Objectives:The Sorbin and SH3 domain containing 1(SORBS1),a protein linked to insulin signaling CBL interaction,was investigated for its role in pancreatic cancer apoptosis.This study explored polyphyllin H(PPH)’s ab...Objectives:The Sorbin and SH3 domain containing 1(SORBS1),a protein linked to insulin signaling CBL interaction,was investigated for its role in pancreatic cancer apoptosis.This study explored polyphyllin H(PPH)’s ability to restore SORBS1-knockdown-mediated repair functions.Methods:PANC-1 cells were divided into Blank,overexpression(OE),and knockdown groups.CCK-8 assays assessed proliferation and drug toxicity.Western blot and flow cytometry analyzed SORBS1 levels and PPH effects.Comet assays quantified DNA damage.Subcutaneous xenograft tumors in nude mice(Blank vs.knockdown)were treated with PPH to evaluate in vivo efficacy.SORBS1-H2AX gene correlation was analyzed Spearman rank clustering(p<0.05).Results:PPH suppressed pancreatic cancer growth in vitro/vivo,but its efficacy was attenuated by SORBS1 downregulation.Clinically,low SORBS1 correlated with poor prognosis.SORBS1 knockdown promoted tumor proliferation and reduced PPH-induced apoptosis.While PPH decreased tumor volume in both Blank and knockdown groups compared to controls,SORBS1 knockdown diminished PPH’s inhibitory effects.Mechanistically,SORBS1 depletion mitigated PPH-triggered DNA damage,circumventing G2/M arrest by modulating WEE1,Cyclin A2,CDK1,and Cyclin B1,thereby impairing apoptosis.Conclusion:SORBS1 knockdown counteracts PPH-mediated S/G2 arrest and apoptosis by alleviating DNA damage in pancreatic cancer.These findings highlight SORBS1 as a critical modulator of PPH’s therapeutic potential,linking its expression to chemoresistance mechanisms.展开更多
The nonchemically amplified(nonCA)polymer resists,including ionic and nonionic types,have achieved higher resolution and smaller line edge roughness(LER)than traditional chemically amplified ones.However,for polymer r...The nonchemically amplified(nonCA)polymer resists,including ionic and nonionic types,have achieved higher resolution and smaller line edge roughness(LER)than traditional chemically amplified ones.However,for polymer resists,chain entanglement is an inevitable limitation for the further reduction of LER.To overcome this problem,it is logical to apply the nonCA concept to molecule-based resists due to their advantages of monodispersity and small size.To date,only a few examples of ionic sulfonium salts-based nonCA molecular glass resists(nonCAMGRs)have been reported.They demonstrated high resolution and small LER well,but their electron beam sensitivity seemed less than ideal.To our knowledge,non-ionic sulfoxime oxime esters-based molecular resists were not reported yet,which leaves room for new round of more in-depth reserch on nonCAMGRs.Here,employing the excellent spirobixanthene backbone,we have first designed non-ionic sulfoxime oxime esters-based nonCAMGRs X4-NI-tf and X4-NI-tfb,for comparison,sulfonium salts-based nonCAMGRs X4-I-otfdm was designed.All exhibit favorable thermal properties(T_(d,5%)>200°C)and filmforming capabilities(RMSs<0.4 nm).Via EBL,X4-I-otfdm achieved higher resolution(16 nm,LER 1.4 nm)than X4-NI-tf and X4-NI-tfb(20 nm,LER 1.6 nm).But contrast curve revealed that the sensitivity of X4-NI-tf and X4-NI-tfb(D_(100):370 and 350μC/cm^(2))was significantly higher than X4-I-otfdm(D_(100):3300μC/cm^(2)),demonstrating that the sensitivity of sulfoxime oxime esters exceeds that of sulfonium salts and introduction of bromine can further enhance the sensitivity;based on above,X4-NI-tfb exhibited the lowest Z-factor and demonstrated the best overall performance.We believe that nonCAMGRs based on sulfoxime oxime esters represent a strong candidate for high-performance photoresists.展开更多
Comprehensive Summary:We developed single-component nonchemically-amplified resists(n-CARs)based on calixarene derivatives for high-resolution nanopatterning with electron beam lithography(EBL)and extreme ultraviolet ...Comprehensive Summary:We developed single-component nonchemically-amplified resists(n-CARs)based on calixarene derivatives for high-resolution nanopatterning with electron beam lithography(EBL)and extreme ultraviolet lithography(EUVL).The calixarene derivatives decorated with 2 and 4 photosensitive sulfonium groups(C2S and C4S,respectively)were synthesized and characterized.Both derivatives exhibit excellent thermal stability and film-forming properties,making them suitable as resist materials.A comparative EBL study reveals that C2S resist exhibits superior lithographic performance.The presence of hydrogen bonds between C2S molecules enhances the mechanical strength and the Young's modulus of the resist film,effectively mitigating pattern collapse.The C2S resist achieved an 18 nm line/space(L/S)pattern and a 14 nm L/2S semi-dense pattern with EBL.Performance studies with EUVL yielded an impressive 14 nm half-pitch(HP)pattern with a remarkably low line-edge roughness(LER)of 1.7 nm.Extensive studies of the EUV exposure mechanism,conducted using in-situ quadrupole mass spectrometry(QMS)and X-ray photoelectron spectroscopy(XPS),demonstrated that the solubility switch of the resist material depends on the decomposition of the sulfonium groups and triflate anions.展开更多
Aryl sulfonate ester modified polystyrenes with different substituents(X–SEPS,X=H–,MeO–,and CN–)were synthesized by reversible addition-fragmentation chain transfer(RAFT)polymerization.The excellent thermal stabil...Aryl sulfonate ester modified polystyrenes with different substituents(X–SEPS,X=H–,MeO–,and CN–)were synthesized by reversible addition-fragmentation chain transfer(RAFT)polymerization.The excellent thermal stability and film-forming capability of these three polymers suggest that they can satisfy the lithography process and are candidates for resist materials.Comparative electron beam lithography(EBL)demonstrates that the three resists(H–SEPS,MeO–SEPS and CN–SEPS)exhibit different EBL performances.Calculation of bond energies for the model compounds suggests that the influence of substituent groups on the bond energy is not the reason for the differences in sensitivity.Results obtained using a fully automated dissipative quartz crystal microbalance(QCM)analyzer confirm that the influence of substituent groups on the solubility behavior of resist films in developers leads to different photolithographic performances.The H–SEPS resist exhibits better comprehensive performance than the MeO–SEPS and CN–SEPS resists,achieving an 18 nm line/space(L/S)pattern and a 10 nm line/4 space(L/4S)semi-dense pattern by EBL at doses of 3200 and 2800μC cm^(−2),respectively.Further extreme ultraviolet lithography(EUVL)demonstrates the capability of H–SEPS resist to form 22 nm half-pitch(HP)patterns.The detailed study of the photochemical reaction and patterning mechanism suggests that the decomposition of sulfonate ester groups into polar sulfonic acid groups,along with a rearrangement,leads to a solubility switch of resist films in the developer.展开更多
