Metabolic reprogramming reshapes the tumor microenvironment(TME)and facilitates metastasis,but its molecular mechanisms remain incompletely understood.Here,we identified enolase 2(ENO2),a critical glycolytic enzyme,as...Metabolic reprogramming reshapes the tumor microenvironment(TME)and facilitates metastasis,but its molecular mechanisms remain incompletely understood.Here,we identified enolase 2(ENO2),a critical glycolytic enzyme,as being associated with lymphatic metastasis in head and neck squamous cell carci-noma(HNSCC).Mechanistically,phosphoenolpyruvate(PEP),the metabolite secreted by ENO2-expressing HNSCC cells,drove histone H3 lysine 18 lactylation(H3K18la)-mediated M2 polarization in macrophages,which,in turn,enhanced the epithelial-mesenchymal transition(EMT)and invasiveness of HNSCC cells.Pharmacological inhibition of ENO2 with POMHEX effectively reversed M2 macrophage polarization and inhibited HNSCC lymphatic metastasis.Collectively,our findings underscore the prog-nostic significance of ENO2 and highlight its potential as a therapeutic target for metastatic HNSCC.Furthermore,we reveal a previously underappreciated role of PEP in modulating the tumor immune microenvironment and tumor metastasis via epigenetic modification.展开更多
Circular RNAs(circRNAs)are a type of non coding RNA that possess unique single stranded circular structures formed through reverse splicing mechanisms.Due to the lack of a free end that is typically susceptible to deg...Circular RNAs(circRNAs)are a type of non coding RNA that possess unique single stranded circular structures formed through reverse splicing mechanisms.Due to the lack of a free end that is typically susceptible to degradation by nucleases,circular RNAs exhibit resistance to ribonuclease R,making them highly stable in eukaryotic cells.The complex relationship between circRNA dysregulation and various pathophysiological conditions,especially cancer.Tumor microenvironment(TME)is a collective term for various components surrounding tumors and is an important factor affecting tumor development.Simultaneous infiltration of TME by different types of immune cells;These immune cells interact with the TME,collectively forming the so-called“tumor immune microenvironment”.The complex interactions between tumor cells and TME profoundly affect the behavior of malignant tumors,and circRNAs derived from tumor cells and TME cell components have become important mediators of immune response and evasion within the TME.CircRNAs can directly or indirectly regulate immune cells,thereby modulating anti-tumor immunity.This review highlights how circRNAs,especially those encapsulated in extracellular vesicles like exosomes,influence the differentiation,chemotaxis,and anti-tumor immune functions of immune cells within the TME.Metabolic reprogramming plays an important role in this process.The process of circRNAs regulating tumor immunity is affected by multiple factors,such as hypoxia and viral infection.This review emphasizes the roles of the interaction between circRNAs and the TME in tumor immune regulation and prospects the guiding significance of circRNAs in tumor immune checkpoint therapy.展开更多
In this article,we study the meromorphic solutions of the following non-linear differential equation■where n and k are integers with n≥k≥3,P_(d)(z,f)is a differential polynomial in f of degree d≤n−1,p′js andα′j...In this article,we study the meromorphic solutions of the following non-linear differential equation■where n and k are integers with n≥k≥3,P_(d)(z,f)is a differential polynomial in f of degree d≤n−1,p′js andα′js are non-zero constants.We obtain the expressions of meromorphic solutions of the above equations under some restrictions onα′js.Some examples are given to illustrate the possibilities of our results.展开更多
Objective:To investigate current status of diagnosis and treatment of bladder cancer in China.Methods:A database was generated by Chinese Bladder Cancer Consortium(CBCC).From January 2007 to December 2012,14,260 cases...Objective:To investigate current status of diagnosis and treatment of bladder cancer in China.Methods:A database was generated by Chinese Bladder Cancer Consortium(CBCC).From January 2007 to December 2012,14,260 cases from 44 CBCC centers were included.Data of diagnosis,treatment and pathology were collected.Results:The average age was 63.5 year-old and most patients were male(84.3%).The most common histologic types were urothelial carcinoma(91.4%),adenocarcinoma(1.8%),and squamous carcinoma(1.9%).According to 1973 and 2004 WHO grading system,42.0%,41.0%,and 17.0% of patients were grade 1,2,and 3,and 16.0%,48.7%,and 35.3% of patients were papillary urothelial neoplasms of low malignant potential,low,and high grade,respectively.Non-muscle invasive bladder cancer(NMIBC)and muscle invasive bladder cancer(MIBC)were 25.2% and 74.1%,respectively(0.8% not clear).Carcinoma in situ was only 2.4%.Most patients were diagnosed by white-light cystoscopy with biopsy(74.3%).Fluorescence and narrow band imaging cystoscopy had additional detection rate of 1.0% and 4.0%,respectively.Diagnostic transurethral resection(TUR)provided detection rate of 16.9%.Most NMIBCs were treated with TUR(89.2%).After initial TUR,2.6%accepted second TUR,and 45.7%,69.9%,and 58.7% accepted immediate,induced,and maintenance chemotherapy instillation,respectively.Most MIBCs were treated with radical cystectomy(RC,59.7%).Laparoscopic RCs were 35.1%,while open RC 63.4%.Extended and standard pelvic lymph node dissection were 7% and 66%,respectively.Three most common urinary diversions were orthotopic neobladder(44%),ileal conduit(31%),and ureterocutaneostomy(23%).Only 2.3% of patients accepted neo-adjuvant chemotherapy and only 18%of T3 and T4 patients accepted adjuvant chemotherapy.Conclusion:Disease characteristics are similar to international reports,while differences of diagnosis and treatment exist.This study can provide evidences for revisions of the guideline on bladder cancer in China.展开更多
