OBJECTIVE: To explore the possibility of expression of exogenous gene in transduced bone marrow derived stromal cells (BMSCs). METHODS: The marker gene, pbLacZ, was transferred into cultured BMSCs and the expression o...OBJECTIVE: To explore the possibility of expression of exogenous gene in transduced bone marrow derived stromal cells (BMSCs). METHODS: The marker gene, pbLacZ, was transferred into cultured BMSCs and the expression of transduced gene by X-gal staining was examined. Then plasmid pcDNA3-rhBMP7 was delivered to cultured BMSCs. Through immunohistochemical staining and RT-PCR assay, the expression of rhBMP7 gene was detected. RESULTS: The exogenous gene could be expressed efficiently in transduced BMSCs. CONCLUSION: The present study provided a theoretical basis to gene therapy on the problems of bone and cartilage tissue.展开更多
Background:Thimerosal is a mercury-containing preservative widely used in vaccines.This study aimed to investigate its potential antitumor effects and mechanisms in solid malignancies,particularly colorectal cancer(CR...Background:Thimerosal is a mercury-containing preservative widely used in vaccines.This study aimed to investigate its potential antitumor effects and mechanisms in solid malignancies,particularly colorectal cancer(CRC)and melanoma.Methods:A combination of in vitro and in vivo approaches was employed.Cell proliferation,apoptosis,migration,and invasion were assessed using Cell Counting Kit-8(CCK-8),colony formation,ATP viability,Western blotting,flow cytometry,wound-healing and Transwell assays.Subcutaneous,lung metastases,and Azoxymethane/Dextran Sulfate Sodium Salt(AOM/DSS)-induced colitis-associated CRC models were established to examine antitumor efficacy and safety.The functional role of mercury ions was validated using structural analogues.Mechanistic studies included RNA sequencing,Western blot,and immunohistochemical analysis of CD8^(+)T cell infiltration.The synergistic effect with programmed cell death protein 1(PD-1)antibody therapy was also evaluated.Results:Thimerosal potently inhibited tumor growth(with IC50 values ranging from 0.1 to 1μM in vitro)and significantly prolonged survival without overt toxicity in vivo.Mechanistically,mercury ions were identified as critical functional sites mediating Thimerosal’s antitumor effects.Specifically,Thimerosal inhibited the phosphorylation of Janus kinase 1(JAK1)and signal transducer and activator of transcription 3(STAT3).Furthermore,it enhanced the infiltration of CD8^(+)T cells into the tumor microenvironment and synergistically augmented the efficacy of anti-PD-1 therapy.Conclusion:Thimerosal exerts dual antitumor roles by direct JAK1/STAT3 inhibition and immune modulation via CD8^(+)T cell recruitment.It represents a promising repurposed drug and immunotherapeutic adjuvant for CRC and melanoma.展开更多
Background:Breakpoint Cluster Region-Abelson(BCR::ABL1)fusion protein is essential in the pathogenesis of chronic myeloid leukemia(CML);however,the chronic-to-blast phase transformation remains elusive.We identified n...Background:Breakpoint Cluster Region-Abelson(BCR::ABL1)fusion protein is essential in the pathogenesis of chronic myeloid leukemia(CML);however,the chronic-to-blast phase transformation remains elusive.We identified novel kinesin light chain 2(KLC2)mutations in CML-myeloid blast phase patients.We aimed to examine the functional role of KLC2 mutations in leukemogenesis.Methods:To evaluate the biological role of KLC2 mutants(MT)in CML cells,we expressed KLC2-MT in different human CML cell lines harboring BCR::ABL1 and performed immunoblot,immunofluorescence,cell proliferation,differentiation,and apoptosis;Tyrosine kinase inhibitor(TKI)-drug activities;and clonogenic assays for in vitro functional analyses.We co-expressed KLC2-MT and BCR::ABL1 in mouse bone marrow cells(BMCs)to evaluate their clonogenic and self-renewal abilities ex vivo.Furthermore,we examined tumorigenic activity and drug efficacy in the K562 xenograft model.Results:KLC2-MT overexpression in BCR::ABL1-positive K562 and KU812 CML cells promoted cell proliferation and clonogenic potential,decreased imatinib sensitivity,and reduced apoptosis.Serial colony replating assays revealed that KLC2-MT and BCR::ABL1 co-expression enhanced the self-renewal ability of mouse BMCs with immature morphology.In the K562 xenograft model,KLC2-MT enhanced tumorigenic potential and diminished imatinib efficacy.Further studies reported that KLC2-MT augmented signal transducer and activator of transcription 3(STAT3)activation and nuclear accumulation in imatinib-treated CML cells.KLC2-WT and KLC2-MT interacted with mothers against decapentaplegic homolog 2(SMAD2);however,the latter impaired transforming growth factor-beta(TGF-β)–mediated SMAD2/3 activation while enhancing STAT3 phosphorylation.Conclusions:This study demonstrates the biological and functional importance of KLC2 mutation in CML cells,potentially enabling the development of better treatment strategies for CML patients carrying KLC2 mutations and providing enhanced understanding of the disease progression.展开更多
