Pristimerin,which is one of the compounds present in Celastraceae and Hippocrateaceae,has antitumor effects.However,its mechanism of action in esophageal squamous cell carcinoma(ESCC)remains unclear.This study aims to...Pristimerin,which is one of the compounds present in Celastraceae and Hippocrateaceae,has antitumor effects.However,its mechanism of action in esophageal squamous cell carcinoma(ESCC)remains unclear.This study aims to investigate the efficacy and mechanism of pristimerin on ESCC in vitro and in vivo.The inhibitory effect of pristimerin on cell growth was assessed using trypan blue exclusion and colony formation assays.Cell apoptosis was evaluated by flow cytometry.Gene and protein expressions were analyzed through quantitative reverse transcription-polymerase chain reaction(qRT-PCR),Western blotting,and immunohistochemistry.RNA sequencing(RNA-Seq)was employed to identify significantly differentially expressed genes(DEGs).Cell transfection and RNA interference assays were utilized to examine the role of key proteins in pristimerin's effect.Xenograft models were established to evaluate the antitumor efficiency of pristimerin in vivo.Pristimerin inhibited cell growth and induced apoptosis in ESCC cells.Upregulation of Noxa was crucial for pristimerin-induced apoptosis.Pristimerin activated the Forkhead box O3a(FoxO3a)signaling pathway and triggered FoxO3a recruitment to the Noxa promoter,leading to Noxa transcription.Blocking FoxO3a reversed pristimerin-induced Noxa upregulation and cell apoptosis.Pristimerin treatment suppressed xenograft tumors in nude mice,but these effects were largely negated in Noxa-KO tumors.Furthermore,the chemosensitization effects of pristimerin in vitro and in vivo were mediated by Noxa.This study demonstrates that pristimerin exerts an antitumor effect on ESCC by inducing AKT/FoxO3a-mediated Noxa upregulation.These findings suggest that pristimerin may serve as a potent anticancer agent for ESCC treatment.展开更多
Anion exchange membranes(AEMs)combining high hydroxide conductivity and alkali-resistant stability have become a major challenge for the long-term development of anion exchange membrane fuel cells(AEMFCs).Here,we desi...Anion exchange membranes(AEMs)combining high hydroxide conductivity and alkali-resistant stability have become a major challenge for the long-term development of anion exchange membrane fuel cells(AEMFCs).Here,we designed a series of poly(mequitazine-terphenyl piperidinium)(QPMTP-X)AEMs with dual-functionalized quaternary ammonium cations by introducing a certain proportion of large steric hindrance mequitazine(MEQ)molecular building unit into the poly(aryl piperidinium)backbone.QPMTP-X retains the excellent mechanical properties of the poly(aryl piperidinium),while also combining the alkaline stability and high ionic conductivity exhibited by MEQ with flexible quinuclidinium side chains,achieving an overall improvement of membrane performance.Notably,QPMTP-30 exhibits an ultra-high conductivity of up to 206.83 mS cm^(-1)and excellent alkaline stability(over 95%conductivity is maintained after 1000 h of conditioning in 2 M NaOH at 80℃).In fuel cell performance test,QPMTP-30 achieves a peak power density(PPD)of 974.5 mW cm^(-2)and operates stably at 80℃for more than 60 h(0.1 A cm^(-2)).Incorporating large steric hindrance building blocks and multi-cations into the poly(aryl piperidinium)backbone not only synergizes the development of highperformance AEMs but also opens up new ideas for the structural design of future AEMs.展开更多
Zinc-ion hybrid capacitors (ZIHCs) have received increasing attention as energy storage devices owing to their low cost,high safety,and environmental friendliness.However,their progress has been hampered by low energy...Zinc-ion hybrid capacitors (ZIHCs) have received increasing attention as energy storage devices owing to their low cost,high safety,and environmental friendliness.However,their progress has been hampered by low energy and power density,as well as unsatisfactory long-cycle stability,mainly due to the lack of suitable electrode materials.In this context,we have developed manganese single atoms implanted in nitrogen-doped porous carbon nanosheets (MnSAs/NCNs) using a metal salt template method as cathodes for ZIHCs.The metal salt serves a dual purpose in the synthesis process:It facilitates the uniform dispersion of Mn atoms within the carbon matrix and acts as an activating agent to create the porous structure.When applied in ZIHCs,the MnSAs/NCNs electrode demonstrates exceptional performance,including a high capacity of 203 m Ah g^(-1),an energy density of 138 Wh kg^(-1)at 68 W kg^(-1),and excellent cycle stability with 91%retention over 10,000 cycles.Theoretical calculations indicate that the introduced Mn atoms modulate the local charge distribution of carbon materials,thereby improving the electrochemical property.This work demonstrates the significant potential of carbon materials with metal atoms in zinc-ion hybrid capacitors,not only in enhancing electrochemical performance but also in providing new insights and methods for developing high-performance energy storage devices.展开更多
Adoptive immunotherapy expressing synthetic chimeric antigen receptors(CAR)on T cells through in vitro modifications represents a new and innovative strategy in cancer treatment.This new approach enables T cells to re...Adoptive immunotherapy expressing synthetic chimeric antigen receptors(CAR)on T cells through in vitro modifications represents a new and innovative strategy in cancer treatment.This new approach enables T cells to recognize and bind tumor antigens via a single-chain variable fragment recognition domain,circumventing the restriction of major histocompatibility complex.This review summarized the structure/design of CAR-T cells and the evolution process this technology went through,displaying the theoretical foundation for CAR-T therapy,the marketed products and the latest preclinical and clinical research progress.Finally,we provided perspectives on this technology’s development and potential future applications,especially for treating hematological malignant and solid tumors.展开更多
