Myocardial damage resulting from acute myocardial infarction often leads to progressive heart failure and sudden death,highlighting the urgent clinical need for effective therapies.Recently,tanshinoneⅡA has been iden...Myocardial damage resulting from acute myocardial infarction often leads to progressive heart failure and sudden death,highlighting the urgent clinical need for effective therapies.Recently,tanshinoneⅡA has been identified as a promising therapeutic agent for myocardial infarction.However,efficient delivery remains a major issue that limits clinical translation.To address this problem,an injectable thermosensitive poly(lactic acid-co-glycolic acid)-block-poly(ethylene glycol)-block-poly(lactic acid-co-glycolic acid)gel(PLGA-PEG-PLGA)system encapsulating tanshinoneⅡA-loaded reactive oxygen species-sensitive microspheres(Gel-MS/tanshinoneⅡA)has been designed and synthesized in this study.The thermosensitive hydrogel exhibits good mechanical properties after reaching body temperature.Microspheres initially immobilized by the gel exhibit excellent reactive oxygen species-triggered release properties in a high-reactive oxygen species environment after myocardial infarction onset.As a result,encapsulated tanshinoneⅡA is effectively released into the infarcted myocardium,where it exerts local anti-pyroptotic and anti-inflammatory effects.Importantly,the combined advantages of this technique contribute to the mitigation of left ventricular remodeling and the restoration of cardiac function following tanshinoneⅡA.Therefore,this novel,precision-guided intra-tissue therapeutic system allows for customized local release of tanshinoneⅡA,presenting a promising alternative treatment strategy aimed at inducing beneficial ventricular remodeling in the post-infarct heart.展开更多
Ovarian cancer(OC)is one of the most common and recurring malignancies in gynecology.Patients with relapsed OC always develop"cascade drug resistance"(CDR)under repeated chemotherapy,leading to subsequent fa...Ovarian cancer(OC)is one of the most common and recurring malignancies in gynecology.Patients with relapsed OC always develop"cascade drug resistance"(CDR)under repeated chemotherapy,leading to subsequent failure of chemotherapy.To overcome this challenge,amphiphiles(P1)carrying a nitric oxide(NO)donor(Isosorbide 5-mononitrate,ISMN)and high-density disulfide are synthesized for encapsulatingmitochondria-targeted tetravalent platinum prodrug(TPt)to construct a nanocomposite(INP@TPt).Mechanism studies indicated that INP@TPt significantly inhibited drug-resistant cells by increasing cellular uptake and mitochondrial accumulation of platinum,depleting glutathione,and preventing apoptosis escape through generating highly toxic peroxynitrite anion(ONOO−).To better replicate the microenvironmental and histological characteristics of the drug resistant primary tumor,an OC patient-derived tumor xenograft(PDXOC)model in BALB/c nude mice was established.INP@TPt showed the best therapeutic effects in the PDXOC model.The corresponding tumor tissues contained high ONOO−levels,which were attributed to the simultaneous release of O_(2)^(·−)and NO in tumor tissues.Taken together,INP@TPtbased systematic strategy showed considerable potential and satisfactory biocompatibility in overcoming platinum CDR,providing practical applications for ovarian therapy.展开更多
Hepatocellular carcinoma(HCC)is one of the deadliest cancers due to its complexities,reoccurrence after surgical resection,metastasis and heterogeneity.In addition to sorafenib and lenvatinib for the treatment of HCC ...Hepatocellular carcinoma(HCC)is one of the deadliest cancers due to its complexities,reoccurrence after surgical resection,metastasis and heterogeneity.In addition to sorafenib and lenvatinib for the treatment of HCC approved by FDA,various strategies including transarterial chemoembolization,radiotherapy,locoregional therapy and chemotherapy have been investigated in clinics.Recently,cancer nanotechnology has got great attention for the treatment of various cancers including HCC.Both passive and active targetings are progressing at a steady rate.Herein,we describe the lessons learned from pathogenesis of HCC and the understanding of targeted and non-targeted nanoparticles used for the delivery of small molecules,monoclonal antibodies,miRNAs and peptides.Exploring current efficacy is to enhance tumor cell response of chemotherapy.It highlights the opportunities and challenges faced by nanotechnologies in contemporary hepatocellular carcinoma therapy,where personalized medicine is increasingly becoming the mainstay.Overall objective of this review is to enhance our understanding in the design and development of nanotechnology for treatment of HCC.展开更多
The Songliao Basin in Northeast Asia is the largest and longest-lived rift basin and preserves a nearcontinuous continental succession of the most of the Cretaceous period,providing great material to investigate the a...The Songliao Basin in Northeast Asia is the largest and longest-lived rift basin and preserves a nearcontinuous continental succession of the most of the Cretaceous period,providing great material to investigate the adaption of the terrestrial systems to the Cretaceous greenhouse climate and tectonic events.However,the paucity of precise and accurate radioisotopic ages from the Early Cretaceous strata of the Songliao Basin has greatly held back the temporal and causal correlation of the continental records to the global Early Cretaceous records.Three tuff layers intercalated in the Yingcheng Formation have been intercepted by the SK-2 borehole,which offer excellent materials for radioisotopic dating and calibration of the chronostratigraphy of the Lower Cretaceous sequence of Songliao Basin.Moreover,the Yingcheng Formation recorded the largest and the last of the two major volcanic events in Songliao Basin,which also represents a turning point in the basin evolution history of Songliao from syn-rift stage to post-rift stage.Here we report high-precision U–Pb zircon geochronology by the CA-ID-TIMS technique on three tuff samples from the Yingcheng Formation of the SK-2 borehole in the Songliao Basin to construct a greatly improved,absolute age framework for the Yingcheng Formation and provide crucial age constraints for the Songliao Lower Cretaceous Strata.The new CA-ID-TIMS geochronology constrained the Yingcheng Formation at 102.571+0.320/-2.346 Ma to ca.113 Ma,correlating to the Albian Stage.Combined with the previous published Songliao geochronology,the Quantou Formation is constrained to between 96.442+0.475/-0.086 Ma and 91.923+0.475/-0.086 Ma;the Denglouku Formation is constrained to between 102.571+0.320/-2.346 Ma and 96.442+0.475/-0.086 Ma;the age of the Shahezi Formation is estimated at ca.113 Ma to ca.118 Ma,which could extend to ca.125 Ma in some locations in Songliao Basin.The major unconformity between the Yingcheng Formation and the Denglouku Formation,which represents the transition of the basin from syn-rift to post-rift is thus confined to between 102.571+0.320/-2.346 Ma and 96.442+0.475/-0.086 Ma.This is roughly contemporaneous with the change in the direction of the paleo-Pacific plate motion from west-southwest to north or northwest in mid-Cretaceous,suggesting their possible connections.展开更多
Because of the rapid development of industrial processes, increased urban pollution and agricultural chemicals applied in recent years, heavy metal(loid) pollution in soil has been very serious, and there is an urgent...Because of the rapid development of industrial processes, increased urban pollution and agricultural chemicals applied in recent years, heavy metal(loid) pollution in soil has been very serious, and there is an urgent need for fast and efficient removal of heavy metal(loid) pollution. Currently, environmental microorganisms are always used to perform biological alteration or improvement of soils and sewage. Using functional microorganisms that are resistant to toxic heavy metal(loid) ions for alteration and transformation of heavy metal(loid)s in ionic form is an effective measure for microbial remediation of heavy metal(loid)contaminated soil. This paper reviewed the microbial remediation mechanism of heavy metal(loid) contaminated soils, and the approaches for breeding bacteria those can be used for highly efficient removal of heavy metal(loid)s, as well as the application examples of microbial remediation and transformation of heavy metal(loid) contaminated soil, and finally described the future trends and further research work of heavy metal(loid) contaminated soils by microbial remediation.展开更多