Replacing the conventional carbonate electrolyte by solid-state electrolyte (SSE) will offer improved safety for lithium-ion batteries.To further improve the energy density,Silicon (Si) is attractive for next generati...Replacing the conventional carbonate electrolyte by solid-state electrolyte (SSE) will offer improved safety for lithium-ion batteries.To further improve the energy density,Silicon (Si) is attractive for next generation solid-state battery (SSB) because of its high specific capacity and low cost.High energy density and safe Si-based SSB,however,is plagued by large volume change that leads to poor mechanical stability and slow lithium ions transportation at the multiple interfaces between Si and SSE.Herein,we designed a self-integrated and monolithic Si/two dimensional layered T_(3)C_(2)T_(x)(MXene,T_(x) stands for terminal functional groups) electrode architecture with interfacial nitrogen engineering.During a heat treatment process,the polyacrylonitrile not only converts into amorphous carbon (a-C) that shells Si but also forms robust interfacial nitrogen chemical bonds that anchors Si and MXene.During repeated lithiation and delithiation processes,the robust interfacial engineered Si/MXene configuration enhances the mechanical adhesion between Si and MXene that improves the structure stability but also contributes to form stable solid-electrolyte interphase (SEI).In addition,the N-MXene provides fast lithium ions transportation pathways.Consequently,the Si/MXene with interfacial nitrogen engineering (denoted as Si-N-MXene) deliveres high-rate performance with a specific capacity of 1498 m Ah g^(-1) at a high current of 6.4 A g^(-1).A Si-N-MXene/NMC full cell exhibited a capacity retention of 80.5%after 200 cycles.The Si-N-MXene electrode is also applied to SSB and shows a relative stable cycling over 100 cycles,demonstrating the versatility of this concept.展开更多
It is urgent to develop high-performance cathode materials for the emerging aqueous zinc-ion batteries with a facile strategy and optimize the related components.Herein,a Ca0.23V2O5·0.95 H2O nanobelt cathode mate...It is urgent to develop high-performance cathode materials for the emerging aqueous zinc-ion batteries with a facile strategy and optimize the related components.Herein,a Ca0.23V2O5·0.95 H2O nanobelt cathode material with a rather large interlayer spacing of 13.0 A is prepared via a one-step hydrothermal approach.The battery with this cathode material and 3 M Zn(CF3SO3)2 electrolyte displays high specific capacity(355.2 mAh g^(-1)at 0.2 A g^(-1)),great rate capability(240.8 mAh g^(-1)at 5 A g^(-1)),and excellent cyclability(97.7%capacity retention over 2000 cycles).Such superior performances are ascribed to fast electrochemical kinetics,outstanding electrode/electrolyte interface stability,and nearly dendrite-free characteristic.Instead,when ZnSO4 or Zn(ClO4)2 is used to replace Zn(CF3SO3)2,the electrochemical performances become much inferior,due to the slow electrochemical kinetics,inhomogeneous Zn stripping/plating process,and the formation of large dendrites and byproducts.This work not only discloses a high-performance cathode material for aqueous zinc-ion batteries but also offers a reference for the choice of electrolyte salt.展开更多
Thanks to low cost,high safety,and large energy density,aqueous zinc-ion batteries have attracted tremendous interest worldwide.However,it remains a challenge to develop high-performance cathode materials with an appr...Thanks to low cost,high safety,and large energy density,aqueous zinc-ion batteries have attracted tremendous interest worldwide.However,it remains a challenge to develop high-performance cathode materials with an appropriate method that is easy to realize massive production.Herein,we use a molten salt method to synthesize nanostructured manganese oxides.The crystalline phases of the manganese oxides can be tuned by changing the amount of reduced graphene oxide added to the reactant mixture.It is found that the α-MnO_(2)/Mn_(2)O_(3) nanocomposite with the largest mass ratio of Mn_(2)O_(3) delivers the best electrochemical performances among all the products.And its rate capability and cyclability can be significantly improved by modifying the Zn anode with carbon black coating and nanocellulose binder.In this situation,the nanocomposite can deliver high discharging capacities of 322.1 and 213.6 mAh g^(-1) at 0.2 and 3 Ag^(-1),respectively.After 1000 cycles,it can retain 86.2% of the capacity at the 2 nd cycle.Thus,this nanocomposite holds great promise for practical applications.展开更多
Li metal has been regarded as the holy grail for the next-generation Li-ion battery.Li dendrites issues,however,impede its practical application.In general,prolonging the sand time of Li nucleation and regulating homo...Li metal has been regarded as the holy grail for the next-generation Li-ion battery.Li dendrites issues,however,impede its practical application.In general,prolonging the sand time of Li nucleation and regulating homogeneous Li^(+) flux are effective approaches to suppress the dendrites formation and growth.Regarding this view,a functional polypropylene (PP) separator is developed to regulate ion transportation via a newly designed Li-based metal-organic framework (Li-MOF) coating.The Li-MOF crystallizes in the orthorhombic space group P212121 and features a double-walled three-dimensional (3D) structure with 1D channels.The well-defined intrinsic nanochannels of Li-MOF and the steric-hinerance effect both restrict free migration of anions,contributing to a high Li^(+) transference number of 0.65,which improve the Sand time of Li nucleation.Meanwhile,the Li-MOF coating with uniform porous structure promotes homogeneous Li^(+) flux at the surface of Li metal.Furthermore,the Li-MOF coating layer helps to build solid-electrolyte interphase (SEI) layer that comprises of inorganic Li F and Li_(3)N,which further prohibits the dendrites growth.Consequently,a highly stable Li plating/stripping cycling for over 1000 h is achieved.The functional separator also enables high-performance full lithium metal cells,the high-rate and long-stable cycling performance of Li Ni_(0.8)Mn_(0.1)Co_(0.1)(NMC811)-Li and Li Co O_(2)(LCO)-Li cells further demonstrate the feasibility of this concept.展开更多
