In this letter,high power density AlGaN/GaN high electron-mobility transistors(HEMTs)on a freestanding GaN substrate are reported.An asymmetricΓ-shaped 500-nm gate with a field plate of 650 nm is introduced to improv...In this letter,high power density AlGaN/GaN high electron-mobility transistors(HEMTs)on a freestanding GaN substrate are reported.An asymmetricΓ-shaped 500-nm gate with a field plate of 650 nm is introduced to improve microwave power performance.The breakdown voltage(BV)is increased to more than 200 V for the fabricated device with gate-to-source and gate-to-drain distances of 1.08 and 2.92μm.A record continuous-wave power density of 11.2 W/mm@10 GHz is realized with a drain bias of 70 V.The maximum oscillation frequency(f_(max))and unity current gain cut-off frequency(f_(t))of the AlGaN/GaN HEMTs exceed 30 and 20 GHz,respectively.The results demonstrate the potential of AlGaN/GaN HEMTs on freestanding GaN substrates for microwave power applications.展开更多
This study conducted a comparative analysis of extractable hopanoid hydrocarbons and those released via stepwise pyrolysis of typical Eocene immature oil shales in China,namely the Huadian,Maoming,and Fushun shales.Bo...This study conducted a comparative analysis of extractable hopanoid hydrocarbons and those released via stepwise pyrolysis of typical Eocene immature oil shales in China,namely the Huadian,Maoming,and Fushun shales.Both the Huadian and Maoming shales exhibit immature indicators in extractable and kerogen-bound hopanoids(notably,high abundance of C_(29)to C_(32)17β,21β-hopanes and unsaturated hopenes).In contrast,the Fushun oil shale's hopanoids from extracts and pyrolyzates suggest a higher maturity level.The absence of neohopenes in the pyrolyzates of the shales underpins that the kerogenbound hopanoid skeletons resist rearrangement.However,the Huadian oil shale's asymmetric distribution of C_(29)and C_(30)hopenes and neohopenes hints at the presence of an additional source.Novel unsaturated hopenes,such as hop-20(21)-enes,identified in pyrolyzates of the three kerogens at various pyrolysis temperatures,reveal the occurrence of double bonds in kerogen-bound hopanoid skeletons without methyl rearrangements.The absence of hop-20-(21)-ene in extracts suggests that it might act as an intermediate of these novel hopenes during the epimerization of hopanoid skeletons within kerogen.The extractable and pyrolytic hopanoids'stereochemical alignment indicates that epimerization may occur in both ring systems and alkyl side chains of kerogen-bound hopanoid skeletons.Sequential stepwise pyrolysis proves to be a quick screening method for geological hopanoids without causing any significant alteration to the original skeletons even when cracking multiple covalent bonds is necessary.展开更多
Extracorporeal membrane oxygenation(ECMO)is a technology that can temporarily take over the functions of the heart and lungs.Acute kidney injury is a common issue in patients receiving ECMO treatment,with reported inc...Extracorporeal membrane oxygenation(ECMO)is a technology that can temporarily take over the functions of the heart and lungs.Acute kidney injury is a common issue in patients receiving ECMO treatment,with reported incidence rates ranging from 70%to 85%.[1]To maintain the balance of fluids and electrolytes in patients,continuous renal replacement therapy(CRRT)is frequently employed.展开更多
Electrocatalytic water splitting provides an efficient method for the production of hydrogen.In electrocatalytic water splitting,the oxygen evolution reaction(OER)involves a kinetically sluggish four-electron transfer...Electrocatalytic water splitting provides an efficient method for the production of hydrogen.In electrocatalytic water splitting,the oxygen evolution reaction(OER)involves a kinetically sluggish four-electron transfer process,which limits the efficiency of electrocatalytic water splitting.Therefore,it is urgent to develop highly active OER catalysts to accelerate reaction kinetics.Coupling single atoms and clusters in one system is an innovative approach for developing efficient catalysts that can synergistically optimize the adsorption and configuration of intermediates and improve catalytic activity.However,research in this area is still scarce.Herein,we constructed a heterogeneous single-atom cluster system by anchoring Ir single atoms and Co clusters on the surface of Ni(OH)_(2)nanosheets.Ir single atoms and Co clusters synergistically improved the catalytic activity toward the OER.Specifically,Co_(n)Ir_(1)/Ni(OH)_(2)required an overpotential of 255 mV at a current density of 10 mA·cm^(−2),which was 60 mV and 67 mV lower than those of Co_(n)/Ni(OH)_(2)and Ir1/Ni(OH)_(2),respectively.The turnover frequency of Co_(n)Ir_(1)/Ni(OH)_(2)was 0.49 s^(−1),which was 4.9 times greater than that of Co_(n)/Ni(OH)_(2)at an overpotential of 300 mV.展开更多
Rheumatoid arthritis(RA)is a chronic inflammatory and destructive arthropathy with a high deformity rate.Despite numerous studies and clinical trials,no curative treatment is available for large weight-bearing joints....Rheumatoid arthritis(RA)is a chronic inflammatory and destructive arthropathy with a high deformity rate.Despite numerous studies and clinical trials,no curative treatment is available for large weight-bearing joints.Intra-articular(IA)injections could deliver high concentrations of drug to the afflicted joint and improve the drug efficacy while reducing systemic toxicity.However,free drugs are rapidly cleared from synovial fluid and do not significantly halt the progression of joint disease.Herein,a phospholipids-based controlledrelease gel was prepared for sustained IA delivery of celastrol(CEL)and the therapeutic efficiencywas evaluated in a rheumatoid arthritis rabbitmodel.The CEL-loaded gel(CEL-gel)contained up to 70%phospholipids yetwas easy to inject.After injecting into the joint cavity,CEL-gel achieved sol to gel phase transition without special stimuli and gelling agent.In vitro release and in vivo pharmacokinetic studies evidenced the stable and sustained release action of CEL-gel.A single IA injection of CEL-gel could maintain therapeutic efficiency for about 25 d and showed much better anti-arthritic efficacy compared to repeated injections of free drug solution(CEL-sol).Furthermore,the IA injection of CEL-gel greatly reduced the systemic toxicity of CEL.With good biocompatibility and biodegradability,CEL-gel might be a promising IA drug delivery system.展开更多
Individual hydrocarbons identified to be macrocyclic alkanes in a torbanite from the Sydney Basin(Australia)were successfully isolated from its extracts using preparative gas chromatography and analyzed by NMR.Saturat...Individual hydrocarbons identified to be macrocyclic alkanes in a torbanite from the Sydney Basin(Australia)were successfully isolated from its extracts using preparative gas chromatography and analyzed by NMR.Saturated cyclic structures were confirmed by single peaks in the NMR~1H and~(13)C spectra indicating single forms of H and C atoms exist in these biomarker molecules.This is consistent with the methylene unit in a ring system assignment of the macrocyclic alkanes and accounts for a formula of(CH2)n.The unusual molecular structures of these compounds are consistent with those that were identified from previous GC retention index data and co-injection with a standard supports the previous research.The mass spectral fragmentation behaviors of representative cyclic alkanes were further investigated by comparing them with the mass spectra of isolated individual macrocyclic alkanes.The characteristic fragment ions in the macrocyclic alkanes of(M–28)+and base peaks of m/z 97,111,125,etc.,can be assigned as being generated by simple a-/i-cleavage and hydrogen rearrangement.These fragmentation pathways combined with retention indices should assist in differentiating these compounds from monounsaturated alkenes and alkylated monocyclics having similar mass spectral characteristics in other geological samples.展开更多
