Shale oil resources are abundant on Earth,of which hybrid sedimentary shale(HSS)oil is an important component,including high and medium-low organic matter content(TOC).Oil content,especially the oiliness gradation,is ...Shale oil resources are abundant on Earth,of which hybrid sedimentary shale(HSS)oil is an important component,including high and medium-low organic matter content(TOC).Oil content,especially the oiliness gradation,is a key parameter for shale oil evaluation and numerous studies had been conducted.However,most studies concentrated on the HSS with high TOC,making oil content evaluation of the HSS with medium-low TOC challenging.The Paleocene Shahejie Formation(E2s)shale in Dongpu Depression is a typical HSS with low-moderate TOC,showing great shale oil resource potential.Integrated geochemical characterization of 270 core samples were conducted and results show that,the E2s shale has fairgood hydrocarbon generation potential,with TOC ranging from 0.06%to 3.6%(Avg.0.86%)andⅡ1-Ⅱ2 kerogen type in thermally mature.The hydrocarbon generation potential decreases with kerogen types changing from type I toⅢ,but S1C and the oil saturation index(OSI)(S1*100/TOC>100)increase from type I toⅡ1,and then decrease from typeⅡ2 toⅢ,indicating shale with typeⅡ2 kerogen have the greatest oil content.This is related to the diferences in hydrocarbon expulsion efciency caused by diferential hydrocarbon generation potential and pore-microfractures evolution among shales with diferent kerogen types.Signifcant oil micro-migration occurred in E2s shale,with micro-migration quantity(∆Q)ranging from-846 to 993 mg/g(Avg.-120 mg/g),and 90%and 10%shale exhibit hydrocarbon intra-micro-migration(∆Q<0)and extra-micro-migration(∆Q>0).The shale with typeⅡ2 kerogen has the greatest intra-micro-migration.Based on S1C,TOC and OSI values and their evolution pattern,shale oil resources were classifed into enriched,moderately enriched,less efcient and invalid resources,accounting for 11%,53%,16%and 21%respectively,with S1C thresholds of 3.5 and 0.5 mg/g,OSI threshold of 100 mg/g.Compared with previous grading criteria,the gradation criterion established in this study is relatively lower,which is mainly due to the lower TOC and clay mineral content in HSS.Enriched and moderately enriched resources are mainly shales with typeⅡ2 kerogen,followed by typeⅡ1 kerogen,and the E2s4 U and E2s3 L shale are the most favorable targets for further shale oil exploration.The established oiliness gradation criteria are applicable for the HSS with TOC in other parts of the world.展开更多
This review explores the pivotal role of circadian rhythm regulators,particularly the PER genes,in Oral Squamous Cell Carcinoma(OSCC).As key constituents of the biological clock,PERs exhibit a downregulated expression...This review explores the pivotal role of circadian rhythm regulators,particularly the PER genes,in Oral Squamous Cell Carcinoma(OSCC).As key constituents of the biological clock,PERs exhibit a downregulated expression pattern in OSCC,and the expression levels of PERs in OSCC patients are correlated with a favorable prognosis.PERs impact the occurrence and development of OSCC through multiple pathways.In the regulation of cell proliferation,they can function not only through cell cycle regultion but also via metabolic pathways.For example,PER1 can interact with receptors for activated C kinase 1(RACK1)and phosphatidylinositol 3-kinase(PI3K)through its PAS domain to inhibit glycolysis and thereby reduce cell proliferation.Regarding the regulation of cell death,PERs mediate various types of cell death in OSCC cells,such as p53-dependent apoptosis,protein kinase B(AKT)/mammalian target of rapamycin(mTOR)dependent autophagy,or hypoxia-inducible factor l-alpha(HIF-1a)mediated ferroptosis.In regulating epithelia-mesenchymal transition(EMT),PERs can lead to the downregulation of EMT related genes,such as zinc finger E-box binding homeobox 1/2(ZEBI/2),twist family BHLH transcription factor 1/2(TWIST1/2),and Vimentin,thereby influencing the migration and invasion capabilities of OSCC cells.In tumor angiogenesis,PERs exert regulatory effects on related factors,such as methionyl aminopeptidase 2(MetAP2)and vascular endothelial growth factor(VEGF).In the tumor immune microenvironment,PERs can inhibit the inhibitor of kappa B kinase(IKK)/nuclear factor kappa B(NF-kB)pathway and programmed cell death ligand 1(PD-L1)expression,thereby enhancing the cytotoxic effect of CD8+T cells on OSCC cells.In-depth studies focusing on elucidating the precise regulatory mechanisms of PERs can facilitate the development of therapeutic strategies targeting PERs,including restoration of PERs expression/activity,targeting PERs-regulated pathways,combination therapies,and chronotherapy.These furnish a theoretical foundation for formulating individualized treatment plans to achieve precise treatment for patients with OSCC.展开更多
High ionic conductivity,good electrochemical stability,and satisfactory mechanical property are the crucial factors for polymer solid state electrolytes.Herein,fast ion conductor LiAlSiO_4(LASO) is incorporated into p...High ionic conductivity,good electrochemical stability,and satisfactory mechanical property are the crucial factors for polymer solid state electrolytes.Herein,fast ion conductor LiAlSiO_4(LASO) is incorporated into polyethylene oxide(PEO)-based solid-state electrolytes(SSEs).The SSEs containing LASO exhibit enhanced mechanical properties performance compared to pristine PEO-LiTFSI electrolyte.A reduced melting transition temperature of 40.57℃ is enabled by introducing LASO in to PEO-based SSE,which is beneficial to the motion of PEO chain and makes it possible for working at a moderate environment.Coupling with the enhanced motion of PEO,dissociation of the lithium salt,and conducting channel of LASO,the optimized composite polymer SSE exhibits a high ionic conductivity of 4.68×10^(-4),3.16×10^(-4) and 1.62×10^(-4) S cm^(-1) at 60,50 and 40℃,respectively.The corresponding LiFePO_4//Li solid-state battery exhibits high specific capacities of 166,160 and 139 mAh g^(-1) at 0.2 C under 60,40 and 25℃.In addition,it remains 130 mAh g^(-1) at 4.0 C,and maintains 91.74% after 500 cycles at 1.0 C under 60℃.This study provides a simple approach for developing ionic conductor-filled polymer electrolytes in solid-state lithium battery application.展开更多