In this study,an optical setup for generating terahertz(THz)pulses through a two-color femtosecond laser filament was carefully designed to achieve a precise overlap of two-color laser pulses in space and time.β-bari...In this study,an optical setup for generating terahertz(THz)pulses through a two-color femtosecond laser filament was carefully designed to achieve a precise overlap of two-color laser pulses in space and time.β-barium borate(BBO),α-BBO,and a dual-wavelength plate were used to compensate the phase delay of the two-color lasers.Tilting ofα-BBO could further realize the precise spatial overlap of the two beams by counteracting the walk-off effect.The maximum out-put THz pulse energy reached 21μJ in argon gas when using a commercial Ti:sapphire laser with a pulse energy of 6 mJ at a 1 kHz repetition rate.The corresponding conversion efficiency exceeded 0.35%.展开更多
We present a novel sea-ice classification framework based on locality preserving fusion of multi-source images information.The locality preserving fusion arises from two-fold,i.e.,the local characterization in both sp...We present a novel sea-ice classification framework based on locality preserving fusion of multi-source images information.The locality preserving fusion arises from two-fold,i.e.,the local characterization in both spatial and feature domains.We commence by simultaneously learning a projection matrix,which preserves spatial localities,and a similarity matrix,which encodes feature similarities.We map the pixels of multi-source images by the projection matrix to a set fusion vectors that preserve spatial localities of the image.On the other hand,by applying the Laplacian eigen-decomposition to the similarity matrix,we obtain another set of fusion vectors that preserve the feature local similarities.We concatenate the fusion vectors for both spatial and feature locality preservation and obtain the fusion image.Finally,we classify the fusion image pixels by a novel sliding ensemble strategy,which enhances the locality preservation in classification.Our locality preserving fusion framework is effective in classifying multi-source sea-ice images(e.g.,multi-spectral and synthetic aperture radar(SAR)images)because it not only comprehensively captures the spatial neighboring relationships but also intrinsically characterizes the feature associations between different types of sea-ices.Experimental evaluations validate the effectiveness of our framework.展开更多
Since the azo dyes widely used in textile-dyeing industry are toxic, highly persistent, and ubiquitously distributed in the environment, their treatment efficiencies and fade in ecosystems have received worldwide atte...Since the azo dyes widely used in textile-dyeing industry are toxic, highly persistent, and ubiquitously distributed in the environment, their treatment efficiencies and fade in ecosystems have received worldwide attention. Due to the microbes play important roles in azo-dye degradation, exogenous nutrient addition is used as a promising biostimulation strategy to improve the treatment efficiencies of azo-dye wastewater. However, little is known about the effects of different kinds of exogenous nutrients on the azo-dye wastewater treatment directly. Here, three kinds of common nutrients, glucose, starch and yeast extract, were added to the sequencing batch reactors (SBR) for the treatment of wastewater containing acid red 73 to compare the biostimulation efficiencies by investigating the dye's removal efficiencies and the changes of related water qualities. Our results showed that the reactors added yeast extract had highest removal efficiencies and chemical oxygen demand (COD) as well, followed by glucose and starch. The removal rates of acid red 73 and COD were 90.63% and 8713% in the reactors added yeast extract, respectively, while 86.49% and 78.4% in those with glucose and 85.38% and 75.2% in those with starch. This study provided some useful information for the biostimulation strategy of azo-dye wastewater treatment and preliminarily suggested that yeast extract would be the optimal choice.展开更多
Hepatocellular carcinoma is a common and fatal malignancy for which there is no effective systemic therapeutic strategy.Dihydroartemisinin(DHA),a derivative of artemisinin,has been shown to exert anti-tumor effects th...Hepatocellular carcinoma is a common and fatal malignancy for which there is no effective systemic therapeutic strategy.Dihydroartemisinin(DHA),a derivative of artemisinin,has been shown to exert anti-tumor effects through the production of reactive oxygen species(ROS)and resultant mitochondrial damage.However,clinical translation is limited by several drawbacks,such as insolubility,instability and low bioavailability.Here,based on a nanomedicine-based delivery strategy,we fabricated mitochondria-targeted carrier-free nanoparticles coupling DHA and triphenylphosphonium(TPP),aiming to improve bioavailability and mitochondrial targeting.DHA-TPP nanoparticles can be passively delivered to the tumor site by enhanced penetration and retention and then internalized.Flow cytometry and Western blot analysis showed that DHA-TPP nanoparticles increased intracellular ROS,which increased mitochondrial stress and in turn upregulated the downstream Bcl-2 pathway,leading to apoptosis.In vivo experiments showed that DHA-TPP nanoparticles exhibited anti-tumor effects in a mouse model of hepatocellular carcinoma.These findings suggest carrier-free DHA-TPP nanoparticles as a potential therapeutic strategy for hepatocellular carcinoma.展开更多
In order to decipher element mobility in UHP meta-sedimentary rocks in the continental subduction zone,major and trace element compositions are investigated for a continuous profile from a representative UHP region in...In order to decipher element mobility in UHP meta-sedimentary rocks in the continental subduction zone,major and trace element compositions are investigated for a continuous profile from a representative UHP region in the Dabie Mountains.Among the lithologic contact zone,contents of K,Ca,LREE,and LILE exhibit varying degrees of downward trends in both marble and eclogite toward the contact zone,indicating that marble and their associated eclogite can release a large amount of K,Ca,and a small number of LILEs and LREEs.Titanite is the main Ti phase in both marble and eclogite.Titanite rims around rutile can occasionally be seen in eclogite.Contents of Ti and HFSE exhibit a well-coupled relation among marble and eclogite,indicating that substantial Ti and HFSEs were migrated from eclogite to marble,in accord with the capacity of a melt medium.Rutiles and titanites in marble exhibit a relatively limited variation in Nb/Ta ratios(12.9-16.2),similar to those of titanites in eclogite(14.2-16.7),which demonstrates that rutiles and titanites in marble were sourced from eclogite because of short-distance migrations of Ti and HFSEs.According to the P-T path and the temperature and pressure conditions of the peak metamorphism reported by previous studies,the eclogite associated with marble may not form supercritical fluids in the subduction zone because of the addition of carbonate minerals.展开更多
