Rearranging Spin Electrons by Axial-Ligand-Induced Orbital Splitting to Regulate Enzymatic Activity of Single-Atom Nanozyme with Destructive d-π Conjugation.

Most of the nanozymes have been obtained based on trial and error, for which the application is usually compromised by enzymatic activity regulation due to a vague catalytic mechanism. Herein, a hollow axial Mo-Pt single-atom nanozyme (H-MoN5@PtN4/C) is constructed by a two-tier template capture strategy. The axial ligand can induce Mo 4d orbital splitting, leading to a rearrangement of spin electrons (↑ ↑ → ↑↓) to regulate enzymatic activity. This creates catalase-like activity and enhances oxidase-like activity to catalyze cascade enzymatic reactions (H2O2 → O2 → O2•-), which can overcome tumor hypoxia and accumulate cytotoxic superoxide radicals (O2•-). Significantly, H-MoN5@PtN4/C displays destructive d-π conjugation between the metal and substrate to attenuate the restriction of orbitals and electrons. This markedly improves enzymatic performance (catalase-like and oxidase-like activity) of a Mo single atom and peroxidase-like properties of a Pt single atom. Furthermore, the H-MoN5@PtN4/C can deplete overexpressed glutathione (GSH) through a redox reaction, which can avoid consumption of ROS (O2•- and •OH). As a result, H-MoN5@PtN4/C can overcome limitations of a complex tumor microenvironment (TME) for tumor-specific therapy based on TME-activated catalytic activity.

A dynamic cascade DNA nanocomplex to synergistically disrupt the pyroptosis checkpoint and relieve tumor hypoxia for efficient pyroptosis cancer therapy.

Pyroptosis has attracted widespread concerns in cancer therapy, while the therapeutic efficiency could be significantly restricted by using the crucial pyroptosis checkpoint of autophagy and tumor hypoxia. Herein, a DNA nanocomplex (DNFs@ZnMn), containing cascade DNAzymes, promoter-like ZnO2-Mn nanozymes and photosensitizers, was constructed in one pot through rolling circle amplification reactions to induce pyroptosis through disrupting autophagy. After targeting cancer cells with a high expression of H+ and glutathione, DNFs@ZnMn decomposed to expose DNAzymes and promoter-like ZnO2-Mn nanozymes. Then, sufficient metal ions and O2 were released to promote cascade DNA/RNA cleavage and relieving of tumor hypoxia. The released DNAzyme-1 self-cleaved long DNA strands with Zn2+ as the cofactor and simultaneously exposed DNAzyme-2 to cleave ATG-5 mRNA (with Mn2+ as the cofactor). This cascade DNAzyme-mediated gene regulation process induced downregulation of ATG-5 proteins to disrupt autophagy. Simultaneously, the released ZnO2 donated sufficient H2O2 to generate adequate O2 to relieve tumor hypoxia, obtaining highly cytotoxic 1O2 to trigger pyroptosis. By using dynamic cascade gene silencing to disrupt the pyroptosis checkpoint and synergistic relieving of hypoxia, this DNA nanocomplex significantly weakened cellular resistance to achieve efficient pyroptosis therapy both in vitro and in vivo.

Multienzyme-Like Polyoxometalate-Based Single-Atom Enzymes for Cancer-Specific Therapy Through Acid-Triggered Nontoxicity-to-Toxicity Transition.

Single-atom enzymes (SAzymes) exhibit great potential for chemodynamic therapy (CDT); while, general application is still challenged by their instability and unavoidable side effects during delivery. Herein, a manganese-based polyoxometalate single-atom enzyme (Mn-POM SAE) is first introduced into tumor-specific CDT, which exhibits tumor microenvironment (TME)-activated transition of nontoxicity-to-toxicity. Different from traditional POM materials, the aggregates of low-toxic Mn-POM SAE nanospheres are obtained at neutral conditions, facilitating efficient delivery and avoiding toxicity problems in normal tissues. Under acid TME conditions, these nanospheres are degraded into smaller units of toxic Mn(II)-PW11; thus, initiating cancer cell-specific therapy. The released active units of Mn(II)-PW11 exhibit excellent multienzyme-like activities (including peroxidase (POD)-like, oxidase (OXD)-like, catalase (CAT)-like, and glutathione peroxidase (Gpx)-like activities) for the synergistic cancer therapy due to the stabilized high valence Mn species (MnIII/MnIV). As demonstrated by both intracellular evaluations and in vivo experiments, ROS is generated to cause damage to lysosome membranes, further facilitating acidification and impaired autophagy to enhance cancer therapy. This study provides a detailed investigation on the acid-triggered releasing of active units and the electron transfer in multienzyme-mimic-like therapy, further enlarging the application of POMs from catalytical engineering into cancer therapy.