The horizontally variable density stratification and background currents are taken into the variable-coefficent extended Korteweg-de Vries(evKdV)theory to obtain the geographical and seasonal distribution of kinematic...The horizontally variable density stratification and background currents are taken into the variable-coefficent extended Korteweg-de Vries(evKdV)theory to obtain the geographical and seasonal distribution of kinematic parameters of internal solitary waves in the Andaman Sea(AS).The kinematic parameters include phase speed,dispersion parameter,quadratic and cubic nonlinear parameters.It shows that the phase speed and dispersion parameter are mainly determined by the topographic feature and have limited seasonal variation.The maximum phase speed is 2.6 m/s,which occurs in the cool season(November)in the middle of the AS,while the phase speed in the cool season is slightly larger than those in other seasons,up to 11.4%larger than that in the rainy season(July)in the southern AS.The dispersion parameter in the cool season can be 22.3%larger than that in the hot season.The nonlinear parameters have significant seasonal variation,and they can even change their signs at the continental slope in the north of the AS,from season to season.Meanwhile,the algebraic solitons dominate in the AS with minimum amplitudes(aal)ranging from 0.1 m to 102 m,and the maximum aal occurs in the cool season in the southern AS.The effect of the background flow on the parameters is also studied.The background flow has a great influence on the nonlinear parameters,e.g.,the value of cubic nonlinear parameter can be reduced by 1/3 when the background flow is not considered.展开更多
Hepatocellular carcinoma(HCC)is an aggressive malignancy that is highly prevalent worldwide.It is often diagnosed at an advanced stage,which poses challenges for curative treatment and leads to an unfavorable prognosi...Hepatocellular carcinoma(HCC)is an aggressive malignancy that is highly prevalent worldwide.It is often diagnosed at an advanced stage,which poses challenges for curative treatment and leads to an unfavorable prognosis.The introduction of targeted therapy drugs,such as tyrosine kinase inhibitors,and immunotherapeutic drugs,including immune checkpoint inhibitors,has substantially improved the thera-peutic effectiveness for advanced HCC.However,their efficacy remains suboptimal,owing to challenges related to patient responsiveness and drug resistance.To address these challenges,researchers have investigated combination therapies,including targeted immunother-apy,and triple therapies based on targeted immunotherapy,such as a combination of radiotherapy and targeted immunotherapy.In ad-dition,they conducted a comprehensive investigation of potential new targets and drugs,yielding a series of significant findings.This re-view presents an outline of the treatment mechanisms and associated clinical research findings on mainstream targeted therapies,immu-notherapies,and combination therapies.It also summarizes the current status of combination therapies for advanced HCC and anticipates future developments and trends in this field.展开更多
After online publication of the article1,the authors noticed one inadvertent mistake in Acknowledgements part that needs to be corrected.The correct grant number for the“National High Level Hospital Clinical Research...After online publication of the article1,the authors noticed one inadvertent mistake in Acknowledgements part that needs to be corrected.The correct grant number for the“National High Level Hospital Clinical Research Funding”should be“2022-CICAMS80102022503”.展开更多
Despite the lack of predictive biomarkers and a prognostic stratification strategy,immune checkpoint inhibitor(ICI)has shown promise in improving outcomes for patients with limited-stage small cell lung cancer(LS-SCLC...Despite the lack of predictive biomarkers and a prognostic stratification strategy,immune checkpoint inhibitor(ICI)has shown promise in improving outcomes for patients with limited-stage small cell lung cancer(LS-SCLC).We evaluated the potential of circulating tumor DNA(ctDNA)to dynamically predict outcomes in patients with LS-SCLC receiving concurrent chemoradiotherapy(CCRT)with or without consolidation ICI.We analyzed 490 serial samples collected from 144 LS-SCLC patients at baseline(t0),post-induction chemotherapy and pre-thoracic radiotherapy(t1),post-radiotherapy(t2),and progressive disease(t3).For 44 patients receiving consolidation ICI with serplulimab,an investigational PD-1 inhibitor,ctDNA dynamics during consolidation ICI were also assessed at multiple time points.Patients with undetectable ctDNA after CCRT had good outcomes with or without consolidation ICI,whereas ctDNA-positive patients at t2,indicating poor response to CCRT,derived survival benefit from consolidation ICI.Notably,ctDNA status at t1 appeared more predictive than at t2.A three-level risk stratification strategy integrating t1 ctDNA status with radiological tumor shrinkage identified a high-risk subgroup of patients who achieved significantly improved progression-free survival(PFS)(hazard ratio[HR],0.24;95%confidence interval[CI],0.08-0.75;p=0.014)and overall survival(OS)(HR,0.06;95%CI,0.00-0.42;p=0.001)from consolidation ICI,prioritizing CCRT plus consolidation ICI.Furthermore,maintaining ctDNA negativity during consolidation ICI was associated with favorable outcomes.These data provide valuable insights into the individualized management of LS-SCLC in the era of immunotherapy.展开更多