Spinel LiNi_(0.5)Mn_(1.5)O_(4)(LNMO),a 5 V class high voltage cathode,has been regarded as an attractive candidate to further improve the energy density of lithium-ion battery.The issue simultaneously enabling side st...Spinel LiNi_(0.5)Mn_(1.5)O_(4)(LNMO),a 5 V class high voltage cathode,has been regarded as an attractive candidate to further improve the energy density of lithium-ion battery.The issue simultaneously enabling side stability and maintaining high interfacial kinetics,however,has not yet been resolved.Herein,we design a coherent Li_(1.3)A_(l0.3)Ti_(1.7)(PO)_(4)(LATP)layer that is crystally connected to the spinel LNMO host lattices,which offers fast lithium ions transportation as well as enhances the mechanical stability that prevents the particle fracture.Furthermore,the inactive Li_(3)BO_(3)(LBO)coating layer inhibits the corrosion of transition metals and continuous side reactions.Consequently,the coherent-engineered LNMO-LATPLBO cathode material exhibits superior electrochemical cycling stability in a window of 3.0–5.0 V,for example a high-capacity retention that is 89.7%after 500 cycles at 200 m A g-1obtained and enhanced rate performance(85.1 m A h g^(-1)at 800 m A g^(-1))when tested with a LiPF6-based carbonate electrolyte.Our work presents a new approach of engineering 5 V class spinel oxide cathode that combines interfacial coherent crystal lattice design and surface coating.展开更多
Recently,aqueous zinc-ion batteries with intrinsic safety,low cost,and environmental benignity have attracted tremendous research interest.However,zinc dendrites,harmful side reactions,and zinc metal corrosion stand i...Recently,aqueous zinc-ion batteries with intrinsic safety,low cost,and environmental benignity have attracted tremendous research interest.However,zinc dendrites,harmful side reactions,and zinc metal corrosion stand in the way.Herein,we use lepidocrocite-type sodium titanate hollow microspheres assembled by nanotubes to constitute an artificial solid electrolyte interface layer on the zinc metal electrode.Thanks to the hierarchical structure with abundant open voids,negative-charged layered framework,low hydrophilicity,electrically insulting nature,and large ionic conductivity,the sodium titanate coating layer can effectively homogenize the electric field,promote the Zn^(2+)ion transfer,guide the Zn^(2+)ion flux,reduce the desolvation barrier,improve the exchange current density,and accommodate the plated zinc metal.Consequently,this coating layer can effectively suppress zinc dendrites and other unfavorable effects.With this coating layer,the Zn//Zn symmetric cell is able to provide an impressive cumulative zinc plating capacity of 1375 m Ah cm^(-2) at a current density of 5 m A cm^(-2).This coating layer also contributes to significantly improved electrochemical performances of Zn//MnO_(2) battery and zincion hybrid capacitor.This work offers new insights into the modifications of zinc metal electrodes.展开更多
In this article, we consider the non-linear difference equation(f(z + 1)f(z)-1)(f(z)f(z-1)-1) =P(z, f(z))/Q(z, f(z)),where P(z, f(z)) and Q(z, f(z)) are relatively prime polynomials in f(z) with rational coefficients....In this article, we consider the non-linear difference equation(f(z + 1)f(z)-1)(f(z)f(z-1)-1) =P(z, f(z))/Q(z, f(z)),where P(z, f(z)) and Q(z, f(z)) are relatively prime polynomials in f(z) with rational coefficients. For the above equation, the order of growth, the exponents of convergence of zeros and poles of its transcendental meromorphic solution f(z), and the exponents of convergence of poles of difference △f(z) and divided difference △f(z)/f(z)are estimated. Furthermore, we study the forms of rational solutions of the above equation.展开更多
Osteosarcoma is a kind of bone tumor with highly proliferative and invasive properties,a high incidence of pulmonary metastasis and a poor prognosis.Chemotherapy is the mainstay of treatment for osteosarcoma.Currently...Osteosarcoma is a kind of bone tumor with highly proliferative and invasive properties,a high incidence of pulmonary metastasis and a poor prognosis.Chemotherapy is the mainstay of treatment for osteosarcoma.Currently,there are no molecular targeted drugs approved for osteosarcoma treatment,particularly effective drugs for osteosarcoma with pulmonary metastases.It has been reported that fibroblast activation protein alpha(FAPa)is upregulated in osteosarcoma and critically associated with osteosarcoma progression and metastasis,demonstrating that FAPa-targeted agents might be a promising therapeutic strategy for osteosarcoma.In the present study,we reported that the FAPa-activated vinblastine prodrug Z-GP-DAVLBH exhibited potent antitumor activities against FAPa-positive osteosarcoma cells in vitro and in vivo.Z-GP-DAVLBH inhibited the growth and induced the apoptosis of osteosarcoma cells.Importantly,it also decreased the migration and invasion capacities and reversed epithelial-mesenchymal transition(EMT)of osteosarcoma cells in vitro and suppressed pulmonary metastasis of osteosarcoma xenografts in vivo.Mechanistically,Z-GP-DAVLBH suppressed the AXL/AKT/GSK-3β/β-catenin pathway,leading to inhibition of the growth and metastatic spread of osteosarcoma cells.These findings demonstrate that Z-GP-DAVLBH is a promising agent for the treatment of FAPa-positive osteosarcoma,particularly osteosarcoma with pulmonary metastases.展开更多
Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer(LNM-CRC) cel...Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer(LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha(FAPα) expression in LNM-CRC cells. Gain-or loss-function experiments demonstrated that FAPα enhanced tumor cell migration, invasion, epithelial-mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAPα in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis(CRCLNM). Z-GP-DAVLBH, a FAPα-activated prodrug, inhibited CRCLNM by targeting FAPα-positive LNM-CRC cells. Our study highlights the role of FAPα in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM.展开更多