In order to clarify the effect of a buoyancy force on conduction–convection coupled heat transfer in a hollow cylinder, the flow and thermal characteristics were analyzed using an RNG k-ε turbulence model. The Reyno...In order to clarify the effect of a buoyancy force on conduction–convection coupled heat transfer in a hollow cylinder, the flow and thermal characteristics were analyzed using an RNG k-ε turbulence model. The Reynolds number was fixed at 1.014 × 10^(6), and the Rayleigh number varied from 1.122 × 10^(10)to 1.088 × 10^(11). Results have shown that, when considering the effect of an opposed buoyancy force, increasing the Rayleigh number has a positive impact on the rate of change and uniformity of the cylinder temperature. The temperature distributions along the axial and circumferential directions are similar for different Rayleigh numbers, but extreme values differ.Along the axial direction, the maximum temperature is obtained at the interface between the variable-diameter part and the constant-diameter part. The maximum dimensionless temperature value decreases to 0.12 when the Rayleigh number increases to 1.088 × 10^(11). Along the circumferential direction, the temperature distribution is affected by the buoyancy force, which results in the temperature of the upper part being higher than that of the lower part. After nondimensionalization of the temperature and time, a correlation was proposed to illustrate the transient heat transfer process quantitatively. The standard deviation of the maximum relative temperature, representing the temperature uniformity, was also calculated. It was found that the difference in the direction of the buoyancy force made a huge difference. Compared with the opposed buoyancy force, the maximum dimensionless temperature is almost two times higher with an assisted buoyancy force. Similarly, the heat transfer coefficient with an assisted buoyancy force is half of that with an opposed buoyancy force. Overall, an assisted buoyancy force plays a negative role in terms of thermal characteristics. The flow field around the hollow cylinder was also illustrated to reveal the mechanism of the buoyancy force on magnitude and direction aspects.展开更多
A multiwavelength tunable ring-cavity erbium-doped fiber laser(EDFL)based on a Lyot filter was presented.For the proposed Lyot filter,a comb filter consisting of an EDF-polarization-maintaining fiber(EDF-PMF),a polari...A multiwavelength tunable ring-cavity erbium-doped fiber laser(EDFL)based on a Lyot filter was presented.For the proposed Lyot filter,a comb filter consisting of an EDF-polarization-maintaining fiber(EDF-PMF),a polarization controller(PC),and a circulator with four ports was used to suppress the mode competition.The light transmission direction was guaranteed by the circulator.For the proposed fiber laser,tunable single,dual,triple,quadruple,quintuple,sextuple,and septuple wavelengths were realized.A single-wavelength laser output with an optical signal-to-noise ratio(SNR)of up to30.56 dB was realized,and a tuning range of 1590.54 nm to 1599.54 nm was achieved by tuning the PC.The stability of the single,dual,triple,and quadruple-wavelength center power fluctuations was less than 0.05 dB,0.98 dB,5.07 dB,and7.71 dB respectively.When the laser was operated in the multiwavelength condition,the SNR was more than 20.97 dB.The proposed erbium-doped fiber laser is suitable for fiber-sensing system applications.展开更多
Carbonaceous material with favorable K^(+)intercalation feature is considered as a compelling anode for potassium-ion batteries(PIBs).However,the inferior rate performance and cycling stability impede their large-scal...Carbonaceous material with favorable K^(+)intercalation feature is considered as a compelling anode for potassium-ion batteries(PIBs).However,the inferior rate performance and cycling stability impede their large-scale application.Here,a facile template method is utilized to synthesize boron doping carbon nanobubbles(BCNBs).The incorporation of boron into the carbon structure introduces abundant defective sites and improves conductivity,facilitating both the intercalation-controlled and capacitivecontrolled capacities.Moreover,theoretical calculation proves that boron doping can effectively improve the conductivity and facilitate electrochemical reversibility in PIBs.Correspondingly,the designed BCNBs anode delivers a high specific capacity(464 mAh g^(-1)at 0.05 A g^(-1))with an extraordinary rate performance(85.7 mAh g^(-1)at 50 A g^(-1)),and retains a considerable capacity retention(95.2%relative to the 100th charge after 2000 cycles).Besides,the strategy of pre-forming stable artificial inorganic solid electrolyte interface effectively realizes high initial coulombic efficiency of 79.0%for BCNBs.Impressively,a dual-carbon potassium-ion capacitor coupling BCNBs anode displays a high energy density(177.8 Wh kg^(-1)).This work not only shows great potential for utilizing heteroatom-doping strategy to boost the potassium ion storage but also paves the way for designing high-energy/power storage devices.展开更多
Over the past two decades,non-small cell lung cancer(NSCLC)has witnessed encouraging advancements in basic and clinical research.However,substantial unmet needs remain for patients worldwide,as drug resistance persist...Over the past two decades,non-small cell lung cancer(NSCLC)has witnessed encouraging advancements in basic and clinical research.However,substantial unmet needs remain for patients worldwide,as drug resistance persists as an inevitable reality.Meanwhile,the journey towards amplifying the breadth and depth of the therapeutic effect requires comprehending and integrating diverse and profound progress.In this review,therefore,we aim to comprehensively present such progress that spans the various aspects of molecular pathology,encompassing elucidations of metastatic mechanisms,identification of therapeutic targets,and dissection of spatial omics.Additionally,we also highlight the numerous small molecule and antibody drugs,encompassing their application alone or in combination,across later-line,frontline,neoadjuvant or adjuvant settings.Then,we elaborate on drug resistance mechanisms,mainly involving targeted therapies and immunotherapies,revealed by our proposed theoretical models to clarify interactions between cancer cells and a variety of non-malignant cells,as well as almost all the biological regulatory pathways.Finally,we outline mechanistic perspectives to pursue innovative treatments of NSCLC,through leveraging artificial intelligence to incorporate the latest insights into the design of finely-tuned,biomarker-driven combination strategies.This review not only provides an overview of the various strategies of how to reshape available armamentarium,but also illustrates an example of clinical translation of how to develop novel targeted drugs,to revolutionize therapeutic landscape for NSCLC.展开更多
