Equatorial Plasma Bubbles(EPBs)are ionospheric irregularities that take place near the magnetic equator.EPBs most commonly occur after sunset during the equinox months,although they can also be observed during other s...Equatorial Plasma Bubbles(EPBs)are ionospheric irregularities that take place near the magnetic equator.EPBs most commonly occur after sunset during the equinox months,although they can also be observed during other seasons.The phenomenon significantly disrupts radio wave signals essential to communication and navigation systems.The national network of Global Navigation Satellite System(GNSS)receivers in Indonesia(>30°longitudinal range)provides an opportunity for detailed EPB studies.To explore this,we conducted preliminary 3D tomography of total electron content(TEC)data captured by GNSS receivers following a geomagnetic storm on December 3,2023,when at least four EPB clusters occurred in the Southeast Asian sector.TEC and extracted TEC depletion with a 120-minute running average were then used as inputs for a 3D tomography program.Their 2D spatial distribution consistently captured the four EPB clusters over time.These tomography results were validated through a classical checkerboard test and comparisons with other ionospheric data sources,such as the Global Ionospheric Map(GIM)and International Reference Ionosphere(IRI)profile.Validation of the results demonstrates the capability of the Indonesian GNSS network to measure peak ionospheric density.These findings highlight the potential for future three-dimensional research of plasma bubbles in low-latitude regions using existing GNSS networks,with extensive longitudinal coverage.展开更多
This geo-historical case study analyses Vistelius’ingenious idea of conceptual stochastic models and their application as Markov chain analysis in the geosciences.Vistelius(1915–1995)is regarded as one of the founde...This geo-historical case study analyses Vistelius’ingenious idea of conceptual stochastic models and their application as Markov chain analysis in the geosciences.Vistelius(1915–1995)is regarded as one of the founders of mathematical geology.He was the fi rst to defi ne mathematical geology as“a scientifi c discipline concerned with the construction,analysis and use of conceptual mathematical models of geological events to solve concrete problems”(Vistelius in Principles of mathematical geology,Nauka,Leningrad,1980;Principles of mathematical geology,Kluwer Academic Publishers,Dordrecht,1992).Mathematical models in this context should be primarily probabilistic because of the large number of infl uencing natural factors.They must be conceptual to avoid fundamental errors in application.Vistelius devoted his seminal book to geological random sequences and their description and analysis using Markov models as stochastic tools.He applied this approach to grain sequences in granitic intrusive rocks and to sedimentary rock layers.Among other things,Vistelius has used Markov chain analysis in mineral resource exploration to distinguish between“ideal”granites,which are not subsequently mineralized,and mainly hydrothermally mineralized,sometimes ore-bearing granites which contain at least two generations of main minerals.The application of this special conceptual stochastic model is demonstrated on Lusatian granite(Saxony,Germany).展开更多
Balancing high display performance with energy efficiency is crucial for global sustainability.Lowering operating frequencies—such as enabling 1 Hz operation in fringe-field switching(FFS)liquid crystal displays—red...Balancing high display performance with energy efficiency is crucial for global sustainability.Lowering operating frequencies—such as enabling 1 Hz operation in fringe-field switching(FFS)liquid crystal displays—reduces power consumption but is hindered by image flicker.While negative dielectric anisotropy liquid crystals(nLCs)mitigate flicker,their high driving voltages and production costs limit adoption.Positive dielectric anisotropy liquid crystals(pLCs)offer lower operating voltages,faster response times,and broader applicability,making them a more viable alternative.This study introduces a novel approach to minimizing flexoelectric effects in pLCs by investigating how single components influence flexoelectric behavior in mixtures through an effective experimental methodology.Two innovative measurement techniques—(1)flexoelectric coefficient difference analysis and(2)displacement-current measurement(DCM)—are presented,marking the first application of DCM for verifying flexoelectric effects.The proposed system eliminates uncertainties associated with previous methods,providing a reliable framework for selecting liquid crystal components with minimal flexoelectric effects while preserving key electro-optic properties.Given pLCs'higher reliability,lower production costs,and broader material selection,these advancements hold significant potential for low-power displays.We believe this work enhances flexoelectric analysis in nematic liquid crystals and contributes to sustainable innovation in the display industry,aligning with global energy-saving goals.展开更多
Development of sustainable construction materials has been the focus of research efforts worldwide in recent years.Concrete is a major construction material;hence,finding alternatives to ordinary Portland cement is of...Development of sustainable construction materials has been the focus of research efforts worldwide in recent years.Concrete is a major construction material;hence,finding alternatives to ordinary Portland cement is of extreme importance due to the high levels of carbon dioxide emissions associated with its manufacturing process.This study investigates the geopolymerization process.Specimens with,two different water/binder weight ratios,0.30 and 0.35,were monitored using acoustic emission.Results show that there is a significant difference in the acquisition data between the two different water/binder weight ratios.In addition,acoustic emission can be used to beneficially monitor and investigate the early geopolymerization process.The acoustic emission data were processed through pattern recognition.Two clusters were identified,assigned to a specific mechanism depending on their characteristics.SEM observations were coincided with pattern recognition findings.展开更多
Photodynamic therapy(PDT)has been established as one of the most promising novel cancer therapies with fewer side-effects and enhanced efficacy compared to the currently available conventional treatments.However,its a...Photodynamic therapy(PDT)has been established as one of the most promising novel cancer therapies with fewer side-effects and enhanced efficacy compared to the currently available conventional treatments.However,its application has been hindered by the limitations that photosensitizers(PS)have.The combination of PS with metallic nanoparticles like platinum nanoparticles(PtNPs),can help to overcome these intrinsic drawbacks.In this work,the combination of PtNPs and the natural photosensitizer riboflavin(RF)is proposed.PtNPs are synthesized using RF(Pt@RF)as reducing and stabilizing agent in a one-step method,obtaining nanoparticles with mesoporous structure for UV triggered PDT.In view of possible future UV irradiation treatments,the degradation products of RF,ribitol(RB)and lumichrome(LC),this last being a photosensitizing byproduct,are also employed for the synthesis of porous PtNPs,obtaining Pt@LC and Pt@RB.When administered in vitro to lung cancer cells,all the samples elicit a strong decrease of cell viability and a decrease of intracellular ATP levels.The antitumoral effect of both Pt@RF and Pt@LC is triggered by UV-A irradiation.This antitumoral activity is caused by the induction of oxidative stress,shown in our study by the decrease in intracellular glutathione and increased expression of antioxidant enzymes.展开更多