From the theoretical perspective of the Marxist conception of space-time,this paper explores its innovative application in the practice of modern museum cultural communication.Through an in-depth interpretation of the...From the theoretical perspective of the Marxist conception of space-time,this paper explores its innovative application in the practice of modern museum cultural communication.Through an in-depth interpretation of the Marxist space-time concept combined with theoretical frameworks from museology and communication studies,this study analyzes how contemporary museums employ Marxist space-time theory to innovate their cultural communication practices.The research indicates that the Marxist conception of s pace-time provides important guidance for exhibition design,narrative approaches,and interactive experiences in modern museums,offering new ideas and methods to enhance the effectiveness of museum cultural communication.展开更多
Numerous internal solitary waves(ISWs)have been observed in the southern Andaman Sea.In this study,the twodimensional Massachusetts Institute of Technology general circulation model is applied to investigate the dynam...Numerous internal solitary waves(ISWs)have been observed in the southern Andaman Sea.In this study,the twodimensional Massachusetts Institute of Technology general circulation model is applied to investigate the dynamics of ISWs and explore the effects of the bottom topography and tidal forcing on the generation and propagation of ISWs in the southern Andaman Sea.The results show that the large-amplitude depression ISWs are mainly generated via the oscillating tidal flow over the sill of the Great Channel,and the generation of ISWs is subject to the lee wave regime.The Dreadnought Bank cannot generate ISWs itself;however,it can enhance the amplitudes of eastward-propagating ISWs generated from sill A,owing to constructive interference of internal tide generation between the sill of the Great Channel and the Dreadnought Bank.The eastward-propagating ISWs generated by the eastern shallow sill near the continental shelf can propagate to the shelf,where they evolve into elevation waves because of the shallow water.Sensitivity runs show that both the semidiurnal and diurnal tides over the sill of the Great Channel can generate ISWs in this area.However,the ISWs generated by diurnal tides are much weaker than those generated by semidiurnal tides.Mixed tidal forcing has no significant effect on the generation of ISWs.展开更多
Lipid nanoparticles(LNPs)are nanocarriers composed of four lipid components and can be used for gene therapy,protein replacement,and vaccine development.However,LNPs also face several challenges,such as toxicity,immun...Lipid nanoparticles(LNPs)are nanocarriers composed of four lipid components and can be used for gene therapy,protein replacement,and vaccine development.However,LNPs also face several challenges,such as toxicity,immune activation,and low delivery efficiency.To overcome these challenges,artificial intelligence can be used to optimize the design and formulation of LNPs,as well as to predict their properties and performance.Moreover,antibody-targeted conjugation can be used to enhance the specificity and selectivity of LNPs by attaching an antibody that recognizes a specific antigen on the cell surface to LNPs.展开更多
With the proliferation of energy storage and power applications, electric vehicles particularly, solid-state batteries are considered as one of the most promising strategies to address the ever-increasing safety conce...With the proliferation of energy storage and power applications, electric vehicles particularly, solid-state batteries are considered as one of the most promising strategies to address the ever-increasing safety concern and high energy demand of power devices. Here, we demonstrate the Al4B2O9 nanorods-modified poly(ethylene oxide) (PEO)-based solid polymer electrolyte (ASPE) with high ionic conductivity, wide electrochemical window, decent mechanical property and nonflammable performance. Specifically, because of the longer-range ordered Li+ transfer channels conducted by the interaction between Al4B2O9 nanorods and PEO, the optimal ASPE (ASPE-1) shows excellent ionic conductivity of 4.35×10^−1 and 3.1×10^−1 S cm^−1 at 30 and 60℃, respectively. It also has good electrochemical stability at 60℃ with a decomposition voltage of 5.1 V. Besides, the assembled LiFePO4//Li cells show good cycling performance, delivering 155 mA h g−1 after 300 cycles at 1 C under 60℃, and present excellent low temperature adaptability, retaining over 125 mA h g^−1 after 90 cycles at 0.2 C under 30℃. These results verify that the addition of Al4B2O9 nanorods can effectively promote the integrated performance of solid polymer electrolyte.展开更多
