Diabetic chronic wound, plagued by hyperglycemia-driven oxidative stress, bacterial infection, and impaired angiogenesis, represent a critical biomedical challenge with limited treatment options and dire clinical outcomes. Herein, a glucose-responsive “sense-and-treat” microneedle (MN) patch was designed for on-demand drug release and comprehensive diabetic chronic wound therapy. The multifunctional MN patch (denoted EAG-MNs patch) was fabricated from two functional precursors. Solution A was consisted of phenylboronic acid modified gelatin (PBA-Gel) complexed with epigallocatechin gallate (EGCG) through dynamic boronic ester bonds to provide glucose responsiveness. Solution B contained silver nanoparticle-decorated graphene oxide (AgGO) dispersed in hyaluronic acid (HA) to enable sustained antibacterial action. Upon exposure to hyperglycemic wound microenvironment, the boronic ester bonds undergo dissociation, triggering the rapid release of EGCG to scavenge reactive oxygen species, alleviate inflammation, and promote angiogenesis. Simultaneously, the dissolved AgGO component ensures robust and long-lasting antibacterial activity against prevalent pathogens. In an infected diabetic mouse wound model, the EAG-MNs patch significantly accelerated wound closure, reduced granulation tissue formation, enhanced collagen deposition and vascularization, and effectively eliminated bacterial infection compared to control groups. This intelligent MNs platform exemplifies a novel “sense-and-treat” paradigm for diabetic chronic wound management by actively sensing pathological cues and executing synergistic therapeutic actions, offering a promising versatile strategy for advanced wound care.

To simultaneously improve the critical factors in photocatalytic H2 production, the population of active photogenerated electrons, the adsorption and activation of H2O molecules, and the surface dehydrogenation efficiency, we propose a synergistic strategy for TiO2 modification by combining transition metal (TM) doping and N-doped carbon (N-C) coating. The targeted Cr-TiO2@N-C heterojunction exhibits dramatically enhanced H2 production under blue light irradiation, contrasting sharply with a negligible production by pristine TiO2. Comprehensive structural characterization and theoretical calculations confirm the uniform substitution of Cr into the TiO2 lattice, promoting the formation of adjacent oxygen vacancies (VO). The synergistic effect of Cr doping and VO extends the light absorption range into the visible region. The coated N-C layer facilitates the efficient separation of photogenerated charge carriers, boosting the population of active electrons. Critically, the combined action of VO and N-C layer enhances the adsorption and activation of H2O molecules while effectively improving the subsequent surface dehydrogenation efficiency. Significantly, this strategy demonstrates broad universality: Analogous TM-TiO2@N-C heterojunctions (TM = Mn, Co, Ni, Cu, and Zn) synthesized via the same approach all show substantially improved H2 production performance over pristine TiO2.

Transmembrane receptors orchestrate cell fate decisions and maintain tissue homeostasis through exquisitely regulated signaling cascades, whereas their dysregulation drives disease initiation and progression. Although a variety of stimulus-responsive strategies have been developed to manipulate receptor activity, regulation of cellular processes in response to spatially defined cues, such as molecular proximity, remains a major challenge. Herein, we developed a proximity-induced phosphatase-recruiting DNA feedback switch (PPDFS) that emulates natural receptor feedback regulation to achieve specific and self-adaptive modulation of receptor signaling. Leveraging the programmability of DNA nanostructures and aptamer-mediated molecular recognition, the proximity sensors of PPDFS sensitively detect receptor dimerization at the cell surface and activate an actuator module to recruit the phosphatase PTPRF. Receptor proximity thus not only initiates signaling activation but also simultaneously triggers the inhibitory response of PPDFS, thereby maintaining signaling homeostasis and restraining malignant cellular behaviors. Furthermore, PPDFS-mediated regulation of cellular responses elucidates the complete cascade linking receptor signaling to epithelial-mesenchymal transition (EMT), cytoskeletal reorganization, and cell movement. With its modular design, PPDFS can be readily adapted to diverse receptor systems for precise control of transmembrane signaling. Our work presents a bioinspired nanomedicine platform that bridges receptor signaling, DNA nanotechnology, and adaptive therapy.

