查看更多>>摘要：An approach utilizing N-heterocyclic carbene for nitrile formation and desymmetrization reaction is developed.The process involves kinetic resolution,with the axially chiral aryl monoaldehydes obtained in moderate yields with excellent optical purities.These axially chiral aryl monoaldehydes can be conveniently transformed into functionalized molecules,showing great potential as catalysts in organic chemistry.
查看更多>>摘要：The depth of light penetration and tumor hypoxia restrict the efficacy of photodynamic therapy(PDT)in triple-negative breast cancer(TNBC),while the overproduction of lactate(LA)facilitates the development,aggressiveness,and therapy resistance of TNBC.To address these issues,a self-acting PDT nanosystem(HL@hMnO2-LOx@HA)is fabricated by loading 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-alpha(HPPH),luminol,and LA oxidase(LOx)in a hyaluronic acid(HA)-coated hollow manganese dioxide(hMnO2)nanoparticle.LOx catalyzes the oxidation of LA into pyruvate and hydrogen peroxide(H2O2),thus depleting the overproduced intratumoral LA.In the acidic tumor microenvironment,H2O2 reacts with luminol and hMnO2 to yield blue luminescence as well as O2 and Mn2+,respectively.Mn2+could further enhance this chemiluminescence.HPPH is then excited by the chemiluminescence through chemiluminescence resonance energy transfer for self-illuminated PDT.The generated O2 alleviates the hypoxia state of the TNBC tumor to produce sufficient 1O2 for self-oxygenation PDT.The Mn2+performs T1 magnetic resonance imaging to trace the self-acting PDT process.This work provides a biocompatible strategy to conquer the limits of light penetration and tumor hypoxia on PDT against TNBC as well as LA overproduction.
查看更多>>摘要：Photodynamic therapy(PDT)has emerged as a promising approach for squamous cell carcinoma treatment but hindered by tumor hypoxia,acquired resistance,phototoxicity,and so on.To address these issues,we developed a smart strategy utilizing activable photosensitizers delivered by an aptamer-functionalized DNA probe(ADP).The ADP incorporated an AS1411 aptamer for tumor targeting and a linear antisense oligonucleotide(ASO)for recognition of Survivin mRNA.In the absence of the target,PDT remained quenched,thereby avoiding phototoxicity during circulation and nonselective distribution.With the aid of the aptamer,ADP achieved selective targeting of tumors.Upon internalization,ADP targeted recognized Survivin mRNA,triggering PDT activation,and releasing ASO to down-regulate Survivin expression and reverse tumor resistance.Consequently,the activable photosensitizers exhibited an"AND"logic gate,combining tumor-targeting delivery and tumor-related gene activation,thus enhancing its specificity.Additionally,the incorporation of hemin into the ADP provided catalase activity,converting tumor-abundant H2O2 into O2,thereby ameliorating tumor hypoxia.The resulting functionalized G-quadruplex/hemin-DNA probe complex demonstrated targeted delivery and activation,minimized side effects,and enhanced PDT efficacy in both xenograft tumor-bearing mice and patient-derived xenograft models.This study offers a unique and promising platform for efficient and safe PDT,thus holding great potential for future clinical translation and improved cancer therapy.
查看更多>>摘要：Mixtures of active self-propelled and passive colloidal particles promise rich assembly and dynamic states that are beyond reach via equilibrium routes.Yet,controllable transition between different dynamic states remains rare.Here,we reveal a plethora of dynamic behaviors emerging in assemblies of chemically propelled snowman-like active colloids and passive spherical particles as the particle shape,size,and composition are tuned.For example,assembles of one or more active colloids with one passive particle exhibit distinct translating or orbiting states while those composed of one active colloid with 2 passive particles display persistent"8"-like cyclic motion or hopping between circling states around one passive particle in the plane and around the waist of 2 passive ones out of the plane,controlled by the shape of the active colloid and the size of the passive particles,respectively.These morphology-tailored dynamic transitions are in excellent agreement with state diagrams predicted by mesoscale dynamics simulations.Our work discloses new dynamic states and corresponding transition strategies,which promise new applications of active systems such as micromachines with functions that are otherwise impossible.
