Correction: Study on the circadian rhythm and sleep state characteristics of patients with acute cerebral infarction accompanied by sleep-breathing disorders.

[This corrects the article DOI: 10.1007/s41105-024-00516-1.].

Study on the circadian rhythm and sleep state characteristics of patients with acute cerebral infarction accompanied by sleep-breathing disorders.

There is limited research on the circadian rhythm and sleep state in patients with acute cerebral infarction (ACI) accompanied by sleep-breathing disorders (SDB). This study aims to provide a scientific basis for individualized diagnosis and treatment for stroke-related SDB patients. The SC-500 sleep monitor was used to continuously monitor 1367 ACI patients over 5 days. Based on the apnea-hypopnea index (AHI), patients were divided into non-SDB group (normal) and SDB group (mild, moderate, severe, fluctuating). Interdaily stability (IS) and intradaily variability (IV) were calculated through heart rate monitoring, and sleep states and their correlations were analyzed. Compared to the non-SDB group, patients with moderate-to-severe ACI accompanied by SDB showed decreased IS, increased IV, and sleep fragmentation. Significant statistical differences were observed in total sleep time (TST), rapid eye movement latency (REML), sleep efficiency (SE), non-rapid eye movement stages 1-2 (NREM stages1-2), non-rapid eye movement stages 3-4 (NREM stages 3-4), proportion of non-rapid eye movement (NREM%), wake after sleep onset (WASO), and number of awakenings (NOA) between the SDB group and the non-SDB group (P < 0.05). AHI showed a strong negative correlation with IS and a strong positive correlation with IV. AHI was positively correlated with sleep latency (SL), REML, NREM stages1-2, NREM%, proportion of rapid eye movement (REM%), WASO, time out of bed (TOB), and NOA, and negatively correlated with TST, SE, NREM stages 3-4, and rapid eye movement (REM), all with statistical significance (P < 0.05). There were significant statistical differences in the Mini-Mental State Examination (MMSE) between patients with and without SDB, and among mild, moderate, severe, and fluctuating groups (P < 0.05). Patients with moderate-to-severe ACI accompanied by SDB are more likely to experience changes in circadian rhythm and sleep states, which in turn affect cognitive functions. Supplementary Information: The online version contains supplementary material available at 10.1007/s41105-024-00516-1.

H2O2/acid self-supplying double-layer electrospun nanofibers based on ZnO2 and Fe3O4 nanoparticles for efficient catalytic therapy of wound infection.

Catalytic therapy based on nanozymes is promising for the treatment of bacterial infections. However, its therapeutic efficacy is usually restricted by the limited amount of hydrogen peroxide and the weak acidic environment in infected tissues. To solve these issues, we prepared polyvinyl alcohol (PVA)-polyacrylic acid (PAA)-iron oxide (Fe3O4)/polyvinyl alcohol (PVA)-zinc peroxide (ZnO2) double-layer electrospun nanofibers (PPF/PZ NFs). In this design, PVA serves as the carrier for ZnO2 nanoparticles (NPs), Fe3O4 NPs, and PAA. The double-layer structure of nanofibers can spatially separate the PAA and ZnO2 to avoid their reaction with each other during preparation and storage, while in the wet wound bed, PVA can dissolve and PAA can provide H+ ions to promote the generation of hydrogen peroxide and subsequent conversion to hydroxyl radicals for bacteria killing. In vitro experimental results demonstrated that PPF/PZ NFs can reduce the methicillin-resistant Staphylococcus aureus by 3.1 log (99.92%). Moreover, PPF/PZ NFs can efficiently treat the bacterial infection in a mouse wound model and promote wound healing with negligible toxicity to animals, indicating their potential use as "plug-and-play" antibacterial wound dressings. This work provides a novel strategy for the construction of double-layer electrospun nanofibers as catalytic wound dressings with hydrogen peroxide/acid self-supplying properties for the efficient treatment of bacterial infections.

Phase and Defect Engineering of MoSe2 Nanosheets for Enhanced NIR-II Photothermal Immunotherapy.

Inducing immunogenic cell death (ICD) during photothermal therapy (PTT) has the potential to effectively trigger photothermal immunotherapy (PTI). However, ICD induced by PTT alone is often limited by inefficient PTT, low immunogenicity of tumor cells, and a dysregulated redox microenvironment. Herein, we develop MoSe2 nanosheets with high-percentage metallic 1T phase and rich exposed active Mo centers through phase and defect engineering of MoSe2 as an effective nanoagent for PTI. The metallic 1T phase in MoSe2 nanosheets endows them with strong PTT performance, and the abundant exposed active Mo centers endow them with high activity for glutathione (GSH) depletion. The MoSe2-mediated high-performance PTT synergizing with efficient GSH depletion facilitates the release of tumor-associated antigens to induce robust ICD, thus significantly enhancing checkpoint blockade immunotherapy and activating systemic immune response in mouse models of colorectal cancer and triple-negative metastatic breast cancer.

