Ultrafast and Highly Specific Detection of One-Base Mutated Cell-Free DNA at a Very Low Abundance.

Liquid biopsy as well as genotyping plays important roles in guiding the use of tumor-targeted drugs and monitoring the generation of drug resistance. However, current methods, such as next-generation sequencing (NGS) and pyrosequencing, require long analysis time and complicated steps. To achieve ultrafast and highly specific detection of cell-free DNA (cfDNA) from blood, we improved our recently developed FEN1-aided RPA (FARPA), which combined flap endonuclease 1 (FEN1)-catalyzed invasive reactions with recombinase polymerase amplification (RPA) by inactivating the RPA enzymes before invasive reactions, designing short RPA primers, and changing invasive reaction conditions. Using the L858R and T790M mutations as examples, FARPA was sensitive to detect 5 copies of targeted mutants, specific to sense the mutants with an abundance as low as 0.01% from blood, and ultrafast to get results within 40 min. The method was readily expended to genotyping, and 15 min was enough to report the allele species directly from oral swab samples by coupling quick DNA extraction reagents. Validation was carried out by detecting clinical samples, including 20 cfDNA from patients with non-small cell lung cancer (NSCLC) for liquid biopsy and 43 human genomic DNA (gDNA) purified from blood (33) or lysed from oral swabs (10) for genotyping, giving 100% agreement with NGS and pyrosequencing, respectively. Furthermore, a portable battery-driven device with dual-channel fluorescence detection was successfully constructed to facilitate point-of-care testing (POCT) of liquid biopsy and genotyping, providing doctors with a potential tool to achieve genotyping- or mutant-guided personalized medicine at emergency or source-limited regions.

FARPA-based tube array coupled with quick DNA extraction enables ultra-fast bedside detection of antibiotic-resistant pathogens.

Rapid and accurate detection of pathogens and antimicrobial-resistant (AMR) genes of the pathogens are crucial for the clinical diagnosis and effective treatment of infectious diseases. However, the time-consuming steps of conventional culture-based methods inhibit the precise and early application of anti-infection therapy. For the prompt treatment of pathogen-infected patients, we have proposed a novel tube array strategy based on our previously reported FARPA (FEN1-aided recombinase polymerase amplification) principle for the ultra-fast detection of antibiotic-resistant pathogens on site. The entire process from "sample to result" can be completed in 25 min by combining quick DNA extraction from a urine sample with FARPA to avoid the usually complicated DNA extraction step. Furthermore, a 36-tube array made from commercial 384-well titre plates was efficiently introduced to perform FARPA in a portable analyser, achieving an increase in the loading sample throughput (from several to several tens), which is quite suitable for the point-of-care testing (POCT) of multiple pathogens and multiple samples. Finally, we tested 92 urine samples to verify the performance of our proposed method. The sensitivities for the detection of E. coli, K. pneumoniae, E. faecium, and E. faecalis were 92.7%, 93.8%, 100% and 88.9%, respectively. The specificities for the detection of the four pathogens were 100%. Consequently, our rapid, low-cost and user-friendly POCT method holds great potential for guiding the rational use of antibiotics and reducing bacterial resistance.

Prediction of superhard C1+xN1-x compounds with metal-free magnetism and narrow band gaps.