Acute liver injury(ALI)has an elevated fatality rate due to untimely and ineffective treatment.Although,schisandrin B(SchB)has been extensively used to treat diverse liver diseases,its therapeutic efficacy on ALI was ...Acute liver injury(ALI)has an elevated fatality rate due to untimely and ineffective treatment.Although,schisandrin B(SchB)has been extensively used to treat diverse liver diseases,its therapeutic efficacy on ALI was limited due to its high hydrophobicity.Palmitic acid-modified serum albumin(PSA)is not only an effective carrier for hydrophobic drugs,but also has a superb targeting effect via scavenger receptor-A(SR-A)on the M1 macrophages,which are potential therapeutic targets for ALI.Compared with the common macrophage-targeted delivery systems,PSA enables site-specific drug delivery to reduce off-target toxicity.Herein,we prepared SchB-PSA nanoparticles and further assessed their therapeutic effect on ALI.In vitro,compared with human serum albumin encapsulated SchB nanoparticles(SchB-HSA NPs),the SchB-PSA NPs exhibited more potent cytotoxicity on lipopolysaccharide(LPS)stimulated Raw264.7(LAR)cells,and LAR cells took up PSA NPs 8.79 times more than HSA NPs.As expected,the PSA NPs also accumulated more in the liver.Moreover,SchB-PSA NPs dramatically reduced the activation of NF-κB signaling,and significantly relieved inflammatory response and hepatic necrosis.Notably,the high dose of SchB-PSA NPs improved the survival rate in 72 h of ALI mice to 75%.Hence,SchB-PSA NPs are promising to treat ALI.展开更多
The demand for clean and sustainable energy has encouraged the production of hydrogen from water electrolyzers.To overcome the obstacle to improving the efficiency of water electrolyzers,it is highly desired to fabric...The demand for clean and sustainable energy has encouraged the production of hydrogen from water electrolyzers.To overcome the obstacle to improving the efficiency of water electrolyzers,it is highly desired to fabricate active electrocatalysts for the sluggish oxygen evolution process.However,there is generally an intrinsic gap between the as-prepared and real electrocatalysts due to structure evolution under the oxidative reaction conditions.Here,we combine in-situ anionic leaching and atomic deposition to realize single-atom catalysts with self-optimized structures.The introduced F ions facilitate structural transformation from Co(OH)xF into CoOOH(F),which generates an amorphous edge surface to provide more anchoring sites for Ir single atoms.Meanwhile,the in-situ anionic leaching of F ions elevates the Co valence state of Ir_(1)/CoOOH(F)more significantly than the counterpart without F ions(Ir_(1)/CoOOH),leading to stronger adsorption of oxygenated intermediates.As revealed by electrochemical measurements,the increased Ir loading together with the favored adsorption of*OH intermediates improve the catalytic activity of Ir_(1)/CoOOH(F).Specifically,Ir_(1)/CoOOH(F)delivered a current density of 10 mA cm-2at an overpotential of 238 mV,being lower than 314 mV for Ir_(1)/CoOOH.The results demonstrated the facility of the in-situ optimization process to optimize catalyst structure for improved performance.展开更多
Three kerogen samples(JJZG-1,JJZG-2 and JJZG-3)isolated from the Permian Lucaogou shales of varying biodegradation levels(BLs≈0,3 and 7,respectively)were subjected to sequential stepwise pyrolysis combined with on-li...Three kerogen samples(JJZG-1,JJZG-2 and JJZG-3)isolated from the Permian Lucaogou shales of varying biodegradation levels(BLs≈0,3 and 7,respectively)were subjected to sequential stepwise pyrolysis combined with on-line detection of gas chromatography-mass spectrometry(GC-MS).Occluded fractions(bitumenⅡ)released at low-temperature steps(≥410℃)show consistent biodegradative signatures with that reported for solvent-extracted fractions(bitumenⅠ)of the original shales,e.g.,broad range of abundant n-alkanes,isoprenoids and regular hopanes for the non-biodegraded JJZG-1;trace n-alkanes and abundant hopanes for the moderately biodegraded JJZG-2;and no n-alkanes but still prominent hopanes including the microbially produced 25-nohopanes for the severely biodegraded JJZG-3.This consistency between bitumenⅡand bitumenⅠfractions indicates the biodegradability of the kerogenoccluded bitumenⅡwith limited protection from host kerogen.A minor level of protection was suggested by the trace distribution of n-alkanes in the bitumenⅡof JJZG-2,whereas the bitumenⅠhad no nalkanes.The kerogen itself was more resistant to biodegradation as reflected by the persistence of high abundances of both n-alkanes and hopanes in the high temperature(≥460℃)products of all three kerogen samples.However,the relative abundances of these product groups did show some evidence of biodegradation alteration,e.g.,ratios of n-C_(15)alkene/C_(27)hop-17(21)-ene at 510℃pyrolysis decreased by order of magnitude from the non-biodegraded(JJZG-1=27.4)to highly biodegraded(0.3 for JJZG-3)samples.The reduced biodegradation impact on the kerogen fraction(Cf.bitumen fractions)was also evident by the absence of 25-norhopanes in the high-temperature analysis of the JJZG-3 kerogen.展开更多
Photodynamic therapy(PDT)is highly effective in treating tumors located near body surface,offering strong tumor suppression and low damage to normal tissue nearby.PDT is also effective for treating a number of other c...Photodynamic therapy(PDT)is highly effective in treating tumors located near body surface,offering strong tumor suppression and low damage to normal tissue nearby.PDT is also effective for treating a number of other conditions.PDT not only provide a precise and selective method for the treatment of various diseases by itself,it can also be used in combination with other traditional therapies.Because PDT uses light as the unique targeting mechanism,it has simpler and more direct targeting capability than traditional therapies.The core material of a PDT system is the photosensitizer which converts light energy to therapeutic factors/substances.Different photosensitizers have their distinct characteristics,leading to different advantages and disadvantages.These could be enhanced or compensated by using proper PDT system.Therefore,the selected type of photosensitizer would heavily influence the overall design of a PDT system.In this article,we evaluated major types of inorganic and organic PDT photosensitizers,and discussed future research directions in the field.展开更多