Anticancer platinum prodrugs that can be controllably activated are highly desired for personalized precision medicine and patient compliance in cancer therapy.However,the clinical application of platinum(Ⅳ)prodrugs(...Anticancer platinum prodrugs that can be controllably activated are highly desired for personalized precision medicine and patient compliance in cancer therapy.However,the clinical application of platinum(Ⅳ)prodrugs(Pt(Ⅳ))is restricted by tissue penetration of external irradiation.Here,we report a novel Pt(Ⅳ)activation strategy based on endogenous luminescence of tumor microenvironment responsiveness,which completely circumvents the limitation of external irradiation.The designed Pt(Ⅳ)–Lu,a mixture of trans,trans,trans-[Pt(N_(3))_(2)(OH)_(2)(py)_(2)]and luminol(Lu),has controllable activation property:it remains inert in reductant environment and normal tissues,but under tumor microenvironment,Lu will be oxidized to produce blue luminescence,which rapidly reduce Pt(Ⅳ)to Pt(Ⅱ)without the need of any external activator.Pt(Ⅳ)–Lu shows excellent responsive antitumor ability both in vitro and in vivo.Compared to cisplatin,the median lethal dose in BALB/c mice increased by an order of magnitude.Our results suggest that Pt(Ⅳ)–Lu exhibits highly controllable activation property,superior antitumor activity,and good biosafety,which may provide a novel strategy for the design of platinum prodrugs.展开更多
Recently,the utilization of nonsteroidal anti-inflammatory drugs(NSAIDs)to sensitize cisplatin(CDDP)has gained substantial traction in the treatment of ovarian cancer(OC).However,even widely employed NSAIDs such as ce...Recently,the utilization of nonsteroidal anti-inflammatory drugs(NSAIDs)to sensitize cisplatin(CDDP)has gained substantial traction in the treatment of ovarian cancer(OC).However,even widely employed NSAIDs such as celecoxib and naproxen carry an elevated risk of cardiovascular events,notably throm-bosis.Furthermore,the diminished sensitivity to CDDP therapy in OC is multifactorial,rendering the ap-plication of NSAIDs only partially effective due to their cyclooxygenase-2(COX-2)inhibiting mechanism.Hence,in this study,reactive oxygen species(ROS)-responsive composite nano-hydrangeas loaded with the Chinese medicine small molecule allicin and platinum(IV)prodrug(DTP@AP NPs)were prepared to achieve comprehensive chemosensitization.On one front,allicin achieved COX-2 blocking therapy,en-compassing the inhibition of proliferation,angiogenesis and endothelial mesenchymal transition(EMT),thereby mitigating the adverse impacts of CDDP chemotherapy.Simultaneously,synergistic chemosensi-tization was achieved from multifaceted mechanisms by decreasing CDDP inactivation,damaging mito-chondria and inhibiting DNA repair.In essence,these findings provided an optimized approach for syner-gizing CDDP with COX-2 inhibitors,offering a promising avenue for enhancing OC treatment outcomes.展开更多
Liposomes are one of the significant classes of antitumor nanomaterials and the most successful nanomedicine drugs in clinical translation. However, it is difficult to accurately reveal liposome delivery modes and dru...Liposomes are one of the significant classes of antitumor nanomaterials and the most successful nanomedicine drugs in clinical translation. However, it is difficult to accurately reveal liposome delivery modes and drug release rates at different p H values to assess the biodistribution and drug delivery pathways in vivo. Here, we established a strategy to integrate Bi-doped carbon quantum dots(CQDs)with liposomes to produce fluorescence visualization and therapeutic effects, namely lipo/Bi-doped CQDs.Lipo/Bi-doped CQDs show good water solubility and physicochemical properties, which can be used for in vitro labeling of colon cancer(CT26) cells and in vivo imaging localization tracking tumors for monitoring. Simultaneously, thanks to the excellent p H sensitivity and ion doping characteristic of Bi-doped CQDs, lipo/Bi-doped CQDs can be used to reveal the drug release rate of liposomes at different p H values and exhibit potential effects in vivo antitumor therapy.展开更多
Low tumor immunogenicity,immunosuppressive tumor microenvironment,and bacterial infections have emerged as significant challenges in postsurgical immunotherapy and skin regeneration for preventing melanoma recurrence....Low tumor immunogenicity,immunosuppressive tumor microenvironment,and bacterial infections have emerged as significant challenges in postsurgical immunotherapy and skin regeneration for preventing melanoma recurrence.Herein,an immunotherapeutic hydrogel booster(GelMA-CJCNPs)was developed to prevent postoperative tumor recurrence and promote wound healing by incorporating ternary carrier-free nanoparticles(CJCNPs)containing chlorine e6(Ce6),a BRD4 inhibitor(JQ1),and a glutaminase inhibitor(C968)into methacrylic anhydride-modified gelatin(GelMA)dressings.GelMA-CJCNPs reduced glutathione production by inhibiting glutamine metabolism,thereby preventing the destruction of reactive oxygen species generated by photodynamic therapy,which could amplify oxidative stress to induce severe cell death and enhance immunogenic cell death.In addition,GelMA-CJCNPs reduced M2-type tumor-associated macrophage polarization by blocking glutamine metabolism to reverse the immunosuppressive tumor microenvironment,recruiting more tumor-infiltrating T lymphocytes.GelMA-CJCNPs also downregulated IFN-γ-induced expression of programmed cell death ligand 1 to mitigate acquired immune resistance.Benefiting from the amplified systemic antitumor immunity,GelMA-CJCNPs markedly inhibited the growth of both primary and distant tumors.Moreover,GelMA-CJCNPs demonstrated satisfactory photodynamic antibacterial effects against Staphylococcus aureus infections,thereby promoting postsurgical wound healing.Hence,this immunotherapeutic hydrogel booster,as a facile and effective postoperative adjuvant,possesses a promising potential for inhibiting tumor recurrence and accelerating skin regeneration.展开更多
The field of artificial intelligence and neural computing has been rapidly expanding due to the imple-mentation of resistive random-access memory(RRAM)based artificial synaptic.However,the low flexibility of conventio...The field of artificial intelligence and neural computing has been rapidly expanding due to the imple-mentation of resistive random-access memory(RRAM)based artificial synaptic.However,the low flexibility of conventional RRAM materials hinders their ability to mimic synaptic behavior accurately.To overcome such limitation,organic-2D composites with high mechanical properties are proposed as the active layer of RRAM.Moreover,we enhance the reliability of the device by ZrO_(2)insertion layer,resulting in stable synaptic performance.The Ag/PVA:h-BN/ZrO_(2)/ITO devices show stable bipolar resistive switching behavior with an ON/OFF ratio of over 5×10^(2),a~2400 cycles endurance and a long retention time(>6×10^(3)s),which are essential for the development of high-performance RRAMs.We also study the possible synaptic mechanism and dynamic plasticity of the memory device,observing the transition from short-term potentiation(STP)to long-term potentiation(LTP)under the effect of continuous voltage pulses.Moreover,the device exhibits both long-term depression(LTD)and paired-pulse facili-tation(PPF)properties,which have significant implications for the design of organic-2D composite material RRAMs that aim to mimic biological synapses,representing promising avenues for the devel-opment of advanced neuromorphic computing systems.展开更多
Over the years,electroconductive hydrogels(ECHs)have been extensively applied for stimulating nerve regeneration and restoring locomotor function after peripheral nerve injury(PNI)with diabetes,given their favorable m...Over the years,electroconductive hydrogels(ECHs)have been extensively applied for stimulating nerve regeneration and restoring locomotor function after peripheral nerve injury(PNI)with diabetes,given their favorable mechanical and electrical properties identical to endogenous nerve tissue.Nevertheless,PNI causes the loss of locomotor function and inflammatory pain,especially in diabetic patients.It has been established that bone marrow stem cells-derived exosomes(BMSCs-Exos)have analgesic,anti-inflammatory and tissue regeneration properties.Herein,we designed an ECH loaded with BMSCs-Exos(ECH-Exos)electroconductive nerve dressing to treat diabetic PNI to achieve functional recovery and pain relief.Given its potent adhesive and self-healing properties,this laminar dressing is convenient for the treatment of damaged nerve fibers by automatically wrapping around them to form a size-matched tube-like structure,avoiding the cumbersome implantation process.Our in vitro studies showed that ECH-Exos could facilitate the attachment and migration of Schwann cells.Meanwhile,Exos in this system could modulate M2 macrophage polarization via the NF-κB pathway,thereby attenuating inflammatory pain in diabetic PNI.Additionally,ECH-Exos enhanced myelinated axonal regeneration via the MEK/ERK pathway in vitro and in vivo,consequently ameliorating muscle denervation atrophy and further promoting functional restoration.Our findings suggest that the ECH-Exos system has huge prospects for nerve regeneration,functional restoration and pain relief in patients with diabetic PNI.展开更多