Lifestyle factors play a critical role in promoting healthy aging and extending life expectancy Lifestyle factors(Zhao et al.2023,2022;Ofori-Asenso et al.2019).However,the biological mechanisms through which lifestyle...Lifestyle factors play a critical role in promoting healthy aging and extending life expectancy Lifestyle factors(Zhao et al.2023,2022;Ofori-Asenso et al.2019).However,the biological mechanisms through which lifestyle modifications mitigate adverse health outcomes have not yet been fully elucidated.展开更多
The global population is aging rapidly,with those aged 65 years and older projected to reach 2.2 billion by the 2070s,surpassing the number of children.1 This demographic shift presents profound healthcare and socioec...The global population is aging rapidly,with those aged 65 years and older projected to reach 2.2 billion by the 2070s,surpassing the number of children.1 This demographic shift presents profound healthcare and socioeconomic challenges,driven by the growing burden of chronic diseases such as diabetes,cardiovascular conditions,and neurodegenerative disorders among the elderly.展开更多
Recruitment of polymorphonuclear MDSCs(PMN-MDSCs)in the TME suppresses the antitumor activity of tumor-infiltrating CD8^(+)T cells(CD8^(+)TILs).Little is known about the role of antitumoral CD8^(+)TILs in actively ini...Recruitment of polymorphonuclear MDSCs(PMN-MDSCs)in the TME suppresses the antitumor activity of tumor-infiltrating CD8^(+)T cells(CD8^(+)TILs).Little is known about the role of antitumoral CD8^(+)TILs in actively initiating an immune-tolerant microenvironment,particularly in the recruitment of PMN-MDSCs.In this study,we found that immunotherapy-activated CD8^(+)TILs significantly increased PNM-MDSC infltration in the TME,resulting in antitumor resistance.When CD8^(+)T cells are activated,lipocalin-2(LCN2)expression is strongly upregulated,which significantly enhances PMN-MDSC chemotaxis.Mechanistically,immune activation increased fatty acid synthesis in CD8T cells,particularly oleic acid(OA),which induced lysosomal membrane permeabilization,releasing cathepsin B and subsequently activating NF-kB to promote LCN2 expression.Moreover,we showed that glucagon-like peptide 1(GLP1)effectively inhibited OA synthesis in activated CD8^(+)T cells,reducing LCN2 production.We then developed a recombinant adenovirus encoding GLP1(AdV-GLP1),which significantly reduced PMN-MDSC infiltration and reinvigorated the antitumor activity of CD8^(+)TILs.In various pancreatic cancer models,including subcutaneous,orthotopic,and humanized CDX/PDX models,AdV-GLP1 displayed excellent antitumor efficacy.Our work advances the understanding of how immunotherapy-activated CD8^(+)TILs initiate PMN-MDSC infiltration and provides a clinically relevant strategy to target this interaction and improvecancer immunotherapy.展开更多
Group 3 innate lymphoid cells(ILC3s)control tissue homeostasis and orchestrate mucosal inflammation;however,the precise mechanisms governing ILC3 activity are fully understood.Here,we identified the transmembrane prot...Group 3 innate lymphoid cells(ILC3s)control tissue homeostasis and orchestrate mucosal inflammation;however,the precise mechanisms governing ILC3 activity are fully understood.Here,we identified the transmembrane protein neuropilin-1(NRP1)as a positive regulator of interleukin(IL)-17-producing ILC3s in the intestine.NRP1 was markedly upregulated in intestinal mucosal biopsies from patients with inflammatory bowel disease(IBD)compared with healthy controls.Genetic deficiency of NRP1 reduces the frequency of ILC3s in the gut and impairs their production of IL-17A in an NF-κB signaling-dependent and cell-intrinsic manner.The diminished IL-17A production in ILC3s altered the composition of the microbiota and improved the outcome of dextran sodium sulfate(DSS)-induced colitis.Furthermore,pharmacological inhibition of NRP1 with EG00229 alleviated the severity of colitis.These observations demonstrated the critical role of NRP1 in the control of intestinal ILC3s,suggesting that NRP1 is a potential therapeutic target for IBD.展开更多
Perfluoroalkyl acids(PFAAs)are emerging persistent organic pollutants that are globally distributed in the environment.In the present review,the occurrence of PFAAs and their behavior in aquatic ecosystem were summari...Perfluoroalkyl acids(PFAAs)are emerging persistent organic pollutants that are globally distributed in the environment.In the present review,the occurrence of PFAAs and their behavior in aquatic ecosystem were summarized,and the health and ecological risk assessment and the multimedia fate simulation were investigated.PFAAs are most likely to exist in the aqueous phase,and PFAAs in atmosphere are also able to enter water bodies through diffusion and wet and dry deposition and eventually become widely distributed in various environmental media.The air-solid partition is considered to be one of the major factors in the long-distance transportation of the pollutants.The pKa values and organic carbon fraction of the sediment could influence the partition of PFAAs between water and sediment.Otherwise,PFAAs have teratogenic,mutagenic and other toxic effects and they could be accumulated by biota,and magnified through trophic level.The ecological and health risks of PFOA and PFOS were assessment.In order to explore the partition mechanism and reduce the uncertainty of the simulation of the transport,transformation and fate,the experimental methods on physicochemical properties of PFAAs should be developed.Moreover,further studies on toxicities of PFAAs are necessary for health and ecological risk assessment.展开更多
Evading TGF-β-mediated growth inhibition is often associated with tumorigenesis in liver, including hepatocellular carcinoma （HCC）. To better understand the functions and the underlying molecular mechanisms of TGF-...Evading TGF-β-mediated growth inhibition is often associated with tumorigenesis in liver, including hepatocellular carcinoma （HCC）. To better understand the functions and the underlying molecular mechanisms of TGF-β in HCC initiation and progression, we carried out transcriptome sequencing （RNA-Seq） to identify the target genes of TGF-β. CXXCS, a member of the CXXC-type zinc finger domain-containing protein family, was identified as a novel TGF-β target gene in Hep3B HCC cells. Knockdown of CXXC5 attenuated the expression of a substantial portion of TGF-p target genes and ameliorated TGF-13-induced growth inhibition or apoptosis of Hep3B cells, suggesting that CXXC5 is required for TGF-p-mediated inhibition of HCC progression. Analysis of the TCGA database indicated that CXXC5 expression is reduced in the majority of HCC tissue samples in comparison to that in normal tissues. Furthermore, CXXC5 associates with the histone deacetylase HDAC1 and competes its interaction with Smad2/3, thereby abolishing the inhibitory effect of HDAC1 on TGF-β signaling. These observations together suggest that CXXC5 may act as a tumor suppressor by promoting TGF-β signaling via a positive feedback loop, and reveal a strategy for HCC to bypass TGF-β-mediated cytostasis by disrupting the positive feedback regulation. Our findings shed new light on TGF-β signaling regulation and demon- strate the function of CXXC5 in HCC development.展开更多