Tumor-activated in situ synthesis of single-atom catalysts for O2-independent photodynamic therapy based on water-splitting.

Single-atom catalysts (SACs) have attracted interest in photodynamic therapy (PDT), while they are normally limited by the side effects on normal tissues and the interference from the Tumor Microenvironment (TME). Here we show a TME-activated in situ synthesis of SACs for efficient tumor-specific water-based PDT. Upon reduction by upregulated GSH in TME, C3N4-Mn SACs are obtained in TME with Mn atomically coordinated into the cavity of C3N4 nanosheets. This in situ synthesis overcomes toxicity from random distribution and catalyst release in healthy tissues. Based on the Ligand-to-Metal charge transfer (LMCT) process, C3N4-Mn SACs exhibit enhanced absorption in the red-light region. Thereby, a water-splitting process is induced by C3N4-Mn SACs under 660 nm irradiation, which initiates the O2-independent generation of highly toxic hydroxyl radical (·OH) for cancer-specific PDT. Subsequently, the ·OH-initiated lipid peroxidation process is demonstrated to devote effective cancer cell death. The in situ synthesized SACs facilitate the precise cancer-specific conversion of inert H2O to reactive ·OH, which facilitates efficient cancer therapy in female mice. This strategy achieves efficient and precise cancer therapy, not only avoiding the side effects on normal tissues but also overcoming tumor hypoxia.

DNA conformational change embrace ultraviolet photolysis: A dual-mode sensing platform for electrochemical and fluorescent signaling.

We developed a dual-mode biosensor that utilizes DNA conformational changes and ultraviolet photolysis for electrochemical (EC) and fluorescence (FL) detection. In this study, a stem-loop-structured carcinoembryonic antigen (CEA) aptamer was modified on an Au electrode, and this aptamer contained a redox-labeled methylene blue (MB), short-chain DNA with a 6-carboxylic fluorescein (FAM) and a PC linker that can be cleaved by ultraviolet light. Subsequently, CEA and CEA antibody-modified upconversion nanoparticle bioconjugates (CEA-Ab@UCNPs) were added. In the presence of CEA, Ab@UCNPs can bind CEA and push the MB which was originally close to the electrode surface, away from the electrode surface, resulting in a reduced redox current. Under irradiation with a 980 nm laser, the UCNPs emit ultraviolet light, leading to photocleavage of the PC linker and the release of FAM for FL sensing. Under optimal conditions, the EC and FL modes showed good responses to CEA within 0.01-50 ng/mL and 0.1-80 ng/mL, respectively.

Synergistically remodulating H+/Ca2+ gradients to induce mitochondrial depolarization for enhanced synergistic cancer therapy.

The remodulation of H+/Ca2+ gradients in the mitochondria matrix could be effective to induce mitochondria depolarization for the enhancement of cancer therapy. However, it is still challenged by H+ homeostasis, insufficient Ca2+, uncoordinated regulations, and inefficient loading/delivery strategies. Herein, a supramolecular DNA nanocomplex (Ca@DNA-MF) was prepared to synergistically remodulate H+/Ca2+ gradients for mitochondrial depolarization. Upon targeted functionalization and TME-triggered delivery, multiple reagents were released in cancer cells for synergistic three-channel mitochondrial depolarization: the gene reagent of siMCT4 blocked the LA metabolism to induce mitochondrial acidification by downregulating monocarboxylate transporter 4 (MCT4); released Ca2+ disrupted Ca2+ homeostasis to facilitate Ca2+-based mitochondrial depolarization; specifically, TME-activated glutathione (GSH) depletion facilitated efficient generation of hydroxyl radicals (˙OH), further enhancing the mitochondrial depolarization. The remodulation not only triggered apoptosis but also led to ferroptosis to generate abundant ROS for efficient LPO-based apoptosis, providing a synergistic strategy for enhanced synergistic cancer therapy.