Visible-Light-Promoted Thiolation of Benzyl Chlorides with Thiosulfonates via a Photoactive Electron Donor-Acceptor Complex.

Visible-light-promoted thiolation of benzyl chlorides with thiosulfonates is disclosed via an electron donor-acceptor complex strategy. In addition to efficiently delivering a series of arylbenzylsulfide compounds, versatile thioglycosides were also successfully constructed by applying the metal- and photocatalyst-free protocol. Preliminary mechanistic studies suggest that a radical-radical coupling process was involved in this transformation.

Ultrasound-responsive gallium protoporphyrin and oxygen loaded perfluoropentane nanodroplets for effective sonodynamic therapy of implant infections.

Implant infections are severe complications in clinical treatment, which often accompany the formation of bacterial biofilms with high antibiotic resistance. Sonodynamic therapy (SDT) is an antibiotic-free method that can generate reactive oxygen species (ROS) to kill bacteria under ultrasound (US) treatment. However, the extracellular polymeric substances (EPS) barrier of bacterial biofilms and the hypoxic microenvironment significantly limit the antibiofilm activity of SDT. In this study, lipid-shelled perfluoropentane (PFP) nanodroplets loaded with gallium protoporphyrin IX (GaPPIX) and oxygen (O2) (LPGO NDs) were developed for the treatment of implant infections. Under US stimulation, LPGO NDs undergo the cavitation effect and disrupt the biofilm structure like bombs due to liquid-gas phase transition. Meanwhile, the LPGO NDs release O2 and GaPPIX upon US stimulation. The released O2 can alleviate the hypoxic microenvironment in the biofilm and enhance the ROS formation by GaPPIX for enhanced bacterial killing. In vivo experimental results demonstrate that the LPGO NDs can efficiently treat implant infections of methicillin-resistant Staphylococcus aureus (MRSA) in a mouse model by disrupting the biofilm structure, alleviating hypoxia, and enhancing bacterial killing by SDT. Therefore, this work provides a new multifunctional sonosensitizer to overcome the limitations of SDT for treating implant infections.

Multi-mode resonance of bound states in the continuum in dielectric metasurfaces.

Bound states in the continuum (BIC) represent distinct non-radiative states endowed with infinite lifetime and vanishing resonance linewidth. Introducing asymmetric perturbation to the system can convert true BICs into high quality leaky modes which is useful in many photonic applications. Previously, such perturbation and resonance of interest is only limited to a single factor. However, different perturbations by unit cell gap, geometry and rotation angle result distinctive resonance modes. The combination of two perturbation factors can excite multi-mode resonance contributed from each asymmetric factor which coexist simultaneously; thus, the number of reflectance peaks can be controlled. In addition, we have carefully analyzed the electric field variations under different perturbation factors, followed by a multipolar decomposition of resonances to reveal underlying mechanisms of distinct resonance modes. Through simulations, we find that the introduction of multiple asymmetric perturbations also influences the metasurface sensitivity in refractive index sensing and compare the performance of different resonance modes. These observations provide structural design insights for achieving high quality resonance with multiple modes and ultra-sensitive sensing.

Conformal Neuromorphic Bioelectronics for Sense Digitalization.

Sense digitalization, the process of transforming sensory experiences into digital data, is an emerging research frontier that links the physical world with human perception and interaction. This field is largely inspired by the adaptability, fault tolerance, robustness, and energy efficiency inherent in biological senses, driving the development of numerous innovative digitalization techniques. Among these techniques, neuromorphic bioelectronics, characterized by biomimetic adaptability, stand out for their seamless bidirectional interactions with biological entities through stimulus-response and feedback loops, incorporating bio-neuromorphic intelligence for information exchange. This review illustrates recent progress in sensory digitalization, encompassing not only the digital representation of physical sensations such as touch, light, and temperature, correlating to tactile, visual, and thermal perceptions, but also the detection of biochemical stimuli such as gases, ions, and neurotransmitters, mirroring olfactory, gustatory, and neural processes. It thoroughly examines the material design, device manufacturing, and system integration, offering detailed insights. However, the field faces significant challenges, including the development of new device/system paradigms, forging genuine connections with biological systems, ensuring compatibility with the semiconductor industry, and overcoming the absence of standardization. Looking ahead, the ambition is to realize biocompatible neural prosthetics, exoskeletons, soft humanoid robots, and cybernetic devices that integrate smoothly with both biological tissues and artificial components, bridging the gap between organic and synthetic realms. This article is protected by copyright. All rights reserved.