A novel ultra-small dual-mode pyrenyl nanoprobe (PQL-B NPs, approximately 1.47 nm) was constructed for selective detection of H2O2 using quaternized quinoline unit and boronate as mitochondrial targeting moiety and reactive recognition group, respectively. PQL-B NPs exhibit a distinct fluorescence shift from orange-red to bright blue after reacting with H2O2, accompanying a clear visible color change from yellow to colorless. In particular, this dual-mode sensing mechanism was confirmed by 1H NMR spectra and DFT calculations. The PQL-B NPs probe encapsulated with amphiphilic DSPE-mPEG-2000 possesses good biocompatibility, superior specificity, and satisfactory sensitivity (LOD, 0.59 μM) and has been successfully used to image hydrogen peroxide in living HeLa cells with excellent mitochondrial-targeting ability.

The construction of S-scheme heterojunctions is constrained by stringent work function (Φ) matching between oxidation and reduction photocatalysts, which limits material selection. Here, we present an innovative interfacial engineering strategy to overcome Φ-mismatched barriers by introducing a nitrogen-doped carbon (N-C) mediator and Cu nanoparticles at the WO3/Cu2O interface. Through a "post-deposition and pyrolysis" approach, we fabricated a tightly integrated Z-scheme WO3/N-C/Cu/Cu2O heterojunction, where the N-C layer and metallic Cu synergistically redirect photogenerated carrier recombination, preserving the high redox potentials of WO3 (VB: +2.62 V) and Cu2O (CB: -1.41 V). Femtosecond transient absorption spectroscopy and electron paramagnetic resonance data revealed that interfacial electrons from WO3 transferred to N-C and recombined with holes originating from Cu2O on Cu via the directional N-C/Cu insertion layer. The optimized heterojunction exhibits exceptional photocatalytic performance under blue light (450 nm), achieving a 99% yield in homo-coupling of terminal alkynes to 1,3-conjugated diynes and a hydrogen evolution rate 300-fold higher than that of conventional WO3/Cu2O. This work provides a universal paradigm for designing Z-scheme systems with mismatched components, unlocking new possibilities for solar energy conversion and organic synthesis.

The chain conformation of conjugated oligomers are critical for constructing ultrafine fluorescent nanoprobes with outstanding sensing performances owing to their suitable molecular flexibility and fine-tuned aggregation state. Herein, a series of pyrenyl-pyridine oligomers (OPPs) were designed and conveniently prepared by one-pot Sonogashira coupling of flexible 2,6-bis(ethynyl)pyridine with different rigid pyrene unit. Novel fluorescent nanoprobes (OPPNPs, ca. 2.50–25.4 nm in diameter) were hence readily fabricated through a microemulsion route, showcasing significantly distinct detecting properties due to their distinctive chain conformations. In particular, ultrasmall OPP1NPs ( 3.75 nm) bearing zig-zag-shaped 1,6-substituted pyrenyl-pyridyl conjugated chain presented superior π–π stacking, strong excimer emission and best sensing performances for Fe3+ via electron transfer (ET) and OPP1NPs aggregation-based fluorescence quenching. Additionally, ascorbic acid (AA) could act as an effective reducer and chelator, resulting in the fluorescence recovery of OPP1NPs. Under the optimal conditions, ultralow detection limits of OPP1NPs for Fe3+ (LOD, 0.06 nM, S/N = 3) and AA (LOD, 8 nM) were achieved. Furthermore, small and biocompatible OPP1NPs enabled efficient fluorescence imaging of Fe3+ and AA in live cells. Moreover, the conformation-regulated sensing strategy and ET mechanism are also supported by DFT calculations.