Ultrathin 2D Pd/Cu Single-Atom MOF Nanozyme to Synergistically Overcome Chemoresistance for Multienzyme Catalytic Cancer Therapy.

Single-atom nanozymes (SAzymes) have obtained increasing interest to mimic natural enzymes for efficient cancer therapy, while challenged by chemoresistance from cellular redox homeostasis and the interface of reductive species in tumor microenvironment (TME). Herein, a dual single-atomic ultrathin 2D metal organic framework (MOF) nanosheet of multienzyme (Pd/Cu SAzyme@Dzy) is prepared to synergistically overcome chemoresistance for multienzyme enhanced cancer catalytic therapy. The Pd SAzyme exhibits peroxidase (POD)-like catalytic activity for overcoming chemoresistance via disturbing cellular redox balance. This is further enhanced by cascade generation of more ∙OH via Cu+ -catalyzed POD-like reactions, initiated by in situ-reduction of Cu2+ into Cu+ upon GSH depletion. This process can also avoid the consumption of ∙OH by endogenous reductive GSH in TME, ensuring the adequate amount of ∙OH for highly efficient therapy. Besides, the DNAzyme is also delivered for gene therapy of silencing cancer-cell-targeting VEGFR2 protein to further enhance the therapy. Based on both experiments and theoretical calculations, the synergetic multienzyme-based cancer therapy is examined and the enhancement by the cascade tumor antichemoresistance is revealed.

Oxygen Bridge Formed by Doping Nonmetal Atoms into Cationic Vacancies To Enhance the Photoelectrochemical Oxygen Evolution Reaction.

To enhance photoelectrochemical (PEC) water splitting for renewable energy conversion, the conventional strategy is doping nonmetals into anionic vacancies. Compared to anionic vacancies, cationic vacancies are theoretically more effective and reliable for anchoring nonmetals owing to their larger radii and unique advantages. The current research mainly focuses on anionic vacancies, while there are few studies on cationic vacancies due to high formation energy and challenging characterizations by convenient techniques. To overcome the current limitations, nonmetallic S and P atoms are successfully doped into cationic vacancies on the TiO2 surface for tuning local electronic structures. In contrast to the traditional strategy of reducing the bandgaps, nonmetallic atom doping into cationic vacancies facilitates efficient electronic regulation for PEC enhancement without changing the bandgap. The enhanced performance is attributed to the formation of an oxygen bridge, which can accumulate electrons from surrounding S/P atoms. Significantly, the electron-enriched oxygen bridge efficiently transfers electrons to activate reaction site Ti, which can promote the oxygen evolution reaction performance. Density functional theory calculations reveal that the decrease of reaction energy barriers and the optimization of local electron distribution are conducive to electronic transmission. This would provide a high-efficiency electronic tuning strategy for improving PEC performance.

Dual Active Centers Linked by a Reversible Electron Station as a Multifunctional Nanozyme to Induce Synergetically Enhanced Cascade Catalysis for Tumor-Specific Therapy.