Metabolic Modulation-Mediated Antibiotic and Immune Activation for Treatment of Chronic Lung Infections.

The Pseudomonas aeruginosa biofilm in recalcitrant chronic lung infections not only develops high antimicrobial tolerance but also induces an aberrant host inflammatory response. The metabolic condition plays a vital role in both the antimicrobial susceptibility of bacteria and the inflammatory response of immune cells, thereby offering a potential therapeutic target. Herein, we described a metabolic modulation strategy by using ultrasound-responsive liposomal nanoparticles containing a sonosensitizer and a hypoxia-activated prodrug against biofilm-associated chronic lung infections. Under ultrasound stimulation, the sonosensitizer generates antibacterial reactive oxygen species by oxygen consumption. Subsequently, the oxygen consumption-mediated hypoxia not only induces the anaerobic metabolism of bacteria for antibiotic activation but also triggers the glycolysis pathway of immune cells for inflammatory activation. Such metabolic modulation strategy demonstrated efficient therapeutic efficacy for P. aeruginosa biofilm-induced chronic lung infections in mice models and provides a promising way for combating biofilm-associated chronic infections.

Programmably engineered stochastic RNA nanowalker for ultrasensitive miRNA detection.

A programmably engineered stochastic RNA nanowalker powered by duplex-specific nuclease (DSN) is developed. By utilizing poly-adenine-based spherical nucleic acids (polyA-SNA) to accurately regulate the densities of DNA tracks, the nanowalker showcases its capability to identify miRNA-21, miRNA-486, and miRNA-155 with quick kinetics and attomolar sensitivity, positioning it as a promising option for cancer clinical surveillance.

Customized Self-Assembled Gold Nanoparticle-DNA Origami Composite Templates for Shape-Directed Growth of Plasmonic Structures.

The metal plasmonic nanostructure has the optical property of plasmon resonance, which holds great potential for development in nanophotonics, bioelectronics, and molecular detection. However, developing a general and straightforward method to prepare metal plasmonic nanostructures with a controllable size and morphology still poses a challenge. Herein, we proposed a synthesis strategy that utilized a customizable self-assembly template for shape-directed growth of metal structures. We employed gold nanoparticles (AuNPs) as connectors and DNA nanotubes as branches, customizing gold nanoparticle-DNA origami composite nanostructures with different branches by adjusting the assembly ratio between the connectors and branches. Subsequently, various morphologies of plasmonic metal nanostructures were created using this template shape guided strategy, which exhibited enhancement of surface-enhanced Raman scattering (SERS) signals. This strategy provides a new approach for synthesizing metallic nanostructures with multiple morphologies and opens up another possibility for the development of customizable metallic plasmonic structures with broader applications.

A DNA origami device spatially controls CD95 signalling to induce immune tolerance in rheumatoid arthritis.

DNA origami is capable of spatially organizing molecules into sophisticated geometric patterns with nanometric precision. Here we describe a reconfigurable, two-dimensional DNA origami with geometrically patterned CD95 ligands that regulates immune cell signalling to alleviate rheumatoid arthritis. In response to pH changes, the device reversibly transforms from a closed to an open configuration, displaying a hexagonal pattern of CD95 ligands with ~10 nm intermolecular spacing, precisely mirroring the spatial arrangement of CD95 receptor clusters on the surface of immune cells. In a collagen-induced arthritis mouse model, DNA origami elicits robust and selective activation of CD95 death-inducing signalling in activated immune cells located in inflamed synovial tissues. Such localized immune tolerance ameliorates joint damage with no noticeable side effects. This device allows for the precise spatial control of cellular signalling, expanding our understanding of ligand-receptor interactions and is a promising platform for the development of pharmacological interventions targeting these interactions.

A photo-responsive self-healing hydrogel loaded with immunoadjuvants and MoS2 nanosheets for combating post-resection breast cancer recurrence.