查看更多>>摘要：Cross-talks(e.g.,host-driven iron withdrawal and microbial iron uptake between host gastrointestinal tract and commensal microbes)regulate immunotolerance and intestinal homeostasis.However,underlying mechanisms that regulate the cross-talks remain poorly understood.Here,we show that bacterial products up-regulate iron-transporter transferrin and transferrin acts as an immunosuppressor by interacting with cluster of differentiation 14(CD14)to inhibit pattern recognition receptor(PRR)signaling and induce host immunotolerance.Decreased intestinal transferrin is found in germ-free mice and human patients with ulcerative colitis,which are characterized by impaired intestinal immunotolerance.Intestinal transferrin and host immunotolerance are returned to normal when germ-free mice get normal microbial commensalism,suggesting an association between microbial commensalism,transferrin,and host immunotolerance.Mouse colitis models show that transferrin shortage impairs host's tolerogenic responses,while its supplementation promotes immunotolerance.Designed peptide blocking transferrin-CD14 interaction inhibits immunosuppressive effects of transferrin.In monkeys with idiopathic chronic diarrhea,transferrin shows comparable or even better therapeutic effects than hydrocortisone.Our findings reveal that by up-regulating host transferrin to silence PRR signaling,commensal bacteria counteract immune activation induced by themselves to shape host immunity and contribute for intestinal tolerance.
查看更多>>摘要：Subcellular mitochondria serve as sensors for energy metabolism and redox balance,and the dynamic regulation of functional and dysfunctional mitochondria plays a crucial role in determining cells'fate.Selective removal of dysfunctional mitochondria at the subcellular level can provide chondrocytes with energyto prevent degeneration,thereby treating osteoarthritis.Herein,to achieve an ideal subcellular therapy,cartilage affinity peptide(WYRGRL)-decorated liposomes loaded with mitophagy activator(urolithin A)were integrated into hyaluronic acid methacrylate hydrogel microspheres through microfluidic technology,named HM@WY-Lip/UA,that could efficiently target chondrocytes and selectively remove subcellular dysfunctional mitochondria.As a result,this system demonstrated an advantage in mitochondria function restoration,reactive oxygen species scavenging,cell survival rescue,and chondrocyte homeostasis maintenance through increasing mitophagy.In a rat post-traumatic osteoarthritis model,the intra-articular injection of HM@WY-Lip/UA ameliorated cartilage matrix degradation,osteophyte formation,and subchondral bone sclerosis at 8 weeks.Overall,this study indicated that HM@WY-Lip/UA provided a protective effect on cartilage degeneration in an efficacious and clinically relevant manner,and a mitochondrial-oriented strategy has great potential in the subcellular therapy of osteoarthritis.
查看更多>>摘要：In the post-COVID-19 pandemic era,the long-term surveillance of pathogens is still important.The rapid detection of pathogens facilitates the accurate and convenient real-time monitoring of microbial contamination and improves the management of diseases.Here,a novel surface plasmon resonance(SPR)-based point of care testing(POCT)approach of microorganism nucleic acids with the guidance of CRISPR enzyme is described,including the application of optical fiber-based detection of trace SARS-CoV2 virus in sewage water on SPR and validation of the plasmonic biosensor for the detection of single-nucleotide mutations in natural water samples.
查看更多>>摘要：Biocompatible connections between external artificial devices and living organisms show promise for future neuroprosthetics and therapeutics.The study in Science by Zhao and colleagues introduces a cascade-heterogated biphasic gel(HBG)iontronic device,which facilitates electronic-to-multi-ionic signal transduction for abiotic-biotic interfaces.Inspired by neuron signaling,the HBG device demonstrated its biocompatibility by regulating neural activity in biological tissue,paving the way for wearable and implantable devices,including brain-computer interfaces.
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