Nanozymes have shown great promise in reactive oxygen species (ROS)-mediated tumor therapy with mitigated side effects but are normally limited by the complex tumor microenvironment (TME). Herein, to overcome the adverse effects of TME, such as tumor hypoxia and high endogenous glutathione (GSH), an aptamer-functionalized Pd@MoO3-x nano-hydrangea (A-Pd@MoO3-x NH) is constructed for high-efficiency cancer therapy. Utilizing the irregular shape characteristics of nano Pd, the A-Pd@MoO3-x NH nanozyme simultaneously exposes catalase-like Pd(111) and oxidase-like Pd(100) surface facets as dual active centers. This can catalyze cascade enzymatic reactions to overcome the negative effects of tumor hypoxia caused by the accumulation of cytotoxic superoxide (O2•-) radicals in TME without any external stimuli. In addition, the nanozyme can effectively degrade the overexpressed glutathione (GSH) through the redox reaction to avoid nontherapeutic consumption of O2•- radicals. More significantly, as a reversible electron station, MoO3-x can extract electrons from H2O2 decomposing on Pd(111) or GSH degradation and transfer them back to Pd(100) through oxygen bridges or few Mo-Pd bonds. This can synergistically enhance enzyme-like activities of dual active centers and the GSH-degrading ability to enrich O2•- radicals. In this way, the A-Pd@MoO3-x NH nanozyme can selectively and remarkably kill tumor cells while keeping the normal cell line unharmed.

Regulating donor-acceptor system toward highly efficient dual-state emission for sensitive response of nitroaromatic explosives.

Dual-state emission luminogens (DSEgens) as fluorophores emit efficiently in solution and solid forms have gained increasing concern in the field of chemical sensing. Recent efforts by our group led to the identification of DSEgens as an easy-to-visualize nitroaromatic explosives (NAEs) detection platform. However, none of the previously studied NAEs probes show effective improvement in sensitivity. Here, we designed a series of benzoxazole-based DSEgens through multiple strategies driven by theoretical calculations, revealing their improved detecting performance on NAEs. Compounds 4a-4e exhibit thermal- and photo-stability, large Stokes shift as well as sensitivity solvatochromism (except for 4a and 4b). A subtle balance between rigid conjugation and distorted conformation endows these D-A type fluorophores 4a-4e with DSE properties. Furthermore, 4d and 4e show aggregation-induced emission phenomenon caused by distorted molecular conformation and restricted intramolecular rotation. Interestingly, DSEgen 4e displays anti-interference and sensitivity towards NAEs with a detection limit of 10-8 M. It can be applied for expedient and distinct visual identification of NAEs not only in solution but also on filter paper and film, supporting this new DSEgen as reliable NAEs chemoprobe.

Examination of electronically mismatched Diels-Alder reaction by on-line mass spectrometry.

RATIONALE: Electronically mismatched Diels-Alder reactions have gained much attention as an alternative pathway for C-C bond formation. To facilitate the development of facile organic transformations, mechanistic investigations are required. Spectroscopic methods (NMR, electron paramagnetic resonance and UV-visible) are normally adopted for mechanistic examinations, but further improvements in directly obtaining structural information of short-lived intermediates are encouraged. Herein, an electronically mismatched Diels-Alder reaction between indole and 1,3-cyclohexadiene was studied using in situ electrospray ionization mass spectrometry (in situ ESI-MS). Based on direct sampling and detection of the in situ ESI-MS without sample pretreatment, the structures and dynamics of important intermediates were examined on-line. METHODS: A syringe-based photocatalytic reactor and in situ ambient MS (AMS) evaluation system was constructed for mechanism studies. The role of oxygen was confirmed via control reaction employed in the N2 -bubbled system. The stepwise cation radical-based pathway and the [2 + 2] cycloaddition process were determined through a series of experiments, including solvent evaluation, MS/MS experiments and dynamic monitoring. RESULTS: The dependence of the reaction on solvent polarity demonstrated that the reaction occurs via the formation of cation radicals, which were captured, identified and dynamically monitored via in situ ESI-MS. Without pre-separation, the intermediate of [2 + 2] cycloaddition was identified and the cycloaddition process was thereby determined to be the combination of [4 + 2] cycloaddition and [2 + 2] cycloaddition. In addition, oxygen was proved to act as an electron mediator for both catalyst Ru(bpz)3 (PF6 )2 and radical cations. CONCLUSIONS: The mechanism of an electronically mismatched Diels-Alder reaction was successfully deduced by in situ MS associated with a syringe-based photocatalytic reactor. The structures and dynamics of cation radicals, the effect of O2 for the reaction and the detailed process of [2 + 2] cycloaddition have been well demonstrated. This work could not only promote the understanding and development of facile photocatalytic transformations, but also enlarge the application range of AMS in on-line monitoring.