Photodeposition is widely adopted for implanting metal/metal oxide cocatalysts on semiconductors.However,it is prerequisite that the photon energy should be sufficient to excite the host semiconductor.Here,we report a...Photodeposition is widely adopted for implanting metal/metal oxide cocatalysts on semiconductors.However,it is prerequisite that the photon energy should be sufficient to excite the host semiconductor.Here,we report a lower-energy irradiation powered deposition strategy for implanting CrO_(x) cocatalyst on TiO_(2).Excitingly,CrO_(x)-400 implanted under visible-light irradiation significantly promotes the CH4 evolution rate on TiO_(2)to 8.4μmolg·^(-1)h^(-1) with selectivity of98%from photocatalytic CO_(2)reduction,which is 15 times of that on CrO_(x)-200 implanted under UV-visible-light irradiation.Moreover,CrO_(x)-400 is identified to be composed of higher valence Cr species compared to CrO_(x)-200.This valence states regulation of Cr species is indicated to provide more active sites for CO_(2) adsorption/activation and to modulate the reaction mechanism from single Cr site to Cr-Cr dual sites,thus endowing the superior CH_(4)production.This work demonstrates an alternative strategy for constructing efficient metal oxides cocatalysts on wide bandgap semiconductor.展开更多
Continuous-wave cavity ring-down spectroscopy(CW-CRDS)is an important technical means to monitor greenhouse gases in atmospheric environment.In this paper,a CW-CRDS system is built to meet the needs of atmospheric met...Continuous-wave cavity ring-down spectroscopy(CW-CRDS)is an important technical means to monitor greenhouse gases in atmospheric environment.In this paper,a CW-CRDS system is built to meet the needs of atmospheric methane monitoring.The problem of mode matching is explained from the perspective of transverse mode and longitudinal mode,and the influence of laser injection efficiency on measurement precision is further analyzed.The results of cavity ring-down time measurement show that the measurement precision is higher when the laser is coupled with the fundamental mode.In the experiment,DFB laser is used to calibrate the system with standard methane concentration,and the measurement residual is less than±4×10^(-4)μs^(-1).The methane concentration in the air is monitored in real time for two days.The results show the consistency of the concentration changes over the two days,which further demonstrates the reliability of the system for the measurement of trace methane.By analyzing the influence of mode matching,it not only assists the adjustment of the optical path,but also further improves the sensitivity of the system measurement.展开更多
Metastasis is closely related to the high mortality of cancer patients,which is regulated by multiple signaling pathways.Hence,multiphase blocking of this biological process is beneficial for cancer treatments.Herein,...Metastasis is closely related to the high mortality of cancer patients,which is regulated by multiple signaling pathways.Hence,multiphase blocking of this biological process is beneficial for cancer treatments.Herein,we establish a multifunctional self-delivering system by synthesizing D-α-tocopheryl succinates(TOS)-conjugated chondroitin sulfate(CS)(CT NPs),which both serve as nanocarrier and antimetastatic agent that affects different phases of the metastatic cascade.TOS as the hydrophobic segment of CT NPs can inhibit the secretion of matrix metalloproteinase-9,while the hydrophilic segment CS targets B16F10 cells through CD44 receptors and reduces the interaction between tumor cells and platelets.The results show that CT NPs are able to inhibit metastasis successfully both in vitro and in vivo by interfering the multiphase of the metastatic cascade.Following encapsulating chemotherapeutic drug doxorubicin(DOX),the obtained micelles CT/DOX efficiently suppress both primary-tumor growth and metastases in B16F10 bearing mice.As a result,the rationally designed multifunctional NPs composing of biocompatible materials provide excellent therapeutic effects on solid tumors and metastases。展开更多
The Fe3O4@SiO2 composite nanoparticles were obtained from as-synthesized magnetite (Fe3O4) nanoparticles through the modified St?ber method. Then, the Fe3O4 nanoparticles and Fe3O4@SiO2 composite nanoparticles were ch...The Fe3O4@SiO2 composite nanoparticles were obtained from as-synthesized magnetite (Fe3O4) nanoparticles through the modified St?ber method. Then, the Fe3O4 nanoparticles and Fe3O4@SiO2 composite nanoparticles were characterized by means of X-ray diffraction (XRD), Raman spectra, scanning electron microscope (SEM) and vibrating sample magnetometer (VSM). Recently, the studies focus on how to improve the dispersion of composite particle and achieve good magnetic performance. Hence effects of the volume ratio of tetraethyl orthosilicate (TEOS) and magnetite colloid on the structural, morphological and magnetic properties of the composite nanoparticles were systematically investi-gated. The results revealed that the Fe3O4@SiO2 had better thermal stability and dispersion than the magnetite nanoparticles. Furthermore, the particle size and magnetic property of the Fe3O4@SiO2 composite nanoparticles can be adjusted by changing the volume ratio of TEOS and magnetite colloid.展开更多
The optimal spectral excitation and acquisition scheme is explored by studying the effect of the lensto-sample distance(LTSD)on the spatial homogeneity and emission spectra of flat-top laser converging spot induced pl...The optimal spectral excitation and acquisition scheme is explored by studying the effect of the lensto-sample distance(LTSD)on the spatial homogeneity and emission spectra of flat-top laser converging spot induced plasma.The energy distribution characteristics before and after the convergence of the laser beam with quasi flat-top intensity profile used in this study are theoretically simulated and experimentally measured.For an aspheric converging mirror with a focal length of100 mm,the LTSD(106 mm≥LTSD≥96 mm)was changed by raising the stainless-steel sample height.The plasma images acquired by ICCD show that there is air breakdown when the sample is below the focal point,and a ring-like plasma is produced when the sample is above the focal point.When the sample is located near the focal point,the plasma shape resembles a hemisphere.Since the spectral acquisition region is confined to the plasma core and the image contains all the optical information of the plasma,it has a lower relative standard deviation(RSD)than the spectral lines.When the sample surface is slightly higher than the focal plane of the lens,the converging spot has a quasi flat-top distribution,the spatial distribution of the plasma is more uniform,and the spectral signal is more stable.Simultaneously,there is little difference between the RSD of the plasma image and the laser energy.In order to further improve the stability of the spectral signal,it is necessary to expand the spectral acquisition area.展开更多