Carbon dots(CDs), a new building unit, have been revolutionizing the fields of biomedicine, bioimaging, and optoelectronics with their excellent physical, chemical, and biological properties. However, the difficulty o...Carbon dots(CDs), a new building unit, have been revolutionizing the fields of biomedicine, bioimaging, and optoelectronics with their excellent physical, chemical, and biological properties. However, the difficulty of preparing excitation-dependent full-spectrum fluorescent CDs has seriously hindered their further research in fluorescence emission mechanisms and biomedicine. Here, we report full-spectrum fluorescent CDs that exhibit controlled emission changes from purple(380 nm) to red(613 nm) at room temperature by changing the excitation wavelength, and the excitation dependence was closely related to the regulation of sp2 and sp3 hybrid carbon structures by β-cyclodextrin-related groups. In addition,by regulating the content of β-cyclodextrin, the optimal quantum yields of full-spectrum fluorescent CDs were 8.97%, 8.35%, 7.90%, 9.69% and 17.4% at the excitation wavelengths of 340, 350, 390, 410 and 540 nm,respectively. Due to their excellent biocompatibility and color tunability, full-spectrum fluorescent CDs emitted bright and steady purple, blue, green, yellow, and red fluorescence in MCF-7 cells. Moreover, we optimized the imaging conditions of CDs and mitochondrial-specific dyes;and realized the mitochondrialtargeted co-localization imaging of purple, blue and green fluorescence. After that, we also explored the effect of full-spectrum fluorescent CDs in vivo fluorescence imaging through the intratumorally, subcutaneously, and caudal vein, and found that full-spectrum fluorescent CDs had good fluorescence imaging ability in vivo.展开更多
Prodrug self-delivery carriers with targeting that specifically responded to tumor microenvironments have good potential to improve the application dilemma of approved clinical therapeutic drugs(systemic distribution ...Prodrug self-delivery carriers with targeting that specifically responded to tumor microenvironments have good potential to improve the application dilemma of approved clinical therapeutic drugs(systemic distribution and side effects).It's noted the conversion of gemcitabine(GEM)to inactive ingredients under the action of cytidine deaminase(CDA)during metabolism in vivo limits its clinical effect.A high level of reactive oxygen species(ROS)results in a high level of oxidative stress in tumor cells,which changes the expression of CDA and optimizes the metabolism of GEM in vivo and overcome drug resistance.In this study,the ROS responsive and ROS self-supplied prodrug of artemisia(ART)-thioacetal bond(TK)-GEM was synthesized and self-vectors based on ART-TK-GEM(TK@FA NPs)was prepared by using nano precipitation.ROS responsive characteristics ensure specific release of prodrugs in tumor cells with high level of ROS thereby reducing side effects on normal cells and tissues.The endogenous ROS and newly generated ROS by ART can reduce the expression of CDA and optimizes the metabolism of GEM,and the accumulated ROS can also induce apoptosis of tumor cells,realizing synergistic anti-tumor effect of chemical drugs and traditional Chinese medicines.This paper proposes a simple method by using clinically approved drugs to improve the insufficient effect of existing chemotherapy and overcome resistance,which has potential to appropriately shorten the drug development cycle and accelerate the clinical investigation of drugs.展开更多
Photodynamic therapy(PDT)has shown great application potential in cancer treatment and the important manifestation of PDT in the inhibition of tumors is the activation of immunogenic cell death(ICD)effects.However,the...Photodynamic therapy(PDT)has shown great application potential in cancer treatment and the important manifestation of PDT in the inhibition of tumors is the activation of immunogenic cell death(ICD)effects.However,the strategy is limited in the innate hypoxic tumor microenvironment.There are two key elements for the realization of enhanced PDT:specific cellular uptake and release of the photosensitizer in the tumor,and a sufficient amount of oxygen to ensure photodynamic efficiency.Herein,self-oxygenated biomimetic nanoparticles(CS@M NPs)co-assembled by photosensitizer prodrug(Ce6-S-S-LA)and squalene(SQ)were engineered.In the treatment of triple negative breast cancer(TNBC),the oxygen carried by SQ can be converted to reactive oxygen species(ROS).Meanwhile,glutathione(GSH)consumption during transformation from Ce6-S-S-LA to chlorin e6(Ce6)avoided the depletion of ROS.The co-assembled(CS NPs)were encapsulated by homologous tumor cell membrane to improve the tumor targeting.The results showed that the ICD effect of CS@M NPs was confirmed by the significant release of calreticulin(CRT)and high mobility group protein B1(HMGB1),and it significantly activated the immune system by inhibiting the hypoxia inducible factor-1alpha(HIF-1α)-CD39-CD73-adenosine a2a receptor(A2AR)pathway,which not only promoted the maturation of dendritic cells(DC)and the presentation of tumor specific antigens,but also induced effective immune infiltration of tumors.Overall,the integrated nanoplatform implements the concept of multiple advantages of tumor targeting,reactive drug release,and synergistic photodynamic therapy-immunotherapy,which can achieve nearly 90%tumor suppression rate in orthotopic TNBC models.展开更多
基金supported by the National Natural Science Foundation of China(82104962,82104647,82274271)Scientific Research Project of Guangdong Provincial Administration of Traditional Chinese Medicine(20211070)+2 种基金Science and Technology Planning Project of Guangzhou(202102010301)Young Talents Support Project from China Association of Chinese Medicine(2019-QNRC2-C06)Team of Prevention and Treatment of Acute Myocardial Infarction with Chinese Medicine(2019KCXTD009)
文摘Myocardial damage resulting from acute myocardial infarction often leads to progressive heart failure and sudden death,highlighting the urgent clinical need for effective therapies.Recently,tanshinoneⅡA has been identified as a promising therapeutic agent for myocardial infarction.However,efficient delivery remains a major issue that limits clinical translation.To address this problem,an injectable thermosensitive poly(lactic acid-co-glycolic acid)-block-poly(ethylene glycol)-block-poly(lactic acid-co-glycolic acid)gel(PLGA-PEG-PLGA)system encapsulating tanshinoneⅡA-loaded reactive oxygen species-sensitive microspheres(Gel-MS/tanshinoneⅡA)has been designed and synthesized in this study.The thermosensitive hydrogel exhibits good mechanical properties after reaching body temperature.Microspheres initially immobilized by the gel exhibit excellent reactive oxygen species-triggered release properties in a high-reactive oxygen species environment after myocardial infarction onset.As a result,encapsulated tanshinoneⅡA is effectively released into the infarcted myocardium,where it exerts local anti-pyroptotic and anti-inflammatory effects.Importantly,the combined advantages of this technique contribute to the mitigation of left ventricular remodeling and the restoration of cardiac function following tanshinoneⅡA.Therefore,this novel,precision-guided intra-tissue therapeutic system allows for customized local release of tanshinoneⅡA,presenting a promising alternative treatment strategy aimed at inducing beneficial ventricular remodeling in the post-infarct heart.