Germacrane Sesquiterpene Dilactones from Mikania micrantha and Their Antibacterial and Cytotoxic Activity.

Four new germacrane sesquiterpene dilactones, 2ß-hydroxyl-11ß,13-dihydrodeoxymikanolide (1), 3ß-hydroxyl-11ß,13-dihydrodeoxymikanolide (2), 1α,3ß-dihydroxy-4,9-germacradiene-12,8:15,6-diolide (3), and (11ß,13-dihydrodeoxymikanolide-13-yl)-adenine (4), together with five known ones (5-9) were isolated from the aerial parts of Mikania micrantha. Their structures were elucidated on the basis of extensive spectroscopic analysis. Compound 4 is featured with an adenine moiety in the molecule, which is the first nitrogen-containing sesquiterpenoid so far isolated from this plant species. These compounds were evaluated for their in vitro antibacterial activity against four Gram-(+) bacteria of Staphyloccocus aureus (SA), methicillin-resistant Staphylococcus aureus (MRSA), Bacillus cereus (BC) and Curtobacterium. flaccumfaciens (CF), and three Gram-(-) bacteria of Escherichia coli (EC), Salmonella. typhimurium (SA), and Pseudomonas Solanacearum (PS). Compounds 4 and 7-9 were found to show strong in vitro antibacterial activity toward all the tested bacteria with the MIC values ranging from 1.56 to 12.5 µg/mL. Notably, compounds 4 and 9 showed significant antibacterial activity against the drug-resistant bacterium of MRSA with MIC value 6.25 µg/mL, which was close to reference compound vancomycin (MIC 3.125 µg/mL). Compounds 4 and 7-9 were further revealed to show in vitro cytotoxic activity toward human tumor A549, HepG2, MCF-7, and HeLa cell lines, with IC50 values ranging from 8.97 to 27.39 µM. No antibacterial and cytotoxic activity were displayed for the other compounds. The present research provided new data to support that M. micrantha is rich in structurally diverse bioactive compounds worthy of further development for pharmaceutical applications and for crop protection in agricultural fields.

Computation-Assisted Design of ssDNA Framework Nanorobots for Cancer Logical Recognition, Toehold Disintegration, Visual Dual-Diagnosis, and Synergistic Therapy.

Single-stranded DNA (ssDNA) allows flexible and directional modifications for multiple biological applications, while being greatly limited by their poor stability, increased folding errors, and complicated sequence optimizations. This greatly challenges the design and optimization of ssDNA sequences to fold stable 3D structures for diversified bioapplications. Herein, the stable pentahedral ssDNA framework nanorobots (ssDNA nanorobots) were intelligently designed, assisted by examining dynamic folding of ssDNA in self-assemblies via all-atom molecular dynamics simulations. Assisted by two functional siRNAs (S1 and S2), two ssDNA strands were successfully assembled into ssDNA nanorobots, which include five functional modules (skeleton fixation, logical dual recognition of tumor cell membrane proteins, enzyme loading, dual-miRNA detection and synergy siRNA loading) for multiple applications. By both theoretical calculations and experiments, ssDNA nanorobots were demonstrated to be stable, flexible, highly utilized with low folding errors. Thereafter, ssDNA nanorobots were successfully applied to logical dual-recognition targeting, efficient and cancer-selective internalization, visual dual-detection of miRNAs, selective siRNA delivery and synergistic gene silencing. This work has provided a computational pathway for constructing flexible and multifunctional ssDNA frameworks, enlarging biological application of nucleic acid nanostructures.

Single-Molecule Evaluation of the SARS-CoV-2 Nucleocapsid Protein Using Gold Particle-in-a-Frame Nanostructures Enhanced Fluorescent Assay.

