If PB-EMATs are used as both the receiver and transmitter,the excitation efficiency can be further increased by 113%.
基金Supported by the Natural Science Foundation of Jiangxi Province,No.20242BAB25489National Natural Science Foundation of China,No.82260211 and No.81460092+1 种基金Key Research and Development Project in Jiangxi Province,No.20203BBG73058Chinese Medicine Science and Technology Project in Jiangxi Province,No.2020A0166。
文摘BACKGROUND Diabetic retinopathy(DR)is the leading cause of vision loss in patients with diabetes.The vascular endothelial growth factor(VEGF)pathway plays a critical role in the pathogenesis of DR,and ranibizumab,an anti-VEGF agent,has shown promise in its treatment.Signal transducer and activator of transcription 3(STAT3)is involved in inflammatory processes and cellular signaling,while glial fibrillary acidic protein(GFAP)is a marker of glial cell activation,both contributing to retinal damage in DR.However,the mechanisms by which ranibizumab affect early-stage DR through the VEGF/STAT3/GFAP pathway are not fully understood.AIM To investigate the role of ranibizumab in early DR via the VEGF/STAT3/GFAP pathway.METHODS Adult retinal pigment epithelial 19(ARPE-19)cells and human retinal microvascular endothelial cells(HRMECs)were cultured under high-glucose conditions to simulate a diabetic environment.The effects of ranibizumab on cytokine mRNA and protein expression were analyzed by quantitative polymerase chain reaction and Western blot analysis.A diabetic rat model was induced with streptozotocin(60 mg/kg).Retinal changes,including retinal ganglion cell(RGC)apoptosis,vascular alterations,and cytokine expression,were evaluated using fundus fluorescein angiography,hematoxylin and eosin and periodic acid Schiff staining,immunofluorescence,confocal imaging,and Western blot analysis.RESULTS High-glucose conditions significantly increased the mRNA and protein levels of VEGF,STAT3,GFAP,and other cytokines in ARPE-19 and HRMECs.However,these levels were partially suppressed by ranibizumab.RGC apoptosis,vascular leakage,and elevated cytokine expression were observed during early-stage DR in diabetic rats.Ranibizumab treatment in diabetic rats reduced cytokine expression,restored RGCs,and repaired vascular networks.CONCLUSION Intravitreal ranibizumab modulates the VEGF/STAT3/GFAP pathway,suppresses cytokine expression,and promotes retinal repair,effectively delaying or preventing early DR progression.
基金Supported by the National Natural Science Foundation of China,No.82372646Research Fund of Anhui Institute of Translational Medicine,No.2023zhyx-C70 and No.2023zhyx-C80.
文摘BACKGROUND Helicobacter pylori(H.pylori)infection is widely considered to be a major risk factor for gastric cancer,contributing to its development through the Correa cascade.Yin Yang 1(YY1)is a transcription factor that acts as a promoter or suppressor of cancer progression.However,the role of YY1 in the inflammatory transformation associated with H.pylori-induced gastric cancer remains unclear.AIM To explore the expression of YY1 in gastric cancer and its impact on cancer progression with H.pylori infection.METHODS H.pylori bacteria were cocultured with GSE1 cells,AGS cells,and SGC7901 cells,as well as in infected and xenograft mouse models.Expression of YY1,members of the Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)signaling pathway,and epithelial-mesenchymal transition(EMT)-related proteins in gastric cancer was examined using Western blotting,quantitative realtime polymerase chain reaction,and immunohistochemistry.Survival analysis was performed using the Kaplan-Meier method with the log-rank test.The role of YY1 in gastric cancer cell proliferation was further evaluated through in vitro and in vivo assays.RESULTS YY1 was highly expressed in gastric cancer tissues and cells.Kaplan-Meier survival curves indicated that high YY1 expression correlated with a poor prognosis.YY1 expression showed a gradually increasing trend in H.pyloriinduced gastritis and gastric tumors.In vivo and in vitro experiments demonstrated that H.pylori infection promoted phosphorylation of JAK2 and STAT3,thereby activating the EMT pathway,in which YY1 played a key role.YY1 and JAK2 interaction was validated by chromatin immunoprecipitation.YY1 knockdown or pharmacological inhibition reversed EMT and suppressed gastric cancer cell proliferation and metastasis.CONCLUSION These results suggest that YY1 plays an important role in progression of H.pylori-induced gastric cancer by activating EMT.