In this paper,an interference cancellation based neural receiver for superimposed pilot(SIP)in multi-layer transmission is proposed,where the data and pilot are non-orthogonally superimposed in the same time-frequency...In this paper,an interference cancellation based neural receiver for superimposed pilot(SIP)in multi-layer transmission is proposed,where the data and pilot are non-orthogonally superimposed in the same time-frequency resource.Specifically,to deal with the intra-layer and inter-layer interference of SIP under multi-layer transmission,the interference cancellation with superimposed symbol aided channel estimation is leveraged in the neural receiver,accompanied by the pre-design of pilot code-division orthogonal mechanism at transmitter.In addition,to address the complexity issue for inter-vendor collaboration and the generalization problem in practical deployments,respectively,this paper also provides a fixed SIP(F-SIP)design based on constant pilot power ratio and scalable mechanisms for different modulation and coding schemes(MCSs)and transmission layers.Simulation results demonstrate the superiority of the proposed schemes on the performance of block error rate and throughput compared with existing counterparts.展开更多
This study aims to examine the challenges and future directions of large-scale wooden construction education at universities in Japan and Finland.It compares the wooden construction curricula at universities and the a...This study aims to examine the challenges and future directions of large-scale wooden construction education at universities in Japan and Finland.It compares the wooden construction curricula at universities and the architectural education initiatives undertaken by firms specializing in large-scale wood construction design in both countries.The target applications for large-scale wooden construction are residential,commercial,and public buildings.Comparing university education revealed many commonalities between the two countries,allowing them to be classified into two types:“seminar-centered”and“lecture-centered”.Japanese universities are categorized by building type and scale for educational purposes.Finnish universities focus their education on the properties and functions of wood.Based on these results,we infer that incorporating both Japan’s architecture-planning-focused education and Finland’s materials-focused education into teaching,using familiar housing buildings as a theme,will lead to the wider adoption of large-scale wooden construction.展开更多
Network attacks have become a critical issue in the internet security domain.Artificial intelligence technology-based detection methodologies have attracted attention;however,recent studies have struggled to adapt to ...Network attacks have become a critical issue in the internet security domain.Artificial intelligence technology-based detection methodologies have attracted attention;however,recent studies have struggled to adapt to changing attack patterns and complex network environments.In addition,it is difficult to explain the detection results logically using artificial intelligence.We propose a method for classifying network attacks using graph models to explain the detection results.First,we reconstruct the network packet data into a graphical structure.We then use a graph model to predict network attacks using edge classification.To explain the prediction results,we observed numerical changes by randomly masking and calculating the importance of neighbors,allowing us to extract significant subgraphs.Our experiments on six public datasets demonstrate superior performance with an average F1-score of 0.960 and accuracy of 0.964,outperforming traditional machine learning and other graph models.The visual representation of the extracted subgraphs highlights the neighboring nodes that have the greatest impact on the results,thus explaining detection.In conclusion,this study demonstrates that graph-based models are suitable for network attack detection in complex environments,and the importance of graph neighbors can be calculated to efficiently analyze the results.This approach can contribute to real-world network security analyses and provide a new direction in the field.展开更多
The Permian-Triassic(P/T)transition is marked by the most severe mass-extinction event of the Phanerozoic.Although much is known about this event in the marine realm,there are many open questions regarding what happen...The Permian-Triassic(P/T)transition is marked by the most severe mass-extinction event of the Phanerozoic.Although much is known about this event in the marine realm,there are many open questions regarding what happened during this period to many continental biota.In the case of plants,a drastic mass-extinction event has even been negated by some authors.To add about the knowledge on continental biota in India during this crucial time period,the present study analysed the palynology,palynofacies,organic geochemistry(biomarkers),stable isotopes,and charcoal within the subsurface Gondwana deposits of the Kamthi Formation(late Permian-early Triassic)from core TTB-7 from the Tribida block,located in the Talcher Coalfield of the Mahanadi Basin,India.The primary objectives are to validate the age of the strata,ascertain the palaeodepositional setting of the palaeomire,and propose palaeobotanical evidence regarding the occurrence of wildfires within this stratigraphic succession and changes in floral content across the P/T transition.The palynological study proposes two palynoassemblage zones,Densipollenites magnicorpus and Klausipollenites schaubergeri,suggesting a latest Permian(Lopingian)and early Triassic(Induan?)age for the studied succession,respectively.The age is also inferred based on correlation with coeval assemblages from India and other Gondwana continents.The palynoassemblages reveal the dominance of Glossopteridales and Coniferales along with Filicales,Lycopsidales,Equisetales,Cordaitales and Peltaspermales.The relatively higher values of the carbon preference index and terrigenous/aquatic ratio also suggest higher plant input.However,a bimodal n-alkane distribution pattern suggests the contribution of terrigenous and microbial sources.Although the occurrences of long-chain alkanes indicate input of higher plants,the low Pwax values(<0.26)suggest relatively less contribution.The Paqvalues(≅1)and amorphous organic matter(av.33.24%)suggest a significant macrophyte input in the studied samples,pointing to the occurrence of moderate aquatic conditions in the basin.Furthermore,the distribution of hopanoids and the content of degraded organic matter(av.29.96%)reflect the bacterial degradation of organic matter.Also,the δ^(13)C values of the studied section varied from−31.2‰to−21.8‰.A large carbon isotopic offset of 9.4‰across the P/T transition,Pr/Ph ratio(0.3–1.3)and shift in the distribution pattern of palynofacies components is indicating a significant change in climatic conditions.Moreover,the presence of macroscopic charcoal fragments of gymnospermous affinity with pre-charring colonization by fungi provides evidence for wildfire occurring during the Lopingian(Late Permian)in this basin.展开更多
