Seamless Integration of Rapid Separation and Ultrasensitive Detection for Complex Biological Samples Using Multistage Annular Functionalized Carbon Nanotube Arrays.

Efficient separation, enrichment, and detection of bacteria in diverse media are pivotal for identifying bacterial diseases and their transmission pathways. However, conventional bacterial detection methods that split the separation and detection steps are plagued by prolonged processing times. Herein, a multistage annular functionalized carbon nanotube array device designed for the seamless integration of complex biological sample separation and multimarker detection is introduced. This device resorts to the supersmooth fluidity of the liquid sample in the carbon nanotubes interstice through rotation assistance, achieving the ability to quickly separate impurities and capture biomarkers (1 mL sample cost time of 2.5 s). Fluid dynamics simulations show that the reduction of near-surface hydrodynamic resistance drives the capture of bacteria and related biomarkers on the functionalized surface of carbon nanotube in sufficient time. When further assembled as an even detection device, it exhibited fast detection (<30 min), robust linear correlation (101 -107 colony-forming units [CFU] mL-1 , R2 = 0.997), ultrasensitivity (limit of detection = 1.7 CFU mL-1 ), and multitarget detection (Staphylococcus aureus, extracellular vesicles, and enterotoxin proteins). Collectively, the material and system offer an expanded platform for real-time diagnostics, enabling integrated rapid separation and detection of various disease biomarkers.

Living Magnetotactic Microrobots Based on Bacteria with a Surface-Displayed CRISPR/Cas12a System for Penaeus Viruses Detection.

Bacterial microrobots are an emerging living material in the field of diagnostics. However, it is an important challenge to make bacterial microrobots with both controlled motility and specific functions. Herein, magnetically driven diagnostic bacterial microrobots are prepared by standardized and modular synthetic biology methods. To ensure mobility, the Mms6 protein is displayed on the surface of bacteria and is exploited for magnetic biomineralization. This gives the bacterial microrobot the ability to cruise flexibly and rapidly with a magnetization intensity up to about 18.65 emu g-1. To achieve the diagnostic function, the Cas12a protein is displayed on the bacterial surface and is used for aquatic pathogen nucleic acid detection. This allows the bacterial microrobot to achieve sensitive, rapid, and accurate on-site nucleic acid detection, with detection limits of 8 copies µL-1 for decapod iridescent virus 1 (DIV1) and 7 copies µL-1 for white spot syndrome virus (WSSV). In particular, the diagnostic results based on the bacterial microrobots remained consistent with the gold standard test results when tested on shrimp tissue. This approach is a flexible and customizable strategy for building bacterial microrobots, providing a reliable and versatile solution for the design of bacterial microrobots.

Photo-Fenton self-cleaning carbon fibers membrane supported with Zr-MOF@Fe2O3 for effective phosphate removal from algae-rich water.

Adsorbents featuring abundant binding sites and high affinity to phosphate have been used to resolve water eutrophication. However, most of the developed adsorbents were focused on improving the adsorption ability of phosphate but ignored the effect of biofouling on the adsorption process especially used in the eutrophic water body. Herein, a novel MOF-supported carbon fibers (CFs) membrane with high regeneration and antifouling capability, was prepared by in-situ synthesis of well-dispersed MOF on CFs membrane, to remove phosphate from algae-rich water. The hybrid UiO-66-(OH)2@Fe2O3@CFs membrane exhibits a maximum adsorption capacity of 333.3 mg g-1 (pH 7.0) and excellent selectivity for phosphate sorption over coexisting ions. Moreover, the Fe2O3 nanoparticles anchored on the surface of UiO-66-(OH)2 through 'phenol-Fe(III)' reaction can endow the membrane with the robust photo-Fenton catalytic activity, which improves long-term reusability even under algae-rich condition. After 4 times photo-Fenton regenerations, the regeneration efficiency of the membrane could remain 92.2%, higher than that of hydraulic cleaning (52.6%). Moreover, the growth of C. pyrenoidosa was significantly reduced by 45.8% within 20 days via metabolism inhibition due to membrane-induced P-deficient conditions. Hence, the developed UiO-66-(OH)2@Fe2O3@CFs membrane holds significant prospects for large-scale application in phosphate sequestration of eutrophic water bodies.