Tumor recurrence after surgical resection remains a significant challenge in breast cancer treatment. Immune checkpoint blockade therapy, as a promising alternative therapy, faces limitations in combating tumor recurrence due to the low immune response rate. In this study, we developed an implantable photo-responsive self-healing hydrogel loaded with MoS2 nanosheets and the immunoadjuvant R837 (PVA-MoS2-R837, PMR hydrogel) for in situ generation of tumor-associated antigens at the post-surgical site of the primary tumor, enabling sustained and effective activation of the immune response. This PMR hydrogel exhibited potential for near-infrared (NIR) light response, tissue adhesion, self-healing, and sustained adjuvant release. When implanted at the site after tumor resection, NIR irradiation triggered a photothermal effect, resulting in the ablation of residual cancer cells. The in situ-generated tumor-associated antigens promoted dendritic cell (DC) maturation. In a mouse model, PMR hydrogel-mediated photothermal therapy combined with immune checkpoint blockade effectively inhibited the recurrence of resected tumors, providing new insights for combating post-resection breast cancer recurrence.

Mechanoelectronic stimulation of autologous extracellular vesicle biosynthesis implant for gut microbiota modulation.

Pathogenic gut microbiota is responsible for a few debilitating gastrointestinal diseases. While the host immune cells do produce extracellular vesicles to counteract some deleterious effects of the microbiota, the extracellular vesicles are of insufficient doses and at unreliable exposure times. Here we use mechanical stimulation of hydrogel-embedded macrophage in a bioelectronic controller that on demand boost production of up to 20 times of therapeutic extracellular vesicles to ameliorate the microbes' deleterious effects in vivo. Our miniaturized wireless bioelectronic system termed inducible mechanical activation for in-situ and sustainable generating extracellular vesicles (iMASSAGE), leverages on wireless electronics and responsive hydrogel to impose mechanical forces on macrophages to produce extracellular vesicles that rectify gut microbiome dysbiosis and ameliorate colitis. This in vivo controllable extracellular vesicles-produced system holds promise as platform to treat various other diseases.

Comparative transcriptomics and proteomics analysis of the symbiotic germination of Paphiopedilum barbigerum with Epulorhiza sp. FQXY019.

Introduction: Paphiopedilum barbigerum is currently the rarest and most endangered species of orchids in China and has significant ornamental value. The mature seeds of P. barbigerum are difficult to germinate owing to the absence of an endosperm and are highly dependent on mycorrhizal fungi for germination and subsequent development. However, little is known about the regulation mechanisms of symbiosis and symbiotic germination of P. barbigerum seeds. Methods: Herein, transcriptomics and proteomics were used to explore the changes in the P. barbigerum seeds after inoculation with (FQXY019 treatment group) or without (control group) Epulorhiza sp. FQXY019 at 90 days after germination. Results: Transcriptome sequencing revealed that a total of 10,961 differentially expressed genes (DEGs; 2,599 upregulated and 8,402 downregulated) were identified in the control and FQXY019 treatment groups. These DEGs were mainly involved in carbohydrate, fatty acid, and amino acid metabolism. Furthermore, the expression levels of candidate DEGs related to nodulin, Ca2+ signaling, and plant lectins were significantly affected in P. barbigerum in the FQXY019 treatment groups. Subsequently, tandem mass tag-based quantitative proteomics was performed to recognize the differentially expressed proteins (DEPs), and a total of 537 DEPs (220 upregulated and 317 downregulated) were identified that were enriched in processes including photosynthesis, photosynthesis-antenna proteins, and fatty acid biosynthesis and metabolism. Discussion: This study provides novel insight on the mechanisms underlying the in vitro seed germination and protocorm development of P. barbigerum by using a compatible fungal symbiont and will benefit the reintroduction and mycorrhizal symbiotic germination of endangered orchids.

Deformable Smart DNA Nanomachine for Synergistic Intracellular Cancer-Related miRNAs Imaging and Chemo-Gene Therapy of Drug-Resistant Tumors.

Diagnosis and treatment of tumor especially drug-resistant tumor remains a huge challenge, which requires intelligent nanomedicines with low toxic side effects and high efficacy. Herein, deformable smart DNA nanomachines are developed for synergistic intracellular cancer-related miRNAs imaging and chemo-gene therapy of drug-resistant tumors. The tetrahedral DNA framework (MA-TDNA) with fluorescence quenched component and five antennas is self-assembled first, and then DOX molecules are loaded on the MA-TDNAs followed by linking MUC1-aptamer and Mcl-1 siRNA to the antennas of MA-TDNA, so that the apt-MA-TDNA@DOX-siRNA (DNA nanomachines) is constructed. The DNA nanomachine can respond to two tumor-related miRNAs in vitro and in vivo, which can undergo intelligent miRNA-triggered opening of the framework, resulting in the "turn on" of the fluorescence for sensitively and specifically sensing intracellular miRNAs. Meanwhile, both miRNA-responded rapid release and pH-responded release of DOX are achieved for chemotherapy of tumor. In addition, the gene therapy of the DNA nanomachines is achieved due to the miRNA-specific capture and the RNase H triggered release of Mcl-1 siRNA. The DNA nanomachines intergrading both tumor imaging and chemo-gene therapy in single nanostructures realized efficient tumor-targeted, image-guided, and microenvironment-responsive tumor diagnosis and treatment, which provides a synergetic antitumor effect on drug-resistant tumor.