This study investigates the properties of high-purity starches extracted from Polygonum multiflorum(PMS)and Smilax glabra(SGS).The starches were characterized by scanning electron microscopy,Fouriertransform infrared ...This study investigates the properties of high-purity starches extracted from Polygonum multiflorum(PMS)and Smilax glabra(SGS).The starches were characterized by scanning electron microscopy,Fouriertransform infrared spectroscopy,X-ray diffraction,high-performance anion-exchange chromatography,and differential scanning calorimetry.Significant differences were observed in their morphological,physicochemical,and functional properties.PMS had a smaller particle size(13.68 μm),irregular polygonal shape,A-type,lower water absorption(62.67 %),and higher oil absorption(51.17 %).In contrast,SGS exhibited larger particles(31.75 μm),a nearly spherical shape,B-type,higher crystallinity(50.66 %),and greater amylose content(21.54 %),with superior thermal stability,shear resistance,and gelatinization enthalpy.SGS also contained higher resistant starch(83.28 %) and longer average chain length(20.58 %),but showed lower solubility,swelling power,light transmittance,and freeze-thaw stability.The physicochemical properties differences in crystal pattern and particle morphology between PMS and SGS lead to distinct behaviors during in vitro digestion and fermentation.These findings highlight the potential of medicinal plant starches in functional ingredients and industrial processes.展开更多
Schizophrenia is a complex psychiatric disorder marked by positive and negative symptoms,leading to mood disturbances,cognitive impairments,and social withdrawal.While anti-psychotic medications remain the cornerstone...Schizophrenia is a complex psychiatric disorder marked by positive and negative symptoms,leading to mood disturbances,cognitive impairments,and social withdrawal.While anti-psychotic medications remain the cornerstone of treatment,they often fail to fully address certain symptoms.Additionally,treatment-resistant schizophrenia,affecting 30%-40%of patients,remains a substantial clinical challenge.Positive,negative symptoms and cognitive impairments have been linked to disruptions in the glutamatergic,serotonin,GABAergic,and muscarinic pathways in the brain.Recent advances using genome-wide association study and other approaches have uncovered a significant number of new schizophrenia risk genes that uncovered new,and reinforced prior,concepts on the genetic and neurological underpinnings of schizophrenia,including abnormalities in synaptic function,immune processes,and lipid metabolism.Concurrently,new therapeutics targeting different modalities,which are expected to address some of the limitations of anti-psychotic drugs currently being offered to patients,are currently being evaluated.Collectively,these efforts provide new momentum for the next phase of schizophrenia research and treatment.展开更多
Silica aerogel has broad applications in the field of high-temperature thermal insulation due to its low density,low thermal conductivity and high stability.However,its thermal insulation performance deteriorates sign...Silica aerogel has broad applications in the field of high-temperature thermal insulation due to its low density,low thermal conductivity and high stability.However,its thermal insulation performance deteriorates significantly at elevated temperatures exceeding 600℃,primarily due to the collapse of pore structure.Meanwhile,the shielding capacity of SiO_(2) aerogel to the infrared radiation at high temperature is rather low due to the intrinsic properties of SiO_(2).Herein,a strategy for improving the high-temperature stability and infrared shielding properties of SiO_(2) aerogel via Ca doping was explored.Calcium-doped silica aerogel(CSA)powders were prepared by Sol-Gel,hydrothermal,and ambient pressure drying(APD)techniques using water glass and anhydrous calcium chloride as precursors and trimethylchlorosilane as a hydrophobic modifier.The effects of Ca/Si molar ratio in the precursor and hydrothermal conditions(temperature and pH)on the crystalline properties,microscopic morphology and pore structure of CSAs were investigated.The results show that the Ca/Si molar ratio and hydrothermal treatment have significant effects on the microstructure and heat resistance of CSAs in the temperature range of 400-1000℃.The samples sintered at 1000℃have a high specific surface area of 100.1 m^(2)/g and a pore volume of 0.8705 cm^(3)/g,indicating that the CSA has good heat resistance.One-side insulation tests at temperatures up to 600℃show that the sample with a Ca/Si molar ratio of 1.0 has the best insulation performance,with a cold surface temperature of 450℃,which is 27℃lower than that of the pure silica aerogel.展开更多
The uplift resistance of the soil overlying shield tunnels significantly impacts their anti-floating stability.However,research on uplift resistance concerning special-shaped shield tunnels is limited.This study combi...The uplift resistance of the soil overlying shield tunnels significantly impacts their anti-floating stability.However,research on uplift resistance concerning special-shaped shield tunnels is limited.This study combines numerical simulation with machine learning techniques to explore this issue.It presents a summary of special-shaped tunnel geometries and introduces a shape coefficient.Through the finite element software,Plaxis3D,the study simulates six key parameters—shape coefficient,burial depth ratio,tunnel’s longest horizontal length,internal friction angle,cohesion,and soil submerged bulk density—that impact uplift resistance across different conditions.Employing XGBoost and ANN methods,the feature importance of each parameter was analyzed based on the numerical simulation results.The findings demonstrate that a tunnel shape more closely resembling a circle leads to reduced uplift resistance in the overlying soil,whereas other parameters exhibit the contrary effects.Furthermore,the study reveals a diminishing trend in the feature importance of buried depth ratio,internal friction angle,tunnel longest horizontal length,cohesion,soil submerged bulk density,and shape coefficient in influencing uplift resistance.展开更多
It is crucial to develop arsenic removal adsorbents with strong sulfur resistance under middle-low-temperature flue gas conditions(<400℃).In this work,five Fe-Ce-La oxides were prepared by co-precipitation method,...It is crucial to develop arsenic removal adsorbents with strong sulfur resistance under middle-low-temperature flue gas conditions(<400℃).In this work,five Fe-Ce-La oxides were prepared by co-precipitation method,and FeCeLaO/SiO_(2)-Al_(2)O_(3) composite adsorbents were prepared by coupling fly ash-based Si-Al carriers.The active components Fe-Ce-La oxides and Si-Al carriers were characterized by TPD,TG,XRF,BET and XPS,respectively.The effects of temperature,Si/Al ratio and FeCeLaO loading rate on the sulfur resistance were investigated.Results show that the SO_(2) promotes the arsenic removal of Fe_(2)O_(3),CeLaO and FeCeLaO.At 400℃,the arsenic removal efficiencies of the three oxides increase from 45.3%,72.5% and 81.3% without SO_(2) to 62.6%,80.5%and 91.0%,respectively.The SO_(2) inhibits the arsenic removal of La_(2)O_(2)CO_(3) and FeLaO,and the inhibition effect is pronounced at high temperatures.The sulfur poisoning resistance of Si-Al carriers increases with the increase of Si/Al ratio.When the Si/Al ratio is increased to 9.74,the arsenic removal efficiency in the SO_(2) environment is 13.9% higher than that in the absence of SO_(2).Introducing FeCeLaO active components is beneficial for enhancing the SO_(2) poisoning resistance of Si-Al carriers.The strong sulfur resistance of the FeCeLaO/SiO_(2)-Al_(2)O_(3) composite adsorbent results from multiple factors:protective effects of Ce on Fe,La and Al;sulfation-induced generation of Ce^(3+)and surface-adsorbed oxygen;and strong surface acidity of SiO_(2).展开更多