基金Supported by the National Natural Science Foundation of China,No.81270465the Sichuan Science and Technology Program,No.2024NSFSC0631,No.2023JDRC0088,and No.MZGC20240097+4 种基金the Basic Research Cultivation Support Program of Fundamental Research Funds for the Central Universities,No.2682023ZTPY071the Baiqiuen Public Welfare Foundation Program,No.BCF-LX-XH-20221014-12the Third People’s Hospital of Chengdu Clinical Research Program,No.CSY-YN-01-2023-012the Yibin Science and Technology Program,No.2021ZYY009the Chengdu Medical Research Project Foundation,No.2022284.
文摘Mast cells(MCs)under stress conditions contribute to the development of irritable bowel syndrome(IBS),yet their precise mechanisms in IBS remain unclear.AIM To investigate the role of MC-derived thymosinβ4(Tβ4)in stress-induced intestinal barrier dysfunction.METHODS The colonic mucus Tβ4 levels in IBS patients were determined and their effects on the epithelial barrier were assessed in vitro and in vivo.Specifically,rats genetically deficient in Tβ4(Tβ4^(-/-))or mice deficient in MCs(Kit^(w-sh/w-sh))were used to observe the effects of reintroducing Tβ4 or wild-type peritoneal MCs(wt-PMCs)into these animals.Additionally,the regulatory mechanism underlying Tβ4 secretion in MCs was investigated.RESULTS We demonstrated that high levels of Tβ4 in IBS mucus and intestinal MCs mediate stress-associated disruptive changes to the epithelial barrier.Moreover,Tβ4 treatment of wild-type or MC-deficient Kit^(w-sh/w-sh)mice caused a reduction in tight junction proteins and the interleukin 22 receptor A1(IL22RA1)/Reg3γcascade,but an increase in myosin light chain kinase.Furthermore,Tβ4^(-/-)rats were resistant to stress,though reintroduction of Tβ4 or wt-PMCs restored stress or corticotropin-releasing hormone(CRH)-induced barrier disturbance.Consistently,Tβ4 release from MCs was dependent on the CRH receptor 1,but not degranulation.The effect of Tβ4 was accompanied by IL22RA1/Janus kinase 1(JAK1)/signal transducer and activation of transcription 3(STAT3)pathway inhibition,suggesting a mechanism for physical and immune barrier suppression.CONCLUSION Collectively,these results suggest that Tβ4,which is abundant in IBS mucus and the secretome of MCs,plays a crucial role in the pathogenesis of IBS via IL22RA1/JAK1/STAT3 signaling,with potential implications for diagnostic and therapeutic targeting.
基金Supported by the Fundamental Research Grant Scheme of the Ministry of Higher Education,Malaysia,No.FRGS/1/2024/SKK10/USM/02/8.
文摘Diabetes mellitus(DM)and its complications continue to impose a substantial burden on healthcare systems worldwide.Diabetic neuropathy(DN)is one of the most common chronic microvascular and neurodegenerative complications of DM.It is clinically characterized by allodynia,hyperalgesia,and abnormal or absent nerve fiber sensation,which collectively contribute to poor quality of life,sleep disturbances,depression,and increased mortality.Although several pharmacological agents are available to alleviate DN-related symptoms,their limited long-term efficacy and adverse side effects underscore the urgent need for novel therapeutic approaches.This limitation may be attributed to an incomplete understanding of the underlying mechanisms of DN.Accumulating evidence has highlighted the contribution of glial cells including astrocytes,microglia,and oligodendrocytes to the pathogenesis of DN.However,the specific role of astrocytes remains insufficiently defined.Therefore,this review provides a comprehensive evaluation of current knowledge regarding astrocyte involvement in DN mechanisms,with the goal of clarifying their contribution to disease progression and identifying potential therapeutic targets.