Osteoarthritis (OA) is a complex and multifactorial joint disorder. Currently, there are few therapies to slow the progression of OA. Combining symptomatic slow-acting drugs and reactive oxygen species (ROS) scavenging reagents in the inflamed joint shows a promising therapeutic approach for OA. Nonetheless, the short residence time of free drugs in the joint cavity hinders their further application. Herein, an injectable composite of hydrogel and chondroitin sulfate@resveratrol liposome package (Gel/Lip@Res + Chs) was developed to improve drug residency ability and enable the simultaneous delivery of hydrophilic Chs and hydrophobic Res in the joint cavity. This injectable hydrogel, based on phenylboronic acid modified hyaluronic acid (HAPBA) and polyvinyl alcohol (PVA), provided ROS-responsive decomposition property and sustained drug release behavior, thereby effectively scavenging ROS, promoting macrophage repolarization, and decreasing the expression of inflammatory mediators and matrix-degrading enzymes in vitro. As a proof of concept, the in vivo therapeutic efficacy of Gel/Lip@Res + Chs was further examined in both monoiodoacetic acid (MIA)-induced and surgical anterior cruciate ligament transection (ACLT)-induced OA mouse models. Benefiting from the extended residence time of loaded drugs in the joint cavity, the Gel/Lip@Res + Chs treatment could effectively suppress cartilage degeneration and increase the synthesis of the cartilage matrix, thus slowing the advancement of OA. The present study provides a reference for improving drug retention and holds great potential for treating OA-related diseases.

Despite noteworthy progress in biomedical applications, aptamers encounter substantial obstacles in the realm of in vivo cancer theranostics, primarily due to the susceptibility of native aptamers to degradation and the compromised affinity of engineered aptamers. Herein, an aptamer/gold nanoclusters (Apt-M/AuNCs)-based system, featuring a facile noncovalent coupling and biomarker-responsive decoupling mechanism, is developed for activated tumor imaging and integrated gene-chemotherapy. Specifically, we employed the tumor biomarker legumain as a model imaging switch and manganese superoxide dismutase (MnSOD) mRNA as a therapeutic target, respectively, facilitated by tailored peptides (bioligands of AuNCs) and the aptamer AS1411-antisense mRNA (Apt-M). Compared to monomeric Apt-M, the Apt-M/AuNCs system exhibited significant improvements in both stability and binding affinity, subsequently translating to notable enhancements in imaging contrast and therapeutic efficacy. Endowed with remarkable biostability, affinity, and specificity, our work offers a facile route for efficient aptamer functionalization and subsequently superior theranostics performance, thereby holding great potential for broadening the application of aptamers into an ever-growing array of research fields.

Aqueous batteries (ABs) based on water-containing electrolytes are intrinsically safe and serve as promising candidates for the grid-scale energy storage and power supplies of wearable electronics. The severe temperature fluctuations...

The aptamer-based strategy for selective protein degradation demonstrates broad application prospects in the field of biomedicine, particularly holding significant therapeutic potential for tumors and other protein dysregulation-related diseases. However, it faces substantial challenges due to on-target off-tumor effects arising from nonspecific expression of target proteins. To address this issue efficiently, we report here a pH-responsive allosteric DNA nanorobot (named A/I) that enhances the precision of aptamer-mediated target protein degradation through tumor microenvironment-specific activation. The allosteric nanorobot is comprised of two modules: the recognition module (A-strand) and the response module (I-strand). To be specific, the A-strand integrates both target recognition and degradation-inducing capabilities, while the I-strand blocks the recognition sites of the A-strand through complementary base pairing and confers pH sensitivity. Under physiological pH conditions, the A/I nanorobot exists stably in the form of a double-stranded structure. When the acidic tumor microenvironment is encountered, the pH-triggered conformational change of the I-strand induces the duplex disassembly, releasing the A-strand, which can specifically bind to the target protein and subsequently induce its degradation. Our findings demonstrate that the activatable allosteric nanorobot achieves targeted protein degradation, significantly inhibiting the proliferative and migratory abilities of tumor cells. In general, the activatable allosteric nanorobot has innovatively overcome the bottleneck of insufficient selectivity in traditional aptamer-based protein degradation strategies, providing a molecular tool for precision tumor therapy technologies. In addition, the allosteric nanorobot features a simple design and enables specific degradation of diverse target proteins by flexible replacement of the recognition module, demonstrating significant potential for constructing a universal protein precise degradation platform.