The present work provides a facile and efficient method for producing ultrafine copper powders.Ultrafine copper powders were synthesized through a solvothermal method,utilizing ethanol both as a solvent and a reducing...The present work provides a facile and efficient method for producing ultrafine copper powders.Ultrafine copper powders were synthesized through a solvothermal method,utilizing ethanol both as a solvent and a reducing agent.Specifically,by exploiting the weak reducing property of ethanol,the copper precursor is first converted to copper oxide and then further reduced to cuprous oxide and pure copper.Such a method can effectively control the morphology and particle size of the copper powder,reduce particle aggregation,and enhance oxidation resistance.It is cost-effective and produces fewer toxic by-products.Spherical copper particles with an average particle size of about 180 nm were obtained.The initial oxidation temperature is approximately 150℃,and the resulting copper powders can be stored stably under ambient conditions for at least 5 months,demonstrating excellent oxidation resistance and thermal stability.展开更多
Platinum group metals have high melting points,strong corrosion resistance,stable chemical properties,and low oxygen permeability in high-temperature oxygen-containing environments.As thermal protective coating materi...Platinum group metals have high melting points,strong corrosion resistance,stable chemical properties,and low oxygen permeability in high-temperature oxygen-containing environments.As thermal protective coating materials,they have gained essential applications in the aerospace field and have excellent prospects for application in frontier military fields,such as protecting hot-end components of hypersonic aircraft.This research reviewed the latest research progress of platinum group metal coatings with hightemperature oxidation resistance,including coating preparation techniques,oxidation failure,and alloying modification.The leading preparation techniques of current platinum group metal coatings were discussed,as well as the advantages and disadvantages of various existing preparation techniques.Besides,the intrinsic properties,failure forms,and failure mechanisms of coatings of single platinum group metal in high-temperature oxygen-containing environments were analyzed.On this basis,the necessity,main methods,and main achievements of alloying modification of platinum group metals were summarized.Finally,the future development of platinum group coatings with high-temperature oxidation resistance was discussed and prospected.展开更多
The in-flight heating process of cerium dioxide(CeO_(2))powders was investigated through experiments and numerical simulations.In the experiment,CeO_(2)powder(average size of 30μm)was injected into radio-frequency(RF...The in-flight heating process of cerium dioxide(CeO_(2))powders was investigated through experiments and numerical simulations.In the experiment,CeO_(2)powder(average size of 30μm)was injected into radio-frequency(RF)argon plasma,and the temperatures were measured using a DPV-2000 monitor.A model combining the electromagnetism,thermal flow,and heat transfer characteristics of powder during in-flight heating in argon plasma was proposed.The melting processes of CeO_(2)powders of different diameters,with and without thermal resistance effect,were investigated.Results show that the heating process of CeO_(2)powder particles consists of three main stages,one of which is relevant to a dimensionless parameter known as the Biot number.When the Biot value≥0.1,thermal resistance increases significantly,especially for the larger powders.The predicted temperature of the particles at the outlet(1800–2880 K)is in good agreement with the experimental result.展开更多
Urinary tract infections(UTIs)are among the most prevalent pediatric bacterial infections,and undertreated episodes may lead to renal scarring,hypertension,or chronic kidney disease.Multidrug-resistant(MDR)Enterobacte...Urinary tract infections(UTIs)are among the most prevalent pediatric bacterial infections,and undertreated episodes may lead to renal scarring,hypertension,or chronic kidney disease.Multidrug-resistant(MDR)Enterobacterales have been increasingly reported in children,with higher rates in Asian and Middle Eastern settings than in high-income countries[1,2].展开更多
Antibiotic resistance genes(ARGs) are recognized as a primary threat to the sustainability of environment and human health in the 21^(st) century.Nanomaterials(NMs) have attracted substantial attention due to their un...Antibiotic resistance genes(ARGs) are recognized as a primary threat to the sustainability of environment and human health in the 21^(st) century.Nanomaterials(NMs) have attracted substantial attention due to their unique dimensions and structures.Unfortunately,emerging evidence suggests that NMs may facilitate the transmission of ARGs.It is crucial to elucidate how NMs affect the evolution and dissemination of ARGs.The current review comprehensively examines the role of NMs in the widespread transmission of ARGs in aquatic environments and the underlying mechanisms involved in the process.It aims to clarify the effects and mechanisms of NMs on the horizontal gene transfer processes that are associated with ARGs,including the enhancement of cell membrane permeability,the formation of nanopores on membranes,promotion of mutagenesis,and the generation of reactive oxygen species(ROSs).Furthermore,the trade-off between the removal of ARGs and horizontal transfer has been elucidated.The review aspires to guide future research directions,advance knowledge on the implications of NMs in the field of ARGs' transmission,and provide a theoretical foundation for the development of safer and more effective applications of NMs.展开更多
Physical activity,moderate aerobic or resistance exercise are well established to offer health benefits and promote healthy aging and longevity.^(1)In contrast,lack of exercise contributes to adverse events,especially...Physical activity,moderate aerobic or resistance exercise are well established to offer health benefits and promote healthy aging and longevity.^(1)In contrast,lack of exercise contributes to adverse events,especially in some patients with organ failure.^(2)Therefore,“exercise pills”and“exercise mimetics”have attracted growing interest because of their potential to induce exercise-related health effects despite physical exercise not being performed.^(3)Robust studies over the past decade have identified many natural biomacromolecules,such as peptide,non-coding Ribonucleic Acid(RNAs),and lipids,that are induced by exercise.^(4-6)These molecules trigger physiological adaptations,including promotion of cardiomyocyte proliferation,anti-apoptotic capacity,and healthy tissue growth.7However,identifying or designing an exercise pill that mimics the extensive benefits of exercise is still challenging.展开更多