A three-in-one point-of-care electrochemical sensing platform for accurate monitoring of diabetes.

A three-in-one electrochemical sensing platform was designed for the simultaneous detection of total hemoglobin (tHb), glycated hemoglobin (HbA1c) and HbA1c% by using a dual-aptamer sensing strategy. The developed sensing platform exhibits excellent sensitivity, selectivity, repeatability and long-term stability, and holds promising prospects in the early diagnosis and long-term monitoring of diabetes.

An intelligent DNA nanodevice for precision thrombolysis.

Thrombosis is a leading global cause of death, in part due to the low efficacy of thrombolytic therapy. Here, we describe a method for precise delivery and accurate dosing of tissue plasminogen activator (tPA) using an intelligent DNA nanodevice. We use DNA origami to integrate DNA nanosheets with predesigned tPA binding sites and thrombin-responsive DNA fasteners. The fastener is an interlocking DNA triplex structure that acts as a thrombin recognizer, threshold controller and opening switch. When loaded with tPA and intravenously administrated in vivo, these DNA nanodevices rapidly target the site of thrombosis, track the circulating microemboli and expose the active tPA only when the concentration of thrombin exceeds a threshold. We demonstrate their improved therapeutic efficacy in ischaemic stroke and pulmonary embolism models, supporting the potential of these nanodevices to provide accurate tPA dosing for the treatment of different thromboses.

Enhancing Point-of-Care Diagnosis of African Swine Fever Virus (ASFV) DNA with the CRISPR-Cas12a-Assisted Triplex Amplified Assay.

Accurate, ultrasensitive, and point-of-care (POC) diagnosis of the African swine fever virus (ASFV) remains imperative to prevent its spread and limit the losses incurred. Herein, we propose a CRISPR-Cas12a-assisted triplex amplified colorimetric assay for ASFV DNA detection with ultrahigh sensitivity and specificity. The specific recognition of recombinase aided amplification (RAA)-amplified ASFV DNA could activate the Cas12a/crRNA/ASFV DNA complex, leading to the digestion of the linker DNA (bio-L1) on magnetic beads (MBs), thereby preventing its binding of gold nanoparticles (AuNPs) network. After magnetic separation, the release of AuNPs network comprising a substantial quantity of AuNPs could lead to a discernible alteration in color and significantly amplify the plasmonic signal, which could be read by spectrophotometers or smartphones. By combining the RAA, CRISPR/Cas12a-assisted cleavage, and AuNPs network-mediated colorimetric amplification together, the assay could detect as low as 0.1 copies/µL ASFV DNA within 1 h. The assay showed an accuracy of 100% for the detection of ASFV DNA in 16 swine tissue fluid samples, demonstrating its potential for on-site diagnosis of ASFV.

Programmed Nanocloak of Commensal Bacteria-Derived Nanovesicles Amplify Strong Immunoreactivity against Tumor Growth and Metastatic Progression.

Recent discoveries in commensal microbiota demonstrate the great promise of intratumoral bacteria as attractive molecular targets of tumors in improving cancer treatment. However, direct leveraging of in vivo antibacterial strategies such as antibiotics to potentiate cancer therapy often leads to uncertain effectiveness, mainly due to poor selectivity and potential adverse effects. Here, building from the clinical discovery that patients with breast cancer featured rich commensal bacteria, we developed an activatable biointerface by encapsulating commensal bacteria-derived extracellular vesicles (BEV) with a responsive nanocloak to potentiate immunoreactivity against intratumoral bacteria and breast cancer. We show that the interfacially cloaked BEV (cBEV) not only overcame serious systemic side responses but also demonstrated heightened immunogenicity by intercellular responsive immunogenicity, facilitating dendritic cell maturation through activating the cGAS-STING pathway. As a preventive measure, vaccination with nanocloaked cBEVs achieved strong protection against bacterial infection, largely providing prophylactic efficiency against tumor challenges. When treated in conjunction with immune checkpoint inhibitor anti-PD-L1 antibodies, the combined approach elicited a potent tumor-specific immune response, synergistically inhibiting tumor progression and mitigating lung metastases.