With the advantages of intrinsic safety,good affordability,environmental friendliness,moderate energy density,and large power density,aqueous zinc ion batteries(AZIBs)have gained considerable research interest.However...With the advantages of intrinsic safety,good affordability,environmental friendliness,moderate energy density,and large power density,aqueous zinc ion batteries(AZIBs)have gained considerable research interest.However,zinc dendrites,hydrogen evolution,inert byproducts,and zinc metal corrosion severely hinder practical applications of AZIBs.In order to address these issues,many research works have been carried out to modify the interface between zinc metal anode and aqueous electrolyte.In fact,the interface engineering takes effect at the surface and near the surface of separator.However,a specialized review on the separators of AZIBs is still lacking.Herein,basic requirements of separators and recent advances on the modification strategies including employment of functional groups,establishment of surface coatings,construction of hybrid architectures,regulations of porosity,and utilization of bipolar membrane are reviewed.Besides,the perspectives for further investigations on the separators of AZIBs are outlined.This review could offer useful guidance for the future explorations of separators for AZIBs.展开更多
With low cost and high safety,aqueous zinc-based batteries have received considerable interest.Nevertheless,the excess utilization of zinc metal in the anodes of these batteries reduces energy density and increases co...With low cost and high safety,aqueous zinc-based batteries have received considerable interest.Nevertheless,the excess utilization of zinc metal in the anodes of these batteries reduces energy density and increases costs.Herein,an ultrathin electrode of approximately 6.2μm thick is constructed by coating Ti_(3)C_(2)T_(x)/nanocellulose hybrid onto a stainless steel foil.This electrode is used as the Zn-free anode for aqueous hybrid Zn-Na battery,in which,a concentrated electrolyte is used to improve electrochemical reversibility.The Ti_(3)C_(2)T_(x)/nanocellulose coating is found to improve the electrolyte wettability,facilitate desolvation process of hydrated Zn^(2+) ions,lower nucleation overpotential,improve zinc plating kinetics,guide horizontal zinc plating along the Zn(002)facet,and inhibit parasitic side reactions.It is also found that the Na_(3)V_(2)(PO_(4))_(3) cathode material adopts a highly reversible Zn^(2+)/Na^(+)co-intercalation charge storage mechanism in this system.Thanks to these benefits,the assembled hybrid Zn-Na battery exhibits excellent rate capability,superior cyclability,and good anti-freezing ability.This work provides a new concept of electrode design for electrochemical energy storage.展开更多
Solid-state batteries(SSBs)will potentially offer increased energy density and,more importantly,improved safety for next generation lithium-ion(Li-ion)batteries.One enabling technology is solid-state composite cathode...Solid-state batteries(SSBs)will potentially offer increased energy density and,more importantly,improved safety for next generation lithium-ion(Li-ion)batteries.One enabling technology is solid-state composite cathodes with high operating voltage and area capacity.Current composite cathode manufacturing technologies,however,suffer from large interfacial resistance and low active mass loading that with excessive amounts of polymer electrolytes and conductive additives.Here,we report a liquidphase sintering technology that offers mixed ionic-electronic interphases and free-standing electrode architecture design,which eventually contribute to high area capacity.A small amount(~4 wt.%)of lithium hydroxide(LiOH)and boric acid(H_(3)BO_(3))with low melting point are utilized as sintering additives that infiltrate into single-crystal Ni-rich LiNi_(0.8)Mn_(0.1)Co_(0.1)(NMC811)particles at a moderately elevated temperature(~350℃)in a liquid state,which not only enable intimate physical contact but also promote the densification process.In addition,the liquid-phase additives react and transform to ionic-conductive lithium boron oxide,together with the indium tin oxide(ITO)nanoparticle coating,mixed ionic-electronic interphases of composite cathode are successfully fabricated.Furthermore,the liquid-phase sintering performed at high-temperature(~800℃)also enables the fabrication of highly dense and thick composite cathodes with a novel free-standing architecture.The promising performance characteristics of such composite cathodes,for example,delivering an area capacity above 8 mAh·cm^(−2) within a wide voltage window up to 4.4 V,open new opportunities for SSBs with a high energy density of 500 Wh·kg^(−1) for safer portable electronic and electrical transport.展开更多
基金supported by grants from the National Natural Science Foundation of China(82204428,U24A20815,82304526,82204427,82201001,82430108,82293681(82293680),82273941)the National High-level Personnelof Special Support Program(to Dongmei Zhang and Minfeng Chen)+5 种基金the Natural Science Foundation of Guangdong Province(2023A1515010361 and 2022A1515011813)the Guangdong Basic and Applied Basic Research Foundation(2024B1515020098)the Science and Technology Program of Guangzhou(SL2024A04J00410,SL2024A04J00374,SL2024A04J00280)the Fundamental Research Funds for The Central Universities(21624103)the Science and Technology Projects in Guangzhou(2023A03J1030,202201010173,202102070001)the Clinical Frontier Technology Program of the First Affiliated Hospital of Jinan University,China(JNU1AF-CFTP-2022-a01210).
文摘Metabolic reprogramming reshapes the tumor microenvironment(TME)and facilitates metastasis,but its molecular mechanisms remain incompletely understood.Here,we identified enolase 2(ENO2),a critical glycolytic enzyme,as being associated with lymphatic metastasis in head and neck squamous cell carci-noma(HNSCC).Mechanistically,phosphoenolpyruvate(PEP),the metabolite secreted by ENO2-expressing HNSCC cells,drove histone H3 lysine 18 lactylation(H3K18la)-mediated M2 polarization in macrophages,which,in turn,enhanced the epithelial-mesenchymal transition(EMT)and invasiveness of HNSCC cells.Pharmacological inhibition of ENO2 with POMHEX effectively reversed M2 macrophage polarization and inhibited HNSCC lymphatic metastasis.Collectively,our findings underscore the prog-nostic significance of ENO2 and highlight its potential as a therapeutic target for metastatic HNSCC.Furthermore,we reveal a previously underappreciated role of PEP in modulating the tumor immune microenvironment and tumor metastasis via epigenetic modification.