Brown spot(BS)of rice,caused by Bipolaris oryzae,is a serious concern that not only causes quantitative losses but also affects grain quality.To manage this disease,the use of resistant genetic sources and QTLs is an ...Brown spot(BS)of rice,caused by Bipolaris oryzae,is a serious concern that not only causes quantitative losses but also affects grain quality.To manage this disease,the use of resistant genetic sources and QTLs is an eco-friendly and economical option.In the current study,F_(3) progenies derived from a cross of susceptible parent PMS-18-B(PAU 10845-1-1-1-1)×resistant parent RP Path 77(RP patho-17)were used to identify potential QTLs linked to BS resistance and to associate this resistance with a temporal spike in defense-related enzymes.展开更多
Enzyme-Induced Carbonate Precipitation(EICP)is an innovative technique to improve soil strength and reduce permeability.However,the use of EICP for reinforcing underwater sand beds remains largely unexplored.To advanc...Enzyme-Induced Carbonate Precipitation(EICP)is an innovative technique to improve soil strength and reduce permeability.However,the use of EICP for reinforcing underwater sand beds remains largely unexplored.To advance EICP implementation in various geotechnical applications,this paper develops a model box system to investigate the effectiveness of the EICP technique in reinforcing underwater sand beds.An"injection-extraction"system is designed to facilitate the flow of the EICP solution through underwater sand layers.Key parameters,including conductivity,pH,and Ca^(2+)concentration of the solution,are measured and analyzed.Electrical resistivity tomography(ERT)is utilized to evaluate the reinforcement effect in the underwater sand bed.The permeability of the model is tested to verify the feasibility of EICP technology for strengthening underwater sands.Furthermore,scanning electron microscope(SEM)is performed to investigate the growth mechanisms of calcium carbonate(CaCO_(3))crystals.The results show that the permeability of the model decreases from 1.28×10^(-2)m/s to 9.66×10^(-5)m/s,representing a reduction of approximately three orders of magnitude.This verifies that the EICP technology can greatly reduce the permeability of underwater sand beds.With increasing grouting cycles,the resistivity of the underwater sand initially decreases and then increases.This variation in sand resistivity is significantly influenced by the ion concentration in the solution,resulting in marked differences in resistivity at various depths and positions within the sand.The findings from this study offer a theoretical basis for the application of EICP technology in reinforcing seabed foundations and supporting marine infrastructure such as offshore pipelines,wind turbines,and oil platforms.展开更多
Wheat(Triticum aestivum)faces significant threats from diseases such as powdery mildew(Blumeria graminis)and Fusarium head blight(FHB;caused by Fusarium graminearum),which cause severe yield losses.Moreover,the antago...Wheat(Triticum aestivum)faces significant threats from diseases such as powdery mildew(Blumeria graminis)and Fusarium head blight(FHB;caused by Fusarium graminearum),which cause severe yield losses.Moreover,the antagonism between yield-related traits and disease resistance makes yield resistance coordination a major challenge in wheat breeding.The lack of genetic resources combining both disease resistance and high yield constrains the elucidation of underlying resistance-yield trade-off mechanisms,thereby hindering the development of high-yield and disease-resistant wheat cultivars.Remarkably,Yangmai 33(YM33),a notable wheat cultivar with resistance to both powdery mildew and FHB as well as high-yield performance,was recently developed.It offers a unique opportunity to dissect the genomic architecture underlying the coordination between disease resistance and yield.展开更多
Frequent droughts pose considerable threat to global forest carbon uptake,but little is known about the response of forest carbon fluxes in climatic transition zones to seasonal drought.In this study,the responses of ...Frequent droughts pose considerable threat to global forest carbon uptake,but little is known about the response of forest carbon fluxes in climatic transition zones to seasonal drought.In this study,the responses of carbon fluxes to seasonal drought in two natural forests(Quercus aliena var.acute serrata Maxim and Pinus tabuliformis Carr.)in the Baotianman Nature Reserve were investigated.The Q.aliena forest exhibited a high resilience with stable gross primary productivity(GPP).However,ecosystem respiration(Re)significantly declined by 18.4%compared with normal years,leading to an increase in net carbon sequestration capacity of 4.1%.This resilience was attributed to its deep root system accessing soil water(SWC_(50cm))to sustain stomatal openness,coupled with the efficient utilization of photosynthetically active radiation to drive photosynthesis.In contrast,the P.tabuliformis forest,which relied on shallow soil moisture(SWC_(20cm)),experienced simultaneous decreases in both GPP and Re during drought,with a sharply greater decrease in GPP,resulting in low net carbon sink capacity.Further analysis revealed that the Q.aliena forest prioritized carbon assimilation through a deep water-stomatal synergy strategy(anisohydric behavior),whereas the P.tabuliformis forest adopted an isohydric strategy favoring water conservation at the expense of carbon fixation efficiency.These findings highlight distinct mechanisms underlying drought adaptation between forest types,providing critical insight into optimizing forest carbon cycle models and selecting drought-resistant species under the influence of climate change.展开更多
Breast cancer is one of the most prevalent malignancies among women and comprises a heterogeneous spectrum of molecular subtypes with distinct biological behaviors.Among various regulatory molecules,sphingolipids play...Breast cancer is one of the most prevalent malignancies among women and comprises a heterogeneous spectrum of molecular subtypes with distinct biological behaviors.Among various regulatory molecules,sphingolipids play pivotal roles in dynamically modulating fundamental cellular processes such as proliferation,apoptosis,and metastasis through metabolic interconversions,including phosphorylation,glycosylation,and the generation of sphingosine-1-phosphate.This review aims to elucidate the mechanisms through which sphingolipid metabolism orchestrates cancer cell fate and drives breast cancer progression.Particular emphasis is placed on the balance between proapoptotic ceramides and pro-survival metabolites,such as sphingosine-1-phosphate,which collectively influence tumor growth and the therapeutic response.Additional sphingolipid species,including glucosylceramide and gangliosides(GD2,GD3,GM1,and GM3),have also been implicated in promoting breast cancer development.Furthermore,sphingolipid-based therapeutic strategies,including immunotherapy and antibody therapy,are discussed.By providing a comprehensive overview of sphingolipid metabolism,this review aims to identify novel therapeutic targets that may help overcome treatment resistance and improve clinical outcomes in breast cancer.展开更多
基金funded by the National Natural Science Foundation of China(No.81973192 and 82304782)the Key Research and Development Program of Shaanxi Province(No.2024SF-ZDCYL-03-17)+1 种基金the Social R&D Program of Shaanxi Province(No.2023-YBSF-514,2023-YBSF-170 and 2025SF-YBXM-477)the Project of Shaanxi Administration of Traditional Chinese Medicine(No.SZY-KJCYC-2023-001).