Together with the blooming of portable smart devices and electric vehicles in the last decade,electrochemical energy storage(EES)devices capable of high-energy and high-power storage are urgently needed.Two-dimensiona...Together with the blooming of portable smart devices and electric vehicles in the last decade,electrochemical energy storage(EES)devices capable of high-energy and high-power storage are urgently needed.Two-dimensional(2D)materials,benefiting from the short solid-state diffusion distance,are well recognized to possess excellent electrochemical performance.However,liquid diffusion,the rate-determining process in thick electrodes,is notably slow in 2D materials-based electrodes stemming from their stacking during electrode processing,which considerably limits their applications for high energy storage.To fully exploit intrinsic advantages of 2D materials for scalable energy storage devices,this review summarizes several important strategies,ranging from assembly to template methods,to fabricate vertically aligned 2D materials-based electrodes.We further discuss the advantages and challenges of these methods in terms of key features of thick electrodes and illustrate the design principles for high-energy/power devices.展开更多
Lithium-sulfur(Li-S)batteries are regarded as one of the most promising next-generation energy storage systems due to their high theoretical energy density and low material cost.However,the conventional ether-based el...Lithium-sulfur(Li-S)batteries are regarded as one of the most promising next-generation energy storage systems due to their high theoretical energy density and low material cost.However,the conventional ether-based electrolytes of Li-S batteries are extremely flammable and have high solubility of lithium polysulfides(LiPS),resulting in a high safety risk and a poor life cycle.Herein,we report an ether/carbonate co-solvent fluorinated electrolyte with a special solvation sheath of Li^(+),which can prevent the formation of dissoluble long-chain LiPS of the sulfur cathode,restrict Li dendrite growth at the anode side,and show fire resistance in combustion experiments.As a result,the proposed Li-S batteries with 70 wt%sulfur content in its cathode deliver stable life cycle,low self-discharge ratio,and intrinsic safety.Therefore,the unique passivation characteristics of the designed fluorinated electrolyte break several critical limitations of the traditional“liquid phase”-based Li-S batteries,offering a facile and promising way to develop long-life and high-safety Li-S batteries.展开更多
Metal anodes(e.g.,Li and Zn)are promising candidates for high-energy and high-power rechargeable batteries.However,the commercialization of metal anodes is hampered by irregular dendrite growth,which severely deterior...Metal anodes(e.g.,Li and Zn)are promising candidates for high-energy and high-power rechargeable batteries.However,the commercialization of metal anodes is hampered by irregular dendrite growth,which severely deteriorates the safety and cyclability of metal anodes.Optimizing the electrolyte by nanostructured additives to regulate the metal deposition shows great potential since the electrochemically nonreactive feature endows the regulation function with good sustainability.In this manuscript,the fundamental dendrite formation models and key parameters for stabilizing metal anode are first discussed.The progress and functional mechanism of nanostructured additives for regulating the metal deposition are summarized in terms of regulatory model,i.e.,deposition-,adsorption-and dispersion-type.Finally,we also provide a detailed concluding outlook,pointing out the future trend of selecting new nanostructured additive candidates and elucidating synergistic effects and underlying mechanisms with the key attention being given to the assessments of practicality.展开更多
Solid-state electrolytes(SSEs)are recognized as attractive candidates to real-ize safe and high-energy-density lithium metal batteries(LMBs).However,the practical application of SSEs still faces challenges such as ins...Solid-state electrolytes(SSEs)are recognized as attractive candidates to real-ize safe and high-energy-density lithium metal batteries(LMBs).However,the practical application of SSEs still faces challenges such as insufficient room-temperature ionic conductivity,unsatisfactory mechanical properties,and large internal resistance.Extensive research efforts have been made to explore new electrochemistry and technologies to address those challenges.Among them,the construction of order-structured SSEs has emerged as a promising strategy.The anisotropic behavior induced by the orientation offers SSEs with desired properties targeting specific functions,and therefore the rational design of the order-structured SSE provides an alternative solution to achieve an ideal SSE.This review discusses the structure-property correlation of SSEs,and then sum-marizes the design strategies to construct order-structured SSEs.Finally,the current challenges and possible future research directions for order-structured SSEs for scalable high-energy-density LMBs are presented.展开更多
TiO2 is a latent anode material for rechargeable lithium batteries. Our simulation models, basing lepidocrocite and 2-MnO2 type TiO2 were investigated by density functional theory （DFT）. The key issues are focused o...TiO2 is a latent anode material for rechargeable lithium batteries. Our simulation models, basing lepidocrocite and 2-MnO2 type TiO2 were investigated by density functional theory （DFT）. The key issues are focused on the lithium insertion sites, electronic structures, and the conducting paths of Li＋ ions. Our calculated data indicate the calculated voltage of 2-MnO2 type TiO2 is higher than that of lepidocrocite type TiO2. The Li＋ ion migration energy barrier of lepidocroeite type YiO2 along the [1 0 0] direction （0.45 eV） is lower than that of along the [110] direction （0.57 eV）. The energy barriers of 2-MnO2 type TiO2 to move a Li＋ ion among the adjacent embedded sites （16c or 8a sites） is 0.68 eV.展开更多