The scarcity of superhard materials with magnetism or a narrow band gap, despite their potential applications in various fields, makes it desirable to design such materials. Here, a series of C1+xN1-x compounds are theoretically designed by replacing different numbers of nitrogen atoms with carbon atoms in the synthesized C1N1 compound. The results indicate that the compounds C5N3 and C7N1 possess both superhardness and antiferromagnetic ordering due to the introduction of low-coordinated carbon atoms. The hardness of the two compounds is about 40.3 and 54.5 GPa, respectively. The magnetism in both compounds is attributed to the unpaired electrons in low-coordinated carbon atoms, and the magnetic moments are 0.42 and 0.39 µB, respectively. Interestingly, the magnetism in C5N3 remains unaffected by the external pressure used in this study, whereas C7N1 becomes nonmagnetic when the pressure exceeds ∼80 GPa. Electronic calculations reveal that both compounds behave as indirect band gap semiconductors, with narrow energy gaps of about 0.30 and 0.20 eV, respectively. Additionally, the other two compounds, C6N2-I and C6N2-III, exhibit nonmagnetic ordering and possess hardness values of 52.6 and 35.0 GPa, respectively. C6N2-I behaves as a semiconductor with an energy gap of 0.79 eV, and C6N2-III shows metallic behavior. Notably, the energy gaps of C5N3 and C6N2-I remain nearly constant under arbitrary pressure due to their porous and superhard structure. These compounds fill the gap in magnetic or narrow band gap superhard materials, and they can be used in the spintronic or optoelectronic fields where conventional superhard materials are not suitable.

Prediction of pure carbon crystals with intrinsic antiferromagnetism: polymerized from C20 fullerenes.

Pure carbon materials with magnetic properties have attracted considerable research interest due to their advantages over traditional magnetic materials. Nevertheless, such materials are exceedingly rare. Disrupting the Kekulé valence structures in carbon materials potentially leads to the emergence of magnetism. In this study, using first principles calculations, we developed a range of pure carbon allotropes derived from the smallest fullerene C20 which potentially disrupts the Kekulé valence structures after polymerization. The results indicate that some of the allotropes disrupting the Kekulé valence structures exhibit intrinsic antiferromagnetic ordering, and the magnetism originates from the presence of isolated three-fold coordinated C atoms. The other allotropes adhering to the Kekulé valence structures show non-magnetism with all three-fold coordinated C atoms forming dimers. In all magnetic polymers, magnetism arises from unpaired electrons on the isolated three-fold coordinated carbon atoms, with magnetic moments of about 0.40µB at these sites. The adsorption of dopant atoms can significantly alter the magnetic properties of polymers, for instance, the C20-71 polymer with Immm symmetry undergoes a transition from non-magnetic to anti-magnetic ordering upon adsorption of hydrogen atoms. Electronic calculations indicate that these polymers display a range of electronic properties, encompassing both metallic and semiconducting characteristics. Notably, certain magnetic phases exhibit superhard properties, with the hardness value exceeding 40 GPa. This study presents a potential method for designing magnetic carbon materials. Specifically, certain compounds address the gap in magnetic superhard materials composed of light elements, and can be utilized in the field of spintronics where traditional superhard materials are unsuitable.

Mesoporous Nanozyme-Enhanced DNA Tetrahedron Electrochemiluminescent Biosensor with Three-Dimensional Walking Nanomotor-Mediated CRISPR/Cas12a for Ultrasensitive Detection of Exosomal microRNA.

Exosomal microRNAs (exomiRNAs) have emerged as ideal biomarkers for early clinical diagnostics. The accurate detection of exomiRNAs plays a crucial role in facilitating clinical applications. Herein, an ultrasensitive electrochemiluminescent (ECL) biosensor was constructed using three-dimensional (3D) walking nanomotor-mediated CRISPR/Cas12a and tetrahedral DNA nanostructures (TDNs)-modified nanoemitters (TCPP-Fe@HMUiO@Au-ABEI) for exomiR-155 detection. Initially, the 3D walking nanomotor-mediated CRISPR/Cas12a strategy could effectively convert the target exomiR-155 into amplified biological signals for improving the sensitivity and specificity. Then, TCPP-Fe@HMUiO@Au nanozymes with excellent catalytic performance were used to amplify ECL signals because of the enhanced mass transfer and increased catalytic active sites, originating from its high surface areas (601.83 m2/g), average pore size (3.46 nm), and large pore volumes (0.52 cm3/g). Meanwhile, the TDNs as the scaffold to fabricate "bottom-up" anchor bioprobes could improve the trans-cleavage efficiency of Cas12a. Consequently, this biosensor achieved the limit of detection down to 273.20 aM ranging from 1.0 fM to 1.0 nM. Furthermore, the biosensor could discriminate breast cancer patients evidently by analyzing exomiR-155, and these results conformed to that of qRT-PCR. Thus, this work provides a promising tool for early clinical diagnostics.