基金supported by the National Natural Science Foundation of China(82103298)Basic Research Project of Science and Technology Cooperation in Qiandongnan Prefecture(No.2023-16).
文摘Circular RNAs(circRNAs)are a type of non coding RNA that possess unique single stranded circular structures formed through reverse splicing mechanisms.Due to the lack of a free end that is typically susceptible to degradation by nucleases,circular RNAs exhibit resistance to ribonuclease R,making them highly stable in eukaryotic cells.The complex relationship between circRNA dysregulation and various pathophysiological conditions,especially cancer.Tumor microenvironment(TME)is a collective term for various components surrounding tumors and is an important factor affecting tumor development.Simultaneous infiltration of TME by different types of immune cells;These immune cells interact with the TME,collectively forming the so-called“tumor immune microenvironment”.The complex interactions between tumor cells and TME profoundly affect the behavior of malignant tumors,and circRNAs derived from tumor cells and TME cell components have become important mediators of immune response and evasion within the TME.CircRNAs can directly or indirectly regulate immune cells,thereby modulating anti-tumor immunity.This review highlights how circRNAs,especially those encapsulated in extracellular vesicles like exosomes,influence the differentiation,chemotaxis,and anti-tumor immune functions of immune cells within the TME.Metabolic reprogramming plays an important role in this process.The process of circRNAs regulating tumor immunity is affected by multiple factors,such as hypoxia and viral infection.This review emphasizes the roles of the interaction between circRNAs and the TME in tumor immune regulation and prospects the guiding significance of circRNAs in tumor immune checkpoint therapy.
基金supported by the National Natural Science Foundation of China(No.12001117)the Guangdong Basic and Applied Basic Research Foundation(No.2021A1515110654).
文摘In this article,we study the meromorphic solutions of the following non-linear differential equation■where n and k are integers with n≥k≥3,P_(d)(z,f)is a differential polynomial in f of degree d≤n−1,p′js andα′js are non-zero constants.We obtain the expressions of meromorphic solutions of the above equations under some restrictions onα′js.Some examples are given to illustrate the possibilities of our results.
文摘Objective:To investigate current status of diagnosis and treatment of bladder cancer in China.Methods:A database was generated by Chinese Bladder Cancer Consortium(CBCC).From January 2007 to December 2012,14,260 cases from 44 CBCC centers were included.Data of diagnosis,treatment and pathology were collected.Results:The average age was 63.5 year-old and most patients were male(84.3%).The most common histologic types were urothelial carcinoma(91.4%),adenocarcinoma(1.8%),and squamous carcinoma(1.9%).According to 1973 and 2004 WHO grading system,42.0%,41.0%,and 17.0% of patients were grade 1,2,and 3,and 16.0%,48.7%,and 35.3% of patients were papillary urothelial neoplasms of low malignant potential,low,and high grade,respectively.Non-muscle invasive bladder cancer(NMIBC)and muscle invasive bladder cancer(MIBC)were 25.2% and 74.1%,respectively(0.8% not clear).Carcinoma in situ was only 2.4%.Most patients were diagnosed by white-light cystoscopy with biopsy(74.3%).Fluorescence and narrow band imaging cystoscopy had additional detection rate of 1.0% and 4.0%,respectively.Diagnostic transurethral resection(TUR)provided detection rate of 16.9%.Most NMIBCs were treated with TUR(89.2%).After initial TUR,2.6%accepted second TUR,and 45.7%,69.9%,and 58.7% accepted immediate,induced,and maintenance chemotherapy instillation,respectively.Most MIBCs were treated with radical cystectomy(RC,59.7%).Laparoscopic RCs were 35.1%,while open RC 63.4%.Extended and standard pelvic lymph node dissection were 7% and 66%,respectively.Three most common urinary diversions were orthotopic neobladder(44%),ileal conduit(31%),and ureterocutaneostomy(23%).Only 2.3% of patients accepted neo-adjuvant chemotherapy and only 18%of T3 and T4 patients accepted adjuvant chemotherapy.Conclusion:Disease characteristics are similar to international reports,while differences of diagnosis and treatment exist.This study can provide evidences for revisions of the guideline on bladder cancer in China.
基金supported by the National Natural Science Foundation of China(51902165,12004145,52072323)the Natural Science Foundation of Jiangsu Province(BK20200800)+2 种基金the Natural Science Foundation of Jiangxi Province(20192ACBL20048)the Jiangxi Provincial Natural Science Foundation(20212BAB214032)the Nanjing Science&Technology Innovation Project for Personnel Studying Abroad。
文摘Replacing the conventional carbonate electrolyte by solid-state electrolyte (SSE) will offer improved safety for lithium-ion batteries.To further improve the energy density,Silicon (Si) is attractive for next generation solid-state battery (SSB) because of its high specific capacity and low cost.High energy density and safe Si-based SSB,however,is plagued by large volume change that leads to poor mechanical stability and slow lithium ions transportation at the multiple interfaces between Si and SSE.Herein,we designed a self-integrated and monolithic Si/two dimensional layered T_(3)C_(2)T_(x)(MXene,T_(x) stands for terminal functional groups) electrode architecture with interfacial nitrogen engineering.During a heat treatment process,the polyacrylonitrile not only converts into amorphous carbon (a-C) that shells Si but also forms robust interfacial nitrogen chemical bonds that anchors Si and MXene.During repeated lithiation and delithiation processes,the robust interfacial engineered Si/MXene configuration enhances the mechanical adhesion between Si and MXene that improves the structure stability but also contributes to form stable solid-electrolyte interphase (SEI).In addition,the N-MXene provides fast lithium ions transportation pathways.Consequently,the Si/MXene with interfacial nitrogen engineering (denoted as Si-N-MXene) deliveres high-rate performance with a specific capacity of 1498 m Ah g^(-1) at a high current of 6.4 A g^(-1).A Si-N-MXene/NMC full cell exhibited a capacity retention of 80.5%after 200 cycles.The Si-N-MXene electrode is also applied to SSB and shows a relative stable cycling over 100 cycles,demonstrating the versatility of this concept.