基金supported by the Projects of International Cooperation and Exchanges(Nos.G2022027004L,G2022027012L)the Hubei Province Natural Science Foundation of China(No.2022CFB481)+3 种基金the Natural Science Foundation of Hubei Provincial Department of Education(No.T2022021)the Advantages Discipline Group(Biology and Medicine)Project in Higher Education of Hubei Province(2021-2025)(Nos.2025BMXKQY2,2024XKQY26)the Innovative Research Program for Graduates of Hubei University of Medicine(No.YC2024003,YC2022033)the Student's Platform for Innovation and Entrepreneurship Training Program(Nos.202410929010,202210929005)。
文摘Pristimerin,which is one of the compounds present in Celastraceae and Hippocrateaceae,has antitumor effects.However,its mechanism of action in esophageal squamous cell carcinoma(ESCC)remains unclear.This study aims to investigate the efficacy and mechanism of pristimerin on ESCC in vitro and in vivo.The inhibitory effect of pristimerin on cell growth was assessed using trypan blue exclusion and colony formation assays.Cell apoptosis was evaluated by flow cytometry.Gene and protein expressions were analyzed through quantitative reverse transcription-polymerase chain reaction(qRT-PCR),Western blotting,and immunohistochemistry.RNA sequencing(RNA-Seq)was employed to identify significantly differentially expressed genes(DEGs).Cell transfection and RNA interference assays were utilized to examine the role of key proteins in pristimerin's effect.Xenograft models were established to evaluate the antitumor efficiency of pristimerin in vivo.Pristimerin inhibited cell growth and induced apoptosis in ESCC cells.Upregulation of Noxa was crucial for pristimerin-induced apoptosis.Pristimerin activated the Forkhead box O3a(FoxO3a)signaling pathway and triggered FoxO3a recruitment to the Noxa promoter,leading to Noxa transcription.Blocking FoxO3a reversed pristimerin-induced Noxa upregulation and cell apoptosis.Pristimerin treatment suppressed xenograft tumors in nude mice,but these effects were largely negated in Noxa-KO tumors.Furthermore,the chemosensitization effects of pristimerin in vitro and in vivo were mediated by Noxa.This study demonstrates that pristimerin exerts an antitumor effect on ESCC by inducing AKT/FoxO3a-mediated Noxa upregulation.These findings suggest that pristimerin may serve as a potent anticancer agent for ESCC treatment.
基金financial support of this work by the Natural Science Foundation of China(Grant Nos.U24A20505,52473205)Chang Bai Mountain Scholars Program of Jilin Province and Jilin Provincial Science&Technology Department(Grant No.YDZJ202401357).
文摘Anion exchange membranes(AEMs)combining high hydroxide conductivity and alkali-resistant stability have become a major challenge for the long-term development of anion exchange membrane fuel cells(AEMFCs).Here,we designed a series of poly(mequitazine-terphenyl piperidinium)(QPMTP-X)AEMs with dual-functionalized quaternary ammonium cations by introducing a certain proportion of large steric hindrance mequitazine(MEQ)molecular building unit into the poly(aryl piperidinium)backbone.QPMTP-X retains the excellent mechanical properties of the poly(aryl piperidinium),while also combining the alkaline stability and high ionic conductivity exhibited by MEQ with flexible quinuclidinium side chains,achieving an overall improvement of membrane performance.Notably,QPMTP-30 exhibits an ultra-high conductivity of up to 206.83 mS cm^(-1)and excellent alkaline stability(over 95%conductivity is maintained after 1000 h of conditioning in 2 M NaOH at 80℃).In fuel cell performance test,QPMTP-30 achieves a peak power density(PPD)of 974.5 mW cm^(-2)and operates stably at 80℃for more than 60 h(0.1 A cm^(-2)).Incorporating large steric hindrance building blocks and multi-cations into the poly(aryl piperidinium)backbone not only synergizes the development of highperformance AEMs but also opens up new ideas for the structural design of future AEMs.
基金National Natural Science Foundation of China (No. 22179123)Taishan Scholar Program of Shandong Province,China (No. tsqn202211048)Fundamental Research Funds for the Central Universities (No.202262010)。
文摘Zinc-ion hybrid capacitors (ZIHCs) have received increasing attention as energy storage devices owing to their low cost,high safety,and environmental friendliness.However,their progress has been hampered by low energy and power density,as well as unsatisfactory long-cycle stability,mainly due to the lack of suitable electrode materials.In this context,we have developed manganese single atoms implanted in nitrogen-doped porous carbon nanosheets (MnSAs/NCNs) using a metal salt template method as cathodes for ZIHCs.The metal salt serves a dual purpose in the synthesis process:It facilitates the uniform dispersion of Mn atoms within the carbon matrix and acts as an activating agent to create the porous structure.When applied in ZIHCs,the MnSAs/NCNs electrode demonstrates exceptional performance,including a high capacity of 203 m Ah g^(-1),an energy density of 138 Wh kg^(-1)at 68 W kg^(-1),and excellent cycle stability with 91%retention over 10,000 cycles.Theoretical calculations indicate that the introduced Mn atoms modulate the local charge distribution of carbon materials,thereby improving the electrochemical property.This work demonstrates the significant potential of carbon materials with metal atoms in zinc-ion hybrid capacitors,not only in enhancing electrochemical performance but also in providing new insights and methods for developing high-performance energy storage devices.
基金supported by the National Natural Science Foundation of China(Nos.81872823,82073782 and 82241002)the Shanghai Science and Technology Committee(No.19430741500)+1 种基金National Innovation and Entrepreneurship Training Program for Undergraduate(No.202210316145)the Key Laboratory of Modern Chinese Medicine Preparation of Ministry of Education of Jiangxi University of Traditional Chinese Medicine(No.zdsys202103)。
文摘Adoptive immunotherapy expressing synthetic chimeric antigen receptors(CAR)on T cells through in vitro modifications represents a new and innovative strategy in cancer treatment.This new approach enables T cells to recognize and bind tumor antigens via a single-chain variable fragment recognition domain,circumventing the restriction of major histocompatibility complex.This review summarized the structure/design of CAR-T cells and the evolution process this technology went through,displaying the theoretical foundation for CAR-T therapy,the marketed products and the latest preclinical and clinical research progress.Finally,we provided perspectives on this technology’s development and potential future applications,especially for treating hematological malignant and solid tumors.