基金supported by the Guangdong Basic and Applied Basic Research Foundation of China(No.2021A1515011050)President Foundation of The Third Affiliated Hospital of SouthernMedical University[grant number YM202202].
文摘Ovarian cancer(OC)is one of the most common and recurring malignancies in gynecology.Patients with relapsed OC always develop"cascade drug resistance"(CDR)under repeated chemotherapy,leading to subsequent failure of chemotherapy.To overcome this challenge,amphiphiles(P1)carrying a nitric oxide(NO)donor(Isosorbide 5-mononitrate,ISMN)and high-density disulfide are synthesized for encapsulatingmitochondria-targeted tetravalent platinum prodrug(TPt)to construct a nanocomposite(INP@TPt).Mechanism studies indicated that INP@TPt significantly inhibited drug-resistant cells by increasing cellular uptake and mitochondrial accumulation of platinum,depleting glutathione,and preventing apoptosis escape through generating highly toxic peroxynitrite anion(ONOO−).To better replicate the microenvironmental and histological characteristics of the drug resistant primary tumor,an OC patient-derived tumor xenograft(PDXOC)model in BALB/c nude mice was established.INP@TPt showed the best therapeutic effects in the PDXOC model.The corresponding tumor tissues contained high ONOO−levels,which were attributed to the simultaneous release of O_(2)^(·−)and NO in tumor tissues.Taken together,INP@TPtbased systematic strategy showed considerable potential and satisfactory biocompatibility in overcoming platinum CDR,providing practical applications for ovarian therapy.
基金supported by the National Natural Science Foun-dation of China(Grants 81571799,81773193,81771929 and 81773642)
文摘Hepatocellular carcinoma(HCC)is one of the deadliest cancers due to its complexities,reoccurrence after surgical resection,metastasis and heterogeneity.In addition to sorafenib and lenvatinib for the treatment of HCC approved by FDA,various strategies including transarterial chemoembolization,radiotherapy,locoregional therapy and chemotherapy have been investigated in clinics.Recently,cancer nanotechnology has got great attention for the treatment of various cancers including HCC.Both passive and active targetings are progressing at a steady rate.Herein,we describe the lessons learned from pathogenesis of HCC and the understanding of targeted and non-targeted nanoparticles used for the delivery of small molecules,monoclonal antibodies,miRNAs and peptides.Exploring current efficacy is to enhance tumor cell response of chemotherapy.It highlights the opportunities and challenges faced by nanotechnologies in contemporary hepatocellular carcinoma therapy,where personalized medicine is increasingly becoming the mainstay.Overall objective of this review is to enhance our understanding in the design and development of nanotechnology for treatment of HCC.
基金financially supported by the National Key Research and Development Project(2019YFC0605403)National Natural Science Foundation of China grants(Nos.41790451,41688103,42172117,41702109 and 41972096)。
文摘The Songliao Basin in Northeast Asia is the largest and longest-lived rift basin and preserves a nearcontinuous continental succession of the most of the Cretaceous period,providing great material to investigate the adaption of the terrestrial systems to the Cretaceous greenhouse climate and tectonic events.However,the paucity of precise and accurate radioisotopic ages from the Early Cretaceous strata of the Songliao Basin has greatly held back the temporal and causal correlation of the continental records to the global Early Cretaceous records.Three tuff layers intercalated in the Yingcheng Formation have been intercepted by the SK-2 borehole,which offer excellent materials for radioisotopic dating and calibration of the chronostratigraphy of the Lower Cretaceous sequence of Songliao Basin.Moreover,the Yingcheng Formation recorded the largest and the last of the two major volcanic events in Songliao Basin,which also represents a turning point in the basin evolution history of Songliao from syn-rift stage to post-rift stage.Here we report high-precision U–Pb zircon geochronology by the CA-ID-TIMS technique on three tuff samples from the Yingcheng Formation of the SK-2 borehole in the Songliao Basin to construct a greatly improved,absolute age framework for the Yingcheng Formation and provide crucial age constraints for the Songliao Lower Cretaceous Strata.The new CA-ID-TIMS geochronology constrained the Yingcheng Formation at 102.571+0.320/-2.346 Ma to ca.113 Ma,correlating to the Albian Stage.Combined with the previous published Songliao geochronology,the Quantou Formation is constrained to between 96.442+0.475/-0.086 Ma and 91.923+0.475/-0.086 Ma;the Denglouku Formation is constrained to between 102.571+0.320/-2.346 Ma and 96.442+0.475/-0.086 Ma;the age of the Shahezi Formation is estimated at ca.113 Ma to ca.118 Ma,which could extend to ca.125 Ma in some locations in Songliao Basin.The major unconformity between the Yingcheng Formation and the Denglouku Formation,which represents the transition of the basin from syn-rift to post-rift is thus confined to between 102.571+0.320/-2.346 Ma and 96.442+0.475/-0.086 Ma.This is roughly contemporaneous with the change in the direction of the paleo-Pacific plate motion from west-southwest to north or northwest in mid-Cretaceous,suggesting their possible connections.
文摘Because of the rapid development of industrial processes, increased urban pollution and agricultural chemicals applied in recent years, heavy metal(loid) pollution in soil has been very serious, and there is an urgent need for fast and efficient removal of heavy metal(loid) pollution. Currently, environmental microorganisms are always used to perform biological alteration or improvement of soils and sewage. Using functional microorganisms that are resistant to toxic heavy metal(loid) ions for alteration and transformation of heavy metal(loid)s in ionic form is an effective measure for microbial remediation of heavy metal(loid)contaminated soil. This paper reviewed the microbial remediation mechanism of heavy metal(loid) contaminated soils, and the approaches for breeding bacteria those can be used for highly efficient removal of heavy metal(loid)s, as well as the application examples of microbial remediation and transformation of heavy metal(loid) contaminated soil, and finally described the future trends and further research work of heavy metal(loid) contaminated soils by microbial remediation.
基金National Natural Science Foundation of China(12061131010,12074198)Russian Science Foundation(21-49-00023).
文摘In this study,an optical setup for generating terahertz(THz)pulses through a two-color femtosecond laser filament was carefully designed to achieve a precise overlap of two-color laser pulses in space and time.β-barium borate(BBO),α-BBO,and a dual-wavelength plate were used to compensate the phase delay of the two-color lasers.Tilting ofα-BBO could further realize the precise spatial overlap of the two beams by counteracting the walk-off effect.The maximum out-put THz pulse energy reached 21μJ in argon gas when using a commercial Ti:sapphire laser with a pulse energy of 6 mJ at a 1 kHz repetition rate.The corresponding conversion efficiency exceeded 0.35%.