Ultrasensitive evaluation of low-abundance analytes, particularly with limits approaching a single molecule, is a key challenge in the design of an assay for profiling severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen. Herein, we report an aptamer claw strategy for directly evaluating the SARS-CoV-2 antigen based on gold particle-in-a-frame nanostructures (Au PIAFs). Au PIAF was used as a metal-enhanced fluorescence material. The assay integrated with a microplate reader achieved a sensitivity of 44 fg·mL-1 in under 3 min and accurately detected the SARS-CoV-2 nucleocapsid protein (N protein) in human saliva samples. When our assay is combined with a single-molecule counting platform, the limit of detection can be as low as 0.84 ag·mL-1. This rapid and ultrasensitive assay holds promise as a tool for screening SARS-CoV-2 and other contagious viruses.

OH radical-initiated single-electron transfer for accelerated degradation via carbocation intermediates.

Single electron transfer (SET) has made great contributions to a broad range of chemical processes, whose radical cation and carbocation intermediates are important for mechanism studies. Herein, hydroxyl radical (˙OH)-initiated SET was revealed in accelerated degradations, via the online examination of radical cations and carbocations by electrosonic spray ionization mass spectrometry (ESSI-MS). In the green and efficient non-thermal plasma catalysis system (MnO2-plasma), hydroxychloroquine was efficiently degraded upon SET via carbocations. In the plasma field full of active oxygen species, ˙OH was generated on the MnO2 surface to initiate SET-based degradations. Furthermore, theoretical calculations revealed that ˙OH preferred to withdraw the electron from the N atom that was conjugated to the benzene ring. This facilitated the generation of radical cations through SET, which was followed by the sequential formation of two carbocations for accelerated degradations. Transition states and energy barriers were calculated to study the formation of radical cations and subsequent carbocation intermediates. This work demonstrates an ˙OH-initiated SET for accelerated degradation via carbocations, providing a deeper understanding and the potential for the wider application of SET in green degradations.

Confined surface-enhanced indole cation-radical cyclization studied by mass spectrometry.

Reactions in confined spaces exhibit unique reactivity, while how the confinement effect enhances reactions remains unclear. Herein, the reaction in the confined space of a nanopipette reactor was examined by in situ nano-electrospray mass spectrometry (nanoESI-MS). The indole cation-radical cyclization was selected as the model reaction, catalyzed by a common visible-light-harvesting complex Ru(bpz)3(PF6)2 (1% eq.) rather than traditional harsh reaction conditions (high temperature or pressure, etc.). As demonstrated by in situ nanoESI-MS, this reaction was readily promoted in the nanopipette under mild conditions, while it was inefficient in both normal flasks and microdroplets. Both experimental and theoretical evidence demonstrated the formation of concentrated Ru(II)-complexes on the inner surface of the nanopipette, which facilitated the accelerated reactions. As a result, dissociative reactive cation radicals with lower HOMO-LUMO gap were generated from the Ru(II)-complexes by ligand-to-metal charge transfer (LMCT). Furthermore, the crucial cation radical intermediates were captured and dynamically monitored via in situ nanoESI-MS, responsible for the electronically matched [4 + 2] cycloaddition and subsequent intramolecular dehydrogenation. This work inspires a deeper understanding of the unique reactions in confined spaces.

New Perspectives on Sleep Regulation by Tea: Harmonizing Pathological Sleep and Energy Balance under Stress.

Sleep, a conservative evolutionary behavior of organisms to adapt to changes in the external environment, is divided into natural sleep, in a healthy state, and sickness sleep, which occurs in stressful environments or during illness. Sickness sleep plays an important role in maintaining energy homeostasis under an injury and promoting physical recovery. Tea, a popular phytochemical-rich beverage, has multiple health benefits, including lowering stress and regulating energy metabolism and natural sleep. However, the role of tea in regulating sickness sleep has received little attention. The mechanism underlying tea regulation of sickness sleep and its association with the maintenance of energy homeostasis in injured organisms remains to be elucidated. This review examines the current research on the effect of tea on sleep regulation, focusing on the function of tea in modulating energy homeostasis through sickness sleep, energy metabolism, and damage repair in model organisms. The potential mechanisms underlying tea in regulating sickness sleep are further suggested. Based on the biohomology of sleep regulation, this review provides novel insights into the role of tea in sleep regulation and a new perspective on the potential role of tea in restoring homeostasis from diseases.