Additive Manufacturing(AM)can provide customized parts that conventional techniques fail to deliver.One important parameter in AM is the quality of the parts,as a result of the material extrusion 3D printing(3D-P)proc...Additive Manufacturing(AM)can provide customized parts that conventional techniques fail to deliver.One important parameter in AM is the quality of the parts,as a result of the material extrusion 3D printing(3D-P)procedure.This can be very important in defense-related applications,where optimum performance needs to be guaranteed.The quality of the Polyetherimide 3D-P specimens was examined by considering six control parameters,namely,infill percentage,layer height,deposition angle,travel speed,nozzle,and bed temperature.The quality indicators were the root mean square(Rq)and average(Ra)roughness,porosity,and the actual to nominal dimensional deviation.The examination was performed with optical profilometry,optical microscopy,and micro-computed tomography scanning.The Taguchi design of experiments was applied,with twenty-five runs,five levels for each control parameter,on five replicas.Two additional confirmation runs were conducted,to ensure reliability.Prediction equations were constructed to express the quality indicators in terms of the control parameters.Three modeling approaches were applied to the experimental data,to compare their efficiency,i.e.,Linear Regression Model(LRM),Reduced Quadratic Regression Model,and Quadratic Regression Model(QRM).QRM was the most accurate one,still the differences were not high even considering the simpler LRM model.展开更多
In this paper,we present a Deep Neural Network(DNN)based framework that employs Radio Frequency(RF)hologram tensors to locate multiple Ultra-High Frequency(UHF)passive Radio-Frequency Identification(RFID)tags.The RF h...In this paper,we present a Deep Neural Network(DNN)based framework that employs Radio Frequency(RF)hologram tensors to locate multiple Ultra-High Frequency(UHF)passive Radio-Frequency Identification(RFID)tags.The RF hologram tensor exhibits a strong relationship between observation and spatial location,helping to improve the robustness to dynamic environments and equipment.Since RFID data is often marred by noise,we implement two types of deep neural network architectures to clean up the RF hologram tensor.Leveraging the spatial relationship between tags,the deep networks effectively mitigate fake peaks in the hologram tensors resulting from multipath propagation and phase wrapping.In contrast to fingerprinting-based localization systems that use deep networks as classifiers,our deep networks in the proposed framework treat the localization task as a regression problem preserving the ambiguity between fingerprints.We also present an intuitive peak finding algorithm to obtain estimated locations using the sanitized hologram tensors.The proposed framework is implemented using commodity RFID devices,and its superior performance is validated through extensive experiments.展开更多
The global reliance on phosphate rock for agriculture and other industries,coupled with chemical regulations in developed countries,has driven the search for green alternatives in apatite flotation.This review investi...The global reliance on phosphate rock for agriculture and other industries,coupled with chemical regulations in developed countries,has driven the search for green alternatives in apatite flotation.This review investigates eco-friendly collectors’effectiveness in promoting sustainable mineral processing,guiding future alternatives to traditional reagents.The manuscript discussed the surface properties of apatite and its interaction with eco-friendly collectors,assessing existing fundamental studies.This study sought to:(1)define,organize,and classify“eco-friendly”collectors;(2)evaluate their effect in IEP and contact angle;(3)provide a better understanding of the adsorption behavior of the different fatty acid chains into apatite surface;(4)assess their ability to reversely and directly float apatite;(5)address gaps to achieve selectivity and process optimization.Outcomes demonstrated that fatty acids are largely applied,but other renewable sources of these reagents have been promisingly evaluated.In addition,other natural reagents have been tested,and new green synthetics have demonstrated synergistic effects when combined with fatty acids,yielding significant improvements in grade and recovery.However,collector effectiveness varies with ore characteristics,like particle size and surface properties,which remain underexplored.Future research should design tailored collectors that align with mineralogical differences to enhance selectivity.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
Microbes play a critical role in shaping immune development,with growing interest in how rhinovirus(RV)interacts with the host immune system,particularly in individuals with asthma and chronic obstructive pul-monary d...Microbes play a critical role in shaping immune development,with growing interest in how rhinovirus(RV)interacts with the host immune system,particularly in individuals with asthma and chronic obstructive pul-monary disease(COPD).Disruptions in microbial balance during RV infections can impair immune homeostasis and worsen disease outcomes.Recent studies emphasize RV-induced regulation of antiviral defenses,cytokine production,and immune tolerance.This review explores the interplay between RV,the immune system,and microbiota,highlighting the importance of these interactions in guiding effective therapies for respiratory in-fections.It advances existing literature by considering microbiota-mediated therapies as a novel approach to managing RV exacerbations in respiratory diseases like asthma and COPD.展开更多
Planar lightwave circuit(PLC)splitters have long been foundational components in passive optical communication networks,achieving commercial success since the 1990s.However,their inherent fixed splitting ratios impose...Planar lightwave circuit(PLC)splitters have long been foundational components in passive optical communication networks,achieving commercial success since the 1990s.However,their inherent fixed splitting ratios impose significant limitations on capacity expansion,often requiring physical replacement and causing service disruptions.Thermally tunable optical splitters address this challenge by enabling adjustable splitting ratios,but their operation is contingent upon a continuous power supply and complex driving systems.In this work,we present a novel,non-volatile tunable PLC platform based on Sb_(2)S_(3)phase-change materials.The proposed device,which incor-porates a Mach-Zehnder interferometer(MZI)optical switch structure,offers tunable splitting ratios via laser-direct writing or ohmic heating,providing flexible reconfiguration capabilities.Experimental results demonstrate non-volatile power splitting ranging from 50∶50 to 20∶80,with a modest increase of approximately 1 dB in additional loss.This work highlights the potential of the proposed platform for low-power,high-efficiency,and reconfigurable photonic networks.展开更多