文摘Objectives:The Sorbin and SH3 domain containing 1(SORBS1),a protein linked to insulin signaling CBL interaction,was investigated for its role in pancreatic cancer apoptosis.This study explored polyphyllin H(PPH)’s ability to restore SORBS1-knockdown-mediated repair functions.Methods:PANC-1 cells were divided into Blank,overexpression(OE),and knockdown groups.CCK-8 assays assessed proliferation and drug toxicity.Western blot and flow cytometry analyzed SORBS1 levels and PPH effects.Comet assays quantified DNA damage.Subcutaneous xenograft tumors in nude mice(Blank vs.knockdown)were treated with PPH to evaluate in vivo efficacy.SORBS1-H2AX gene correlation was analyzed Spearman rank clustering(p<0.05).Results:PPH suppressed pancreatic cancer growth in vitro/vivo,but its efficacy was attenuated by SORBS1 downregulation.Clinically,low SORBS1 correlated with poor prognosis.SORBS1 knockdown promoted tumor proliferation and reduced PPH-induced apoptosis.While PPH decreased tumor volume in both Blank and knockdown groups compared to controls,SORBS1 knockdown diminished PPH’s inhibitory effects.Mechanistically,SORBS1 depletion mitigated PPH-triggered DNA damage,circumventing G2/M arrest by modulating WEE1,Cyclin A2,CDK1,and Cyclin B1,thereby impairing apoptosis.Conclusion:SORBS1 knockdown counteracts PPH-mediated S/G2 arrest and apoptosis by alleviating DNA damage in pancreatic cancer.These findings highlight SORBS1 as a critical modulator of PPH’s therapeutic potential,linking its expression to chemoresistance mechanisms.
基金supported by the National Natural Science Foundation of China(No.22278059,22174009,22078047)Fundamental Research Funds for the Central Universities(No.DUT24ZD119,DUT22LAB601 and DUT22LAB608).
文摘The nonchemically amplified(nonCA)polymer resists,including ionic and nonionic types,have achieved higher resolution and smaller line edge roughness(LER)than traditional chemically amplified ones.However,for polymer resists,chain entanglement is an inevitable limitation for the further reduction of LER.To overcome this problem,it is logical to apply the nonCA concept to molecule-based resists due to their advantages of monodispersity and small size.To date,only a few examples of ionic sulfonium salts-based nonCA molecular glass resists(nonCAMGRs)have been reported.They demonstrated high resolution and small LER well,but their electron beam sensitivity seemed less than ideal.To our knowledge,non-ionic sulfoxime oxime esters-based molecular resists were not reported yet,which leaves room for new round of more in-depth reserch on nonCAMGRs.Here,employing the excellent spirobixanthene backbone,we have first designed non-ionic sulfoxime oxime esters-based nonCAMGRs X4-NI-tf and X4-NI-tfb,for comparison,sulfonium salts-based nonCAMGRs X4-I-otfdm was designed.All exhibit favorable thermal properties(T_(d,5%)>200°C)and filmforming capabilities(RMSs<0.4 nm).Via EBL,X4-I-otfdm achieved higher resolution(16 nm,LER 1.4 nm)than X4-NI-tf and X4-NI-tfb(20 nm,LER 1.6 nm).But contrast curve revealed that the sensitivity of X4-NI-tf and X4-NI-tfb(D_(100):370 and 350μC/cm^(2))was significantly higher than X4-I-otfdm(D_(100):3300μC/cm^(2)),demonstrating that the sensitivity of sulfoxime oxime esters exceeds that of sulfonium salts and introduction of bromine can further enhance the sensitivity;based on above,X4-NI-tfb exhibited the lowest Z-factor and demonstrated the best overall performance.We believe that nonCAMGRs based on sulfoxime oxime esters represent a strong candidate for high-performance photoresists.
基金supported by the National Natural Science Foundation of China(22090012,22475224,U20A20144)Chinese Academy of Sciences(CAS)is gratefully acknowledged。
文摘Comprehensive Summary:We developed single-component nonchemically-amplified resists(n-CARs)based on calixarene derivatives for high-resolution nanopatterning with electron beam lithography(EBL)and extreme ultraviolet lithography(EUVL).The calixarene derivatives decorated with 2 and 4 photosensitive sulfonium groups(C2S and C4S,respectively)were synthesized and characterized.Both derivatives exhibit excellent thermal stability and film-forming properties,making them suitable as resist materials.A comparative EBL study reveals that C2S resist exhibits superior lithographic performance.The presence of hydrogen bonds between C2S molecules enhances the mechanical strength and the Young's modulus of the resist film,effectively mitigating pattern collapse.The C2S resist achieved an 18 nm line/space(L/S)pattern and a 14 nm L/2S semi-dense pattern with EBL.Performance studies with EUVL yielded an impressive 14 nm half-pitch(HP)pattern with a remarkably low line-edge roughness(LER)of 1.7 nm.Extensive studies of the EUV exposure mechanism,conducted using in-situ quadrupole mass spectrometry(QMS)and X-ray photoelectron spectroscopy(XPS),demonstrated that the solubility switch of the resist material depends on the decomposition of the sulfonium groups and triflate anions.
基金supported by the National Natural Science Foundation of China(22090012,22475224).