Background:Liquid biopsy-based biomarkers,including circulating tumor DNA(ctDNA)and blood tumor muta-tional burden(bTMB),are recognized as promising predictors of prognoses and responses to immune checkpoint inhibitor...Background:Liquid biopsy-based biomarkers,including circulating tumor DNA(ctDNA)and blood tumor muta-tional burden(bTMB),are recognized as promising predictors of prognoses and responses to immune checkpoint inhibitors(ICIs),despite insufficient sensitivity of single biomarker detection.This research aims to determine whether the combinatorial utility of longitudinal ctDNA with bTMB analysis could improve the prognostic and predictive effects.Methods:This prospective two-center cohort trial,consisting of discovery and validation datasets,enrolled unre-sectable locally advanced non-small-cell lung cancer(LA-NSCLC)patients and assigned them to chemoradiother-apy(CRT)or CRT+consolidation ICI cohorts from 2018 to 2022.Blood specimens were collected pretreatment,4 weeks post-CRT,and at progression to assess bTMB and ctDNA using 486-gene next-generation sequencing.DynamicΔbTMB was calculated as post-CRT bTMB minus baseline bTMB levels.Decision curve analyses were performed to calculate Concordance index(C-index).Results:One hundred twenty-eight patients were enrolled.In the discovery dataset(n=73),patients treated with CRT and consolidation ICI had significantly longer overall survival(OS;median not reached[NR]vs 20.2 months;P<0.001)and progression-free survival(PFS;median 25.2 vs 11.4 months;P=0.011)than those without ICI.Longitudinal analysis demonstrated a significant decrease in ctDNA abundance post-CRT(P<0.001)but a relative increase with disease progression.Post-CRT detectable residual ctDNA correlated with significantly shorter OS(median 18.3 months vs NR;P=0.001)and PFS(median 7.3 vs 25.2 months;P<0.001).For patients with residual ctDNA,consolidation ICI brought significantly greater OS(median NR vs 14.8 months;P=0.005)and PFS(median 13.8 vs 6.2 months;P=0.028)benefit,but no significant difference for patients with ctDNA clearance.DynamicΔbTMB was predictive of prognosis.Patients with residual ctDNA and increasedΔbTMB(ΔbTMB>0)had significantly worse OS(median 9.0 vs 23.0 months vs NR;P<0.001)and PFS(median 3.4 vs 7.3 vs 25.2 months;P<0.001).The combinatorial model integrating post-CRT ctDNA withΔbTMB had optimal predictive effects on OS(C-index=0.723)and PFS(C-index=0.693),outperforming individual features.In the independent validation set,we confirmed residual ctDNA predicted poorer PFS(median 50.8 vs 14.3 months;P=0.026)but identified more consolidation ICI benefit(median NR vs 8.3 months;P=0.039).The combined model exhibited a stable predictive advantage(C-index=0.742 for PFS).Conclusions:The multiparameter assay integrating qualitative residual ctDNA testing with quantitativeΔbTMB dynamics improves patient prognostic risk stratification and efficacy predictions,allowing for personalized con-solidation therapy for LA-NSCLC.展开更多
We introduce and study a parallel domain decomposition algorithm for the simulation of blood flow in compliant arteries using a fully-coupled system of nonlinear partial differential equations consisting of a linear e...We introduce and study a parallel domain decomposition algorithm for the simulation of blood flow in compliant arteries using a fully-coupled system of nonlinear partial differential equations consisting of a linear elasticity equation and the incompressible Navier-Stokes equations with a resistive outflow boundary condition.The system is discretized with a finite element method on unstructured moving meshes and solved by a Newton-Krylov algorithm preconditioned with an overlapping restricted additive Schwarz method.The resistive outflow boundary condition plays an interesting role in the accuracy of the blood flow simulation and we provide a numerical comparison of its accuracy with the standard pressure type boundary condition.We also discuss the parallel performance of the implicit domain decomposition method for solving the fully coupled nonlinear system on a supercomputer with a few hundred processors.展开更多
Obesity-prone(OP)individuals exhibit an intrinsic predisposition to obesity and associated metabolic disorders,and early intervention in this population holds significant clinical value;however,the underlying mechanis...Obesity-prone(OP)individuals exhibit an intrinsic predisposition to obesity and associated metabolic disorders,and early intervention in this population holds significant clinical value;however,the underlying mechanisms driving this susceptibility remain largely obscure.This study enrolled 46 OP subjects without diagnosed metabolic diseases and 35 healthy controls.Our findings revealed that,despite not reaching obesity diagnoses,OP subjects exhibited significant metabolic disturbances strongly associated with gut microbiota dysbiosis.They also displayed disturbed bile acid(BA)profiles,with depleted glycodeoxycholic acid(GDCA)identified as the most potent discriminator between the OP and healthy controls.Fecal microbiota transplantation(FMT)recapitulated metabolic dysfunction and BA pool remodeling,mediated by dysregulated hepatic expression of BA synthesis genes of Cyp8a1,Cyp7a1,and Cyp7b1.Notably,FMT-OP mice also phenocopied the diminished GDCA levels observed in OP subjects.GDCA supplementation in obese mice markedly improved body weight,hepatic steatosis,and metabolic dysfunction.Mechanistically,GDCA exerted anti-obesity effects by activating the TGR5 signaling,which enhanced brown adipose tissue(BAT)thermogenesis and stimulated ileal glucagon-like peptide-1(GLP-1)secretion,thereby ameliorating obesity and associated metabolic dysregulation.Thus,these findings indicate that gut microbiota-driven dysregulation of BA signaling,particularly impaired TGR5 activation due to diminished GDCA,underlies glycolipid metabolic dysfunction in OP individuals.展开更多
基金supported by the National Natural Science Foundation of China(U24B6002,42202133,U22B6004)CNPC Innovation Fund(2022DQ02-0106)+5 种基金Key Laboratory of Tectonics and Petroleum Resources of the Ministry of Education(TPR-2023-05)major science and technology projects of CNPC during the"14th five-year plan"(2021DJ0101)National Natural Science Foundation of China(41872148,42072174,42130803)Strategic Cooperation Technology Projects of the CNPC and CUPB(ZLZX2020-01-05)Sinopec Zhongyuan Oilfeld and CUPB Cooperation Project(31300027-23-ZC0613-0013)AAPG Foundation Grantsin-Aid Program(22272306).