This study investigated the hydraulic and mechanical behaviors of unsaturated coarse-grained railway embankment fill materials(CREFMs)using a novel unsaturated large-scale triaxial apparatus equipped with the axis tra...This study investigated the hydraulic and mechanical behaviors of unsaturated coarse-grained railway embankment fill materials(CREFMs)using a novel unsaturated large-scale triaxial apparatus equipped with the axis translation technique(ATT).Comprehensive soil-water retention and constant-suction triaxial compression tests were conducted to evaluate the effects of initial void ratio,matric suction,and confining pressure on the properties of CREFMs.Key findings reveal a primary suction range of 0 e100 kPa characterized by hysteresis,which intensifies with decreasing density.Notably,the air entry value and residual suction are influenced by void ratio,with higher void ratios leading to decreased air entry values and residual suctions,underscoring the critical role of void ratio in hydraulic behavior.Additionally,the critical state line(CSL)in the bi-logarithmic space of void ratio and mean effective stress shifts towards higher void ratios with increasing matric suction,significantly affecting dilatancy and critical states.Furthermore,the study demonstrated that the mobilized friction angle and modulus properties depend on confining pressure and matric suction.A novel modified dilatancy equation was proposed,which enhances the predictability of CREFMs'responses under variable loading,particularly at high stress ratios defined by the deviatoric stress over the mean effective stress.This research advances the understanding of CREFMs'performance,especially under fluctuating environmental conditions that alter suction levels.展开更多
Stab-resistant textiles play a critical role in personal protection,necessitating a deeper understanding of how structural and layering factors influence their performance.The current study experimentally examines the...Stab-resistant textiles play a critical role in personal protection,necessitating a deeper understanding of how structural and layering factors influence their performance.The current study experimentally examines the effects of textile structure,layering,and ply orientation on the stab resistance of multi-layer textiles.Three 3D warp interlock(3DWI)structures({f1},{f2},{f3})and a 2D woven fabric({f4}),all made of high-performance p-aramid yarns,were engineered and manufactured.Multi-layer specimens were prepared and subjected to drop-weight stabbing tests following HOSBD standards.Stabbing performance metrics,including Depth of Trauma(DoT),Depth of Penetration(DoP),and trauma deformation(Ymax,Xmax),were investigated and analyzed.Statistical analyses(Two-and One-Way ANOVA)indicated that fabric type and layer number significantly impacted DoP(P<0.05),while ply orientation significantly affected DoP(P<0.05)but not DoT(P>0.05).Further detailed analysis revealed that 2D woven fabrics exhibited greater trauma deformation than 3D WIF structures.Increasing the number of layers reduced both DoP and DoT across all fabric structures,with f3 demonstrating the best performance in multi-layer configurations.Aligned ply orientations also enhanced stab resistance,underscoring the importance of alignment in dissipating impact energy.展开更多
Time Division Multiplexing-Passive Optical Networks(TDM-PONs)play a vital role in Fiberto-the-Home(FTTH)deployments.To improve the service quality of home networks,FTTH is expanding to the Fiber-to-the-Room(FTTR)scena...Time Division Multiplexing-Passive Optical Networks(TDM-PONs)play a vital role in Fiberto-the-Home(FTTH)deployments.To improve the service quality of home networks,FTTH is expanding to the Fiber-to-the-Room(FTTR)scenario,where fibers are deployed to connect individual rooms(i.e.,Fiber In-premises Network(FIN)in the ITU-T G.9940 standard).In this scenario,a point-to-multipoint(P2MP)fiber network is deployed as FTTR FIN to offer gigabit access to each room,which forms a two-tier cascaded network together with the FTTH segment.To optimize the capacity utilization of the cascaded network and reduce the overall system cost,a centralized architecture,known as Centralized Fixed Access Network(C-FAN),has been introduced.C-FAN centralizes the medium access control(MAC)modules of both the FTTH and FTTR networks at the FTTH’s Optical Line Terminal(OLT)for unified control and management of the cascaded network.We develop a unified bandwidth scheduling protocol by extending the ITU-T PON standard for both the upstream and downstream directions of C-FAN.We also propose a unified dynamic bandwidth allocation(UDBA)algorithm for efficient bandwidth allocation for multiple traffic flows in the two-tier cascaded network.Simulations are conducted to evaluate the performance of the proposed control protocol and the UDBA algorithm.The results show that,in comparison to the conventional DBA algorithm,the UDBA algorithm can utilize upstream bandwidth more efficiently to reduce packet delay and loss,without adversely impacting downstream transmission performance.展开更多
Oral squamous cell carcinoma(OSCC)progresses from preneoplastic precursors via genetic and epigenetic alterations.Previous studies have focused on the treatment of terminally developed OSCC.However,the role of epigene...Oral squamous cell carcinoma(OSCC)progresses from preneoplastic precursors via genetic and epigenetic alterations.Previous studies have focused on the treatment of terminally developed OSCC.However,the role of epigenetic regulators as therapeutic targets during the transition from preneoplastic precursors to OSCC has not been well studied.Our study identified lysine-specific demethylase 1(LSD1)as a crucial promoter of OSCC,demonstrating that its knockout or pharmacological inhibition in mice reversed OSCC preneoplasia.LSD1 inhibition by SP2509 disrupted cell cycle,reduced immunosuppression,and enhanced CD4+and CD8+T-cell infiltration.In a feline model of spontaneous OSCC,a clinical LSD1 inhibitor(Seclidemstat or SP2577)was found to be safe and effectively inhibit the STAT3 network.Mechanistic studies revealed that LSD1 drives OSCC progression through STAT3 signaling,which is regulated by phosphorylation of the cell cycle mediator CDK7 and immunosuppressive CTLA4.Notably,LSD1 inhibition reduced the phosphorylation of CDK7 at Tyr170 and eIF4B at Ser422,offering insights into a novel mechanism by which LSD1 regulates the preneoplastic-to-OSCC transition.This study provides a deeper understanding of OSCC progression and highlights LSD1 as a potential therapeutic target for controlling OSCC progression from preneoplastic lesions.展开更多
基金the National Institute of Information and Communication Technology International Exchange Program 2024−2025(No.2024−007)for their invaluable support in this research.3D tomography software is available at Prof.Kosuke Heki’s(Hokkaido University,Japan)personal homepage(https://www.ep.sci.hokudai.ac.jp/~heki/software.htm).support from the 2024 Japan Student Services Organization Research Follow-up Fellowship for a 90-day research visit at the Institute for Space−Earth Environmental Research,Nagoya University,Japan.PA also acknowledges the support received from Telkom University under the“Skema Penelitian Terapan Periode I Tahun Anggaran 2024”,and the Memorandum of Understanding for Research Collaboration on Regional Ionospheric Observation(No:092/SAM3/TE-DEK/2021).