基金the financial support from the National Natural Science Foundation of China(No.51902165)the Natural Science Foundation of Jiangsu Province(No.BK20170917)+2 种基金the Scientific Research Foundation for High-Level Talents of Nanjing Forestry University(No.GXL2016023)the Program of High-Level Talents in Six Industries of Jiangsu Province(No.XCL-040)the Jiangsu Specially-Appointed Professor Program。
文摘It is urgent to develop high-performance cathode materials for the emerging aqueous zinc-ion batteries with a facile strategy and optimize the related components.Herein,a Ca0.23V2O5·0.95 H2O nanobelt cathode material with a rather large interlayer spacing of 13.0 A is prepared via a one-step hydrothermal approach.The battery with this cathode material and 3 M Zn(CF3SO3)2 electrolyte displays high specific capacity(355.2 mAh g^(-1)at 0.2 A g^(-1)),great rate capability(240.8 mAh g^(-1)at 5 A g^(-1)),and excellent cyclability(97.7%capacity retention over 2000 cycles).Such superior performances are ascribed to fast electrochemical kinetics,outstanding electrode/electrolyte interface stability,and nearly dendrite-free characteristic.Instead,when ZnSO4 or Zn(ClO4)2 is used to replace Zn(CF3SO3)2,the electrochemical performances become much inferior,due to the slow electrochemical kinetics,inhomogeneous Zn stripping/plating process,and the formation of large dendrites and byproducts.This work not only discloses a high-performance cathode material for aqueous zinc-ion batteries but also offers a reference for the choice of electrolyte salt.
基金funded by the National Natural Science Foundation of China(No.51902165)the Natural Science Foundation of Jiangsu Province(No.BK20170917)+2 种基金the Scientific Research Foundation for High-Level Talents of Nanjing Forestry University(No.GXL2016023)the Program of High-Level Talents in Six Industries of Jiangsu Province(No.XCL-040)the Jiangsu Specially-Appointed Professor Program。
文摘Thanks to low cost,high safety,and large energy density,aqueous zinc-ion batteries have attracted tremendous interest worldwide.However,it remains a challenge to develop high-performance cathode materials with an appropriate method that is easy to realize massive production.Herein,we use a molten salt method to synthesize nanostructured manganese oxides.The crystalline phases of the manganese oxides can be tuned by changing the amount of reduced graphene oxide added to the reactant mixture.It is found that the α-MnO_(2)/Mn_(2)O_(3) nanocomposite with the largest mass ratio of Mn_(2)O_(3) delivers the best electrochemical performances among all the products.And its rate capability and cyclability can be significantly improved by modifying the Zn anode with carbon black coating and nanocellulose binder.In this situation,the nanocomposite can deliver high discharging capacities of 322.1 and 213.6 mAh g^(-1) at 0.2 and 3 Ag^(-1),respectively.After 1000 cycles,it can retain 86.2% of the capacity at the 2 nd cycle.Thus,this nanocomposite holds great promise for practical applications.
基金the financial support provided by the National Natural Science Foundation of China (Nos. 21971113, 22175094, 51902165)the Natural Science Foundation of Jiangsu Province (No. BK20200800)+1 种基金Independent Innovation of Agricultural Science and Technology in Jiangsu Province (No. CX(21)3163)Natural Science Foundation of the Jiangsu Higher Education Institutions (No. 20KJA150001)。
文摘Li metal has been regarded as the holy grail for the next-generation Li-ion battery.Li dendrites issues,however,impede its practical application.In general,prolonging the sand time of Li nucleation and regulating homogeneous Li^(+) flux are effective approaches to suppress the dendrites formation and growth.Regarding this view,a functional polypropylene (PP) separator is developed to regulate ion transportation via a newly designed Li-based metal-organic framework (Li-MOF) coating.The Li-MOF crystallizes in the orthorhombic space group P212121 and features a double-walled three-dimensional (3D) structure with 1D channels.The well-defined intrinsic nanochannels of Li-MOF and the steric-hinerance effect both restrict free migration of anions,contributing to a high Li^(+) transference number of 0.65,which improve the Sand time of Li nucleation.Meanwhile,the Li-MOF coating with uniform porous structure promotes homogeneous Li^(+) flux at the surface of Li metal.Furthermore,the Li-MOF coating layer helps to build solid-electrolyte interphase (SEI) layer that comprises of inorganic Li F and Li_(3)N,which further prohibits the dendrites growth.Consequently,a highly stable Li plating/stripping cycling for over 1000 h is achieved.The functional separator also enables high-performance full lithium metal cells,the high-rate and long-stable cycling performance of Li Ni_(0.8)Mn_(0.1)Co_(0.1)(NMC811)-Li and Li Co O_(2)(LCO)-Li cells further demonstrate the feasibility of this concept.