Objectives The discovery of novel molecular targets to enhance the osteogenesis of human bone marrow-derived mesenchymal stem cells(H-BMSCs)represents a promising strategy for preventing and treating osteoporosis.Thus...Objectives The discovery of novel molecular targets to enhance the osteogenesis of human bone marrow-derived mesenchymal stem cells(H-BMSCs)represents a promising strategy for preventing and treating osteoporosis.Thus,the primary objective of this study is to elucidate the mechanisms by which long non-coding RNA FOXD2-AS1(lncRNA FOXD2-AS1)regulates early osteogenic differentiation in H-BMSCs,thereby identifying potential therapeutic targets.Methods Lentivirus-mediated vectors were constructed to either overexpress or silence FOXD2-AS1 in H-BMSCs.The effects of FOXD2-AS1 on osteogenesis were subsequently assessed by analyzing osteogenic marker expression and alkaline phosphatase(ALP)staining.To clarify the role of the Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)pathway in this process,AG490 inhibitor(a JAK2/STAT3 pathway inhibitor)and knockdown of STAT3 were used to investigate the mechanisms of FOXD2-AS1.Results FOXD2-AS1 overexpression increased ALP activity and osteogenic marker expression,while its knockdown had the opposite effects.From a mechanistic perspective,FOXD2-AS1 overexpression promoted JAK2 and STAT3 phosphorylation,whereas its suppression attenuated their activation.Also,the osteogenic increase induced by FOXD2-AS1 overexpression was reversed by AG490 treatment or STAT3 silencing,indicating that the pathway plays a role in this process.Conclusion FOXD2-AS1 was identified as a novel genetic switch driving osteogenic commitment via JAK2/STAT3 activation,revealing a new regulatory mechanism and a potential therapeutic target for osteoporosis.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
OBJECTIVE:To explore the mechanism of Wenshen Zhuanggu Fang(温肾壮骨方,WSZG)against breast cancer bone metastasis from the perspective of macrophage polarization through bioinformatics and experiments.METHODS:Bioinfor...OBJECTIVE:To explore the mechanism of Wenshen Zhuanggu Fang(温肾壮骨方,WSZG)against breast cancer bone metastasis from the perspective of macrophage polarization through bioinformatics and experiments.METHODS:Bioinformatics study was used to explore the mechanism underlying the effect of WSZG on breast cancer bone metastasis.Cell viability,migration,invasion and apoptosis assays were performed to detect the influence of WSZG on breast cancer cell MDA-MB-231BO promoted by macrophages.The protein expression level and cytokine content were detected by western blot and enzyme-linked immunosorbent assay kit in vitro.Tumor growth in vivo were performed to evaluate the effects of WSZG on breast cancer bone metastasis.M2/M1 ratio and the maker protein expression were detected by flow cytometry analysis,immunohistochemistry and immunofluorescence double staining.RESULTS:M2 macrophages associated with poor prognosis and may lead to secondary bone metastasis in patients with triple-negative breast cancer.WSZG could treat breast cancer bone metastasis through regulating macrophage polarization by signal transducers and transcription signaling activators(STAT)signaling pathway.WSZG downregulated STAT6,CD206 and Arginase-1,while upregulated STAT1 and Inducible Nitric Oxide Synthase,thus inhibited the M2 macrophagepromoted invasion and migration capabilities of MDA-MB-231BO cells.WSZG treatment suppressed the bone metastasis of breast cancer,and the M2/M1 ratio was reduced by regulating STAT expression in bone metastatic tissue.CONCLUSION:WSZG inhibited breast cancer bone metastasis by adjusting the promoting effect of macrophages on MDA-MB-231BO breast cancer cells and decreasing M2 polarization by downregulating STAT signaling.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
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
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
文摘OBJECTIVE: To explore the possibility of expression of exogenous gene in transduced bone marrow derived stromal cells (BMSCs). METHODS: The marker gene, pbLacZ, was transferred into cultured BMSCs and the expression of transduced gene by X-gal staining was examined. Then plasmid pcDNA3-rhBMP7 was delivered to cultured BMSCs. Through immunohistochemical staining and RT-PCR assay, the expression of rhBMP7 gene was detected. RESULTS: The exogenous gene could be expressed efficiently in transduced BMSCs. CONCLUSION: The present study provided a theoretical basis to gene therapy on the problems of bone and cartilage tissue.