基金supported by the National Natural Science Foundation of China (No. 51936006)。
文摘In order to clarify the effect of a buoyancy force on conduction–convection coupled heat transfer in a hollow cylinder, the flow and thermal characteristics were analyzed using an RNG k-ε turbulence model. The Reynolds number was fixed at 1.014 × 10^(6), and the Rayleigh number varied from 1.122 × 10^(10)to 1.088 × 10^(11). Results have shown that, when considering the effect of an opposed buoyancy force, increasing the Rayleigh number has a positive impact on the rate of change and uniformity of the cylinder temperature. The temperature distributions along the axial and circumferential directions are similar for different Rayleigh numbers, but extreme values differ.Along the axial direction, the maximum temperature is obtained at the interface between the variable-diameter part and the constant-diameter part. The maximum dimensionless temperature value decreases to 0.12 when the Rayleigh number increases to 1.088 × 10^(11). Along the circumferential direction, the temperature distribution is affected by the buoyancy force, which results in the temperature of the upper part being higher than that of the lower part. After nondimensionalization of the temperature and time, a correlation was proposed to illustrate the transient heat transfer process quantitatively. The standard deviation of the maximum relative temperature, representing the temperature uniformity, was also calculated. It was found that the difference in the direction of the buoyancy force made a huge difference. Compared with the opposed buoyancy force, the maximum dimensionless temperature is almost two times higher with an assisted buoyancy force. Similarly, the heat transfer coefficient with an assisted buoyancy force is half of that with an opposed buoyancy force. Overall, an assisted buoyancy force plays a negative role in terms of thermal characteristics. The flow field around the hollow cylinder was also illustrated to reveal the mechanism of the buoyancy force on magnitude and direction aspects.
基金Beijing Great Wall Scholars Program(Grant No.CIT&TCD20190323)Beijing Youth Talent Support Program(Grant No.Z2019042)the National Natural Science Foundation of China(Grant No.61875237).
文摘A multiwavelength tunable ring-cavity erbium-doped fiber laser(EDFL)based on a Lyot filter was presented.For the proposed Lyot filter,a comb filter consisting of an EDF-polarization-maintaining fiber(EDF-PMF),a polarization controller(PC),and a circulator with four ports was used to suppress the mode competition.The light transmission direction was guaranteed by the circulator.For the proposed fiber laser,tunable single,dual,triple,quadruple,quintuple,sextuple,and septuple wavelengths were realized.A single-wavelength laser output with an optical signal-to-noise ratio(SNR)of up to30.56 dB was realized,and a tuning range of 1590.54 nm to 1599.54 nm was achieved by tuning the PC.The stability of the single,dual,triple,and quadruple-wavelength center power fluctuations was less than 0.05 dB,0.98 dB,5.07 dB,and7.71 dB respectively.When the laser was operated in the multiwavelength condition,the SNR was more than 20.97 dB.The proposed erbium-doped fiber laser is suitable for fiber-sensing system applications.
基金supported by the National Natural Science Foundation of China(No.22179123 and 21471139)the Shandong Provincial Natural Science Foundation,China(ZR2020ME038)the Fundamental Research Funds for the Central Universities(No.202262010 and 201941010)
文摘Carbonaceous material with favorable K^(+)intercalation feature is considered as a compelling anode for potassium-ion batteries(PIBs).However,the inferior rate performance and cycling stability impede their large-scale application.Here,a facile template method is utilized to synthesize boron doping carbon nanobubbles(BCNBs).The incorporation of boron into the carbon structure introduces abundant defective sites and improves conductivity,facilitating both the intercalation-controlled and capacitivecontrolled capacities.Moreover,theoretical calculation proves that boron doping can effectively improve the conductivity and facilitate electrochemical reversibility in PIBs.Correspondingly,the designed BCNBs anode delivers a high specific capacity(464 mAh g^(-1)at 0.05 A g^(-1))with an extraordinary rate performance(85.7 mAh g^(-1)at 50 A g^(-1)),and retains a considerable capacity retention(95.2%relative to the 100th charge after 2000 cycles).Besides,the strategy of pre-forming stable artificial inorganic solid electrolyte interface effectively realizes high initial coulombic efficiency of 79.0%for BCNBs.Impressively,a dual-carbon potassium-ion capacitor coupling BCNBs anode displays a high energy density(177.8 Wh kg^(-1)).This work not only shows great potential for utilizing heteroatom-doping strategy to boost the potassium ion storage but also paves the way for designing high-energy/power storage devices.
基金received funding from Research Projects of Biomedical Center of Hubei Cancer Hospital(2022SWZX01).
文摘Over the past two decades,non-small cell lung cancer(NSCLC)has witnessed encouraging advancements in basic and clinical research.However,substantial unmet needs remain for patients worldwide,as drug resistance persists as an inevitable reality.Meanwhile,the journey towards amplifying the breadth and depth of the therapeutic effect requires comprehending and integrating diverse and profound progress.In this review,therefore,we aim to comprehensively present such progress that spans the various aspects of molecular pathology,encompassing elucidations of metastatic mechanisms,identification of therapeutic targets,and dissection of spatial omics.Additionally,we also highlight the numerous small molecule and antibody drugs,encompassing their application alone or in combination,across later-line,frontline,neoadjuvant or adjuvant settings.Then,we elaborate on drug resistance mechanisms,mainly involving targeted therapies and immunotherapies,revealed by our proposed theoretical models to clarify interactions between cancer cells and a variety of non-malignant cells,as well as almost all the biological regulatory pathways.Finally,we outline mechanistic perspectives to pursue innovative treatments of NSCLC,through leveraging artificial intelligence to incorporate the latest insights into the design of finely-tuned,biomarker-driven combination strategies.This review not only provides an overview of the various strategies of how to reshape available armamentarium,but also illustrates an example of clinical translation of how to develop novel targeted drugs,to revolutionize therapeutic landscape for NSCLC.
基金supported by grants from the National Science Foundation of China(32200536,32288101)Shanghai Municipal Science and Technology Major Project(2023SHZDZX02,2017SHZDZX01)+1 种基金the Science and Technology Development Fund of Shanghai Pudong New Area(PKJ2023-Y04)the Key Specialty Construction Project of Pudong Health and Family Planning Commission of Shanghai(PWZxk2022-01).