DNA-Guided Extracellular-Vesicle Metallization with High Catalytic Activity for Accurate Diagnosis of Pulmonary Nodules.

Sensitive and specific analysis of extracellular vesicles (EVs) offers a promising minimally invasive way to identify malignant pulmonary nodules from benign lesions. However, accurate analysis of EVs is subject to free target proteins in blood samples, which compromises the clinical diagnosis value of EVs. Here a DNA-guided extracellular-vesicle metallization (DEVM) strategy is described for ultrasensitive and specific analysis of EV protein biomarkers and classification of pulmonary nodules. The facile DEVM process mainly includes the incorporation of DNA labeled with cholesterol and thiol groups into EV membranes and subsequent deposition of Au3+ and Pt4+ to allow the DNA-functionalized EVs to be encapsulated with AuPt nanoshells. It is found that the synthesized AuPt-metallized EVs possess extrinsic peroxidase-like activity. Utilizing the feature of the catalytic metal nanoshells just growth on the EV membranes, the DEVM method enables multiparametric recognition of target proteins and EV membranes and can produce an amplified colorimetric signal, avoiding the interference of free proteins. By profiling four surface proteins of EVs from 48 patients with pulmonary nodules, the highest area under the receiver operating characteristic curve (0.9983) is obtained. Therefore, this work provides a feasible EVs analysis tool for accurate pulmonary nodules management.

Visualized RNA detection of SARS-CoV-2 in a closed tube by coupling RT-PCR with nested invasive reaction.

A simple, cost-effective and reliable diagnosis of pathogen nucleic acids assay is much required for controlling a pandemic of a virus disease, such as COVID-19. Our previously developed visualized detection of pathogen DNA in a single closed tube is very suitable for POCT. However, virus RNA could not be detected directly and should be reverse-transcribed into cDNA in advance. To enable this visualized assay to detect virus RNA directly, various types of reverse transcriptase were investigated, and finally we found that HiScript II reverse transcriptase could keep active and be well adapted to the one-pot visualized assay in optimized conditions. Reverse transcription, template amplification and amplicon identification by PCR coupled with invasive reaction, as well as visualization by self-assembling of AuNP probes could be automatically and sequentially performed in a closed tube under different temperature conditions, achieving "sample (RNA)-in-result (red color)-out" only by a simple PCR engine plus the naked eye. The visualized RT-PCR is sensitive to unambiguous detection of 5 copies of the N and ORFlab genes of SARS-CoV-2 RNA comparing favourably with qPCR methods (commercialized kit), is specific to genotype 3 variants (Alpha, Beta and Omicron) of SARS-CoV-2, and is very accurate for picking up 0.01% Omicron variant from a large amount of sequence-similar backgrounds. The method is employed in detecting 50 clinical samples, and 10 of them were detected as SARS-CoV-2 positive samples, identical to those by conventional RT-PCR, indicating that the method is cost-effective and labor-saving for pathogen RNA screening in resource-limited regions.

Superhard bulk C4N3 compounds with metal-free magnetism assembled from two-dimensional C4N3: a first-principles study.