基金supported by the National Natural Science Foundation of China(82441036)Ganzhou Municipal Science and Technology Project(2022-RC1342)+3 种基金Guangdong Basic and Applied Basic Research Foundation(2022B1515130004)Key-Area Research and Development Program of Guangdong Province(2019B020234003)Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer(2020B121201004)Open Project Fund Project of Guangdong Academy of Medical Sciences(YKY-KF202210).
文摘Background:Thimerosal is a mercury-containing preservative widely used in vaccines.This study aimed to investigate its potential antitumor effects and mechanisms in solid malignancies,particularly colorectal cancer(CRC)and melanoma.Methods:A combination of in vitro and in vivo approaches was employed.Cell proliferation,apoptosis,migration,and invasion were assessed using Cell Counting Kit-8(CCK-8),colony formation,ATP viability,Western blotting,flow cytometry,wound-healing and Transwell assays.Subcutaneous,lung metastases,and Azoxymethane/Dextran Sulfate Sodium Salt(AOM/DSS)-induced colitis-associated CRC models were established to examine antitumor efficacy and safety.The functional role of mercury ions was validated using structural analogues.Mechanistic studies included RNA sequencing,Western blot,and immunohistochemical analysis of CD8^(+)T cell infiltration.The synergistic effect with programmed cell death protein 1(PD-1)antibody therapy was also evaluated.Results:Thimerosal potently inhibited tumor growth(with IC50 values ranging from 0.1 to 1μM in vitro)and significantly prolonged survival without overt toxicity in vivo.Mechanistically,mercury ions were identified as critical functional sites mediating Thimerosal’s antitumor effects.Specifically,Thimerosal inhibited the phosphorylation of Janus kinase 1(JAK1)and signal transducer and activator of transcription 3(STAT3).Furthermore,it enhanced the infiltration of CD8^(+)T cells into the tumor microenvironment and synergistically augmented the efficacy of anti-PD-1 therapy.Conclusion:Thimerosal exerts dual antitumor roles by direct JAK1/STAT3 inhibition and immune modulation via CD8^(+)T cell recruitment.It represents a promising repurposed drug and immunotherapeutic adjuvant for CRC and melanoma.
基金supported by grants from the Ministry of Science and Technology,Taiwan(MOST108-2314-B-182-006,MOST109-2314-B-182-071:Lee-Yung Shih)the Ministry of Health and Welfare,Taiwan(MOHW110-TDU-B-212-134011:Lee-Yung Shih)+3 种基金Chang Gung Memorial Hospital(CMRPG3D1524,OMRPG3E0031:Lee-Yung Shih)the Grant-in-Aid for the Japan Society for the Promotion of Science(JSPS)KAKENHI(JP19H05656:Seishi Ogawa,22K16320:Yotaro Ochi)the Japan Agency for Medical Research and Development(AMED)(JP19cm0106501h0004,JP19ck0106250h0003:Seishi Ogawa)the Ministry of Education,Culture,Sports,Science and Technology of Japan(MEXT)(hp200138,hp210167:Seishi Ogawa)。
文摘Background:Breakpoint Cluster Region-Abelson(BCR::ABL1)fusion protein is essential in the pathogenesis of chronic myeloid leukemia(CML);however,the chronic-to-blast phase transformation remains elusive.We identified novel kinesin light chain 2(KLC2)mutations in CML-myeloid blast phase patients.We aimed to examine the functional role of KLC2 mutations in leukemogenesis.Methods:To evaluate the biological role of KLC2 mutants(MT)in CML cells,we expressed KLC2-MT in different human CML cell lines harboring BCR::ABL1 and performed immunoblot,immunofluorescence,cell proliferation,differentiation,and apoptosis;Tyrosine kinase inhibitor(TKI)-drug activities;and clonogenic assays for in vitro functional analyses.We co-expressed KLC2-MT and BCR::ABL1 in mouse bone marrow cells(BMCs)to evaluate their clonogenic and self-renewal abilities ex vivo.Furthermore,we examined tumorigenic activity and drug efficacy in the K562 xenograft model.Results:KLC2-MT overexpression in BCR::ABL1-positive K562 and KU812 CML cells promoted cell proliferation and clonogenic potential,decreased imatinib sensitivity,and reduced apoptosis.Serial colony replating assays revealed that KLC2-MT and BCR::ABL1 co-expression enhanced the self-renewal ability of mouse BMCs with immature morphology.In the K562 xenograft model,KLC2-MT enhanced tumorigenic potential and diminished imatinib efficacy.Further studies reported that KLC2-MT augmented signal transducer and activator of transcription 3(STAT3)activation and nuclear accumulation in imatinib-treated CML cells.KLC2-WT and KLC2-MT interacted with mothers against decapentaplegic homolog 2(SMAD2);however,the latter impaired transforming growth factor-beta(TGF-β)–mediated SMAD2/3 activation while enhancing STAT3 phosphorylation.Conclusions:This study demonstrates the biological and functional importance of KLC2 mutation in CML cells,potentially enabling the development of better treatment strategies for CML patients carrying KLC2 mutations and providing enhanced understanding of the disease progression.