Objective:The aim of this study was to discover the potential biomarkers changes on a rat model of isoproterenol (ISO) induced myocardial ischaemia before and after treatment with a Xiangdan submicron emulsion and to ...Objective:The aim of this study was to discover the potential biomarkers changes on a rat model of isoproterenol (ISO) induced myocardial ischaemia before and after treatment with a Xiangdan submicron emulsion and to explore the unclearing mechanisms by urinary metabolomics.Methods:Three active traditional Chinese medicine (TCM) ingredients were formulated into a lyophilized submicron emulsion powder with hydroxypropyl-β-cyclodextrin encapsulation by high pressure homogenization technology.The three ingredients were given both separately and combined,and the corresponding effects of the three drugs were compared.Principal component analysis (PCA) and the HPLC-UV analytical method was applied to explore the change of composition of urine metabolites in a rat model of isoproterenol induced myocardial ischaemia.Results:Analytical methods measuring the three active ingredients in urine samples were established.PCA score plots revealed that the therapeutic effect of the Xiangdan submicron emulsion was more significant than that of the Xiangdan injection.There was a synergistic effect among the three active ingredients.Furthermore,studies of rat metabolism changes and structure analysis of biological markers indicated that the mechanism of Xiangdan formulations was related to the inhibition of abnormal tryptophan metabolism.Conclusion:Xiangdan preparations had a confirmed effect in the treatment of coronary heart disease,especially with the novel Xiangdan submicron emulsion formulation.Urinary metabolomics methods to monitor special biomarker changes is an excellent method to reveal the mechanism of action of TCM drugs.展开更多
Immune evasion has made ovarian cancer notorious for its refractory features, making the development of immunotherapy highly appealing to ovarian cancer treatment. The immune-stimulating cytokine IL-12 exhibits excell...Immune evasion has made ovarian cancer notorious for its refractory features, making the development of immunotherapy highly appealing to ovarian cancer treatment. The immune-stimulating cytokine IL-12 exhibits excellent antitumor activities. However, IL-12 can induce IFN-γ release and subsequently upregulate PDL-1 expression on tumor cells. Therefore, the tumor-targeting folate-modified delivery system F-DPC is constructed for concurrent delivery of IL-12 encoding gene and small molecular PDL-1 inhibitor(i PDL-1) to reduce immune escape and boost anti-tumor immunity. The physicochemical characteristics, gene transfection efficiency of the F-DPC nanoparticles in ovarian cancer cells are analyzed. The immune-modulation effects of combination therapy on different immune cells are also studied. Results show that compared with non-folate-modified vector, folate-modified F-DPC can improve the targeting of ovarian cancer and enhance the transfection efficiency of p IL-12. The underlying anti-tumor mechanisms include the regulation of T cells proliferation and activation, NK activation,macrophage polarization and DC maturation. The F-DPC/p IL-12/i PDL-1 complexes have shown outstanding antitumor effects and low toxicity in peritoneal model of ovarian cancer in mice. Taken together, our work provides new insights into ovarian cancer immunotherapy. Novel F-DPC/p IL-12/i PDL-1 complexes are revealed to exert prominent anti-tumor effect by modulating tumor immune microenvironment and preventing immune escape and might be a promising treatment option for ovarian cancer treatment.展开更多
Osteosarcoma is usually resistant to immunotherapy and,thus primarily relies on surgical resection and high-dosage chemotherapy.Unfortunately,less invasive or toxic therapies such as photothermal therapy(PTT)and chemo...Osteosarcoma is usually resistant to immunotherapy and,thus primarily relies on surgical resection and high-dosage chemotherapy.Unfortunately,less invasive or toxic therapies such as photothermal therapy(PTT)and chemodynamic therapy(CDT)generally failed to show satisfactory outcomes.Adequate multimodal therapies with proper safety profiles may provide better solutions for osteosarcoma.Herein,a simple nanocomposite that synergistically combines CDT,PTT,and chemotherapy for osteosarcoma treatment was fabricated.In this composite,small 2D Ni Fe-LDH flakes were processed into 3D hollow nanospheres via template methods to encapsulate 5-Fluorouracil(5-FU)with high loading capacity.The nanospheres were then adsorbed onto larger 2D Ti3C2MXene monolayers and finally shielded by bovine serum albumin(BSA)to form 5-FU@Ni Fe-LDH/Ti3C2/BSA nanoplatforms(5NiTiB).Both in vitro and in vivo data demonstrated that the 5-FU induced chemotherapy,Ni Fe-LDH driven chemodynamic effects,and MXene-based photothermal killing collectively exhibited a synergistic“all-in-one”anti-tumor effect.5NiTiB improved tumor suppression rate from<5%by 5-FU alone to~80.1%.This nanotherapeutic platform achieved higher therapeutic efficacy with a lower agent dose,thereby minimizing side effects.Moreover,the composite is simple to produce,enabling the fine-tuning of dosages to suit different requirements.Thus,the platform is versatile and efficient,with potential for further development.展开更多
Recent clinical studies have shown that mutation of phosphatase and tensin homolog deleted on chromosome 10(PTEN)gene in cancer cells may be associated with immunosuppressive tumor microenvironment(TME)and poor respon...Recent clinical studies have shown that mutation of phosphatase and tensin homolog deleted on chromosome 10(PTEN)gene in cancer cells may be associated with immunosuppressive tumor microenvironment(TME)and poor response to immune checkpoint blockade(ICB)therapy.Therefore,efficiently restoring PTEN gene expression in cancer cells is critical to improving the responding rate to ICB therapy.Here,we screened an adeno-associated virus(AAV)capsid for efficient PTEN gene delivery into B16F10 tumor cells.We demonstrated that intratumorally injected AAV6-PTEN successfully restored the tumor cell PTEN gene expression and effectively inhibited tumor progression by inducing tumor cell immunogenic cell death(ICD)and increasing immune cell infiltration.Moreover,we developed an anti-PD-1 loaded phospholipid-based phase separation gel(PPSG),which formed an in situ depot and sustainably release anti-PD-1 drugs within 42 days in vivo.In order to effectively inhibit the recurrence of melanoma,we further applied a triple therapy based on AAV6-PTEN,PPSG^(@anti-PD-1)and CpG,and showed that this triple therapy strategy enhanced the synergistic antitumor immune effect and also induced robust immune memory,which completely rejected tumor recurrence.We anticipate that this triple therapy could be used as a new tumor combination therapy with stronger immune activation capacity and tumor inhibition efficacy.展开更多
文摘In this letter,high power density AlGaN/GaN high electron-mobility transistors(HEMTs)on a freestanding GaN substrate are reported.An asymmetricΓ-shaped 500-nm gate with a field plate of 650 nm is introduced to improve microwave power performance.The breakdown voltage(BV)is increased to more than 200 V for the fabricated device with gate-to-source and gate-to-drain distances of 1.08 and 2.92μm.A record continuous-wave power density of 11.2 W/mm@10 GHz is realized with a drain bias of 70 V.The maximum oscillation frequency(f_(max))and unity current gain cut-off frequency(f_(t))of the AlGaN/GaN HEMTs exceed 30 and 20 GHz,respectively.The results demonstrate the potential of AlGaN/GaN HEMTs on freestanding GaN substrates for microwave power applications.