To facilitate on-site detection by nonspecialists, there is a demand for the development of portable "sample-to-answer" devices capable of executing all procedures in an automated or easy-to-operate manner. Here, we developed an automated detection device that integrated a magnetofluidic manipulation system and a signal acquisition system. Both systems were controllable via a smartphone. In the device, the mixing of solutions and magnetic beads in the static chamber was enhanced by steel bead agitation, which improved the reaction efficiency. We demonstrate the performance of the device using myoglobin detection as an example. During the detection process, the plasma was separated from the whole blood sample using a homemade mini-centrifuge, and subsequently, the plasma, magnetic beads, and reagents were added to a magnetofluidic chip with multiple chambers. After the chip was loaded, the device was initiated with a smartphone App via Bluetooth. Then, the magnetic beads were shuttled through different chambers of the chip and multiple steps were completed automatically: first, the targets were separated and enriched using antibody-modified magnetic beads, followed by washing, binding with aptamer-functionalized G-quadruplex, signal amplifying (optional), and chromogenic reaction. Finally, the images of colored solutions were captured and processed by a smartphone to obtain the concentrations of myoglobin. The detection limits depended on the mode of signal conversion, which were 0.1 or 2.7 nM (with or without signal amplifying). With its simple operation, compact design, low cost, and ease of scalability, this automated detection device holds potential applications in human health, food safety, environmental monitoring, etc.

This study introduces the first example of a photocatalytic [3 + 2] cycloaddition reaction to efficiently generate novel chiral imidazolidines using a chiral sulfinamide. A broad range of substrates, including different (S)-N-tert-butanesulfinyl imines and dipole precursors, were found to be compatible, delivering chiral imidazolidines in good yields with high diastereoselectivity (up to 93% yield, up to >25:1 dr). The reaction mechanism was investigated through radical trapping experiments. Furthermore, chiral 1,2-diamines were efficiently obtained with excellent enantioselectivities (up to 100:0 er).

Real-time optogenetic devices that can intelligently react to abnormal changes in the electrophysiological signals of epilepsy patients are crucial for timely seizure control. Inspired by electrical synapses, we report a bionic synapse built with entirely transparent ionic conductors. This system forms a soft, flexible network that allows free ionic movement, mimicking natural synaptic behavior. The bionic conductive technology is demonstrated in the application for brain signal recording-an emotion detection sensor. We also explore the potential of this technology for use in neural activity detections during optogenetic stimulation and emphasize its advantages in compromising optical recording. Furthermore, we have implemented this device for epileptic seizure control by real-time optogenetic modulation, which offers good potential for brain-machine interfaces in the monitoring and treatment of diseases. Our work highlights the advantages of transparent ionic conductors in combining electrophysiological recording and neural modulation, advancing both neurotechnology and bioelectronics.

The intrinsic safety and cost-effectiveness of the aqueous zinc ion batteries hold the potential for grid-scale energy storage. However, the uncontrolled dendrite growth, parasitic reactions, and electrochemical corrosion of the anode due to the random Zn2+ transport near the anode hinder its practical applications. Herein, a pre-solvated artificial protective layer (ps-APL) with a nitrogen-containing functional group is constructed by an in situ polymerization strategy to stabilize the Zn anode via boosted Zn2+ mass transport kinetics and oriented exposure of the Zn(002) facets. The preferential electrostatic interaction between the nitrogen atoms and Zn2+ induces accelerated migration kinetics in the partially solvated protective layer, which homogenizes the ion flux and nucleation sites. Moreover, the optimized adsorption behavior of the polymer on the Zn surfaces facilitates the Zn(002)-orientated deposition, which substantially suppresses the dendrites growth. Consequently, the ps-APL-coated Zn anode delivers a stability for 2200 h at 1 mA cm-2, enabling an 8.8-time enhancement in comparison to the bare Zn anode. More impressively, the protected Zn anode stably cycles for over 1000 h at a high current density of 5 mA cm-2, displaying a 10-time enhancement. Consequently, Zn||VO2 full battery exhibits stable cycling for 2100 cycles with excellent safety at 1 A g-1.