基金The National Natural Science Foundation of China under contract No.61671481the Qingdao Applied Fundamental Research under contract No.16-5-1-11-jchthe Fundamental Research Funds for Central Universities under contract No.18CX05014A
文摘We present a novel sea-ice classification framework based on locality preserving fusion of multi-source images information.The locality preserving fusion arises from two-fold,i.e.,the local characterization in both spatial and feature domains.We commence by simultaneously learning a projection matrix,which preserves spatial localities,and a similarity matrix,which encodes feature similarities.We map the pixels of multi-source images by the projection matrix to a set fusion vectors that preserve spatial localities of the image.On the other hand,by applying the Laplacian eigen-decomposition to the similarity matrix,we obtain another set of fusion vectors that preserve the feature local similarities.We concatenate the fusion vectors for both spatial and feature locality preservation and obtain the fusion image.Finally,we classify the fusion image pixels by a novel sliding ensemble strategy,which enhances the locality preservation in classification.Our locality preserving fusion framework is effective in classifying multi-source sea-ice images(e.g.,multi-spectral and synthetic aperture radar(SAR)images)because it not only comprehensively captures the spatial neighboring relationships but also intrinsically characterizes the feature associations between different types of sea-ices.Experimental evaluations validate the effectiveness of our framework.
基金supported by the National Natural Science Foundation of China(51308133)Guangdong Provincial National Natural Science Foundation(2014A030308019)+1 种基金Science and Technology Planning Project of Guangdong Province(2015A020215016)the support of Guangdong Institute of Microbiology
文摘Since the azo dyes widely used in textile-dyeing industry are toxic, highly persistent, and ubiquitously distributed in the environment, their treatment efficiencies and fade in ecosystems have received worldwide attention. Due to the microbes play important roles in azo-dye degradation, exogenous nutrient addition is used as a promising biostimulation strategy to improve the treatment efficiencies of azo-dye wastewater. However, little is known about the effects of different kinds of exogenous nutrients on the azo-dye wastewater treatment directly. Here, three kinds of common nutrients, glucose, starch and yeast extract, were added to the sequencing batch reactors (SBR) for the treatment of wastewater containing acid red 73 to compare the biostimulation efficiencies by investigating the dye's removal efficiencies and the changes of related water qualities. Our results showed that the reactors added yeast extract had highest removal efficiencies and chemical oxygen demand (COD) as well, followed by glucose and starch. The removal rates of acid red 73 and COD were 90.63% and 8713% in the reactors added yeast extract, respectively, while 86.49% and 78.4% in those with glucose and 85.38% and 75.2% in those with starch. This study provided some useful information for the biostimulation strategy of azo-dye wastewater treatment and preliminarily suggested that yeast extract would be the optimal choice.
基金funded and supported by the Department of Science and Technology of Guangdong Province(No.2022B1111020005)Key Laboratory of Guangdong Provincial Food and Drug Administration(No.2021ZDB03)+3 种基金the 2020 Guangdong Provincial Science and Technology Innovation Strategy Special Fund(Guangdong-Hong Kong-Macao Joint Lab,No.2020B1212030006)Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme(No.Guochao Liao,2019)Guangdong Basic and Applied Basic Research Foundation(Nos.2020B1515130005,2022A1515110270,202201011563)The Bureau of Science and Technology of Guangzhou City(No.HMJH_(2)019000)。
文摘Hepatocellular carcinoma is a common and fatal malignancy for which there is no effective systemic therapeutic strategy.Dihydroartemisinin(DHA),a derivative of artemisinin,has been shown to exert anti-tumor effects through the production of reactive oxygen species(ROS)and resultant mitochondrial damage.However,clinical translation is limited by several drawbacks,such as insolubility,instability and low bioavailability.Here,based on a nanomedicine-based delivery strategy,we fabricated mitochondria-targeted carrier-free nanoparticles coupling DHA and triphenylphosphonium(TPP),aiming to improve bioavailability and mitochondrial targeting.DHA-TPP nanoparticles can be passively delivered to the tumor site by enhanced penetration and retention and then internalized.Flow cytometry and Western blot analysis showed that DHA-TPP nanoparticles increased intracellular ROS,which increased mitochondrial stress and in turn upregulated the downstream Bcl-2 pathway,leading to apoptosis.In vivo experiments showed that DHA-TPP nanoparticles exhibited anti-tumor effects in a mouse model of hepatocellular carcinoma.These findings suggest carrier-free DHA-TPP nanoparticles as a potential therapeutic strategy for hepatocellular carcinoma.
基金financially supported by the National Natural Science Foundation of China(No.41972198)the Science and Technology Innovation Program of Hunan Province(No.2021RC4055)+2 种基金the Cooperation Foundation of Key Laboratory of Mineralogy and Metallogeny,Guangzhou Institute of GeochemistryCAS(No.KLMM20180201)the Scientific Research Starting Foundation of Central South University。
文摘In order to decipher element mobility in UHP meta-sedimentary rocks in the continental subduction zone,major and trace element compositions are investigated for a continuous profile from a representative UHP region in the Dabie Mountains.Among the lithologic contact zone,contents of K,Ca,LREE,and LILE exhibit varying degrees of downward trends in both marble and eclogite toward the contact zone,indicating that marble and their associated eclogite can release a large amount of K,Ca,and a small number of LILEs and LREEs.Titanite is the main Ti phase in both marble and eclogite.Titanite rims around rutile can occasionally be seen in eclogite.Contents of Ti and HFSE exhibit a well-coupled relation among marble and eclogite,indicating that substantial Ti and HFSEs were migrated from eclogite to marble,in accord with the capacity of a melt medium.Rutiles and titanites in marble exhibit a relatively limited variation in Nb/Ta ratios(12.9-16.2),similar to those of titanites in eclogite(14.2-16.7),which demonstrates that rutiles and titanites in marble were sourced from eclogite because of short-distance migrations of Ti and HFSEs.According to the P-T path and the temperature and pressure conditions of the peak metamorphism reported by previous studies,the eclogite associated with marble may not form supercritical fluids in the subduction zone because of the addition of carbonate minerals.
基金supported by the National Natural Science Foundation of China(Nos.32201171 and 82372115)the Science and Technology Program of Guangzhou(No.202102021266)。
文摘Anticancer platinum prodrugs that can be controllably activated are highly desired for personalized precision medicine and patient compliance in cancer therapy.However,the clinical application of platinum(Ⅳ)prodrugs(Pt(Ⅳ))is restricted by tissue penetration of external irradiation.Here,we report a novel Pt(Ⅳ)activation strategy based on endogenous luminescence of tumor microenvironment responsiveness,which completely circumvents the limitation of external irradiation.The designed Pt(Ⅳ)–Lu,a mixture of trans,trans,trans-[Pt(N_(3))_(2)(OH)_(2)(py)_(2)]and luminol(Lu),has controllable activation property:it remains inert in reductant environment and normal tissues,but under tumor microenvironment,Lu will be oxidized to produce blue luminescence,which rapidly reduce Pt(Ⅳ)to Pt(Ⅱ)without the need of any external activator.Pt(Ⅳ)–Lu shows excellent responsive antitumor ability both in vitro and in vivo.Compared to cisplatin,the median lethal dose in BALB/c mice increased by an order of magnitude.Our results suggest that Pt(Ⅳ)–Lu exhibits highly controllable activation property,superior antitumor activity,and good biosafety,which may provide a novel strategy for the design of platinum prodrugs.