基金funded by the Natural Science Foundation of China(No.42373028,No.42072154).
文摘This study conducted a comparative analysis of extractable hopanoid hydrocarbons and those released via stepwise pyrolysis of typical Eocene immature oil shales in China,namely the Huadian,Maoming,and Fushun shales.Both the Huadian and Maoming shales exhibit immature indicators in extractable and kerogen-bound hopanoids(notably,high abundance of C_(29)to C_(32)17β,21β-hopanes and unsaturated hopenes).In contrast,the Fushun oil shale's hopanoids from extracts and pyrolyzates suggest a higher maturity level.The absence of neohopenes in the pyrolyzates of the shales underpins that the kerogenbound hopanoid skeletons resist rearrangement.However,the Huadian oil shale's asymmetric distribution of C_(29)and C_(30)hopenes and neohopenes hints at the presence of an additional source.Novel unsaturated hopenes,such as hop-20(21)-enes,identified in pyrolyzates of the three kerogens at various pyrolysis temperatures,reveal the occurrence of double bonds in kerogen-bound hopanoid skeletons without methyl rearrangements.The absence of hop-20-(21)-ene in extracts suggests that it might act as an intermediate of these novel hopenes during the epimerization of hopanoid skeletons within kerogen.The extractable and pyrolytic hopanoids'stereochemical alignment indicates that epimerization may occur in both ring systems and alkyl side chains of kerogen-bound hopanoid skeletons.Sequential stepwise pyrolysis proves to be a quick screening method for geological hopanoids without causing any significant alteration to the original skeletons even when cracking multiple covalent bonds is necessary.
文摘Extracorporeal membrane oxygenation(ECMO)is a technology that can temporarily take over the functions of the heart and lungs.Acute kidney injury is a common issue in patients receiving ECMO treatment,with reported incidence rates ranging from 70%to 85%.[1]To maintain the balance of fluids and electrolytes in patients,continuous renal replacement therapy(CRRT)is frequently employed.
基金supported by the National Key Research and Development Program of China(2021YFA1500500,2019-YFA0405600)the CAS Project for Young Scientists in Basic Research(YSBR-051)+6 种基金the National Science Fund for Distinguished Young Scholars(21925204)the National Natural Science Foundation of China(22202192,U19A2015,22221003,22250007,22163002)the Collaborative Innovation Program of Hefei Science Center,CAS(2022HSCCIP004)the International Partnership,the DNL Cooperation Fund,CAS(DNL202003)the USTC Research Funds of the Double First-Class Initiative(YD9990002016,YD999000-2014)the Program of Chinese Academy of Sciences(123GJHZ2022101GC)the Fundamental Research Funds for the Central Universities(WK9990000095,WK999000-0124).
文摘Electrocatalytic water splitting provides an efficient method for the production of hydrogen.In electrocatalytic water splitting,the oxygen evolution reaction(OER)involves a kinetically sluggish four-electron transfer process,which limits the efficiency of electrocatalytic water splitting.Therefore,it is urgent to develop highly active OER catalysts to accelerate reaction kinetics.Coupling single atoms and clusters in one system is an innovative approach for developing efficient catalysts that can synergistically optimize the adsorption and configuration of intermediates and improve catalytic activity.However,research in this area is still scarce.Herein,we constructed a heterogeneous single-atom cluster system by anchoring Ir single atoms and Co clusters on the surface of Ni(OH)_(2)nanosheets.Ir single atoms and Co clusters synergistically improved the catalytic activity toward the OER.Specifically,Co_(n)Ir_(1)/Ni(OH)_(2)required an overpotential of 255 mV at a current density of 10 mA·cm^(−2),which was 60 mV and 67 mV lower than those of Co_(n)/Ni(OH)_(2)and Ir1/Ni(OH)_(2),respectively.The turnover frequency of Co_(n)Ir_(1)/Ni(OH)_(2)was 0.49 s^(−1),which was 4.9 times greater than that of Co_(n)/Ni(OH)_(2)at an overpotential of 300 mV.
基金financially supported by the National Natural Science Foundation of China (Nos. 82173758, China)Sichuan major science and technology project on biotechnology and medicine (2018SZDZX0018, China)
文摘Rheumatoid arthritis(RA)is a chronic inflammatory and destructive arthropathy with a high deformity rate.Despite numerous studies and clinical trials,no curative treatment is available for large weight-bearing joints.Intra-articular(IA)injections could deliver high concentrations of drug to the afflicted joint and improve the drug efficacy while reducing systemic toxicity.However,free drugs are rapidly cleared from synovial fluid and do not significantly halt the progression of joint disease.Herein,a phospholipids-based controlledrelease gel was prepared for sustained IA delivery of celastrol(CEL)and the therapeutic efficiencywas evaluated in a rheumatoid arthritis rabbitmodel.The CEL-loaded gel(CEL-gel)contained up to 70%phospholipids yetwas easy to inject.After injecting into the joint cavity,CEL-gel achieved sol to gel phase transition without special stimuli and gelling agent.In vitro release and in vivo pharmacokinetic studies evidenced the stable and sustained release action of CEL-gel.A single IA injection of CEL-gel could maintain therapeutic efficiency for about 25 d and showed much better anti-arthritic efficacy compared to repeated injections of free drug solution(CEL-sol).Furthermore,the IA injection of CEL-gel greatly reduced the systemic toxicity of CEL.With good biocompatibility and biodegradability,CEL-gel might be a promising IA drug delivery system.