Biomineralization of DNA Nanoframeworks for Intracellular Delivery, On-Demand Diagnosis, and Synergistic Cancer Treatments.

DNA nanoframeworks, with great biological information and controlled framework structures, exhibit great potentials in biological applications. Their applications are normally limited by unstable structures susceptible to hydrolysis, depurination, depyrimidination, oxidation, alkylation, or nuclease degradations. Herein, to ensure the mechanical and chemical stabilities of DNA nanoframeworks for intracellular applications, biomineralization of multifunctional DNA nanoframeworks with a tetrahedral skeleton is employed. Via silicification, the S-S bond is simultaneously introduced to obtain the silica-armored DNA nanoframeworks (Si-DNA nanoframeworks), mechanically and chemically stabilized for efficient intracellular deliveries. This successfully prevents degradations and leakages of reagents loaded on Si-DNA nanoframeworks, including biomolecular siRNA and small DOX drugs. Furthermore, the nucleic acid strands of the nanoframeworks are labeled with FAM and the quencher, facilitating miRNA detection upon "turn-on" signals from hybridizations. Therefore, the nanoframeworks collapse via double responses of the silica coating (silica acidic dissolution and S-S reduction by GSH) in cancer cells, realizing on-demand reagent release for miRNA detection and synergistic treatments (by siRNA and DOX). Demonstrated by both in vivo and in vitro experiments, the biomineralization has stabilized DNA nanomaterials for biological applications.

CRISPR/Cas9-based coronal nanostructures for targeted mitochondria single molecule imaging.

The biological state at the subcellular level is highly relevant to many diseases, and the monitoring of organelles such as mitochondria is crucial based on this. However, most DNA and protein based nanoprobes used for the detection of mitochondrial RNAs (mitomiRs) lack spatial selectivity, which leads to inefficiencies in probe delivery and signal turn-on. Herein, we constructed a novel DNA nanoprobe named protein delivery nano-corona (PDNC) to improve the delivery efficiency of Cas protein, for spatially selective imaging of mitomiRs in living cells switched on by a CRISPR/Cas system. Combined with a single-molecule counting method, this strategy enables highly sensitive detection of low-abundance mitomiR. Therefore, the strategy in this work opens up new opportunities for cell identification, early clinical diagnosis, and research in biological behaviour at the subcellular level.

Identification of a apoptosis-related LncRNA signature to improve prognosis prediction and immunotherapy response in lung adenocarcinoma patients.

Apoptosis is closely associated with the development of various cancers, including lung adenocarcinoma (LUAD). However, the prognostic value of apoptosis-related lncRNAs (ApoRLs) in LUAD has not been fully elucidated. In the present study, we screened 2, 960 ApoRLs by constructing a co-expression network of mRNAs-lncRNAs associated with apoptosis, and identified 421 ApoRLs that were differentially expressed between LUAD samples and normal lung samples. Sixteen differentially expressed apoptosis-related lncRNAs (DE-ApoRLs) with prognostic relevance to LUAD patients were screened using univariate Cox regression analysis. An apoptosis-related lncRNA signature (ApoRLSig ) containing 10 ApoRLs was constructed by applying the Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression method, and all LUAD patients in the TCGA cohort were divided into high or low risk groups. Moreover, patients in the high-risk group had a worse prognosis (p < 0.05). When analyzed in conjunction with clinical features, we found ApoRLSig to be an independent predictor of LUAD patients and established a prognostic nomogram combining ApoRLSig and clinical features. Gene set enrichment analysis (GSEA) revealed that ApoRLSig is involved in many malignancy-associated immunomodulatory pathways. In addition, there were significant differences in the immune microenvironment and immune cells between the high-risk and low-risk groups. Further analysis revealed that the expression levels of most immune checkpoint genes (ICGs) were higher in the high-risk group, which suggested that the immunotherapy effect was better in the high-risk group than in the low-risk group. And we found that the high-risk group was also better than the low-risk group in terms of chemotherapy effect. In conclusion, we successfully constructed an ApoRLSig which could predict the prognosis of LUAD patients and provide a novel strategy for the antitumor treatment of LUAD patients.