基金supported by National Natural Science Foundation of China Grant Program(No.81603555).
文摘Background:This investigation aimed to evaluate the therapeutic impact of the Yigan Xiaozheng formula on liver cirrhosis in rats,particularly induced by diethylnitrosamine(DEN).The study focused on analyzing liver structure,cell apoptosis,and the modulation of the Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)signaling pathway,employing a combination of network pharmacology and experimental approaches.Methods:A DEN-induced rat model of liver cirrhosis was established to assess the formula’s effectiveness.Parameters such as overall health,liver morphology,and survival were monitored.Network pharmacology was employed to decipher the active compounds and key targets of the formula in addressing liver cirrhosis.Predictions made via network pharmacology were substantiated through experimental validation in the animal model.Results:Administration of the Yigan Xiaozheng formula led to noticeable improvements in clinical symptoms of liver cirrhosis in rats,marked by enhanced body weight,lessened liver pathology,and higher survival rates.Network pharmacological analysis unveiled intricate interactions between active ingredients of the formula and cirrhosis-related targets.Protein-protein interaction(PPI)networks pinpointed crucial proteins and regulatory modules.Enrichment analysis underscored a significant involvement of the JAK2/STAT3 signaling pathway.On a molecular scale,the formula was observed to reduce the expression of BCL-2 associated X protein(Bax)and cytochrome C(Cyt-C),diminish the Bax/B-cell lymphoma 2(Bcl-2)ratio,and impede JAK2/STAT3 pathway activation,thereby curtailing liver fibrosis and cellular apoptosis.Conclusion:The study demonstrates the Yigan Xiaozheng formula’s capacity to ameliorate liver cirrhosis in a DEN-induced model,primarily through its active ingredients’interactions with cirrhosis targets and modulation of the JAK2/STAT3 pathway.These findings endorse the potential of this traditional Chinese medicinal formula as a viable treatment option for liver cirrhosis.
基金Supported by the Science and Technology Research Project of Hubei Province,No.2021CFB210Central Guiding Local Science and Technology Development Fund Project(Science and Technology Department of Xizang Autonomous Region),No.XZ202401YD0002C。
文摘BACKGROUND Inflammatory bowel disease(IBD)is a chronic,progressive inflammatory condition of the intestine.Mesenchymal stem cell(MSC)therapy for IBD has made significant progress in recent years.To better exploit the therapeutic potential of MSCs,pretreatment strategies are employed to enhance their therapeutic capabilities.As a compound with diverse pharmacological effects,quercetin(QUR)is applied to pretreat human umbilical cord-derived MSCs(hUCMSCs)in this study,thereby augmenting their immunotherapeutic potential.AIM To evaluate the therapeutic efficacy of QUR-pretreated hUCMSCs.METHODS We induced colitis in a mouse model using a 2,4,6-trinitrobenzenesulfonic acid solution.Intraperitoneal injection of QUR-pretreated hUCMSCs significantly improved clinical and pathological manifestations of colitis compared to the model group.Interestingly,the therapeutic effect was superior to that of untreated hUCMSCs.Mice exhibited significantly reduced weight loss,diminished infiltration of inflammatory cells observed in hematoxylin and eosin staining,improved Disease Activity Index and Histological Activity Index scores.Furthermore,colonic tissue analysis revealed a significant upregulation of the anti-inflammatory cytokine interleukin 10(IL-10),accompanied by a downregulation of the pro-inflammatory cytokine IL-6.Further tests also suggested that QUR pretreatment led to inhibition of Janus kinase/signal transducer and activator of transcription(STAT)phosphorylation.RESULTS Our study demonstrated that QUR pretreatment of hUCMSCs significantly enhanced their immune-regulatory capacity.This approach effectively mitigated colonic inflammation in a mouse colitis model by modulating the IL-10/Janus kinase/STAT signaling pathway.CONCLUSION These findings suggest that QUR pretreatment acts synergistically to augment the inherent anti-inflammatory and immune-regulatory properties of hUCMSCs,resulting in enhanced therapeutic efficacy for IBD treatment.
基金Supported by the General Program of the Natural Science Foundation of Guangdong Province,No.2025A1515011163.