基金the financial support from The Strategic Priority Research Program of the Chinese Academy of Sciences(XDA14010102)Chinese National Science Foundation grants(4197306941673045)。
文摘Individual hydrocarbons identified to be macrocyclic alkanes in a torbanite from the Sydney Basin(Australia)were successfully isolated from its extracts using preparative gas chromatography and analyzed by NMR.Saturated cyclic structures were confirmed by single peaks in the NMR~1H and~(13)C spectra indicating single forms of H and C atoms exist in these biomarker molecules.This is consistent with the methylene unit in a ring system assignment of the macrocyclic alkanes and accounts for a formula of(CH2)n.The unusual molecular structures of these compounds are consistent with those that were identified from previous GC retention index data and co-injection with a standard supports the previous research.The mass spectral fragmentation behaviors of representative cyclic alkanes were further investigated by comparing them with the mass spectra of isolated individual macrocyclic alkanes.The characteristic fragment ions in the macrocyclic alkanes of(M–28)+and base peaks of m/z 97,111,125,etc.,can be assigned as being generated by simple a-/i-cleavage and hydrogen rearrangement.These fragmentation pathways combined with retention indices should assist in differentiating these compounds from monounsaturated alkenes and alkylated monocyclics having similar mass spectral characteristics in other geological samples.
基金This project is financially supported by grants from the National Natural Science Foundation of China(82173758 and 81872804)Sichuan major science and technology project on biotechnology and medicine(2018SZDZX0018).
文摘Acute liver injury(ALI)has an elevated fatality rate due to untimely and ineffective treatment.Although,schisandrin B(SchB)has been extensively used to treat diverse liver diseases,its therapeutic efficacy on ALI was limited due to its high hydrophobicity.Palmitic acid-modified serum albumin(PSA)is not only an effective carrier for hydrophobic drugs,but also has a superb targeting effect via scavenger receptor-A(SR-A)on the M1 macrophages,which are potential therapeutic targets for ALI.Compared with the common macrophage-targeted delivery systems,PSA enables site-specific drug delivery to reduce off-target toxicity.Herein,we prepared SchB-PSA nanoparticles and further assessed their therapeutic effect on ALI.In vitro,compared with human serum albumin encapsulated SchB nanoparticles(SchB-HSA NPs),the SchB-PSA NPs exhibited more potent cytotoxicity on lipopolysaccharide(LPS)stimulated Raw264.7(LAR)cells,and LAR cells took up PSA NPs 8.79 times more than HSA NPs.As expected,the PSA NPs also accumulated more in the liver.Moreover,SchB-PSA NPs dramatically reduced the activation of NF-κB signaling,and significantly relieved inflammatory response and hepatic necrosis.Notably,the high dose of SchB-PSA NPs improved the survival rate in 72 h of ALI mice to 75%.Hence,SchB-PSA NPs are promising to treat ALI.
基金supported by National Key Research and Development Program of China(2021YFA1500500,2019YFA0405600,2017YFA0204904,2019YFA0405602,and 2017YFA0403402)the National Science Fund for Distinguished Young Scholars(21925204)+8 种基金the National Natural Science Foundation of China(21972132,U1732149,U19A2015,U1732272,21673214,92045301,and 21902149)the Fundamental Research Funds for the Central Universities(20720220010)the Provincial Key Research and Development Program of Anhui(202004a05020074)the Anhui Natural Science Foundation for Young Scholars(2208085QB52)K.C.Wong Education(GJTD2020-15)the Hefei Municipal Natural Science Foundation(2021018)the DNL Cooperation Fund,CAS(DNL202003)Users with Excellence Program of Hefei Science Center CAS(2020HSCUE001)USTC Research Funds of the Double First-Class Initiative(YD2340002002)。
文摘The demand for clean and sustainable energy has encouraged the production of hydrogen from water electrolyzers.To overcome the obstacle to improving the efficiency of water electrolyzers,it is highly desired to fabricate active electrocatalysts for the sluggish oxygen evolution process.However,there is generally an intrinsic gap between the as-prepared and real electrocatalysts due to structure evolution under the oxidative reaction conditions.Here,we combine in-situ anionic leaching and atomic deposition to realize single-atom catalysts with self-optimized structures.The introduced F ions facilitate structural transformation from Co(OH)xF into CoOOH(F),which generates an amorphous edge surface to provide more anchoring sites for Ir single atoms.Meanwhile,the in-situ anionic leaching of F ions elevates the Co valence state of Ir_(1)/CoOOH(F)more significantly than the counterpart without F ions(Ir_(1)/CoOOH),leading to stronger adsorption of oxygenated intermediates.As revealed by electrochemical measurements,the increased Ir loading together with the favored adsorption of*OH intermediates improve the catalytic activity of Ir_(1)/CoOOH(F).Specifically,Ir_(1)/CoOOH(F)delivered a current density of 10 mA cm-2at an overpotential of 238 mV,being lower than 314 mV for Ir_(1)/CoOOH.The results demonstrated the facility of the in-situ optimization process to optimize catalyst structure for improved performance.
基金supported by the National Natural Science Foundation of China(grants No.41972163 and 42173055).
文摘Three kerogen samples(JJZG-1,JJZG-2 and JJZG-3)isolated from the Permian Lucaogou shales of varying biodegradation levels(BLs≈0,3 and 7,respectively)were subjected to sequential stepwise pyrolysis combined with on-line detection of gas chromatography-mass spectrometry(GC-MS).Occluded fractions(bitumenⅡ)released at low-temperature steps(≥410℃)show consistent biodegradative signatures with that reported for solvent-extracted fractions(bitumenⅠ)of the original shales,e.g.,broad range of abundant n-alkanes,isoprenoids and regular hopanes for the non-biodegraded JJZG-1;trace n-alkanes and abundant hopanes for the moderately biodegraded JJZG-2;and no n-alkanes but still prominent hopanes including the microbially produced 25-nohopanes for the severely biodegraded JJZG-3.This consistency between bitumenⅡand bitumenⅠfractions indicates the biodegradability of the kerogenoccluded bitumenⅡwith limited protection from host kerogen.A minor level of protection was suggested by the trace distribution of n-alkanes in the bitumenⅡof JJZG-2,whereas the bitumenⅠhad no nalkanes.The kerogen itself was more resistant to biodegradation as reflected by the persistence of high abundances of both n-alkanes and hopanes in the high temperature(≥460℃)products of all three kerogen samples.However,the relative abundances of these product groups did show some evidence of biodegradation alteration,e.g.,ratios of n-C_(15)alkene/C_(27)hop-17(21)-ene at 510℃pyrolysis decreased by order of magnitude from the non-biodegraded(JJZG-1=27.4)to highly biodegraded(0.3 for JJZG-3)samples.The reduced biodegradation impact on the kerogen fraction(Cf.bitumen fractions)was also evident by the absence of 25-norhopanes in the high-temperature analysis of the JJZG-3 kerogen.