文摘Lifestyle factors play a critical role in promoting healthy aging and extending life expectancy Lifestyle factors(Zhao et al.2023,2022;Ofori-Asenso et al.2019).However,the biological mechanisms through which lifestyle modifications mitigate adverse health outcomes have not yet been fully elucidated.
基金supported by the National Natural Science Foundation of China(72474010)Strategic Research and Consulting Project of Chinese Academy of Engineering(2022-XBZD-30).
文摘The global population is aging rapidly,with those aged 65 years and older projected to reach 2.2 billion by the 2070s,surpassing the number of children.1 This demographic shift presents profound healthcare and socioeconomic challenges,driven by the growing burden of chronic diseases such as diabetes,cardiovascular conditions,and neurodegenerative disorders among the elderly.
基金supported by the National Natural Science Foundation of China(82273261 to JW,82073367 to MX),Nanjing University(0214/151130 to JW)the State Key Laboratory of Pharmaceutical Biotechnology,Nanjing University(ZzYJ-202401 to JW).
文摘Recruitment of polymorphonuclear MDSCs(PMN-MDSCs)in the TME suppresses the antitumor activity of tumor-infiltrating CD8^(+)T cells(CD8^(+)TILs).Little is known about the role of antitumoral CD8^(+)TILs in actively initiating an immune-tolerant microenvironment,particularly in the recruitment of PMN-MDSCs.In this study,we found that immunotherapy-activated CD8^(+)TILs significantly increased PNM-MDSC infltration in the TME,resulting in antitumor resistance.When CD8^(+)T cells are activated,lipocalin-2(LCN2)expression is strongly upregulated,which significantly enhances PMN-MDSC chemotaxis.Mechanistically,immune activation increased fatty acid synthesis in CD8T cells,particularly oleic acid(OA),which induced lysosomal membrane permeabilization,releasing cathepsin B and subsequently activating NF-kB to promote LCN2 expression.Moreover,we showed that glucagon-like peptide 1(GLP1)effectively inhibited OA synthesis in activated CD8^(+)T cells,reducing LCN2 production.We then developed a recombinant adenovirus encoding GLP1(AdV-GLP1),which significantly reduced PMN-MDSC infiltration and reinvigorated the antitumor activity of CD8^(+)TILs.In various pancreatic cancer models,including subcutaneous,orthotopic,and humanized CDX/PDX models,AdV-GLP1 displayed excellent antitumor efficacy.Our work advances the understanding of how immunotherapy-activated CD8^(+)TILs initiate PMN-MDSC infiltration and provides a clinically relevant strategy to target this interaction and improvecancer immunotherapy.
基金upported by the following grants:National Natural Science Foundation of China(No.81925018,82130049,82430055,to J.Z.82321001 to Y.Y.,and 82225015 to Q.L.)+1 种基金supported by the National Key Research and Development Project of China(2021ZD0202400,to Q.L.)the New Cornerstone Science Foundation through the XPLORER PRIZE(to Q.L.).
文摘Group 3 innate lymphoid cells(ILC3s)control tissue homeostasis and orchestrate mucosal inflammation;however,the precise mechanisms governing ILC3 activity are fully understood.Here,we identified the transmembrane protein neuropilin-1(NRP1)as a positive regulator of interleukin(IL)-17-producing ILC3s in the intestine.NRP1 was markedly upregulated in intestinal mucosal biopsies from patients with inflammatory bowel disease(IBD)compared with healthy controls.Genetic deficiency of NRP1 reduces the frequency of ILC3s in the gut and impairs their production of IL-17A in an NF-κB signaling-dependent and cell-intrinsic manner.The diminished IL-17A production in ILC3s altered the composition of the microbiota and improved the outcome of dextran sodium sulfate(DSS)-induced colitis.Furthermore,pharmacological inhibition of NRP1 with EG00229 alleviated the severity of colitis.These observations demonstrated the critical role of NRP1 in the control of intestinal ILC3s,suggesting that NRP1 is a potential therapeutic target for IBD.
基金Funding for this study was provided by the National Natural Science Foundation of China(NSFC)(41271462)the Undergraduate Student Research Training Program of the Ministry of Education.
文摘Perfluoroalkyl acids(PFAAs)are emerging persistent organic pollutants that are globally distributed in the environment.In the present review,the occurrence of PFAAs and their behavior in aquatic ecosystem were summarized,and the health and ecological risk assessment and the multimedia fate simulation were investigated.PFAAs are most likely to exist in the aqueous phase,and PFAAs in atmosphere are also able to enter water bodies through diffusion and wet and dry deposition and eventually become widely distributed in various environmental media.The air-solid partition is considered to be one of the major factors in the long-distance transportation of the pollutants.The pKa values and organic carbon fraction of the sediment could influence the partition of PFAAs between water and sediment.Otherwise,PFAAs have teratogenic,mutagenic and other toxic effects and they could be accumulated by biota,and magnified through trophic level.The ecological and health risks of PFOA and PFOS were assessment.In order to explore the partition mechanism and reduce the uncertainty of the simulation of the transport,transformation and fate,the experimental methods on physicochemical properties of PFAAs should be developed.Moreover,further studies on toxicities of PFAAs are necessary for health and ecological risk assessment.
文摘Evading TGF-β-mediated growth inhibition is often associated with tumorigenesis in liver, including hepatocellular carcinoma （HCC）. To better understand the functions and the underlying molecular mechanisms of TGF-β in HCC initiation and progression, we carried out transcriptome sequencing （RNA-Seq） to identify the target genes of TGF-β. CXXCS, a member of the CXXC-type zinc finger domain-containing protein family, was identified as a novel TGF-β target gene in Hep3B HCC cells. Knockdown of CXXC5 attenuated the expression of a substantial portion of TGF-p target genes and ameliorated TGF-13-induced growth inhibition or apoptosis of Hep3B cells, suggesting that CXXC5 is required for TGF-p-mediated inhibition of HCC progression. Analysis of the TCGA database indicated that CXXC5 expression is reduced in the majority of HCC tissue samples in comparison to that in normal tissues. Furthermore, CXXC5 associates with the histone deacetylase HDAC1 and competes its interaction with Smad2/3, thereby abolishing the inhibitory effect of HDAC1 on TGF-β signaling. These observations together suggest that CXXC5 may act as a tumor suppressor by promoting TGF-β signaling via a positive feedback loop, and reveal a strategy for HCC to bypass TGF-β-mediated cytostasis by disrupting the positive feedback regulation. Our findings shed new light on TGF-β signaling regulation and demon- strate the function of CXXC5 in HCC development.