文摘This article comments on the study by Zhang et al,which proposed that exosomes derived from hypoxia-injured endometrial epithelial cells promote human umbilical cord mesenchymal stem cell migration and differentiation into endo-metrial epithelial cells via exosomal miR-137-3p.The authors demonstrated that miR-137-3p targets ubiquitin protein ligase E3C and activates signal transducer and activator of transcription 3 signaling,thereby driving epithelial lineage transition.While this study expands our understanding of exosome-mediated intercellular communication in endometrial repair,several key gaps remain.Notably,microRNA(miRNA)profiling was performed in human umbilical cord mesenchymal stem cells post-exosome treatment,not in the exosomes derived from hypoxia-injured endometrial epithelial cell themselves,leaving open whether miR-137-3p is directly transferred or indirectly induced.In addition,data on exosome characterization were unavailable,and the rationale for selecting miR-137-3p over other differentially expressed miRNAs was not well justified.Future studies should include direct exosomal miRNA content analysis,in vivo validation,and deeper mechanistic exploration of the ubiquitin protein ligase E3C-signal transducer and activator of transcription 3 ubiquitination axis to establish the clinical and biological relevance of this pathway.
基金Supported by Colegio de Ciencia y Tecnología de la Universidad Autónoma de la Ciudad de México,No.CCYT-2025-CON-11.
文摘The canonical signaling of interferon gamma(IFN-γ)through the Janus kinase 1 and 2–signal transducer and activator of transcription 1(STAT1)axis leads to the expression of several interferon-stimulated genes(ISGs),which have diverse effects depending on the cellular context.In glioblastoma,a highly aggressive primary brain tumor in adults,elements of IFN-γcanonical signaling are deregulated,resulting in the overexpression of STAT1-target ISGs associated with tumor progression.This mini-review highlights key ISGs,including STAT1,interferon regulatory factor 1,programmed death-ligand 1,indoleamine 2,3-dioxygenase 1,and interferon-stimulated gene 15,involved in the pathology of glioblastoma.These genes may serve as valuable biomarkers and have therapeutic potential for targeting IFN-γsignaling in this malignancy.
基金Supported by the Chongqing Basic Research and Frontier Exploration Project,No.cstc2018jcyjAX0834.
文摘BACKGROUND At present,the incidence of diabetic nephropathy is increasing year by year,and there are many studies on the pathogenesis of diabetic nephropathy,but it is still not completely clear.The final pathological result of diabetic nephropathy is mainly glomerular cell fibrosis,and the roles of micro-RNA(miRNA)-29 and DNA methyl transferase(DNMTs)in cell fibrosis have been confirmed in other studies,but there is a lack of relevant research in the kidney at present.AIM To study the potential involvement of miRNA-29a-3p in fibrosis related to diabetic kidney disease(DKD).METHODS The expression of miR-29a-3p,DNMT3A/3B,fibrosis-related molecules,Wnt3a,β-catenin,Janus kinase 2,and signal transducer and activator of transcription 3 was assessed in SV40MES13 cells and diabetic mice using quantitative real-time PCR and western blotting.Furthermore,the expression changes of fibrosis-related molecules were further analyzed using immunofluorescence and immunohistochemical blotting.The renal pathological changes of DKD in each group were also studied using hematoxylin-eosin and periodate-Schiff reaction staining.RESULTS In both the in vivo and in vitro experiments,it was observed that high glucose induction significantly decreased miR-29a-3p expression.As a result of this downregulation,DKD-related fibrosis was found to be promoted,as confirmed by elevated expression levels ofα-smooth muscle actin,collagen type I,and fibronectin.MiR-29a-3p targets the 3’non-coding regions of DNMT3A and DNMT3B and inhibits their expression.Inhibition of DNMT3A and DNMT3B can reverse the effect of miR-29a-3p downregulation on DKD-related fibrosis.CONCLUSION MiR-29a-3p can regulate Wnt/β-catenin and Janus kinase/signal transducer and activator of transcription signal pathways by regulating and inhibiting the expression of DNMT3A/3B and thus participate in the inhibition of DKD-related fibrosis.