Enriching the electronic properties of superhard materials is very important to extend their applications, and some superhard materials with metallic or superconducting characteristics have been designed via theoretical or experimental methods. However, their magnetic features have scarcely been studied, since most of them are limited to nonmagnetic ordering. Here, with the help of first-principles calculations, a series of C4N3 compounds are designed by stacking C4N3 sheets with different sequences. As expected, some of them exhibit both magnetic and superhard characteristics. Notably, all these compounds exhibit dynamic and mechanical stabilities, indicating that their dynamic and mechanical stabilities are independent of the stacking sequence. Among them, the ABC-stacked one is energetically favorable, and it exhibits antiferromagnetic ordering and has a hardness of ∼54.0 GPa, and the electronic calculations show that it is a semiconductor with a direct band gap of ∼1.20 eV. Besides, the magnetism of all magnetic C4N3 compounds is caused by the lower coordinated atoms, and the magnetic moments are located on three-fold C or two-fold coordinated N atoms. Additionally, the magnetic property is deeply dependent on the external pressure. This work opens a potential way to design magnetic superhard materials and can arouse their applications in the spintronic field.

Microporous PdCuB nanotag-based electrochemical aptasensor with Au@CuCl2 nanowires interface for ultrasensitive detection of PD-L1-positive exosomes in the serum of lung cancer patients.

Programmed cell death ligand 1 protein-positive (PD-L1+) exosomes have been found to be a potential biomarker for the diagnosis of non-small cell lung cancer (NSCLC). However, the development of highly sensitive detection technique for PD-L1+ exosomes is still a challenge in clinical applications. Herein, a sandwich electrochemical aptasensor based on ternary metal-metalloid palladium-copper-boron alloy microporous nanospheres (PdCuB MNs) and Au@CuCl2 nanowires (NWs) was designed for the detection of PD-L1+ exosomes. The excellent peroxidase-like catalytic activity of PdCuB MNs and the high conductivity of Au@CuCl2 NWs endow the fabricated aptasensor with intense electrochemical signal, thus enabling the detection of low abundance exosomes. The analytical results revealed that the aptasensor maintained favorable linearity over a wide concentration range of 6 orders of magnitude and reached a low detection limit of 36 particles/mL. The aptasensor is successfully applied to the analysis of complex serum samples and achieves the accurate identification of clinical NSCLC patients. Overall, the developed electrochemical aptasensor provides a powerful tool for early diagnosis of NSCLC.

Target response controlled enzyme activity switch for multimodal biosensing detection.

How to achieve delicate regulation of enzyme activity and empower it with more roles is the peak in the field of enzyme catalysis research. Traditional proteases or novel nano-enzymes are unable to achieve stimulus-responsive activity modulation due to their own structural limitations. Here, we propose a novel Controllable Enzyme Activity Switch, CEAS, based on hemin aggregation regulation, to deeply explore its regulatory mechanism and develop multimodal biosensing applications. The core of CEAS relies on the dimerizable inactivation of catalytically active center hemin and utilizes a DNA template to orderly guide the G4-Hemin DNAzyme to tightly bind to DNA-Hemin, thereby shutting down the catalytic ability. By customizing the design of the guide template, different target stimulus responses lead to hemin dimerization dissociation and restore the synergistic catalysis of G4-Hemin and DNA-Hemin, thus achieving a target-regulated enzymatic activity switch. Moreover, the programmability of CEAS allowed it easy to couple with a variety of DNA recognition and amplification techniques, thus developing a series of visual protein detection systems and highly sensitive fluorescent detection systems with excellent bioanalytical performance. Therefore, the construction of CEAS is expected to break the limitation of conventional enzymes that cannot be targetable regulated, thus enabling customizable enzymatic reaction systems and providing a new paradigm for controllable enzyme activities.

Zippered G-quadruplex/hemin DNAzyme: exceptional catalyst for universal bioanalytical applications.