基金support received from Sichuan Science and Technology Program(2019JDJQ0028)。
文摘Photodynamic therapy(PDT)is highly effective in treating tumors located near body surface,offering strong tumor suppression and low damage to normal tissue nearby.PDT is also effective for treating a number of other conditions.PDT not only provide a precise and selective method for the treatment of various diseases by itself,it can also be used in combination with other traditional therapies.Because PDT uses light as the unique targeting mechanism,it has simpler and more direct targeting capability than traditional therapies.The core material of a PDT system is the photosensitizer which converts light energy to therapeutic factors/substances.Different photosensitizers have their distinct characteristics,leading to different advantages and disadvantages.These could be enhanced or compensated by using proper PDT system.Therefore,the selected type of photosensitizer would heavily influence the overall design of a PDT system.In this article,we evaluated major types of inorganic and organic PDT photosensitizers,and discussed future research directions in the field.
基金supported by the National Key Research and Development Program of China(2016YFB0700205,2017YFA0403402,2019YFA0405602,2017YFA0204904)the National Natural Science Foundation of China(52002367,21673214,U1732272,U1632273,U1832165)+1 种基金the foundation from Users with Excellence Program of Hefei Science Center CAS(2020HSC-UE001)the Fundamental Research Funds for the Central Universities(WK2310000093)。
文摘Photodeposition is widely adopted for implanting metal/metal oxide cocatalysts on semiconductors.However,it is prerequisite that the photon energy should be sufficient to excite the host semiconductor.Here,we report a lower-energy irradiation powered deposition strategy for implanting CrO_(x) cocatalyst on TiO_(2).Excitingly,CrO_(x)-400 implanted under visible-light irradiation significantly promotes the CH4 evolution rate on TiO_(2)to 8.4μmolg·^(-1)h^(-1) with selectivity of98%from photocatalytic CO_(2)reduction,which is 15 times of that on CrO_(x)-200 implanted under UV-visible-light irradiation.Moreover,CrO_(x)-400 is identified to be composed of higher valence Cr species compared to CrO_(x)-200.This valence states regulation of Cr species is indicated to provide more active sites for CO_(2) adsorption/activation and to modulate the reaction mechanism from single Cr site to Cr-Cr dual sites,thus endowing the superior CH_(4)production.This work demonstrates an alternative strategy for constructing efficient metal oxides cocatalysts on wide bandgap semiconductor.
基金This research is financial supported by the Natural National Science Foundation of China(Grant Nos.11874364,41877311,and 42005107)the National Key Research and Development Program of China(Grant No.2017YFC0805004)the CAS&Bengbu Technology Transfer Project(Grant No.ZKBB202102).
文摘Continuous-wave cavity ring-down spectroscopy(CW-CRDS)is an important technical means to monitor greenhouse gases in atmospheric environment.In this paper,a CW-CRDS system is built to meet the needs of atmospheric methane monitoring.The problem of mode matching is explained from the perspective of transverse mode and longitudinal mode,and the influence of laser injection efficiency on measurement precision is further analyzed.The results of cavity ring-down time measurement show that the measurement precision is higher when the laser is coupled with the fundamental mode.In the experiment,DFB laser is used to calibrate the system with standard methane concentration,and the measurement residual is less than±4×10^(-4)μs^(-1).The methane concentration in the air is monitored in real time for two days.The results show the consistency of the concentration changes over the two days,which further demonstrates the reliability of the system for the measurement of trace methane.By analyzing the influence of mode matching,it not only assists the adjustment of the optical path,but also further improves the sensitivity of the system measurement.
基金supported by Major Projects of the National Natural Science Foundation of China(81974499)Sichuan Science and Technology Program(2018RZ0136)Sichuan Veterinary Medicine and Drug innovation Group of China Agricultural Research System(SCCXTD-2020-18).
文摘Metastasis is closely related to the high mortality of cancer patients,which is regulated by multiple signaling pathways.Hence,multiphase blocking of this biological process is beneficial for cancer treatments.Herein,we establish a multifunctional self-delivering system by synthesizing D-α-tocopheryl succinates(TOS)-conjugated chondroitin sulfate(CS)(CT NPs),which both serve as nanocarrier and antimetastatic agent that affects different phases of the metastatic cascade.TOS as the hydrophobic segment of CT NPs can inhibit the secretion of matrix metalloproteinase-9,while the hydrophilic segment CS targets B16F10 cells through CD44 receptors and reduces the interaction between tumor cells and platelets.The results show that CT NPs are able to inhibit metastasis successfully both in vitro and in vivo by interfering the multiphase of the metastatic cascade.Following encapsulating chemotherapeutic drug doxorubicin(DOX),the obtained micelles CT/DOX efficiently suppress both primary-tumor growth and metastases in B16F10 bearing mice.As a result,the rationally designed multifunctional NPs composing of biocompatible materials provide excellent therapeutic effects on solid tumors and metastases。
文摘The Fe3O4@SiO2 composite nanoparticles were obtained from as-synthesized magnetite (Fe3O4) nanoparticles through the modified St?ber method. Then, the Fe3O4 nanoparticles and Fe3O4@SiO2 composite nanoparticles were characterized by means of X-ray diffraction (XRD), Raman spectra, scanning electron microscope (SEM) and vibrating sample magnetometer (VSM). Recently, the studies focus on how to improve the dispersion of composite particle and achieve good magnetic performance. Hence effects of the volume ratio of tetraethyl orthosilicate (TEOS) and magnetite colloid on the structural, morphological and magnetic properties of the composite nanoparticles were systematically investi-gated. The results revealed that the Fe3O4@SiO2 had better thermal stability and dispersion than the magnetite nanoparticles. Furthermore, the particle size and magnetic property of the Fe3O4@SiO2 composite nanoparticles can be adjusted by changing the volume ratio of TEOS and magnetite colloid.
基金supported by the Young Scientists Fund of National Natural Science Foundation of China(No.12004388)the National High Technology Research and Development Program of China(No.2021YFB3202402)+1 种基金the Key Research and Development Plan of Anhui Province(No.202104i07020009)the Collaborative Innovation Program of Hefei Science Center,CAS(No.2021HSCCIP005)。
文摘The optimal spectral excitation and acquisition scheme is explored by studying the effect of the lensto-sample distance(LTSD)on the spatial homogeneity and emission spectra of flat-top laser converging spot induced plasma.The energy distribution characteristics before and after the convergence of the laser beam with quasi flat-top intensity profile used in this study are theoretically simulated and experimentally measured.For an aspheric converging mirror with a focal length of100 mm,the LTSD(106 mm≥LTSD≥96 mm)was changed by raising the stainless-steel sample height.The plasma images acquired by ICCD show that there is air breakdown when the sample is below the focal point,and a ring-like plasma is produced when the sample is above the focal point.When the sample is located near the focal point,the plasma shape resembles a hemisphere.Since the spectral acquisition region is confined to the plasma core and the image contains all the optical information of the plasma,it has a lower relative standard deviation(RSD)than the spectral lines.When the sample surface is slightly higher than the focal plane of the lens,the converging spot has a quasi flat-top distribution,the spatial distribution of the plasma is more uniform,and the spectral signal is more stable.Simultaneously,there is little difference between the RSD of the plasma image and the laser energy.In order to further improve the stability of the spectral signal,it is necessary to expand the spectral acquisition area.