文摘Equatorial Plasma Bubbles(EPBs)are ionospheric irregularities that take place near the magnetic equator.EPBs most commonly occur after sunset during the equinox months,although they can also be observed during other seasons.The phenomenon significantly disrupts radio wave signals essential to communication and navigation systems.The national network of Global Navigation Satellite System(GNSS)receivers in Indonesia(>30°longitudinal range)provides an opportunity for detailed EPB studies.To explore this,we conducted preliminary 3D tomography of total electron content(TEC)data captured by GNSS receivers following a geomagnetic storm on December 3,2023,when at least four EPB clusters occurred in the Southeast Asian sector.TEC and extracted TEC depletion with a 120-minute running average were then used as inputs for a 3D tomography program.Their 2D spatial distribution consistently captured the four EPB clusters over time.These tomography results were validated through a classical checkerboard test and comparisons with other ionospheric data sources,such as the Global Ionospheric Map(GIM)and International Reference Ionosphere(IRI)profile.Validation of the results demonstrates the capability of the Indonesian GNSS network to measure peak ionospheric density.These findings highlight the potential for future three-dimensional research of plasma bubbles in low-latitude regions using existing GNSS networks,with extensive longitudinal coverage.
基金Open Access funding enabled and organized by Projekt DEAL.
文摘This geo-historical case study analyses Vistelius’ingenious idea of conceptual stochastic models and their application as Markov chain analysis in the geosciences.Vistelius(1915–1995)is regarded as one of the founders of mathematical geology.He was the fi rst to defi ne mathematical geology as“a scientifi c discipline concerned with the construction,analysis and use of conceptual mathematical models of geological events to solve concrete problems”(Vistelius in Principles of mathematical geology,Nauka,Leningrad,1980;Principles of mathematical geology,Kluwer Academic Publishers,Dordrecht,1992).Mathematical models in this context should be primarily probabilistic because of the large number of infl uencing natural factors.They must be conceptual to avoid fundamental errors in application.Vistelius devoted his seminal book to geological random sequences and their description and analysis using Markov models as stochastic tools.He applied this approach to grain sequences in granitic intrusive rocks and to sedimentary rock layers.Among other things,Vistelius has used Markov chain analysis in mineral resource exploration to distinguish between“ideal”granites,which are not subsequently mineralized,and mainly hydrothermally mineralized,sometimes ore-bearing granites which contain at least two generations of main minerals.The application of this special conceptual stochastic model is demonstrated on Lusatian granite(Saxony,Germany).
基金supported by Basic Science Research Program through the National Research Foundation(NRF)of Korea,funded by the Ministry of Science and ICT(MSIT),Korea[2022R1A2C2091671]by ITECH R&D Program of MOTIE/KEIT(Ministry of Trade,Industry&Energy/Korea Evaluation Institute of Industrial Technology)[20016808].
文摘Balancing high display performance with energy efficiency is crucial for global sustainability.Lowering operating frequencies—such as enabling 1 Hz operation in fringe-field switching(FFS)liquid crystal displays—reduces power consumption but is hindered by image flicker.While negative dielectric anisotropy liquid crystals(nLCs)mitigate flicker,their high driving voltages and production costs limit adoption.Positive dielectric anisotropy liquid crystals(pLCs)offer lower operating voltages,faster response times,and broader applicability,making them a more viable alternative.This study introduces a novel approach to minimizing flexoelectric effects in pLCs by investigating how single components influence flexoelectric behavior in mixtures through an effective experimental methodology.Two innovative measurement techniques—(1)flexoelectric coefficient difference analysis and(2)displacement-current measurement(DCM)—are presented,marking the first application of DCM for verifying flexoelectric effects.The proposed system eliminates uncertainties associated with previous methods,providing a reliable framework for selecting liquid crystal components with minimal flexoelectric effects while preserving key electro-optic properties.Given pLCs'higher reliability,lower production costs,and broader material selection,these advancements hold significant potential for low-power displays.We believe this work enhances flexoelectric analysis in nematic liquid crystals and contributes to sustainable innovation in the display industry,aligning with global energy-saving goals.
基金supported by the U.S.Department of Energy Office of Science,Office of Basic Energy Sciences,and Office of Biological and Environmental Research under Award Number DE-SC-00012530.
文摘Development of sustainable construction materials has been the focus of research efforts worldwide in recent years.Concrete is a major construction material;hence,finding alternatives to ordinary Portland cement is of extreme importance due to the high levels of carbon dioxide emissions associated with its manufacturing process.This study investigates the geopolymerization process.Specimens with,two different water/binder weight ratios,0.30 and 0.35,were monitored using acoustic emission.Results show that there is a significant difference in the acquisition data between the two different water/binder weight ratios.In addition,acoustic emission can be used to beneficially monitor and investigate the early geopolymerization process.The acoustic emission data were processed through pattern recognition.Two clusters were identified,assigned to a specific mechanism depending on their characteristics.SEM observations were coincided with pattern recognition findings.
基金funded by the Horizon Europe Project"PERSEUS"(No.101099423)financed by the Ministry of Universities under application 33.50.460A.752by the European Union NextGenerationEU/PRTR through a contract Margarita Salas from Universidade de Vigo.