G-quadruplex (G4)/hemin DNAzyme is promising horseradish peroxidase (HRP)-mimic candidate in the biological field. However, its relatively unsatisfactory catalytic capacity limits the potential applications. Inspired by nature protease, we conducted a proximity-enhanced cofactor assembly strategy (PECA) to form an exceptional HRP mimic, namely zippered G4/hemin DNAzyme (Z-G4/H). The hybridization of short oligonucleotides induced proximity assembly of the DNA-grafted hemin (DGH) with the complementary G4 sequences (cG4s), mimicking the tight configuration of protease cofactor and apoenzyme. The detailed investigations of catalytic efficiency and mechanism verified the higher activity, more rapid catalytic rate and high environmental tolerance of the Z-G4/H than the classical G4/hemin DNAzymes (C-G4/H). Furthermore, a proximity recognition transducer has been developed based on the PECA for sensitive detection of gene rearrangement and imaging human epidermal growth factor receptor 2 protein (HER2) dimerization on cell surfaces. Our studies demonstrate the high efficiency of Z-G4/H and its universal application potential in clinical diagnostics and biomolecule interaction research. It also may offer significant opportunities and inspiration for the engineering of the protease-free mimic enzyme.

Role of inner solvation sheath within salt-solvent complexes in tailoring electrode/electrolyte interphases for lithium metal batteries.

Functional electrolyte is the key to stabilize the highly reductive lithium (Li) metal anode and the high-voltage cathode for long-life, high-energy-density rechargeable Li metal batteries (LMBs). However, fundamental mechanisms on the interactions between reactive electrodes and electrolytes are still not well understood. Recently localized high-concentration electrolytes (LHCEs) are emerging as a promising electrolyte design strategy for LMBs. Here, we use LHCEs as an ideal platform to investigate the fundamental correlation between the reactive characteristics of the inner solvation sheath on electrode surfaces due to their unique solvation structures. The effects of a series of LHCEs with model electrolyte solvents (carbonate, sulfone, phosphate, and ether) on the stability of high-voltage LMBs are systematically studied. The stabilities of electrodes in different LHCEs indicate the intrinsic synergistic effects between the salt and the solvent when they coexist on electrode surfaces. Experimental and theoretical analyses reveal an intriguing general rule that the strong interactions between the salt and the solvent in the inner solvation sheath promote their intermolecular proton/charge transfer reactions, which dictates the properties of the electrode/electrolyte interphases and thus the battery performances.

Mechanistic insight into the adjuvant effect of co-exposure to ultrafine carbon black and high humidity on allergic asthma.

Respiratory diseases continue to be a major global concern, with allergies and asthma often discussed as critical areas of study. While the role of environmental risk factors, such as non-allergenic pollutants and high humidity, in asthma induction is often mentioned, there is still a lack of thorough research on their co-exposure. This study aims to investigate the adjuvant effect of ultrafine carbon black (30-50 nm) and high humidity (70% relative humidity) on the induction of allergic asthma. A mouse model of asthma was established using ovalbumin, and airway hyperresponsiveness, remodeling, and inflammation were measured as the endpoint effects of asthma. The mediating role of the oxidative stress pathway and the transient receptor potential vanilloid 1 pathway in asthma induction was validated using pathway inhibitors vitamin E and capsaicin, respectively. Co-exposure to ultrafine carbon black and high humidity had a significant impact on metabolic pathways in the lung, including aminoacyl-tRNA biosynthesis, glycerophospholipid metabolism, and ATP-binding cassette transporters. However, administering vitamin E and capsaicin altered the effects of co-exposure on the lung metabolome. These results offer new insights into the health risk assessment of co-exposure to environmental risk factors and provide an important reference point for the prevention and treatment of allergic asthma.

Research progress of visual detection in rapid on-site detection of pathogen nucleic acid.

Nucleic acid detection is widely used in pathogen screening and detection due to its high sensitivity and specificity. With the increase of detection requirements and the development of amplification technology, nucleic acid detection methods are gradually developing towards simple, fast and low-cost. Quantitative polymerase chain reaction (qPCR), as the "gold standard" for nucleic acid detection, relies on expensive equipment and professional operators, which is not suitable for rapid on-site detection of pathogens. The visual detection method without relying on excitation light source or complex equipment can present the detection results in a more intuitive and portable way after combining with rapid and efficient amplification technology, which has the potential of point-of-care testing (POCT). This paper focuses on the reported application of amplification technology and CRISPR/Cas technology in visual detection and compares their advantages and disadvantages, so as to provide reference for POCT strategy based on pathogen nucleic acid.