基金supported by the Natural Science Foundation of Jiangsu Province(BK20200800)the National Natural Science Foundation of China(22209075,51902165,12004145)+1 种基金the Natural Science Foundation of Jiangxi Province(20212BAB214032,20192ACBL20048)the Key Science and Technology Plan Project of Ji’an City(20211-015311)。
文摘Spinel LiNi_(0.5)Mn_(1.5)O_(4)(LNMO),a 5 V class high voltage cathode,has been regarded as an attractive candidate to further improve the energy density of lithium-ion battery.The issue simultaneously enabling side stability and maintaining high interfacial kinetics,however,has not yet been resolved.Herein,we design a coherent Li_(1.3)A_(l0.3)Ti_(1.7)(PO)_(4)(LATP)layer that is crystally connected to the spinel LNMO host lattices,which offers fast lithium ions transportation as well as enhances the mechanical stability that prevents the particle fracture.Furthermore,the inactive Li_(3)BO_(3)(LBO)coating layer inhibits the corrosion of transition metals and continuous side reactions.Consequently,the coherent-engineered LNMO-LATPLBO cathode material exhibits superior electrochemical cycling stability in a window of 3.0–5.0 V,for example a high-capacity retention that is 89.7%after 500 cycles at 200 m A g-1obtained and enhanced rate performance(85.1 m A h g^(-1)at 800 m A g^(-1))when tested with a LiPF6-based carbonate electrolyte.Our work presents a new approach of engineering 5 V class spinel oxide cathode that combines interfacial coherent crystal lattice design and surface coating.
基金the financial support from the National Natural Science Foundation of China(51902165)the Program of HighLevel Talents in Six Industries of Jiangsu Province(XCL-040)the Jiangsu Specially-Appointed Professor Program。
文摘Recently,aqueous zinc-ion batteries with intrinsic safety,low cost,and environmental benignity have attracted tremendous research interest.However,zinc dendrites,harmful side reactions,and zinc metal corrosion stand in the way.Herein,we use lepidocrocite-type sodium titanate hollow microspheres assembled by nanotubes to constitute an artificial solid electrolyte interface layer on the zinc metal electrode.Thanks to the hierarchical structure with abundant open voids,negative-charged layered framework,low hydrophilicity,electrically insulting nature,and large ionic conductivity,the sodium titanate coating layer can effectively homogenize the electric field,promote the Zn^(2+)ion transfer,guide the Zn^(2+)ion flux,reduce the desolvation barrier,improve the exchange current density,and accommodate the plated zinc metal.Consequently,this coating layer can effectively suppress zinc dendrites and other unfavorable effects.With this coating layer,the Zn//Zn symmetric cell is able to provide an impressive cumulative zinc plating capacity of 1375 m Ah cm^(-2) at a current density of 5 m A cm^(-2).This coating layer also contributes to significantly improved electrochemical performances of Zn//MnO_(2) battery and zincion hybrid capacitor.This work offers new insights into the modifications of zinc metal electrodes.
基金supported by the National Natural Science Foundation of China(11371225)National Natural Science Foundation of Guangdong Province(2016A030313686)
文摘In this article, we consider the non-linear difference equation(f(z + 1)f(z)-1)(f(z)f(z-1)-1) =P(z, f(z))/Q(z, f(z)),where P(z, f(z)) and Q(z, f(z)) are relatively prime polynomials in f(z) with rational coefficients. For the above equation, the order of growth, the exponents of convergence of zeros and poles of its transcendental meromorphic solution f(z), and the exponents of convergence of poles of difference △f(z) and divided difference △f(z)/f(z)are estimated. Furthermore, we study the forms of rational solutions of the above equation.
基金supported by National Natural Science Foundation of China(grant numbers:82003796,81803566,81973340 and 81630095)Local Innovative and Research Teams Project of the Guangdong Pearl River Talents Program(grant number:2017BT01Y036,China)+5 种基金National High-level Personnel of the Special Support Program(DM Zhang,China)National Science and Technology Major Project(grant number:2018ZX09711001008-008,China)Key-Area Research and Development Program of Guangdong Province(grant number:2020B1111110004,China)Natural Science Foundation of Guangdong Province(grant number:2019A1515010144,China)Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research,College of Pharmacy(grant number:2020B1212060076,China)Special Funds for the Cultivation of Guangdong College Students’Scientific and Technological Innovation(grant number:pdjh2021a0052,China)。
文摘Osteosarcoma is a kind of bone tumor with highly proliferative and invasive properties,a high incidence of pulmonary metastasis and a poor prognosis.Chemotherapy is the mainstay of treatment for osteosarcoma.Currently,there are no molecular targeted drugs approved for osteosarcoma treatment,particularly effective drugs for osteosarcoma with pulmonary metastases.It has been reported that fibroblast activation protein alpha(FAPa)is upregulated in osteosarcoma and critically associated with osteosarcoma progression and metastasis,demonstrating that FAPa-targeted agents might be a promising therapeutic strategy for osteosarcoma.In the present study,we reported that the FAPa-activated vinblastine prodrug Z-GP-DAVLBH exhibited potent antitumor activities against FAPa-positive osteosarcoma cells in vitro and in vivo.Z-GP-DAVLBH inhibited the growth and induced the apoptosis of osteosarcoma cells.Importantly,it also decreased the migration and invasion capacities and reversed epithelial-mesenchymal transition(EMT)of osteosarcoma cells in vitro and suppressed pulmonary metastasis of osteosarcoma xenografts in vivo.Mechanistically,Z-GP-DAVLBH suppressed the AXL/AKT/GSK-3β/β-catenin pathway,leading to inhibition of the growth and metastatic spread of osteosarcoma cells.These findings demonstrate that Z-GP-DAVLBH is a promising agent for the treatment of FAPa-positive osteosarcoma,particularly osteosarcoma with pulmonary metastases.