文摘Shale oil resources are abundant on Earth,of which hybrid sedimentary shale(HSS)oil is an important component,including high and medium-low organic matter content(TOC).Oil content,especially the oiliness gradation,is a key parameter for shale oil evaluation and numerous studies had been conducted.However,most studies concentrated on the HSS with high TOC,making oil content evaluation of the HSS with medium-low TOC challenging.The Paleocene Shahejie Formation(E2s)shale in Dongpu Depression is a typical HSS with low-moderate TOC,showing great shale oil resource potential.Integrated geochemical characterization of 270 core samples were conducted and results show that,the E2s shale has fairgood hydrocarbon generation potential,with TOC ranging from 0.06%to 3.6%(Avg.0.86%)andⅡ1-Ⅱ2 kerogen type in thermally mature.The hydrocarbon generation potential decreases with kerogen types changing from type I toⅢ,but S1C and the oil saturation index(OSI)(S1*100/TOC>100)increase from type I toⅡ1,and then decrease from typeⅡ2 toⅢ,indicating shale with typeⅡ2 kerogen have the greatest oil content.This is related to the diferences in hydrocarbon expulsion efciency caused by diferential hydrocarbon generation potential and pore-microfractures evolution among shales with diferent kerogen types.Signifcant oil micro-migration occurred in E2s shale,with micro-migration quantity(∆Q)ranging from-846 to 993 mg/g(Avg.-120 mg/g),and 90%and 10%shale exhibit hydrocarbon intra-micro-migration(∆Q<0)and extra-micro-migration(∆Q>0).The shale with typeⅡ2 kerogen has the greatest intra-micro-migration.Based on S1C,TOC and OSI values and their evolution pattern,shale oil resources were classifed into enriched,moderately enriched,less efcient and invalid resources,accounting for 11%,53%,16%and 21%respectively,with S1C thresholds of 3.5 and 0.5 mg/g,OSI threshold of 100 mg/g.Compared with previous grading criteria,the gradation criterion established in this study is relatively lower,which is mainly due to the lower TOC and clay mineral content in HSS.Enriched and moderately enriched resources are mainly shales with typeⅡ2 kerogen,followed by typeⅡ1 kerogen,and the E2s4 U and E2s3 L shale are the most favorable targets for further shale oil exploration.The established oiliness gradation criteria are applicable for the HSS with TOC in other parts of the world.
基金supported by the following funding:National Natural Science Foundations of China(82002888,82272899 and 82370974)Sichuan Science and Technology Program(2022YFS0207 and 2023YFS0127)+1 种基金Scientific Research Foundation,WestChinaHospital of Stomatology SichuanUniversity(RCDWJS2021-8)the CAMS Innovation Fund for Medical Sciences(CIFMS,2019-I2M-5-004).
文摘This review explores the pivotal role of circadian rhythm regulators,particularly the PER genes,in Oral Squamous Cell Carcinoma(OSCC).As key constituents of the biological clock,PERs exhibit a downregulated expression pattern in OSCC,and the expression levels of PERs in OSCC patients are correlated with a favorable prognosis.PERs impact the occurrence and development of OSCC through multiple pathways.In the regulation of cell proliferation,they can function not only through cell cycle regultion but also via metabolic pathways.For example,PER1 can interact with receptors for activated C kinase 1(RACK1)and phosphatidylinositol 3-kinase(PI3K)through its PAS domain to inhibit glycolysis and thereby reduce cell proliferation.Regarding the regulation of cell death,PERs mediate various types of cell death in OSCC cells,such as p53-dependent apoptosis,protein kinase B(AKT)/mammalian target of rapamycin(mTOR)dependent autophagy,or hypoxia-inducible factor l-alpha(HIF-1a)mediated ferroptosis.In regulating epithelia-mesenchymal transition(EMT),PERs can lead to the downregulation of EMT related genes,such as zinc finger E-box binding homeobox 1/2(ZEBI/2),twist family BHLH transcription factor 1/2(TWIST1/2),and Vimentin,thereby influencing the migration and invasion capabilities of OSCC cells.In tumor angiogenesis,PERs exert regulatory effects on related factors,such as methionyl aminopeptidase 2(MetAP2)and vascular endothelial growth factor(VEGF).In the tumor immune microenvironment,PERs can inhibit the inhibitor of kappa B kinase(IKK)/nuclear factor kappa B(NF-kB)pathway and programmed cell death ligand 1(PD-L1)expression,thereby enhancing the cytotoxic effect of CD8+T cells on OSCC cells.In-depth studies focusing on elucidating the precise regulatory mechanisms of PERs can facilitate the development of therapeutic strategies targeting PERs,including restoration of PERs expression/activity,targeting PERs-regulated pathways,combination therapies,and chronotherapy.These furnish a theoretical foundation for formulating individualized treatment plans to achieve precise treatment for patients with OSCC.
基金financially supported by the National Natural Science Foundation of China (51804344)the Huxiang Youth Talent Support Program (Grant No. 2019RS2002)+2 种基金the Innovation and Entrepreneurship Project of Hunan Province, China (Grant No. 2018GK5026)the Innovation-Driven Project of Central South University (2020CX027)the Guangdong YangFan Plan for Postdoctor Program。
文摘High ionic conductivity,good electrochemical stability,and satisfactory mechanical property are the crucial factors for polymer solid state electrolytes.Herein,fast ion conductor LiAlSiO_4(LASO) is incorporated into polyethylene oxide(PEO)-based solid-state electrolytes(SSEs).The SSEs containing LASO exhibit enhanced mechanical properties performance compared to pristine PEO-LiTFSI electrolyte.A reduced melting transition temperature of 40.57℃ is enabled by introducing LASO in to PEO-based SSE,which is beneficial to the motion of PEO chain and makes it possible for working at a moderate environment.Coupling with the enhanced motion of PEO,dissociation of the lithium salt,and conducting channel of LASO,the optimized composite polymer SSE exhibits a high ionic conductivity of 4.68×10^(-4),3.16×10^(-4) and 1.62×10^(-4) S cm^(-1) at 60,50 and 40℃,respectively.The corresponding LiFePO_4//Li solid-state battery exhibits high specific capacities of 166,160 and 139 mAh g^(-1) at 0.2 C under 60,40 and 25℃.In addition,it remains 130 mAh g^(-1) at 4.0 C,and maintains 91.74% after 500 cycles at 1.0 C under 60℃.This study provides a simple approach for developing ionic conductor-filled polymer electrolytes in solid-state lithium battery application.