Digital Nucleic Acid Signal Amplification Platform for Highly Sensitive DNA Mutation Analysis.

Digital nucleic acid analysis technology has shown great application potential due to its excellent performance. However, most current digital nucleic acid detection methods are based on PCR or other template amplification strategies. Here, we present an alternative analysis platform based on digital nucleic acid signal amplification in droplets termed dNASA. Using a bead-based controllable extension bridged cascade signal amplification reaction, we achieved an ultralow background, high efficiency, and highly specific nucleic acid signal amplification analysis. As a "proof of concept", we demonstrated the feasibility of the proposed dNASA platform in single-base DNA mutation analysis using artificially synthesized samples. This platform provides innovative ideas for the field of digital nucleic acid analysis.

Flap Endonuclease-Induced Steric Hindrance Change Enables the Construction of Multiplex and Versatile Lateral Flow Strips for DNA Detection.

A lateral flow strip (LFS) is an ideal tool for point-of-care testing (POCT), but traditional LFSs cannot be used for multiplex detection. Herein, a multiplex and versatile LFS based on flap endonuclease 1 (FEN1)-induced steric hindrance change (FISH-LFS) is proposed. In this method, multiplex PCR coupled with cascade invasive reactions was employed to yield single-stranded flaps, which were target-specific but independent of target sequences. Then, the amplicons were applied for FISH-LFS, and the single-stranded flaps would be efficiently captured by the complementary LFS-probes at different test lines. As flaps were cleaved from the specially designed hairpin probes, competition among flaps and hairpin probes would occur in capturing the probes at test lines. We enabled the hairpin probes to flow through the test lines while the flaps to stay at the test lines by making use of the difference in steric hindrance between hairpin probes and flaps. The assay is able to detect as low as two copies of blood pathogens (HBV, HCV, and HIV), to pick up as low as 0.1% mutants from wild-type gDNA, and to genotype 200 copies of SARS-CoV-2 variants α and ß within 75 min at a conventional PCR engine. As the method is free of dye, a portable PCR engine could be used for a cost-effective multiplex detection on site. Results using an ultrafast mobile PCR system for FISH-LFS showed that as fast as 30 min was achieved for detecting three pathogens (HBV, HCV, and HIV) in blood, very suitable for POCT of pathogen screening. The method is convenient in operation, simple in instrumentation, specific in genotyping, and very easy in setting up multiplex POCT assays.

Multiplexed and Rapid AST for Escherichia coli Infection by Simultaneously Pyrosequencing Multiple Barcodes Each Specific to an Antibiotic Exposed to a Sample.

Antimicrobial susceptibility testing (AST) is an effective way to guide antibiotic selection. However, conventional culture-based phenotypic AST is time-consuming. The key point to shorten the test is to quantify the small change in the bacterial number after the antibiotic exposure. To achieve rapid AST, we proposed a combination of multiplexed PCR with barcoded pyrosequencing to significantly shorten the time for antibiotic exposure. First, bacteria exposed to each antibiotic were labeled with a unique barcode. Then, the pool of the barcoded products was amplified by PCR with a universal primer pair. Finally, barcodes in the amplicons were individually and quantitatively decoded by pyrosequencing. As pyrosequencing is able to discriminate as low as 5% variation in target concentrations, as short as 7.5 min was enough for cultivation to detect the susceptibility of Escherichia coli to an antibiotic. The barcodes enable more than six kinds of drugs or six kinds of concentrations of a drug to be tested at a time. The susceptibility of 6 antibiotics to 43 E. coli-positive samples from 482 clinical urine samples showed a consistency of 99.3% for drug-resistant samples and of 95.7% for drug-sensitive samples in comparison with the conventional method. In addition, the minimum inhibitory concentration (MIC) of 29 E. coli samples was successfully measured. The proposed AST is dye free (pyrosequencing), multiplexed (six antibiotics), fast (a half-working day for reporting the results), and able to detect the MIC, thus having a great potential for clinical use in quick antibiotic selection.