基金supported by the National Natural Science Foundation of China(82273941,81973340,82204427,81803566,82003796,81773758)Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program(2017BT01Y036,China)+9 种基金Natural Science Foundation of Guangdong Province(2022A1515011813,2021A1515110242,2020A1515010071,2019A1515010144,2019A1515110543,2019A1515011934,China)Ministry of Science and Technology of China(2018ZX09711001-008-008)National high-level personnel of special support program(Zhang Dongmei),National Key R&D Program of China(2017YFC 1703800)Technology Key Project of Guangdong Province(2020B1111110004,China)Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drugs Research,College of Pharmacy(2020B1212060076,China)Special Funds for the Cultivation of Guangdong College Students’Scientifc and Technological Innovation(“Climbing Program”Special Funds)(pdjh2021a0052,China)Science and Technology Projects in Guangzhou(2023A03J0602,202201010173,202102070001,202002030010,China)Young S&T Talent Training Program of Guangdong Provincial Association for S&T,China(SKXRC202216)Clinical Frontier Technology Program of the First Affiliated Hospital of Jinan University(JNU1AF-CFTP-2022-a01227,China)China Postdoctoral Science Foundation(2022M 711345,China).
文摘Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer(LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha(FAPα) expression in LNM-CRC cells. Gain-or loss-function experiments demonstrated that FAPα enhanced tumor cell migration, invasion, epithelial-mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAPα in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis(CRCLNM). Z-GP-DAVLBH, a FAPα-activated prodrug, inhibited CRCLNM by targeting FAPα-positive LNM-CRC cells. Our study highlights the role of FAPα in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM.
基金the financial support from the National Natural Science Foundation of China(No.51902165)the Program of High-Level Talents in Six Industries of Jiangsu Province(No.XCL-040)the Jiangsu Specially-Appointed Professor Program.
文摘With the advantages of intrinsic safety,good affordability,environmental friendliness,moderate energy density,and large power density,aqueous zinc ion batteries(AZIBs)have gained considerable research interest.However,zinc dendrites,hydrogen evolution,inert byproducts,and zinc metal corrosion severely hinder practical applications of AZIBs.In order to address these issues,many research works have been carried out to modify the interface between zinc metal anode and aqueous electrolyte.In fact,the interface engineering takes effect at the surface and near the surface of separator.However,a specialized review on the separators of AZIBs is still lacking.Herein,basic requirements of separators and recent advances on the modification strategies including employment of functional groups,establishment of surface coatings,construction of hybrid architectures,regulations of porosity,and utilization of bipolar membrane are reviewed.Besides,the perspectives for further investigations on the separators of AZIBs are outlined.This review could offer useful guidance for the future explorations of separators for AZIBs.
基金We acknowledge the financial support from the National Natural Science Foundation of China(No.51902165)the Program of High-Level Talents in Six Industries of Jiangsu Province(No.XCL-040)the Jiangsu Specially-Appointed Professor Program.
文摘With low cost and high safety,aqueous zinc-based batteries have received considerable interest.Nevertheless,the excess utilization of zinc metal in the anodes of these batteries reduces energy density and increases costs.Herein,an ultrathin electrode of approximately 6.2μm thick is constructed by coating Ti_(3)C_(2)T_(x)/nanocellulose hybrid onto a stainless steel foil.This electrode is used as the Zn-free anode for aqueous hybrid Zn-Na battery,in which,a concentrated electrolyte is used to improve electrochemical reversibility.The Ti_(3)C_(2)T_(x)/nanocellulose coating is found to improve the electrolyte wettability,facilitate desolvation process of hydrated Zn^(2+) ions,lower nucleation overpotential,improve zinc plating kinetics,guide horizontal zinc plating along the Zn(002)facet,and inhibit parasitic side reactions.It is also found that the Na_(3)V_(2)(PO_(4))_(3) cathode material adopts a highly reversible Zn^(2+)/Na^(+)co-intercalation charge storage mechanism in this system.Thanks to these benefits,the assembled hybrid Zn-Na battery exhibits excellent rate capability,superior cyclability,and good anti-freezing ability.This work provides a new concept of electrode design for electrochemical energy storage.
基金supported by Natural Science Foundation of Jiangsu Province(No.BK20200800)the National Natural Science Foundation of China(Nos.51902165,12004145,52072323,and 52122211)+2 种基金Natural Science Foundation of Jiangxi Province(Nos.20192ACBL2004 and 20212BAB214032)Nanjing Science&Technology Innovation Project for Personnel Studying AbroadPart of the calculations were supported by the Center for Computational Science and Engineering at Southern University of Science and Technology,and high-performance computing platform of Jinggangshan University.
文摘Solid-state batteries(SSBs)will potentially offer increased energy density and,more importantly,improved safety for next generation lithium-ion(Li-ion)batteries.One enabling technology is solid-state composite cathodes with high operating voltage and area capacity.Current composite cathode manufacturing technologies,however,suffer from large interfacial resistance and low active mass loading that with excessive amounts of polymer electrolytes and conductive additives.Here,we report a liquidphase sintering technology that offers mixed ionic-electronic interphases and free-standing electrode architecture design,which eventually contribute to high area capacity.A small amount(~4 wt.%)of lithium hydroxide(LiOH)and boric acid(H_(3)BO_(3))with low melting point are utilized as sintering additives that infiltrate into single-crystal Ni-rich LiNi_(0.8)Mn_(0.1)Co_(0.1)(NMC811)particles at a moderately elevated temperature(~350℃)in a liquid state,which not only enable intimate physical contact but also promote the densification process.In addition,the liquid-phase additives react and transform to ionic-conductive lithium boron oxide,together with the indium tin oxide(ITO)nanoparticle coating,mixed ionic-electronic interphases of composite cathode are successfully fabricated.Furthermore,the liquid-phase sintering performed at high-temperature(~800℃)also enables the fabrication of highly dense and thick composite cathodes with a novel free-standing architecture.The promising performance characteristics of such composite cathodes,for example,delivering an area capacity above 8 mAh·cm^(−2) within a wide voltage window up to 4.4 V,open new opportunities for SSBs with a high energy density of 500 Wh·kg^(−1) for safer portable electronic and electrical transport.