基金G.H.Y.acknowledges the funding support from the Center for Mesoscale Transport Properties,an Energy Frontier Research Center supported by the DOE-BES(No.DE-SC0012673).
文摘Together with the blooming of portable smart devices and electric vehicles in the last decade,electrochemical energy storage(EES)devices capable of high-energy and high-power storage are urgently needed.Two-dimensional(2D)materials,benefiting from the short solid-state diffusion distance,are well recognized to possess excellent electrochemical performance.However,liquid diffusion,the rate-determining process in thick electrodes,is notably slow in 2D materials-based electrodes stemming from their stacking during electrode processing,which considerably limits their applications for high energy storage.To fully exploit intrinsic advantages of 2D materials for scalable energy storage devices,this review summarizes several important strategies,ranging from assembly to template methods,to fabricate vertically aligned 2D materials-based electrodes.We further discuss the advantages and challenges of these methods in terms of key features of thick electrodes and illustrate the design principles for high-energy/power devices.
基金financially supported by the National Key R&D Program of China (2018YFB0905400)the National Natural Science Foundation of China (51972131 and 51632001)
文摘Lithium-sulfur(Li-S)batteries are regarded as one of the most promising next-generation energy storage systems due to their high theoretical energy density and low material cost.However,the conventional ether-based electrolytes of Li-S batteries are extremely flammable and have high solubility of lithium polysulfides(LiPS),resulting in a high safety risk and a poor life cycle.Herein,we report an ether/carbonate co-solvent fluorinated electrolyte with a special solvation sheath of Li^(+),which can prevent the formation of dissoluble long-chain LiPS of the sulfur cathode,restrict Li dendrite growth at the anode side,and show fire resistance in combustion experiments.As a result,the proposed Li-S batteries with 70 wt%sulfur content in its cathode deliver stable life cycle,low self-discharge ratio,and intrinsic safety.Therefore,the unique passivation characteristics of the designed fluorinated electrolyte break several critical limitations of the traditional“liquid phase”-based Li-S batteries,offering a facile and promising way to develop long-life and high-safety Li-S batteries.
基金The authors thank the financial support of Natural Science Foundation of China(No:52002138 and 22179123)the Taishan Scholar Program of Shandong Province,China(No.tsqn202306109,tsqn202211048)the Fundamental Research Funds for the Central Universities(No.202312017 and 202262010).
文摘Metal anodes(e.g.,Li and Zn)are promising candidates for high-energy and high-power rechargeable batteries.However,the commercialization of metal anodes is hampered by irregular dendrite growth,which severely deteriorates the safety and cyclability of metal anodes.Optimizing the electrolyte by nanostructured additives to regulate the metal deposition shows great potential since the electrochemically nonreactive feature endows the regulation function with good sustainability.In this manuscript,the fundamental dendrite formation models and key parameters for stabilizing metal anode are first discussed.The progress and functional mechanism of nanostructured additives for regulating the metal deposition are summarized in terms of regulatory model,i.e.,deposition-,adsorption-and dispersion-type.Finally,we also provide a detailed concluding outlook,pointing out the future trend of selecting new nanostructured additive candidates and elucidating synergistic effects and underlying mechanisms with the key attention being given to the assessments of practicality.
基金The authors thank the financial support of Natural Science Foundation of China(grant number:52002138).
文摘Solid-state electrolytes(SSEs)are recognized as attractive candidates to real-ize safe and high-energy-density lithium metal batteries(LMBs).However,the practical application of SSEs still faces challenges such as insufficient room-temperature ionic conductivity,unsatisfactory mechanical properties,and large internal resistance.Extensive research efforts have been made to explore new electrochemistry and technologies to address those challenges.Among them,the construction of order-structured SSEs has emerged as a promising strategy.The anisotropic behavior induced by the orientation offers SSEs with desired properties targeting specific functions,and therefore the rational design of the order-structured SSE provides an alternative solution to achieve an ideal SSE.This review discusses the structure-property correlation of SSEs,and then sum-marizes the design strategies to construct order-structured SSEs.Finally,the current challenges and possible future research directions for order-structured SSEs for scalable high-energy-density LMBs are presented.
基金Acknowledgement This work was financially supported by the Major Program of the Natural Science Foundation of China （Grant No. 51090380）, the National Science Foundation for Distinguished Young Scholars of China （Grant No. 51125018）, the Knowledge Innovation Program of the Chinese Academy of Sciences （KGCX2-YW-214） and the special funds of ＂Mountain Tai Scholar＂ construction project. The computing platform was supported by the Computer Facility for Theoretical and Computational Chemistry, Institute of Chemistry （CFCC）, Chinese Academy of Sciences （CAS）.
文摘TiO2 is a latent anode material for rechargeable lithium batteries. Our simulation models, basing lepidocrocite and 2-MnO2 type TiO2 were investigated by density functional theory （DFT）. The key issues are focused on the lithium insertion sites, electronic structures, and the conducting paths of Li＋ ions. Our calculated data indicate the calculated voltage of 2-MnO2 type TiO2 is higher than that of lepidocrocite type TiO2. The Li＋ ion migration energy barrier of lepidocroeite type YiO2 along the [1 0 0] direction （0.45 eV） is lower than that of along the [110] direction （0.57 eV）. The energy barriers of 2-MnO2 type TiO2 to move a Li＋ ion among the adjacent embedded sites （16c or 8a sites） is 0.68 eV.