Lipid membrane anchoring and highly specific fluorescence detection of cancer-derived exosomes based on postfunctionalized zirconium-metal-organic frameworks.

Cancer-derived exosomes carry a variety of important biomarkers specific to the formation, invasion and metastasis of tumor tissue. Dynamic monitoring of exosomes originated from cancer cells has clinical significance. Here we proposed a novel method to employ zirconium-metal-organic frameworks (Zr-MOFs) for extracting and identifying exosomes from blood. At first UiO-66 was magnetically modified as the adsorbent to anchor exosomes by forming Zr-O-P bonds. Then UiO-66-NH2 modified with anti-EpCAM was used to construct the fluorescent probe to recognize the extracted EpCAM-positive exosomes by forming a "MOF-exosome-MOF" structure. The proposed fluorescence detection method was evaluated by quantifying MCF-7 cell-derived exosomes at the concentration as low as 16.72 particles/µl. This method was successfully applied to analyze exosomes in the plasma samples from healthy donors and breast cancer patients, demonstrating that our method might have a great potential in assisting the early diagnosis and in dynamically monitoring the efficacy of cancer treatment. We believe that the method could be extended to the detection of other biomarkers in exosomes derived from cancer cell.

Dancing in local space: rolling hoop orbital amplification combined with local cascade nanozyme catalytic system to achieve ultra-sensitive detection of exosomal miRNA.

The exosomal miRNA (exo-miRNA) derived from tumor cells contains rich biological information that can effectively aid in the early diagnosis of disease. However, the extremely low abundance imposes stringent requirements for accurate detection techniques. In this study, a novel, protease-free DNA amplification strategy, known as "Rolling Hoop Orbital Amplification" (RHOA), was initially developed based on the design concept of local reaction and inspired by the childhood game of rolling iron ring. Benefiting from the local space constructed by the DNA orbital, the circular DNA enzyme rolls directionally and interacts efficiently with the amplification element, making it nearly 3-fold more productive than conventional free-diffusion amplification. Similarly, the localized cascade nanozyme catalytic system formed by bridging DNA probes also exhibits outperformed than free ones. Therefore, a localized energized high-performance electrochemiluminescence (ECL) biosensor was constructed by bridging cascading nanozymes on the electrode surface through DNA probes generated by RHOA, with an impressive limit of detection (LOD) of 1.5 aM for the detection of exosomal miRNA15a-5p and a stable linearity over a wide concentration range from 10- 2 to 108 fM. Thus, this work is a focused attempt at the localized reaction, which is expected to provide a reliable method for accurately detecting of exo-miRNAs.

Stable High-Temperature Lithium-Metal Batteries Enabled by Strong Multiple Ion-Dipole Interactions.

Lithium-metal batteries (LMBs) capable of operating stably at high temperature application scenarios are highly desirable. Conventional lithium-ion batteries could only work stably under 60 °C because of the thermal instability of electrolyte at elevated temperature. Here we design and develop a thermal stable electrolyte based on stable solvation structure using multiple ion-dipole interactions. The strong coordination in solvated structure of electrolyte defines the Li deposition behaviour and the evolution of solid electrolyte interphase at high temperature, which is important to achieve high Li Coulombic efficiency and avoid Li dendritic growth. For high mass loading LiFePO4 -Li cells, the cells at 60 °C with conventional electrolyte easily run into failures, but the cells with our electrolyte at 90 °C and 100 °C could cycle more than 120 and 50 cycles respectively. This work provides new insight into electrolyte design and contributes to the development of high temperature LMBs.