文摘Aryl sulfonate ester modified polystyrenes with different substituents(X–SEPS,X=H–,MeO–,and CN–)were synthesized by reversible addition-fragmentation chain transfer(RAFT)polymerization.The excellent thermal stability and film-forming capability of these three polymers suggest that they can satisfy the lithography process and are candidates for resist materials.Comparative electron beam lithography(EBL)demonstrates that the three resists(H–SEPS,MeO–SEPS and CN–SEPS)exhibit different EBL performances.Calculation of bond energies for the model compounds suggests that the influence of substituent groups on the bond energy is not the reason for the differences in sensitivity.Results obtained using a fully automated dissipative quartz crystal microbalance(QCM)analyzer confirm that the influence of substituent groups on the solubility behavior of resist films in developers leads to different photolithographic performances.The H–SEPS resist exhibits better comprehensive performance than the MeO–SEPS and CN–SEPS resists,achieving an 18 nm line/space(L/S)pattern and a 10 nm line/4 space(L/4S)semi-dense pattern by EBL at doses of 3200 and 2800μC cm^(−2),respectively.Further extreme ultraviolet lithography(EUVL)demonstrates the capability of H–SEPS resist to form 22 nm half-pitch(HP)patterns.The detailed study of the photochemical reaction and patterning mechanism suggests that the decomposition of sulfonate ester groups into polar sulfonic acid groups,along with a rearrangement,leads to a solubility switch of resist films in the developer.
基金supported by the National Natural Science Foundation of China (No.82174074)。
文摘This study investigates the properties of high-purity starches extracted from Polygonum multiflorum(PMS)and Smilax glabra(SGS).The starches were characterized by scanning electron microscopy,Fouriertransform infrared spectroscopy,X-ray diffraction,high-performance anion-exchange chromatography,and differential scanning calorimetry.Significant differences were observed in their morphological,physicochemical,and functional properties.PMS had a smaller particle size(13.68 μm),irregular polygonal shape,A-type,lower water absorption(62.67 %),and higher oil absorption(51.17 %).In contrast,SGS exhibited larger particles(31.75 μm),a nearly spherical shape,B-type,higher crystallinity(50.66 %),and greater amylose content(21.54 %),with superior thermal stability,shear resistance,and gelatinization enthalpy.SGS also contained higher resistant starch(83.28 %) and longer average chain length(20.58 %),but showed lower solubility,swelling power,light transmittance,and freeze-thaw stability.The physicochemical properties differences in crystal pattern and particle morphology between PMS and SGS lead to distinct behaviors during in vitro digestion and fermentation.These findings highlight the potential of medicinal plant starches in functional ingredients and industrial processes.
基金supported by the Ministry of Health National Medical Research Council (to JL)the National University of Singapore (to JJEC)
文摘Schizophrenia is a complex psychiatric disorder marked by positive and negative symptoms,leading to mood disturbances,cognitive impairments,and social withdrawal.While anti-psychotic medications remain the cornerstone of treatment,they often fail to fully address certain symptoms.Additionally,treatment-resistant schizophrenia,affecting 30%-40%of patients,remains a substantial clinical challenge.Positive,negative symptoms and cognitive impairments have been linked to disruptions in the glutamatergic,serotonin,GABAergic,and muscarinic pathways in the brain.Recent advances using genome-wide association study and other approaches have uncovered a significant number of new schizophrenia risk genes that uncovered new,and reinforced prior,concepts on the genetic and neurological underpinnings of schizophrenia,including abnormalities in synaptic function,immune processes,and lipid metabolism.Concurrently,new therapeutics targeting different modalities,which are expected to address some of the limitations of anti-psychotic drugs currently being offered to patients,are currently being evaluated.Collectively,these efforts provide new momentum for the next phase of schizophrenia research and treatment.
文摘Silica aerogel has broad applications in the field of high-temperature thermal insulation due to its low density,low thermal conductivity and high stability.However,its thermal insulation performance deteriorates significantly at elevated temperatures exceeding 600℃,primarily due to the collapse of pore structure.Meanwhile,the shielding capacity of SiO_(2) aerogel to the infrared radiation at high temperature is rather low due to the intrinsic properties of SiO_(2).Herein,a strategy for improving the high-temperature stability and infrared shielding properties of SiO_(2) aerogel via Ca doping was explored.Calcium-doped silica aerogel(CSA)powders were prepared by Sol-Gel,hydrothermal,and ambient pressure drying(APD)techniques using water glass and anhydrous calcium chloride as precursors and trimethylchlorosilane as a hydrophobic modifier.The effects of Ca/Si molar ratio in the precursor and hydrothermal conditions(temperature and pH)on the crystalline properties,microscopic morphology and pore structure of CSAs were investigated.The results show that the Ca/Si molar ratio and hydrothermal treatment have significant effects on the microstructure and heat resistance of CSAs in the temperature range of 400-1000℃.The samples sintered at 1000℃have a high specific surface area of 100.1 m^(2)/g and a pore volume of 0.8705 cm^(3)/g,indicating that the CSA has good heat resistance.One-side insulation tests at temperatures up to 600℃show that the sample with a Ca/Si molar ratio of 1.0 has the best insulation performance,with a cold surface temperature of 450℃,which is 27℃lower than that of the pure silica aerogel.
基金Guangzhou Metro Scientific Research Project(No.JT204-100111-23001)Chongqing Municipal Special Project for Technological Innovation and Application Development(No.CSTB2022TIAD-KPX0101)Science and Technology Research and Development Program of China State Railway Group Co.,Ltd.(No.N2023G045)。
文摘The uplift resistance of the soil overlying shield tunnels significantly impacts their anti-floating stability.However,research on uplift resistance concerning special-shaped shield tunnels is limited.This study combines numerical simulation with machine learning techniques to explore this issue.It presents a summary of special-shaped tunnel geometries and introduces a shape coefficient.Through the finite element software,Plaxis3D,the study simulates six key parameters—shape coefficient,burial depth ratio,tunnel’s longest horizontal length,internal friction angle,cohesion,and soil submerged bulk density—that impact uplift resistance across different conditions.Employing XGBoost and ANN methods,the feature importance of each parameter was analyzed based on the numerical simulation results.The findings demonstrate that a tunnel shape more closely resembling a circle leads to reduced uplift resistance in the overlying soil,whereas other parameters exhibit the contrary effects.Furthermore,the study reveals a diminishing trend in the feature importance of buried depth ratio,internal friction angle,tunnel longest horizontal length,cohesion,soil submerged bulk density,and shape coefficient in influencing uplift resistance.