基金The Key Research Program of Frontier SciencesChinese Academy of Sciences under contract No.QYZDJ-SSWDQC034+9 种基金the Grant from Southern Marine Science and Engineering Guangdong Laboratory(Guangzhou)under contract No.GML2019ZD0304the National Natural Science Foundation of China under contract Nos 41521005,41776007 and 41776008the Guangdong Natural Science Foundation under contract No.2020A1515010495the Grant from Chinese Academy of Sciences under contract No.ISEE2021PY01the Guangzhou Science and Technology Program under contract No.201804010373the Youth Science and Technology Innovation Talent of Guangdong Te Zhi Plan under contract No.2019TQ05H519the Pearl River S&T Nova Program of Guangzhou under contract No.201806010091the Rising Star Foundation of South China Sea Institute of Oceanology under contract No.NHXX2019WL0201the Youth Innovation Promotion Association of Chinese Academy of Sciences under contract No.2018378the State Key Laboratory of Tropical Oceanolography Independent Research Program under contract No.LTOZZ2001。
文摘The horizontally variable density stratification and background currents are taken into the variable-coefficent extended Korteweg-de Vries(evKdV)theory to obtain the geographical and seasonal distribution of kinematic parameters of internal solitary waves in the Andaman Sea(AS).The kinematic parameters include phase speed,dispersion parameter,quadratic and cubic nonlinear parameters.It shows that the phase speed and dispersion parameter are mainly determined by the topographic feature and have limited seasonal variation.The maximum phase speed is 2.6 m/s,which occurs in the cool season(November)in the middle of the AS,while the phase speed in the cool season is slightly larger than those in other seasons,up to 11.4%larger than that in the rainy season(July)in the southern AS.The dispersion parameter in the cool season can be 22.3%larger than that in the hot season.The nonlinear parameters have significant seasonal variation,and they can even change their signs at the continental slope in the north of the AS,from season to season.Meanwhile,the algebraic solitons dominate in the AS with minimum amplitudes(aal)ranging from 0.1 m to 102 m,and the maximum aal occurs in the cool season in the southern AS.The effect of the background flow on the parameters is also studied.The background flow has a great influence on the nonlinear parameters,e.g.,the value of cubic nonlinear parameter can be reduced by 1/3 when the background flow is not considered.
文摘Hepatocellular carcinoma(HCC)is an aggressive malignancy that is highly prevalent worldwide.It is often diagnosed at an advanced stage,which poses challenges for curative treatment and leads to an unfavorable prognosis.The introduction of targeted therapy drugs,such as tyrosine kinase inhibitors,and immunotherapeutic drugs,including immune checkpoint inhibitors,has substantially improved the thera-peutic effectiveness for advanced HCC.However,their efficacy remains suboptimal,owing to challenges related to patient responsiveness and drug resistance.To address these challenges,researchers have investigated combination therapies,including targeted immunother-apy,and triple therapies based on targeted immunotherapy,such as a combination of radiotherapy and targeted immunotherapy.In ad-dition,they conducted a comprehensive investigation of potential new targets and drugs,yielding a series of significant findings.This re-view presents an outline of the treatment mechanisms and associated clinical research findings on mainstream targeted therapies,immu-notherapies,and combination therapies.It also summarizes the current status of combination therapies for advanced HCC and anticipates future developments and trends in this field.
文摘After online publication of the article1,the authors noticed one inadvertent mistake in Acknowledgements part that needs to be corrected.The correct grant number for the“National High Level Hospital Clinical Research Funding”should be“2022-CICAMS80102022503”.
基金supported by the Beijing Municipal Science&Technology Commission(Z221100007422011)the CAMS Innovation Fund for Medical Sciences(2024-I2M-ZD-004)+2 种基金National High Level Hospital Clinical Research Funding(2022-CICAMS-80102022503)the Noncommunicable Chronic Diseases-National Science and Technology Major Project(2024ZD0520200 and 2024ZD0520202 to Z.J.W.)the Major Research Plan of National Natural Sciences Foundation of China(92474202 to Z.J.W.).
文摘Despite the lack of predictive biomarkers and a prognostic stratification strategy,immune checkpoint inhibitor(ICI)has shown promise in improving outcomes for patients with limited-stage small cell lung cancer(LS-SCLC).We evaluated the potential of circulating tumor DNA(ctDNA)to dynamically predict outcomes in patients with LS-SCLC receiving concurrent chemoradiotherapy(CCRT)with or without consolidation ICI.We analyzed 490 serial samples collected from 144 LS-SCLC patients at baseline(t0),post-induction chemotherapy and pre-thoracic radiotherapy(t1),post-radiotherapy(t2),and progressive disease(t3).For 44 patients receiving consolidation ICI with serplulimab,an investigational PD-1 inhibitor,ctDNA dynamics during consolidation ICI were also assessed at multiple time points.Patients with undetectable ctDNA after CCRT had good outcomes with or without consolidation ICI,whereas ctDNA-positive patients at t2,indicating poor response to CCRT,derived survival benefit from consolidation ICI.Notably,ctDNA status at t1 appeared more predictive than at t2.A three-level risk stratification strategy integrating t1 ctDNA status with radiological tumor shrinkage identified a high-risk subgroup of patients who achieved significantly improved progression-free survival(PFS)(hazard ratio[HR],0.24;95%confidence interval[CI],0.08-0.75;p=0.014)and overall survival(OS)(HR,0.06;95%CI,0.00-0.42;p=0.001)from consolidation ICI,prioritizing CCRT plus consolidation ICI.Furthermore,maintaining ctDNA negativity during consolidation ICI was associated with favorable outcomes.These data provide valuable insights into the individualized management of LS-SCLC in the era of immunotherapy.