文摘Photodynamic therapy(PDT)has been established as one of the most promising novel cancer therapies with fewer side-effects and enhanced efficacy compared to the currently available conventional treatments.However,its application has been hindered by the limitations that photosensitizers(PS)have.The combination of PS with metallic nanoparticles like platinum nanoparticles(PtNPs),can help to overcome these intrinsic drawbacks.In this work,the combination of PtNPs and the natural photosensitizer riboflavin(RF)is proposed.PtNPs are synthesized using RF(Pt@RF)as reducing and stabilizing agent in a one-step method,obtaining nanoparticles with mesoporous structure for UV triggered PDT.In view of possible future UV irradiation treatments,the degradation products of RF,ribitol(RB)and lumichrome(LC),this last being a photosensitizing byproduct,are also employed for the synthesis of porous PtNPs,obtaining Pt@LC and Pt@RB.When administered in vitro to lung cancer cells,all the samples elicit a strong decrease of cell viability and a decrease of intracellular ATP levels.The antitumoral effect of both Pt@RF and Pt@LC is triggered by UV-A irradiation.This antitumoral activity is caused by the induction of oxidative stress,shown in our study by the decrease in intracellular glutathione and increased expression of antioxidant enzymes.
文摘In this paper,an interference cancellation based neural receiver for superimposed pilot(SIP)in multi-layer transmission is proposed,where the data and pilot are non-orthogonally superimposed in the same time-frequency resource.Specifically,to deal with the intra-layer and inter-layer interference of SIP under multi-layer transmission,the interference cancellation with superimposed symbol aided channel estimation is leveraged in the neural receiver,accompanied by the pre-design of pilot code-division orthogonal mechanism at transmitter.In addition,to address the complexity issue for inter-vendor collaboration and the generalization problem in practical deployments,respectively,this paper also provides a fixed SIP(F-SIP)design based on constant pilot power ratio and scalable mechanisms for different modulation and coding schemes(MCSs)and transmission layers.Simulation results demonstrate the superiority of the proposed schemes on the performance of block error rate and throughput compared with existing counterparts.
基金supported by the Sugiyama Jogakuen University’s School Research Fund.
文摘This study aims to examine the challenges and future directions of large-scale wooden construction education at universities in Japan and Finland.It compares the wooden construction curricula at universities and the architectural education initiatives undertaken by firms specializing in large-scale wood construction design in both countries.The target applications for large-scale wooden construction are residential,commercial,and public buildings.Comparing university education revealed many commonalities between the two countries,allowing them to be classified into two types:“seminar-centered”and“lecture-centered”.Japanese universities are categorized by building type and scale for educational purposes.Finnish universities focus their education on the properties and functions of wood.Based on these results,we infer that incorporating both Japan’s architecture-planning-focused education and Finland’s materials-focused education into teaching,using familiar housing buildings as a theme,will lead to the wider adoption of large-scale wooden construction.
基金supported by the MSIT(Ministry of Science and ICT),Republic of Korea,under the ICAN(ICT Challenge and Advanced Network of HRD)support program(IITP-2025-RS-2023-00259497)supervised by the IITP(Institute for Information&Communications Technology Planning&Evaluation)and was supported by Institute of Information&Communications Technology Planning&Evaluation(IITP)grant funded by the Republic of Korea government(MSIT)(No.IITP-2025-RS-2023-00254129+1 种基金Graduate School of Metaverse Convergence(Sungkyunkwan University))was supported by the Basic Science Research Program of the National Research Foundation(NRF)funded by the Republic of Korean government(MSIT)(No.RS-2024-00346737).
文摘Network attacks have become a critical issue in the internet security domain.Artificial intelligence technology-based detection methodologies have attracted attention;however,recent studies have struggled to adapt to changing attack patterns and complex network environments.In addition,it is difficult to explain the detection results logically using artificial intelligence.We propose a method for classifying network attacks using graph models to explain the detection results.First,we reconstruct the network packet data into a graphical structure.We then use a graph model to predict network attacks using edge classification.To explain the prediction results,we observed numerical changes by randomly masking and calculating the importance of neighbors,allowing us to extract significant subgraphs.Our experiments on six public datasets demonstrate superior performance with an average F1-score of 0.960 and accuracy of 0.964,outperforming traditional machine learning and other graph models.The visual representation of the extracted subgraphs highlights the neighboring nodes that have the greatest impact on the results,thus explaining detection.In conclusion,this study demonstrates that graph-based models are suitable for network attack detection in complex environments,and the importance of graph neighbors can be calculated to efficiently analyze the results.This approach can contribute to real-world network security analyses and provide a new direction in the field.
基金The authors are thankful to the Director(Prof.Mahesh G.Thakkar),Birbal Sahni Institute of Palaeosciences,Lucknow for providing the necessary permission and laboratory facilities to carry out this work(BSIP/RDCC/Publication no.73/2024-25)Author(SM)expresses sincere thanks to DST(Govt.of India)project no.EEQ/2018/000303 for the financial support.
文摘The Permian-Triassic(P/T)transition is marked by the most severe mass-extinction event of the Phanerozoic.Although much is known about this event in the marine realm,there are many open questions regarding what happened during this period to many continental biota.In the case of plants,a drastic mass-extinction event has even been negated by some authors.To add about the knowledge on continental biota in India during this crucial time period,the present study analysed the palynology,palynofacies,organic geochemistry(biomarkers),stable isotopes,and charcoal within the subsurface Gondwana deposits of the Kamthi Formation(late Permian-early Triassic)from core TTB-7 from the Tribida block,located in the Talcher Coalfield of the Mahanadi Basin,India.The primary objectives are to validate the age of the strata,ascertain the palaeodepositional setting of the palaeomire,and propose palaeobotanical evidence regarding the occurrence of wildfires within this stratigraphic succession and changes in floral content across the P/T transition.The palynological study proposes two palynoassemblage zones,Densipollenites magnicorpus and Klausipollenites schaubergeri,suggesting a latest Permian(Lopingian)and early Triassic(Induan?)age for the studied succession,respectively.The age is also inferred based on correlation with coeval assemblages from India and other Gondwana continents.The palynoassemblages reveal the dominance of Glossopteridales and Coniferales along with Filicales,Lycopsidales,Equisetales,Cordaitales and Peltaspermales.The relatively higher values of the carbon preference index and terrigenous/aquatic ratio also suggest higher plant input.However,a bimodal n-alkane distribution pattern suggests the contribution of terrigenous and microbial sources.Although the occurrences of long-chain alkanes indicate input of higher plants,the low Pwax values(<0.26)suggest relatively less contribution.The Paqvalues(≅1)and amorphous organic matter(av.33.24%)suggest a significant macrophyte input in the studied samples,pointing to the occurrence of moderate aquatic conditions in the basin.Furthermore,the distribution of hopanoids and the content of degraded organic matter(av.29.96%)reflect the bacterial degradation of organic matter.Also,the δ^(13)C values of the studied section varied from−31.2‰to−21.8‰.A large carbon isotopic offset of 9.4‰across the P/T transition,Pr/Ph ratio(0.3–1.3)and shift in the distribution pattern of palynofacies components is indicating a significant change in climatic conditions.Moreover,the presence of macroscopic charcoal fragments of gymnospermous affinity with pre-charring colonization by fungi provides evidence for wildfire occurring during the Lopingian(Late Permian)in this basin.