文摘It is crucial to develop arsenic removal adsorbents with strong sulfur resistance under middle-low-temperature flue gas conditions(<400℃).In this work,five Fe-Ce-La oxides were prepared by co-precipitation method,and FeCeLaO/SiO_(2)-Al_(2)O_(3) composite adsorbents were prepared by coupling fly ash-based Si-Al carriers.The active components Fe-Ce-La oxides and Si-Al carriers were characterized by TPD,TG,XRF,BET and XPS,respectively.The effects of temperature,Si/Al ratio and FeCeLaO loading rate on the sulfur resistance were investigated.Results show that the SO_(2) promotes the arsenic removal of Fe_(2)O_(3),CeLaO and FeCeLaO.At 400℃,the arsenic removal efficiencies of the three oxides increase from 45.3%,72.5% and 81.3% without SO_(2) to 62.6%,80.5%and 91.0%,respectively.The SO_(2) inhibits the arsenic removal of La_(2)O_(2)CO_(3) and FeLaO,and the inhibition effect is pronounced at high temperatures.The sulfur poisoning resistance of Si-Al carriers increases with the increase of Si/Al ratio.When the Si/Al ratio is increased to 9.74,the arsenic removal efficiency in the SO_(2) environment is 13.9% higher than that in the absence of SO_(2).Introducing FeCeLaO active components is beneficial for enhancing the SO_(2) poisoning resistance of Si-Al carriers.The strong sulfur resistance of the FeCeLaO/SiO_(2)-Al_(2)O_(3) composite adsorbent results from multiple factors:protective effects of Ce on Fe,La and Al;sulfation-induced generation of Ce^(3+)and surface-adsorbed oxygen;and strong surface acidity of SiO_(2).
文摘The present work provides a facile and efficient method for producing ultrafine copper powders.Ultrafine copper powders were synthesized through a solvothermal method,utilizing ethanol both as a solvent and a reducing agent.Specifically,by exploiting the weak reducing property of ethanol,the copper precursor is first converted to copper oxide and then further reduced to cuprous oxide and pure copper.Such a method can effectively control the morphology and particle size of the copper powder,reduce particle aggregation,and enhance oxidation resistance.It is cost-effective and produces fewer toxic by-products.Spherical copper particles with an average particle size of about 180 nm were obtained.The initial oxidation temperature is approximately 150℃,and the resulting copper powders can be stored stably under ambient conditions for at least 5 months,demonstrating excellent oxidation resistance and thermal stability.
文摘Platinum group metals have high melting points,strong corrosion resistance,stable chemical properties,and low oxygen permeability in high-temperature oxygen-containing environments.As thermal protective coating materials,they have gained essential applications in the aerospace field and have excellent prospects for application in frontier military fields,such as protecting hot-end components of hypersonic aircraft.This research reviewed the latest research progress of platinum group metal coatings with hightemperature oxidation resistance,including coating preparation techniques,oxidation failure,and alloying modification.The leading preparation techniques of current platinum group metal coatings were discussed,as well as the advantages and disadvantages of various existing preparation techniques.Besides,the intrinsic properties,failure forms,and failure mechanisms of coatings of single platinum group metal in high-temperature oxygen-containing environments were analyzed.On this basis,the necessity,main methods,and main achievements of alloying modification of platinum group metals were summarized.Finally,the future development of platinum group coatings with high-temperature oxidation resistance was discussed and prospected.
基金National Natural Science Foundation of China(11875039)Shanxi Scholarship Council of China(2023-033)+2 种基金Fundamental Research Program of Shanxi Province(202303021221071)China Baowu Low Carbon Metallurgical Innovation Foundation(2022)2023 Anhui Major Industrial Innovation Plan Project。
文摘The in-flight heating process of cerium dioxide(CeO_(2))powders was investigated through experiments and numerical simulations.In the experiment,CeO_(2)powder(average size of 30μm)was injected into radio-frequency(RF)argon plasma,and the temperatures were measured using a DPV-2000 monitor.A model combining the electromagnetism,thermal flow,and heat transfer characteristics of powder during in-flight heating in argon plasma was proposed.The melting processes of CeO_(2)powders of different diameters,with and without thermal resistance effect,were investigated.Results show that the heating process of CeO_(2)powder particles consists of three main stages,one of which is relevant to a dimensionless parameter known as the Biot number.When the Biot value≥0.1,thermal resistance increases significantly,especially for the larger powders.The predicted temperature of the particles at the outlet(1800–2880 K)is in good agreement with the experimental result.
文摘Urinary tract infections(UTIs)are among the most prevalent pediatric bacterial infections,and undertreated episodes may lead to renal scarring,hypertension,or chronic kidney disease.Multidrug-resistant(MDR)Enterobacterales have been increasingly reported in children,with higher rates in Asian and Middle Eastern settings than in high-income countries[1,2].
基金supported by the State Key Laboratory of Urban Water Resource and Environment (Harbin Institute of Technology) (No.2022TS13)the key projects of National Natural Science Foundation of China (No.2019YFC0408503)the Key Research Program of Wuhan (No.2022022202015015)。
文摘Antibiotic resistance genes(ARGs) are recognized as a primary threat to the sustainability of environment and human health in the 21^(st) century.Nanomaterials(NMs) have attracted substantial attention due to their unique dimensions and structures.Unfortunately,emerging evidence suggests that NMs may facilitate the transmission of ARGs.It is crucial to elucidate how NMs affect the evolution and dissemination of ARGs.The current review comprehensively examines the role of NMs in the widespread transmission of ARGs in aquatic environments and the underlying mechanisms involved in the process.It aims to clarify the effects and mechanisms of NMs on the horizontal gene transfer processes that are associated with ARGs,including the enhancement of cell membrane permeability,the formation of nanopores on membranes,promotion of mutagenesis,and the generation of reactive oxygen species(ROSs).Furthermore,the trade-off between the removal of ARGs and horizontal transfer has been elucidated.The review aspires to guide future research directions,advance knowledge on the implications of NMs in the field of ARGs' transmission,and provide a theoretical foundation for the development of safer and more effective applications of NMs.
基金supported by the National Key Research and Development Project(2022YFA1104500 to JX)the National Natural Science Foundation of China(82020108002 and82225005 to JX and 82370277 to HW)+1 种基金the Science and Technology Commission of Shanghai Municipality(23ZR1422900 to HW and 23410750100 to JX)supported by a Biotechnology and Biological Sciences Research Council(BBSRC)International Partnering Award。
文摘Physical activity,moderate aerobic or resistance exercise are well established to offer health benefits and promote healthy aging and longevity.^(1)In contrast,lack of exercise contributes to adverse events,especially in some patients with organ failure.^(2)Therefore,“exercise pills”and“exercise mimetics”have attracted growing interest because of their potential to induce exercise-related health effects despite physical exercise not being performed.^(3)Robust studies over the past decade have identified many natural biomacromolecules,such as peptide,non-coding Ribonucleic Acid(RNAs),and lipids,that are induced by exercise.^(4-6)These molecules trigger physiological adaptations,including promotion of cardiomyocyte proliferation,anti-apoptotic capacity,and healthy tissue growth.7However,identifying or designing an exercise pill that mimics the extensive benefits of exercise is still challenging.