文摘Objective:The aim of this study was to discover the potential biomarkers changes on a rat model of isoproterenol (ISO) induced myocardial ischaemia before and after treatment with a Xiangdan submicron emulsion and to explore the unclearing mechanisms by urinary metabolomics.Methods:Three active traditional Chinese medicine (TCM) ingredients were formulated into a lyophilized submicron emulsion powder with hydroxypropyl-β-cyclodextrin encapsulation by high pressure homogenization technology.The three ingredients were given both separately and combined,and the corresponding effects of the three drugs were compared.Principal component analysis (PCA) and the HPLC-UV analytical method was applied to explore the change of composition of urine metabolites in a rat model of isoproterenol induced myocardial ischaemia.Results:Analytical methods measuring the three active ingredients in urine samples were established.PCA score plots revealed that the therapeutic effect of the Xiangdan submicron emulsion was more significant than that of the Xiangdan injection.There was a synergistic effect among the three active ingredients.Furthermore,studies of rat metabolism changes and structure analysis of biological markers indicated that the mechanism of Xiangdan formulations was related to the inhibition of abnormal tryptophan metabolism.Conclusion:Xiangdan preparations had a confirmed effect in the treatment of coronary heart disease,especially with the novel Xiangdan submicron emulsion formulation.Urinary metabolomics methods to monitor special biomarker changes is an excellent method to reveal the mechanism of action of TCM drugs.
基金supported by the National Natural Science Foundation of China(Nos.32222046,82172630,82170844 and 82270613,China)the Sichuan Science and Technology Program(Nos.2022YFH0045 and 2022YFH0102,China)the 1·3·5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(No.ZYJC21022,China).
文摘Immune evasion has made ovarian cancer notorious for its refractory features, making the development of immunotherapy highly appealing to ovarian cancer treatment. The immune-stimulating cytokine IL-12 exhibits excellent antitumor activities. However, IL-12 can induce IFN-γ release and subsequently upregulate PDL-1 expression on tumor cells. Therefore, the tumor-targeting folate-modified delivery system F-DPC is constructed for concurrent delivery of IL-12 encoding gene and small molecular PDL-1 inhibitor(i PDL-1) to reduce immune escape and boost anti-tumor immunity. The physicochemical characteristics, gene transfection efficiency of the F-DPC nanoparticles in ovarian cancer cells are analyzed. The immune-modulation effects of combination therapy on different immune cells are also studied. Results show that compared with non-folate-modified vector, folate-modified F-DPC can improve the targeting of ovarian cancer and enhance the transfection efficiency of p IL-12. The underlying anti-tumor mechanisms include the regulation of T cells proliferation and activation, NK activation,macrophage polarization and DC maturation. The F-DPC/p IL-12/i PDL-1 complexes have shown outstanding antitumor effects and low toxicity in peritoneal model of ovarian cancer in mice. Taken together, our work provides new insights into ovarian cancer immunotherapy. Novel F-DPC/p IL-12/i PDL-1 complexes are revealed to exert prominent anti-tumor effect by modulating tumor immune microenvironment and preventing immune escape and might be a promising treatment option for ovarian cancer treatment.
基金supported by the National Science Fund for Excellent Young Scholars(No.82022070,China)National Natural Science Foundation of China(NSFC)General Program(No.81872824,China)。
文摘Osteosarcoma is usually resistant to immunotherapy and,thus primarily relies on surgical resection and high-dosage chemotherapy.Unfortunately,less invasive or toxic therapies such as photothermal therapy(PTT)and chemodynamic therapy(CDT)generally failed to show satisfactory outcomes.Adequate multimodal therapies with proper safety profiles may provide better solutions for osteosarcoma.Herein,a simple nanocomposite that synergistically combines CDT,PTT,and chemotherapy for osteosarcoma treatment was fabricated.In this composite,small 2D Ni Fe-LDH flakes were processed into 3D hollow nanospheres via template methods to encapsulate 5-Fluorouracil(5-FU)with high loading capacity.The nanospheres were then adsorbed onto larger 2D Ti3C2MXene monolayers and finally shielded by bovine serum albumin(BSA)to form 5-FU@Ni Fe-LDH/Ti3C2/BSA nanoplatforms(5NiTiB).Both in vitro and in vivo data demonstrated that the 5-FU induced chemotherapy,Ni Fe-LDH driven chemodynamic effects,and MXene-based photothermal killing collectively exhibited a synergistic“all-in-one”anti-tumor effect.5NiTiB improved tumor suppression rate from<5%by 5-FU alone to~80.1%.This nanotherapeutic platform achieved higher therapeutic efficacy with a lower agent dose,thereby minimizing side effects.Moreover,the composite is simple to produce,enabling the fine-tuning of dosages to suit different requirements.Thus,the platform is versatile and efficient,with potential for further development.
基金This study was supported by National Natural Science Foundation of China(Grant Nos.81925036,China)the Key Research and Development Program of Science and Technology Department of Sichuan Province(Grant No.2020YFS0570,China)111 project(Grant No.B18035,China).
文摘Recent clinical studies have shown that mutation of phosphatase and tensin homolog deleted on chromosome 10(PTEN)gene in cancer cells may be associated with immunosuppressive tumor microenvironment(TME)and poor response to immune checkpoint blockade(ICB)therapy.Therefore,efficiently restoring PTEN gene expression in cancer cells is critical to improving the responding rate to ICB therapy.Here,we screened an adeno-associated virus(AAV)capsid for efficient PTEN gene delivery into B16F10 tumor cells.We demonstrated that intratumorally injected AAV6-PTEN successfully restored the tumor cell PTEN gene expression and effectively inhibited tumor progression by inducing tumor cell immunogenic cell death(ICD)and increasing immune cell infiltration.Moreover,we developed an anti-PD-1 loaded phospholipid-based phase separation gel(PPSG),which formed an in situ depot and sustainably release anti-PD-1 drugs within 42 days in vivo.In order to effectively inhibit the recurrence of melanoma,we further applied a triple therapy based on AAV6-PTEN,PPSG^(@anti-PD-1)and CpG,and showed that this triple therapy strategy enhanced the synergistic antitumor immune effect and also induced robust immune memory,which completely rejected tumor recurrence.We anticipate that this triple therapy could be used as a new tumor combination therapy with stronger immune activation capacity and tumor inhibition efficacy.