基金supported by the Special Project of the National Ethnic Affairs Commission(Grant No.2024-GMXD-008)titled“Research on the Practical Path of Constructing a Shared Spiritual Home of the Chinese Nation in Ethnic Museums Based on the Concept of Time and Space”,and the General Project of the Hunan Provincial Department of Education(Grant No.24C0257)titled“Research on the Implementation Path of Cross-Cultural Communication in Ethnic Museums from the Perspective of the Chinese National Community”.
文摘From the theoretical perspective of the Marxist conception of space-time,this paper explores its innovative application in the practice of modern museum cultural communication.Through an in-depth interpretation of the Marxist space-time concept combined with theoretical frameworks from museology and communication studies,this study analyzes how contemporary museums employ Marxist space-time theory to innovate their cultural communication practices.The research indicates that the Marxist conception of s pace-time provides important guidance for exhibition design,narrative approaches,and interactive experiences in modern museums,offering new ideas and methods to enhance the effectiveness of museum cultural communication.
基金supported by the Key Research Program of Frontier Sciences,Chinese Academy of Sciences(Grant No.QYZDJ-SSW-DQC034)the Southern Marine Science and Engineering Guangdong Laboratory(Guangzhou)(Grant No.GML2019ZD0304)+8 种基金the National Natural Science Foundation of China(Nos.41521005,41776007 and 41776008)the Chinese Academy of Sciences(Grant No.ISEE2021-PY01)the Guangzhou Science and Technology Program(Grant No.201804010373)the Guangdong Natural Science Foundation(Grant No.2020A1514010495)the Youth Science and Technology Innovation Talent of Guangdong TeZhi Plan(Grant No.2019TQ05H519)the Pearl River S&T Nova Program of Guangzhou(Grant No.201806010091)the Youth Innovation Promotion Association of CAS(Grant No.2018378)the LTO Independent Research Program(Grant No.LTOZZ2001)the Rising Star Foundation of SCSIO(Grant No.NHXX2019WL0201).
文摘Numerous internal solitary waves(ISWs)have been observed in the southern Andaman Sea.In this study,the twodimensional Massachusetts Institute of Technology general circulation model is applied to investigate the dynamics of ISWs and explore the effects of the bottom topography and tidal forcing on the generation and propagation of ISWs in the southern Andaman Sea.The results show that the large-amplitude depression ISWs are mainly generated via the oscillating tidal flow over the sill of the Great Channel,and the generation of ISWs is subject to the lee wave regime.The Dreadnought Bank cannot generate ISWs itself;however,it can enhance the amplitudes of eastward-propagating ISWs generated from sill A,owing to constructive interference of internal tide generation between the sill of the Great Channel and the Dreadnought Bank.The eastward-propagating ISWs generated by the eastern shallow sill near the continental shelf can propagate to the shelf,where they evolve into elevation waves because of the shallow water.Sensitivity runs show that both the semidiurnal and diurnal tides over the sill of the Great Channel can generate ISWs in this area.However,the ISWs generated by diurnal tides are much weaker than those generated by semidiurnal tides.Mixed tidal forcing has no significant effect on the generation of ISWs.
文摘Lipid nanoparticles(LNPs)are nanocarriers composed of four lipid components and can be used for gene therapy,protein replacement,and vaccine development.However,LNPs also face several challenges,such as toxicity,immune activation,and low delivery efficiency.To overcome these challenges,artificial intelligence can be used to optimize the design and formulation of LNPs,as well as to predict their properties and performance.Moreover,antibody-targeted conjugation can be used to enhance the specificity and selectivity of LNPs by attaching an antibody that recognizes a specific antigen on the cell surface to LNPs.
基金financially supported by the National Natural Science Foundation of China (51804344)the Huxiang Youth Talent Support Program (2019RS2002)+2 种基金the Innovation and Entrepreneurship Project of Hunan Province,China (2018GK5026)the Innovation-Driven Project of Central South University (2020CX027)Guangdong Yang Fan Plan for Postdoctor Program
文摘With the proliferation of energy storage and power applications, electric vehicles particularly, solid-state batteries are considered as one of the most promising strategies to address the ever-increasing safety concern and high energy demand of power devices. Here, we demonstrate the Al4B2O9 nanorods-modified poly(ethylene oxide) (PEO)-based solid polymer electrolyte (ASPE) with high ionic conductivity, wide electrochemical window, decent mechanical property and nonflammable performance. Specifically, because of the longer-range ordered Li+ transfer channels conducted by the interaction between Al4B2O9 nanorods and PEO, the optimal ASPE (ASPE-1) shows excellent ionic conductivity of 4.35×10^−1 and 3.1×10^−1 S cm^−1 at 30 and 60℃, respectively. It also has good electrochemical stability at 60℃ with a decomposition voltage of 5.1 V. Besides, the assembled LiFePO4//Li cells show good cycling performance, delivering 155 mA h g−1 after 300 cycles at 1 C under 60℃, and present excellent low temperature adaptability, retaining over 125 mA h g^−1 after 90 cycles at 0.2 C under 30℃. These results verify that the addition of Al4B2O9 nanorods can effectively promote the integrated performance of solid polymer electrolyte.
基金funded by National Natural Sciences Foundation Key Program(grant number:82173348)Chinese Academy of Medical Sci-ences Innovation Fund for Medical Sciences(grant number:2021-1-I2M-1-012)the Special Research Fund for Central Universities,Peking Union Medical College(grant number:3332023133).