Synergistic Integration and Pharmacomechanical Function of Enzyme-Magnetite Nanoparticle Swarms for Low-Dose Fast Thrombolysis.

Magnetic micro-/nanoparticles are extensively explored over the past decade as active diagnostic/therapeutic agents for minimally invasive medicine. However, sufficient function integration on these miniaturized bodies toward practical applications remains challenging. This work proposes a synergistic strategy via integrating particle functionalization and bioinspired swarming, demonstrated by recombinant tissue plasminogen activator modified magnetite nanoparticles (rtPA-Fe3 O4 NPs) for fast thrombolysis in vivo with low drug dosage. The synthesized rtPA-Fe3 O4 NPs exhibit superior magnetic performance, high biocompatibility, and thrombolytic enzyme activity. Benefiting from a customized magnetic operation system designed for animal experiments and preclinical development, these agglomeration-free NPs can assemble into micro-/milli-scale swarms capable of robust maneuver and reconfigurable transformation for on-demand tasks in complex biofluids. Specifically, the spinning mode of the swarm exerts focused fluid shear stresses while rubbing on the thrombus surface, constituting a mechanical force for clot breakdown. The synergy of the NPs' inherent enzymatic effect and swarming-triggered fluid forces enables amplified efficacy of thrombolysis in an in vivo occlusion model of rabbit carotid artery, using lower drug concentration than clinical dosage. Furthermore, swarming-enhanced ultrasound signals aid in imaging-guided treatment. Therefore, the pharmacomechanical NP swarms herein represent an injectable thrombolytic tool joining advantages of intravenous drug therapy and robotic intervention.

Synthesis, Bioactivity, and QSAR Study of 3,4-Dichlorophenyl Isoxazole-Substituted Stilbene Derivatives against the Phytopathogenic Fungus Botrytis cinerea.

Gray mold, caused by Botrytis cinerea, is one of the most destructive fungal diseases in crops, responsible for significant economic losses. In search of natural product-based fungicides, we designed and synthesized a series of novel 3,4-dichlorophenyl isoxazole-substituted stilbene derivatives, and their in vivo antifungal activities against B. cinerea were evaluated. The results indicated that some of the target molecules demonstrated remarkable efficiency for the control of tomato gray mold. In particular, compound 5r displayed the highest fungicidal potency with an inhibition rate of 56.11% comparable to that of positive control boscalid (66.96%). Moreover, a hologram quantitative structure-activity relationship (HQSAR) model with good predictive capability was developed to provide in-depth insight into the activity profiles of these compounds. Preliminary mechanism studies suggested that compound 5r might exert its antifungal effect by changing hyphal morphology and increasing the membrane permeability. The present study contributes to the development of natural stilbene derivatives as alternative bioactive agents against B. cinerea.

Nanoliquid Dressing with Enhancing Anti-Infection Performance under the Moderate Photothermal Effect for Wound Treatment.

Nonhealing wounds have become a major healthcare burden worldwide. Chronic wound healing is universally hampered by the presence of bacterial infections that form biofilms. Therefore, in this study, a novel nanoliquid dressing based on a mild photothermal heating strategy was designed to provide safe healing of biofilm-infected wounds. Dilute nitric acid (HNO3) solution was employed to induce a redox process triggered by copper sulfide (CuS) nanoplates in the nanoliquid dressing. This redox process was further promoted by the mild photothermal effect (≤47.5 °C) that generated a sufficient amount of reactive oxygen species, resulting in less thermal injury to normal tissues. Correspondingly, with the safe concentration of CuS nanoplates (0.4 mg/mL), excellent bactericidal efficiencies up to 98.3 and 99.3% against ampicillin-resistant Escherichia coli (Ampr E. coli) and Staphylococcus aureus (S. aureus) were achieved, respectively. Moreover, the nanoliquid dressing exhibited a near-infrared enhanced destructive effect on mature biofilms. According to in vivo wound healing experiments in mice, the nanoliquid dressing increased the healing rate and reduced the inflammatory response. This study provides a novel insight into treating the biofilm-infected chronic wounds in the "post-antibiotic era".

Dual-Antigen-Loaded Hepatitis B Virus Core Antigen Virus-like Particles Stimulate Efficient Immunotherapy Against Melanoma.