基金supported by the Guangdong Basic and Applied Basic Research Foundation of China(No.2021A1515011050)President Foundation of the Third Affiliated Hospital of Southern Medical University(No.YM202202)+1 种基金the Health Economics Association Research Program of Guangdong Province(No.2022-WJZD-20)the Higher Education Teaching Management Association Curriculum Thinking and Administration Program of Guangdong Province(No.X-KCSZ2021082).
文摘Recently,the utilization of nonsteroidal anti-inflammatory drugs(NSAIDs)to sensitize cisplatin(CDDP)has gained substantial traction in the treatment of ovarian cancer(OC).However,even widely employed NSAIDs such as celecoxib and naproxen carry an elevated risk of cardiovascular events,notably throm-bosis.Furthermore,the diminished sensitivity to CDDP therapy in OC is multifactorial,rendering the ap-plication of NSAIDs only partially effective due to their cyclooxygenase-2(COX-2)inhibiting mechanism.Hence,in this study,reactive oxygen species(ROS)-responsive composite nano-hydrangeas loaded with the Chinese medicine small molecule allicin and platinum(IV)prodrug(DTP@AP NPs)were prepared to achieve comprehensive chemosensitization.On one front,allicin achieved COX-2 blocking therapy,en-compassing the inhibition of proliferation,angiogenesis and endothelial mesenchymal transition(EMT),thereby mitigating the adverse impacts of CDDP chemotherapy.Simultaneously,synergistic chemosensi-tization was achieved from multifaceted mechanisms by decreasing CDDP inactivation,damaging mito-chondria and inhibiting DNA repair.In essence,these findings provided an optimized approach for syner-gizing CDDP with COX-2 inhibitors,offering a promising avenue for enhancing OC treatment outcomes.
基金funded by Beijing Natural Science Foundation (Nos.L222109, 3222018)Military Health Care Project(No.22BJZ22)+6 种基金Science Foundation of China University of Petroleum (Nos.2462019QNXZ02, 2462019BJRC007)National Natural Science Foundation of China (Nos.52211530034, 82273236)Guangdong Provincial Basic and Applied Basic Research Foundation (Nos.2022A151522004, 2022A1515220042)Science and Technology Innovation Commission of Shenzhen (Nos.JSGG20210802153410031, JCYJ20220530141609021)Science and Technology Plan of Shenzhen Nanshan District (No.NS016)Discipline Leader Foundation of Huazhong University of Science and Technology Union Shenzhen Hospital (No.YN2021002)Crosswise Project of Daan Gene (No.HXKY2022002)。
文摘Liposomes are one of the significant classes of antitumor nanomaterials and the most successful nanomedicine drugs in clinical translation. However, it is difficult to accurately reveal liposome delivery modes and drug release rates at different p H values to assess the biodistribution and drug delivery pathways in vivo. Here, we established a strategy to integrate Bi-doped carbon quantum dots(CQDs)with liposomes to produce fluorescence visualization and therapeutic effects, namely lipo/Bi-doped CQDs.Lipo/Bi-doped CQDs show good water solubility and physicochemical properties, which can be used for in vitro labeling of colon cancer(CT26) cells and in vivo imaging localization tracking tumors for monitoring. Simultaneously, thanks to the excellent p H sensitivity and ion doping characteristic of Bi-doped CQDs, lipo/Bi-doped CQDs can be used to reveal the drug release rate of liposomes at different p H values and exhibit potential effects in vivo antitumor therapy.
基金supported by the National Natural Science Foundation of China(82372115 and 52073139)the China Postdoctoral Science Foundation(2023M731571)+3 种基金Dongguan Science and Technology of Social Development Program(20231800900322 and 20231800900362)the Postdoctoral Research Project Start-Up Funding of Dongguan People’s Hospital(319341)the Guangdong Basic and Applied Basic Research Foundation(2023B1515120084 and 2023A1515110016)the Training Program of National Natural Science Foundation of Dongguan People’s Hospital(Z202402).
文摘Low tumor immunogenicity,immunosuppressive tumor microenvironment,and bacterial infections have emerged as significant challenges in postsurgical immunotherapy and skin regeneration for preventing melanoma recurrence.Herein,an immunotherapeutic hydrogel booster(GelMA-CJCNPs)was developed to prevent postoperative tumor recurrence and promote wound healing by incorporating ternary carrier-free nanoparticles(CJCNPs)containing chlorine e6(Ce6),a BRD4 inhibitor(JQ1),and a glutaminase inhibitor(C968)into methacrylic anhydride-modified gelatin(GelMA)dressings.GelMA-CJCNPs reduced glutathione production by inhibiting glutamine metabolism,thereby preventing the destruction of reactive oxygen species generated by photodynamic therapy,which could amplify oxidative stress to induce severe cell death and enhance immunogenic cell death.In addition,GelMA-CJCNPs reduced M2-type tumor-associated macrophage polarization by blocking glutamine metabolism to reverse the immunosuppressive tumor microenvironment,recruiting more tumor-infiltrating T lymphocytes.GelMA-CJCNPs also downregulated IFN-γ-induced expression of programmed cell death ligand 1 to mitigate acquired immune resistance.Benefiting from the amplified systemic antitumor immunity,GelMA-CJCNPs markedly inhibited the growth of both primary and distant tumors.Moreover,GelMA-CJCNPs demonstrated satisfactory photodynamic antibacterial effects against Staphylococcus aureus infections,thereby promoting postsurgical wound healing.Hence,this immunotherapeutic hydrogel booster,as a facile and effective postoperative adjuvant,possesses a promising potential for inhibiting tumor recurrence and accelerating skin regeneration.
基金supported by Guangxi Natural Science Foundation(No.2022GXNSFBA035487)Guangxi Science and Technology Project(No.AD21220056,AD19110038)+2 种基金National Natural Science Foundation of China(No.62174041,52061009,52262022)Yunnan Province Major Science and Technology Projects(202102AB080008-2)Guangxi Key Laboratory of Precision Navigation Technology and Application,Guilin University of Electronic Technology(No.DH202203,DH202202,DH202221,DH202222,DH202214).
文摘The field of artificial intelligence and neural computing has been rapidly expanding due to the imple-mentation of resistive random-access memory(RRAM)based artificial synaptic.However,the low flexibility of conventional RRAM materials hinders their ability to mimic synaptic behavior accurately.To overcome such limitation,organic-2D composites with high mechanical properties are proposed as the active layer of RRAM.Moreover,we enhance the reliability of the device by ZrO_(2)insertion layer,resulting in stable synaptic performance.The Ag/PVA:h-BN/ZrO_(2)/ITO devices show stable bipolar resistive switching behavior with an ON/OFF ratio of over 5×10^(2),a~2400 cycles endurance and a long retention time(>6×10^(3)s),which are essential for the development of high-performance RRAMs.We also study the possible synaptic mechanism and dynamic plasticity of the memory device,observing the transition from short-term potentiation(STP)to long-term potentiation(LTP)under the effect of continuous voltage pulses.Moreover,the device exhibits both long-term depression(LTD)and paired-pulse facili-tation(PPF)properties,which have significant implications for the design of organic-2D composite material RRAMs that aim to mimic biological synapses,representing promising avenues for the devel-opment of advanced neuromorphic computing systems.