文摘Background:Liquid biopsy-based biomarkers,including circulating tumor DNA(ctDNA)and blood tumor muta-tional burden(bTMB),are recognized as promising predictors of prognoses and responses to immune checkpoint inhibitors(ICIs),despite insufficient sensitivity of single biomarker detection.This research aims to determine whether the combinatorial utility of longitudinal ctDNA with bTMB analysis could improve the prognostic and predictive effects.Methods:This prospective two-center cohort trial,consisting of discovery and validation datasets,enrolled unre-sectable locally advanced non-small-cell lung cancer(LA-NSCLC)patients and assigned them to chemoradiother-apy(CRT)or CRT+consolidation ICI cohorts from 2018 to 2022.Blood specimens were collected pretreatment,4 weeks post-CRT,and at progression to assess bTMB and ctDNA using 486-gene next-generation sequencing.DynamicΔbTMB was calculated as post-CRT bTMB minus baseline bTMB levels.Decision curve analyses were performed to calculate Concordance index(C-index).Results:One hundred twenty-eight patients were enrolled.In the discovery dataset(n=73),patients treated with CRT and consolidation ICI had significantly longer overall survival(OS;median not reached[NR]vs 20.2 months;P<0.001)and progression-free survival(PFS;median 25.2 vs 11.4 months;P=0.011)than those without ICI.Longitudinal analysis demonstrated a significant decrease in ctDNA abundance post-CRT(P<0.001)but a relative increase with disease progression.Post-CRT detectable residual ctDNA correlated with significantly shorter OS(median 18.3 months vs NR;P=0.001)and PFS(median 7.3 vs 25.2 months;P<0.001).For patients with residual ctDNA,consolidation ICI brought significantly greater OS(median NR vs 14.8 months;P=0.005)and PFS(median 13.8 vs 6.2 months;P=0.028)benefit,but no significant difference for patients with ctDNA clearance.DynamicΔbTMB was predictive of prognosis.Patients with residual ctDNA and increasedΔbTMB(ΔbTMB>0)had significantly worse OS(median 9.0 vs 23.0 months vs NR;P<0.001)and PFS(median 3.4 vs 7.3 vs 25.2 months;P<0.001).The combinatorial model integrating post-CRT ctDNA withΔbTMB had optimal predictive effects on OS(C-index=0.723)and PFS(C-index=0.693),outperforming individual features.In the independent validation set,we confirmed residual ctDNA predicted poorer PFS(median 50.8 vs 14.3 months;P=0.026)but identified more consolidation ICI benefit(median NR vs 8.3 months;P=0.039).The combined model exhibited a stable predictive advantage(C-index=0.742 for PFS).Conclusions:The multiparameter assay integrating qualitative residual ctDNA testing with quantitativeΔbTMB dynamics improves patient prognostic risk stratification and efficacy predictions,allowing for personalized con-solidation therapy for LA-NSCLC.
基金Special thanks to Andrew Barker for his previous work on this project and to Zhenbi Su,Kendall Hunter and Robin Shandas for helpful discussions and acquiring clinical data for our model.
文摘We introduce and study a parallel domain decomposition algorithm for the simulation of blood flow in compliant arteries using a fully-coupled system of nonlinear partial differential equations consisting of a linear elasticity equation and the incompressible Navier-Stokes equations with a resistive outflow boundary condition.The system is discretized with a finite element method on unstructured moving meshes and solved by a Newton-Krylov algorithm preconditioned with an overlapping restricted additive Schwarz method.The resistive outflow boundary condition plays an interesting role in the accuracy of the blood flow simulation and we provide a numerical comparison of its accuracy with the standard pressure type boundary condition.We also discuss the parallel performance of the implicit domain decomposition method for solving the fully coupled nonlinear system on a supercomputer with a few hundred processors.
基金supported by the National Natural Science Foundation of China(Nos.82274379 and 82474371)the Beijing Natural Science Foundation-Daxing Innovation Foundation Joint Project(No.L246067,China).
文摘Obesity-prone(OP)individuals exhibit an intrinsic predisposition to obesity and associated metabolic disorders,and early intervention in this population holds significant clinical value;however,the underlying mechanisms driving this susceptibility remain largely obscure.This study enrolled 46 OP subjects without diagnosed metabolic diseases and 35 healthy controls.Our findings revealed that,despite not reaching obesity diagnoses,OP subjects exhibited significant metabolic disturbances strongly associated with gut microbiota dysbiosis.They also displayed disturbed bile acid(BA)profiles,with depleted glycodeoxycholic acid(GDCA)identified as the most potent discriminator between the OP and healthy controls.Fecal microbiota transplantation(FMT)recapitulated metabolic dysfunction and BA pool remodeling,mediated by dysregulated hepatic expression of BA synthesis genes of Cyp8a1,Cyp7a1,and Cyp7b1.Notably,FMT-OP mice also phenocopied the diminished GDCA levels observed in OP subjects.GDCA supplementation in obese mice markedly improved body weight,hepatic steatosis,and metabolic dysfunction.Mechanistically,GDCA exerted anti-obesity effects by activating the TGR5 signaling,which enhanced brown adipose tissue(BAT)thermogenesis and stimulated ileal glucagon-like peptide-1(GLP-1)secretion,thereby ameliorating obesity and associated metabolic dysregulation.Thus,these findings indicate that gut microbiota-driven dysregulation of BA signaling,particularly impaired TGR5 activation due to diminished GDCA,underlies glycolipid metabolic dysfunction in OP individuals.