文摘Additive Manufacturing(AM)can provide customized parts that conventional techniques fail to deliver.One important parameter in AM is the quality of the parts,as a result of the material extrusion 3D printing(3D-P)procedure.This can be very important in defense-related applications,where optimum performance needs to be guaranteed.The quality of the Polyetherimide 3D-P specimens was examined by considering six control parameters,namely,infill percentage,layer height,deposition angle,travel speed,nozzle,and bed temperature.The quality indicators were the root mean square(Rq)and average(Ra)roughness,porosity,and the actual to nominal dimensional deviation.The examination was performed with optical profilometry,optical microscopy,and micro-computed tomography scanning.The Taguchi design of experiments was applied,with twenty-five runs,five levels for each control parameter,on five replicas.Two additional confirmation runs were conducted,to ensure reliability.Prediction equations were constructed to express the quality indicators in terms of the control parameters.Three modeling approaches were applied to the experimental data,to compare their efficiency,i.e.,Linear Regression Model(LRM),Reduced Quadratic Regression Model,and Quadratic Regression Model(QRM).QRM was the most accurate one,still the differences were not high even considering the simpler LRM model.
基金supported in part by the U.S.National Science Foundation(NSF)under Grants ECCS-2245608 and ECCS-2245607。
文摘In this paper,we present a Deep Neural Network(DNN)based framework that employs Radio Frequency(RF)hologram tensors to locate multiple Ultra-High Frequency(UHF)passive Radio-Frequency Identification(RFID)tags.The RF hologram tensor exhibits a strong relationship between observation and spatial location,helping to improve the robustness to dynamic environments and equipment.Since RFID data is often marred by noise,we implement two types of deep neural network architectures to clean up the RF hologram tensor.Leveraging the spatial relationship between tags,the deep networks effectively mitigate fake peaks in the hologram tensors resulting from multipath propagation and phase wrapping.In contrast to fingerprinting-based localization systems that use deep networks as classifiers,our deep networks in the proposed framework treat the localization task as a regression problem preserving the ambiguity between fingerprints.We also present an intuitive peak finding algorithm to obtain estimated locations using the sanitized hologram tensors.The proposed framework is implemented using commodity RFID devices,and its superior performance is validated through extensive experiments.
基金financially supported by CAMM(Center of Advanced Mining and Metallurgy/Green Flotation),as a center of excellence at the Luleå University of Technology.
文摘The global reliance on phosphate rock for agriculture and other industries,coupled with chemical regulations in developed countries,has driven the search for green alternatives in apatite flotation.This review investigates eco-friendly collectors’effectiveness in promoting sustainable mineral processing,guiding future alternatives to traditional reagents.The manuscript discussed the surface properties of apatite and its interaction with eco-friendly collectors,assessing existing fundamental studies.This study sought to:(1)define,organize,and classify“eco-friendly”collectors;(2)evaluate their effect in IEP and contact angle;(3)provide a better understanding of the adsorption behavior of the different fatty acid chains into apatite surface;(4)assess their ability to reversely and directly float apatite;(5)address gaps to achieve selectivity and process optimization.Outcomes demonstrated that fatty acids are largely applied,but other renewable sources of these reagents have been promisingly evaluated.In addition,other natural reagents have been tested,and new green synthetics have demonstrated synergistic effects when combined with fatty acids,yielding significant improvements in grade and recovery.However,collector effectiveness varies with ore characteristics,like particle size and surface properties,which remain underexplored.Future research should design tailored collectors that align with mineralogical differences to enhance selectivity.
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.
文摘Microbes play a critical role in shaping immune development,with growing interest in how rhinovirus(RV)interacts with the host immune system,particularly in individuals with asthma and chronic obstructive pul-monary disease(COPD).Disruptions in microbial balance during RV infections can impair immune homeostasis and worsen disease outcomes.Recent studies emphasize RV-induced regulation of antiviral defenses,cytokine production,and immune tolerance.This review explores the interplay between RV,the immune system,and microbiota,highlighting the importance of these interactions in guiding effective therapies for respiratory in-fections.It advances existing literature by considering microbiota-mediated therapies as a novel approach to managing RV exacerbations in respiratory diseases like asthma and COPD.
基金sponsored by the National Key Research and Development Program of China(2020YFA0714504,2019YFA0709100)the program of the National Natural Science Foundation of China(U24A20309,62305043).
文摘Planar lightwave circuit(PLC)splitters have long been foundational components in passive optical communication networks,achieving commercial success since the 1990s.However,their inherent fixed splitting ratios impose significant limitations on capacity expansion,often requiring physical replacement and causing service disruptions.Thermally tunable optical splitters address this challenge by enabling adjustable splitting ratios,but their operation is contingent upon a continuous power supply and complex driving systems.In this work,we present a novel,non-volatile tunable PLC platform based on Sb_(2)S_(3)phase-change materials.The proposed device,which incor-porates a Mach-Zehnder interferometer(MZI)optical switch structure,offers tunable splitting ratios via laser-direct writing or ohmic heating,providing flexible reconfiguration capabilities.Experimental results demonstrate non-volatile power splitting ranging from 50∶50 to 20∶80,with a modest increase of approximately 1 dB in additional loss.This work highlights the potential of the proposed platform for low-power,high-efficiency,and reconfigurable photonic networks.