基金supported by the President Foundation of Nanfang Hospital,Southern Medical University(2020C024)the Natural Science Foundation of Fujian Province(2021J011156).
文摘Over the years,electroconductive hydrogels(ECHs)have been extensively applied for stimulating nerve regeneration and restoring locomotor function after peripheral nerve injury(PNI)with diabetes,given their favorable mechanical and electrical properties identical to endogenous nerve tissue.Nevertheless,PNI causes the loss of locomotor function and inflammatory pain,especially in diabetic patients.It has been established that bone marrow stem cells-derived exosomes(BMSCs-Exos)have analgesic,anti-inflammatory and tissue regeneration properties.Herein,we designed an ECH loaded with BMSCs-Exos(ECH-Exos)electroconductive nerve dressing to treat diabetic PNI to achieve functional recovery and pain relief.Given its potent adhesive and self-healing properties,this laminar dressing is convenient for the treatment of damaged nerve fibers by automatically wrapping around them to form a size-matched tube-like structure,avoiding the cumbersome implantation process.Our in vitro studies showed that ECH-Exos could facilitate the attachment and migration of Schwann cells.Meanwhile,Exos in this system could modulate M2 macrophage polarization via the NF-κB pathway,thereby attenuating inflammatory pain in diabetic PNI.Additionally,ECH-Exos enhanced myelinated axonal regeneration via the MEK/ERK pathway in vitro and in vivo,consequently ameliorating muscle denervation atrophy and further promoting functional restoration.Our findings suggest that the ECH-Exos system has huge prospects for nerve regeneration,functional restoration and pain relief in patients with diabetic PNI.
基金supported by the National Natural Science Foundation of China(No.U2230123)the Science Foundation of the Science and Technology Department of Sichuan Province(No.22ZYZYTS0159)+4 种基金Science Foundation of China University of Petroleum(Nos.2462019QNXZ02,2462019BJRC007)Science Foundation of China University of Petroleum(East China)(No.2462020YXZZ018)Science and Technology Innovation Commission of Shenzhen(No.JSGG20210802153410031)Science and Technology Project of Nanshan District(No.NS_(2)021016)the Scientific Research Startup Fund for Discipline Leader of Huazhong University of Science and Technology Union Shenzhen Hospital(Nanshan Hospital)(No.YN2021002)。
文摘Carbon dots(CDs), a new building unit, have been revolutionizing the fields of biomedicine, bioimaging, and optoelectronics with their excellent physical, chemical, and biological properties. However, the difficulty of preparing excitation-dependent full-spectrum fluorescent CDs has seriously hindered their further research in fluorescence emission mechanisms and biomedicine. Here, we report full-spectrum fluorescent CDs that exhibit controlled emission changes from purple(380 nm) to red(613 nm) at room temperature by changing the excitation wavelength, and the excitation dependence was closely related to the regulation of sp2 and sp3 hybrid carbon structures by β-cyclodextrin-related groups. In addition,by regulating the content of β-cyclodextrin, the optimal quantum yields of full-spectrum fluorescent CDs were 8.97%, 8.35%, 7.90%, 9.69% and 17.4% at the excitation wavelengths of 340, 350, 390, 410 and 540 nm,respectively. Due to their excellent biocompatibility and color tunability, full-spectrum fluorescent CDs emitted bright and steady purple, blue, green, yellow, and red fluorescence in MCF-7 cells. Moreover, we optimized the imaging conditions of CDs and mitochondrial-specific dyes;and realized the mitochondrialtargeted co-localization imaging of purple, blue and green fluorescence. After that, we also explored the effect of full-spectrum fluorescent CDs in vivo fluorescence imaging through the intratumorally, subcutaneously, and caudal vein, and found that full-spectrum fluorescent CDs had good fluorescence imaging ability in vivo.
基金financial support from Guangdong Nature Resource Center(GDNRC,No.(2020)037)Natural Science Foundation of Guangdong Province(Nos.22019A1515011498,2019A1515011619)。
文摘Prodrug self-delivery carriers with targeting that specifically responded to tumor microenvironments have good potential to improve the application dilemma of approved clinical therapeutic drugs(systemic distribution and side effects).It's noted the conversion of gemcitabine(GEM)to inactive ingredients under the action of cytidine deaminase(CDA)during metabolism in vivo limits its clinical effect.A high level of reactive oxygen species(ROS)results in a high level of oxidative stress in tumor cells,which changes the expression of CDA and optimizes the metabolism of GEM in vivo and overcome drug resistance.In this study,the ROS responsive and ROS self-supplied prodrug of artemisia(ART)-thioacetal bond(TK)-GEM was synthesized and self-vectors based on ART-TK-GEM(TK@FA NPs)was prepared by using nano precipitation.ROS responsive characteristics ensure specific release of prodrugs in tumor cells with high level of ROS thereby reducing side effects on normal cells and tissues.The endogenous ROS and newly generated ROS by ART can reduce the expression of CDA and optimizes the metabolism of GEM,and the accumulated ROS can also induce apoptosis of tumor cells,realizing synergistic anti-tumor effect of chemical drugs and traditional Chinese medicines.This paper proposes a simple method by using clinically approved drugs to improve the insufficient effect of existing chemotherapy and overcome resistance,which has potential to appropriately shorten the drug development cycle and accelerate the clinical investigation of drugs.
基金supported by the Guangdong Nature Resource Center(No.(2020)037)Natural Science Foundation of Guangdong Province(Nos.22019A1515011498 and 2019A1515011619)+2 种基金Basic and Applied Basic Research Foundation of Guangdong Province(No.2020B1515120063)National Natural Science Foundation of China(No.81803877)supported by the China Postdoctoral Science Foundation(No.2022M721535)。
文摘Photodynamic therapy(PDT)has shown great application potential in cancer treatment and the important manifestation of PDT in the inhibition of tumors is the activation of immunogenic cell death(ICD)effects.However,the strategy is limited in the innate hypoxic tumor microenvironment.There are two key elements for the realization of enhanced PDT:specific cellular uptake and release of the photosensitizer in the tumor,and a sufficient amount of oxygen to ensure photodynamic efficiency.Herein,self-oxygenated biomimetic nanoparticles(CS@M NPs)co-assembled by photosensitizer prodrug(Ce6-S-S-LA)and squalene(SQ)were engineered.In the treatment of triple negative breast cancer(TNBC),the oxygen carried by SQ can be converted to reactive oxygen species(ROS).Meanwhile,glutathione(GSH)consumption during transformation from Ce6-S-S-LA to chlorin e6(Ce6)avoided the depletion of ROS.The co-assembled(CS NPs)were encapsulated by homologous tumor cell membrane to improve the tumor targeting.The results showed that the ICD effect of CS@M NPs was confirmed by the significant release of calreticulin(CRT)and high mobility group protein B1(HMGB1),and it significantly activated the immune system by inhibiting the hypoxia inducible factor-1alpha(HIF-1α)-CD39-CD73-adenosine a2a receptor(A2AR)pathway,which not only promoted the maturation of dendritic cells(DC)and the presentation of tumor specific antigens,but also induced effective immune infiltration of tumors.Overall,the integrated nanoplatform implements the concept of multiple advantages of tumor targeting,reactive drug release,and synergistic photodynamic therapy-immunotherapy,which can achieve nearly 90%tumor suppression rate in orthotopic TNBC models.