基金supported by the Natural Science Foundation of Hubei Province of China(Grant No.2023AFB671)the National Natural Science Foundation of China(Grant Nos.82360177 and 82560182)+1 种基金the Key Project of Jiangxi Provincial Natural Science Foundation(Grant No.20224ACB206011)“Xuncheng Talents”Project in Jiujiang City,Jiangxi Province(Grant No.JJXC2023071).
文摘Objectives The discovery of novel molecular targets to enhance the osteogenesis of human bone marrow-derived mesenchymal stem cells(H-BMSCs)represents a promising strategy for preventing and treating osteoporosis.Thus,the primary objective of this study is to elucidate the mechanisms by which long non-coding RNA FOXD2-AS1(lncRNA FOXD2-AS1)regulates early osteogenic differentiation in H-BMSCs,thereby identifying potential therapeutic targets.Methods Lentivirus-mediated vectors were constructed to either overexpress or silence FOXD2-AS1 in H-BMSCs.The effects of FOXD2-AS1 on osteogenesis were subsequently assessed by analyzing osteogenic marker expression and alkaline phosphatase(ALP)staining.To clarify the role of the Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)pathway in this process,AG490 inhibitor(a JAK2/STAT3 pathway inhibitor)and knockdown of STAT3 were used to investigate the mechanisms of FOXD2-AS1.Results FOXD2-AS1 overexpression increased ALP activity and osteogenic marker expression,while its knockdown had the opposite effects.From a mechanistic perspective,FOXD2-AS1 overexpression promoted JAK2 and STAT3 phosphorylation,whereas its suppression attenuated their activation.Also,the osteogenic increase induced by FOXD2-AS1 overexpression was reversed by AG490 treatment or STAT3 silencing,indicating that the pathway plays a role in this process.Conclusion FOXD2-AS1 was identified as a novel genetic switch driving osteogenic commitment via JAK2/STAT3 activation,revealing a new regulatory mechanism and a potential therapeutic target for osteoporosis.
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National Natural Science Foundation of China:Study on the Scientific Connotation of Traditional Chinese Medicine"Conghua Theory"by Regulating Metastatic Site-specific Polarization of Macrophages in Breast Cancer Lung and Bone Metastases(No.81774308)National Natural Science Foundation of China:Study on the Pharmacodynamic Substances and Mechanism of Wenshen Zhuanggu Recipe Regulating Exocrine Integrin/Sarcoma/Mitogenactivated protein kinase Signal Axis in Intervention of Bone Metastasis Niche Formation in Breast Cancer(No.82174016)。
文摘OBJECTIVE:To explore the mechanism of Wenshen Zhuanggu Fang(温肾壮骨方,WSZG)against breast cancer bone metastasis from the perspective of macrophage polarization through bioinformatics and experiments.METHODS:Bioinformatics study was used to explore the mechanism underlying the effect of WSZG on breast cancer bone metastasis.Cell viability,migration,invasion and apoptosis assays were performed to detect the influence of WSZG on breast cancer cell MDA-MB-231BO promoted by macrophages.The protein expression level and cytokine content were detected by western blot and enzyme-linked immunosorbent assay kit in vitro.Tumor growth in vivo were performed to evaluate the effects of WSZG on breast cancer bone metastasis.M2/M1 ratio and the maker protein expression were detected by flow cytometry analysis,immunohistochemistry and immunofluorescence double staining.RESULTS:M2 macrophages associated with poor prognosis and may lead to secondary bone metastasis in patients with triple-negative breast cancer.WSZG could treat breast cancer bone metastasis through regulating macrophage polarization by signal transducers and transcription signaling activators(STAT)signaling pathway.WSZG downregulated STAT6,CD206 and Arginase-1,while upregulated STAT1 and Inducible Nitric Oxide Synthase,thus inhibited the M2 macrophagepromoted invasion and migration capabilities of MDA-MB-231BO cells.WSZG treatment suppressed the bone metastasis of breast cancer,and the M2/M1 ratio was reduced by regulating STAT expression in bone metastatic tissue.CONCLUSION:WSZG inhibited breast cancer bone metastasis by adjusting the promoting effect of macrophages on MDA-MB-231BO breast cancer cells and decreasing M2 polarization by downregulating STAT signaling.
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(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 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.