基金jointly supported by the Science Fund for Distinguished Young Scholars of Hunan Province,China(Grant No.2024JJ2073)the National Natural Science Foundation of China(Grant No.52178443)the Fundamental Research Funds for the Central Universities of Central South University,China(Grant No.2022ZZTS0620)。
文摘This study investigated the hydraulic and mechanical behaviors of unsaturated coarse-grained railway embankment fill materials(CREFMs)using a novel unsaturated large-scale triaxial apparatus equipped with the axis translation technique(ATT).Comprehensive soil-water retention and constant-suction triaxial compression tests were conducted to evaluate the effects of initial void ratio,matric suction,and confining pressure on the properties of CREFMs.Key findings reveal a primary suction range of 0 e100 kPa characterized by hysteresis,which intensifies with decreasing density.Notably,the air entry value and residual suction are influenced by void ratio,with higher void ratios leading to decreased air entry values and residual suctions,underscoring the critical role of void ratio in hydraulic behavior.Additionally,the critical state line(CSL)in the bi-logarithmic space of void ratio and mean effective stress shifts towards higher void ratios with increasing matric suction,significantly affecting dilatancy and critical states.Furthermore,the study demonstrated that the mobilized friction angle and modulus properties depend on confining pressure and matric suction.A novel modified dilatancy equation was proposed,which enhances the predictability of CREFMs'responses under variable loading,particularly at high stress ratios defined by the deviatoric stress over the mean effective stress.This research advances the understanding of CREFMs'performance,especially under fluctuating environmental conditions that alter suction levels.
文摘Stab-resistant textiles play a critical role in personal protection,necessitating a deeper understanding of how structural and layering factors influence their performance.The current study experimentally examines the effects of textile structure,layering,and ply orientation on the stab resistance of multi-layer textiles.Three 3D warp interlock(3DWI)structures({f1},{f2},{f3})and a 2D woven fabric({f4}),all made of high-performance p-aramid yarns,were engineered and manufactured.Multi-layer specimens were prepared and subjected to drop-weight stabbing tests following HOSBD standards.Stabbing performance metrics,including Depth of Trauma(DoT),Depth of Penetration(DoP),and trauma deformation(Ymax,Xmax),were investigated and analyzed.Statistical analyses(Two-and One-Way ANOVA)indicated that fabric type and layer number significantly impacted DoP(P<0.05),while ply orientation significantly affected DoP(P<0.05)but not DoT(P>0.05).Further detailed analysis revealed that 2D woven fabrics exhibited greater trauma deformation than 3D WIF structures.Increasing the number of layers reduced both DoP and DoT across all fabric structures,with f3 demonstrating the best performance in multi-layer configurations.Aligned ply orientations also enhanced stab resistance,underscoring the importance of alignment in dissipating impact energy.
基金supported by National Nature Science Founding of China(62101372)Open Fund of IPOC(BUPT,IPOC2022A07)+1 种基金State Key Laboratory of Advanced Optical Communication Systems and Networks(2023GZKF11)Leading Youth Talents of Innovation and Entrepreneurship of Gusu(ZXL2023162).
文摘Time Division Multiplexing-Passive Optical Networks(TDM-PONs)play a vital role in Fiberto-the-Home(FTTH)deployments.To improve the service quality of home networks,FTTH is expanding to the Fiber-to-the-Room(FTTR)scenario,where fibers are deployed to connect individual rooms(i.e.,Fiber In-premises Network(FIN)in the ITU-T G.9940 standard).In this scenario,a point-to-multipoint(P2MP)fiber network is deployed as FTTR FIN to offer gigabit access to each room,which forms a two-tier cascaded network together with the FTTH segment.To optimize the capacity utilization of the cascaded network and reduce the overall system cost,a centralized architecture,known as Centralized Fixed Access Network(C-FAN),has been introduced.C-FAN centralizes the medium access control(MAC)modules of both the FTTH and FTTR networks at the FTTH’s Optical Line Terminal(OLT)for unified control and management of the cascaded network.We develop a unified bandwidth scheduling protocol by extending the ITU-T PON standard for both the upstream and downstream directions of C-FAN.We also propose a unified dynamic bandwidth allocation(UDBA)algorithm for efficient bandwidth allocation for multiple traffic flows in the two-tier cascaded network.Simulations are conducted to evaluate the performance of the proposed control protocol and the UDBA algorithm.The results show that,in comparison to the conventional DBA algorithm,the UDBA algorithm can utilize upstream bandwidth more efficiently to reduce packet delay and loss,without adversely impacting downstream transmission performance.
基金NIH/NIDCR grant R01 DE031413 and CTSA pilot grant UL1TR001430 to Manish V.Bais.
文摘Oral squamous cell carcinoma(OSCC)progresses from preneoplastic precursors via genetic and epigenetic alterations.Previous studies have focused on the treatment of terminally developed OSCC.However,the role of epigenetic regulators as therapeutic targets during the transition from preneoplastic precursors to OSCC has not been well studied.Our study identified lysine-specific demethylase 1(LSD1)as a crucial promoter of OSCC,demonstrating that its knockout or pharmacological inhibition in mice reversed OSCC preneoplasia.LSD1 inhibition by SP2509 disrupted cell cycle,reduced immunosuppression,and enhanced CD4+and CD8+T-cell infiltration.In a feline model of spontaneous OSCC,a clinical LSD1 inhibitor(Seclidemstat or SP2577)was found to be safe and effectively inhibit the STAT3 network.Mechanistic studies revealed that LSD1 drives OSCC progression through STAT3 signaling,which is regulated by phosphorylation of the cell cycle mediator CDK7 and immunosuppressive CTLA4.Notably,LSD1 inhibition reduced the phosphorylation of CDK7 at Tyr170 and eIF4B at Ser422,offering insights into a novel mechanism by which LSD1 regulates the preneoplastic-to-OSCC transition.This study provides a deeper understanding of OSCC progression and highlights LSD1 as a potential therapeutic target for controlling OSCC progression from preneoplastic lesions.