基金supported by Punjab Agricultural University,Ludhiana,India,for providing the infrastructure and other facilities for conducting experiments.All other forms of support and financial assistance are duly acknowledged.
文摘Brown spot(BS)of rice,caused by Bipolaris oryzae,is a serious concern that not only causes quantitative losses but also affects grain quality.To manage this disease,the use of resistant genetic sources and QTLs is an eco-friendly and economical option.In the current study,F_(3) progenies derived from a cross of susceptible parent PMS-18-B(PAU 10845-1-1-1-1)×resistant parent RP Path 77(RP patho-17)were used to identify potential QTLs linked to BS resistance and to associate this resistance with a temporal spike in defense-related enzymes.
基金supported by the National Youth Top-notch Talent Support Program of China(Grant No.00389335)the National Natural Science Foundation of China(Grant No.52378392)+1 种基金the“Foal Eagle Program”Youth Top-notch Talent Project of Fujian Province(Grant No.00387088)supports are gratefully acknowledged.
文摘Enzyme-Induced Carbonate Precipitation(EICP)is an innovative technique to improve soil strength and reduce permeability.However,the use of EICP for reinforcing underwater sand beds remains largely unexplored.To advance EICP implementation in various geotechnical applications,this paper develops a model box system to investigate the effectiveness of the EICP technique in reinforcing underwater sand beds.An"injection-extraction"system is designed to facilitate the flow of the EICP solution through underwater sand layers.Key parameters,including conductivity,pH,and Ca^(2+)concentration of the solution,are measured and analyzed.Electrical resistivity tomography(ERT)is utilized to evaluate the reinforcement effect in the underwater sand bed.The permeability of the model is tested to verify the feasibility of EICP technology for strengthening underwater sands.Furthermore,scanning electron microscope(SEM)is performed to investigate the growth mechanisms of calcium carbonate(CaCO_(3))crystals.The results show that the permeability of the model decreases from 1.28×10^(-2)m/s to 9.66×10^(-5)m/s,representing a reduction of approximately three orders of magnitude.This verifies that the EICP technology can greatly reduce the permeability of underwater sand beds.With increasing grouting cycles,the resistivity of the underwater sand initially decreases and then increases.This variation in sand resistivity is significantly influenced by the ion concentration in the solution,resulting in marked differences in resistivity at various depths and positions within the sand.The findings from this study offer a theoretical basis for the application of EICP technology in reinforcing seabed foundations and supporting marine infrastructure such as offshore pipelines,wind turbines,and oil platforms.
基金supported by the National Key R&D Program of China(2024YFD1201100)the research program from the Zhongshan Biological Breeding Laboratory(ZSBBL-KY2023-02)the National Natural Science Foundation of China(32341037).
文摘Wheat(Triticum aestivum)faces significant threats from diseases such as powdery mildew(Blumeria graminis)and Fusarium head blight(FHB;caused by Fusarium graminearum),which cause severe yield losses.Moreover,the antagonism between yield-related traits and disease resistance makes yield resistance coordination a major challenge in wheat breeding.The lack of genetic resources combining both disease resistance and high yield constrains the elucidation of underlying resistance-yield trade-off mechanisms,thereby hindering the development of high-yield and disease-resistant wheat cultivars.Remarkably,Yangmai 33(YM33),a notable wheat cultivar with resistance to both powdery mildew and FHB as well as high-yield performance,was recently developed.It offers a unique opportunity to dissect the genomic architecture underlying the coordination between disease resistance and yield.
基金financially supported by the National Key Research and Development Program of China(2021YFD2200405)the National Natural Science Foundation of China(31930078)special funds for Baotianman Forest Ecosystem Research Station from Chinese Academy of Forestry and Ministry of Science and Technology of China。
文摘Frequent droughts pose considerable threat to global forest carbon uptake,but little is known about the response of forest carbon fluxes in climatic transition zones to seasonal drought.In this study,the responses of carbon fluxes to seasonal drought in two natural forests(Quercus aliena var.acute serrata Maxim and Pinus tabuliformis Carr.)in the Baotianman Nature Reserve were investigated.The Q.aliena forest exhibited a high resilience with stable gross primary productivity(GPP).However,ecosystem respiration(Re)significantly declined by 18.4%compared with normal years,leading to an increase in net carbon sequestration capacity of 4.1%.This resilience was attributed to its deep root system accessing soil water(SWC_(50cm))to sustain stomatal openness,coupled with the efficient utilization of photosynthetically active radiation to drive photosynthesis.In contrast,the P.tabuliformis forest,which relied on shallow soil moisture(SWC_(20cm)),experienced simultaneous decreases in both GPP and Re during drought,with a sharply greater decrease in GPP,resulting in low net carbon sink capacity.Further analysis revealed that the Q.aliena forest prioritized carbon assimilation through a deep water-stomatal synergy strategy(anisohydric behavior),whereas the P.tabuliformis forest adopted an isohydric strategy favoring water conservation at the expense of carbon fixation efficiency.These findings highlight distinct mechanisms underlying drought adaptation between forest types,providing critical insight into optimizing forest carbon cycle models and selecting drought-resistant species under the influence of climate change.
基金supported by National Research Foundation(NRF)of Korea grants funded by the Korean government,the Ministry of Science and ICT[NRF-2022R1A2C1006737 to Joo-Won Park,NRF-2022R1I1A1A0106408112 to Min Hee Kim].
文摘Breast cancer is one of the most prevalent malignancies among women and comprises a heterogeneous spectrum of molecular subtypes with distinct biological behaviors.Among various regulatory molecules,sphingolipids play pivotal roles in dynamically modulating fundamental cellular processes such as proliferation,apoptosis,and metastasis through metabolic interconversions,including phosphorylation,glycosylation,and the generation of sphingosine-1-phosphate.This review aims to elucidate the mechanisms through which sphingolipid metabolism orchestrates cancer cell fate and drives breast cancer progression.Particular emphasis is placed on the balance between proapoptotic ceramides and pro-survival metabolites,such as sphingosine-1-phosphate,which collectively influence tumor growth and the therapeutic response.Additional sphingolipid species,including glucosylceramide and gangliosides(GD2,GD3,GM1,and GM3),have also been implicated in promoting breast cancer development.Furthermore,sphingolipid-based therapeutic strategies,including immunotherapy and antibody therapy,are discussed.By providing a comprehensive overview of sphingolipid metabolism,this review aims to identify novel therapeutic targets that may help overcome treatment resistance and improve clinical outcomes in breast cancer.