Methylation of adenine at the N6 position is a crucial epigenetic modification that profoundly influences gene regulation and expression. Moreover, this modification intricately alters the excited state dynamics of adenine nucleobases. To explore the impact of N6-methyladenine on the excited state dynamics within oligonucleotides, we conducted a comprehensive investigation of two dinucleotides containing N6-methyladenosine, in conjunction with adenosine or guanosine. Using steady-state and time-resolved absorption and fluorescence spectroscopy techniques, we not only observed the customary monomer-like and charge transfer emissive states, as reported in previous dinucleotides, but also identified an additional low-energy emissive state. This unique state exhibits an extraordinary Stokes Shift exceeding 2.3 eV and has a relatively long lifetime of 4-5 ns. We propose that this state corresponds to a bonded exciplex state, governed by ground-state geometries. We discovere that when methylation occurs in a DNA dimer, a low-energy emissive species is induced and it is distinct from the previously reported monomer-like species as well as the charge-transfer exciplex species. image

Multidrug resistance (MDR) is a major factor in the failure of many forms of tumor chemotherapy. Development of a specific ligand for MDR-reversal would enhance the intracellular accumulation of therapeutic agents and effectively improve the tumor treatments. Here, an aptamer was screened against a doxorubicin (DOX)-resistant human hepatocellular carcinoma cell line (HepG2/DOX) via cell-based systematic evolution of ligands by exponential enrichment. A 50 nt truncated sequence termed d3 was obtained with high affinity and specificity for HepG2/DOX cells. Multidrug resistance protein 1 (MDR1) is determined to be a possible recognition target of the selected aptamer. Aptamer d3 binding was revealed to block the MDR of the tumor cells and increase the accumulation of intracellular anticancer drugs, including DOX, vincristine, and paclitaxel, which led to a boost to the cell killing of the anticancer drugs and lowering their survival of the tumor cells. The aptamer d3-mediated MDR-reversal for effective chemotherapy was further verified in an in vivo animal model, and combination of aptamer d3 with DOX significantly improved the suppression of tumor growth by treating a xenograft HepG2/DOX tumor in vivo. This work demonstrates the feasibility of a therapeutic DNA aptamer as a tumor MDR-reversal agent, and combination of the selected aptamer with chemotherapeutic drugs shows great potential for liver cancer treatments.

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Wearable sweat sensors have achieved rapid development since they hold great potential in personalized health monitoring. However, a typical difficulty in practical processes is the control of working conditions for biorecognition elements, e.g., pH level and ionic strength in sweat may decrease the affinity between analytes and recognition elements. Here, we developed a wearable sensing device for cortisol detection in sweat using an aptamer as the recognition element. The device integrated functions of sweat collection, reagent prestorage, and signal conversion. Especially, the components of prestored reagents were optimized according to the inherent characteristics of sweat samples and electrodes, which allowed us to keep optimal conditions for aptamers. The sweat samples were transferred from the inlet of the device to the reagent prestored chamber, and the dry preserved reagents were rehydrated with sweat and then arrived at the aptamer-modified electrodes. Sweat samples of volunteers were analyzed by the wearable sensing device, and the results showed a good correlation with those of the ELISA kit. We believe that this convenient and reliable wearable sensing device has significant potential in self-health monitoring.

Glucose oxidases (GODs) induce the catalyzation from β-d-glucose to gluconic acid in an oxygen-consuming process, providing a potential antibiotic substitution strategy. However, the inadequate properties of existing GODs in parallel hinder the antimicrobial capacity for industrial applications. In this study, PaGOD (WT) from Penicillium amagasakiense was enzymatically improved through computer-aided design based on energy optimization. Two thermostable variants A263P and K424F were selected and combined to generate variant A263P/K424F, superior in both thermostability (t1/2 at 60 °C increased 2.6-fold) and catalytic efficiency (2.1-fold increase in catalytic efficiency), in comparison with the WT. The molecular dynamics simulations revealed the improved rigidity of A263P/K424F is attributed to the formation of hydrogen bonds within the flexible region and the newly-formed salt bridge Lys473: Asp477, following the increased ΔΔG. For improvement of antibacterial capacity, A263P/K424F impressively lower the half maximal inhibitory concentrations (IC50) to 12 and 11 mg/L respectively for Escherichia coli and Staphylococcus aureus (86.4 % and 78.8 % lower than the WT, 65.7 % and 50 % lower than erythromycin). The results indicated that the antibacterial effects of GOD can be improved through in vitro molecular modification, which could be an effective strategy to address antibacterial requirements with antibiotic-free agents.