Tumor cells are rich in antigens, which provide a reliable antigen library for the design of personalized vaccines. However, an effective tumor vaccine vector that can efficiently deliver antigens to lymphoid organs to stimulate strong CD8+ cytotoxic T-lymphocyte immune response is still lacking. Here we designed a dual-antigen delivery system based on hepatitis B virus core antigen virus-like particles (HBc VLPs). We first confirmed that different antigen-loaded HBc VLP monomers could be assembled into nanoparticles (hybrid VLPs). Hybrid VLPs could slightly enhance bone marrow-derived dendritic cell maturation in vitro. Strikingly, hybrid VLPs could generate antigen-specific antitumor immunity and innate immunity in vivo which could significantly inhibit tumor growth or metastatic formation in a subcutaneous tumor or lung metastatic tumor model, respectively. Moreover, dual-epitope vaccination generated enhanced T-cell responses that potently inhibited tumor growth and metastatic formation. Together, this study provides a new powerful concept for cancer immunotherapy and suggests a novel design for VLP-based personalized nanomedicine.

Upconversion nanoparticle and gold nanocage satellite assemblies for sensitive ctDNA detection in serum.

A rapid molecular diagnostic technique targeting circulating tumor DNA (ctDNA) has become one of the most clinically significant liquid biopsy methods for non-invasive and timely diagnosis of cancer. Herein, a sensitive detection system of ctDNA based on a fluorescence resonance energy transfer (FRET) system using upconversion nanoparticles (UCNPs) and gold nanocages (AuNCs) was constructed. Through the doping of Yb and Tm ions, the excitation and emission wavelengths of UCNPs were adjusted to 980 nm and 806 nm, respectively. Subsequently, UCNPs and AuNCs with the corresponding wavelength absorption were linked by complementary pairing of surface-modified DNA to form near-infrared fluorescent nanoprobes (NIR probes). Targeting DNA mutation recognition and signal transduction were realized by using NIR probes through the toehold-mediated strand displacement reaction. This method could detect a single point mutation of the KRAS gene with a wide detection range from 5 pM to 1000 pM and the limit of detection reached 6.30 pM. More importantly, the stable and highly specific NIR probes could be directly used in the serum environment without complicated pretreatment and amplification processes in advance. It could be envisioned that this specific and sensitive ctDNA detection strategy has great potential in clinical diagnosis and monitoring of diverse malignant tumors.

Molybdenum Disulfide Quantum Dots Attenuates Endothelial-to-Mesenchymal Transition by Activating TFEB-Mediated Lysosomal Biogenesis.

A defective lysosome-autophagy degradation pathway contributes to a variety of endothelial-to-mesenchymal transition (EndMT)-related cardiovascular diseases. Molybdenum disulfide quantum dots (MoS2 QDs) are nanoscale sizes in the planar dimensions and atomic structures of transition metal dichalcogenides (TMDs) materials with excellent physicochemical and biological properties, making them ideal for various biomedical applications. In this study, water-soluble MoS2 QDs with an average diameter of about 3.4 nm were synthesized by using a sulfuric acid-assisted ultrasonic method. The as-prepared MoS2 QDs exhibited low cytotoxicity of less than 100 µg/mL in both human umbilical vein endothelial cells and human coronary artery endothelial cells and showed novel biological properties to prevent EndMT and promote angiogenesis in vitro. We found that MoS2 QDs treatment-induced transcription factor (TFEB) mediated lysosomal biogenesis, which could cause autophagy activation. Importantly, using in vitro transforming growth factor (TGF)-ß-induced EndMT model, we demonstrated that the cardiovascular protective effect of MoS2 QDs against EndMT acted through triggering TFEB nucleus translocation and restoring an impairment of autophagic flux, whereas genetic suppression of TFEB impaired the protective action of MoS2 QDs against EndMT. Taken together, these results gain novel insights into the mechanisms by which MoS2 QDs regulate EndMT and facilitate the development of MoS2-based nanoagents for the treatment of EndMT-related cardiovascular diseases.

Molybdenum Disulfide Nanoparticles Resist Oxidative Stress-Mediated Impairment of Autophagic Flux and Mitigate Endothelial Cell Senescence and Angiogenic Dysfunctions.

The impairment of autophagy involves oxidative stress-induced cellular senescence, leading to endothelial dysfunctions and the onset of cardiovascular diseases. As molybdenum disulfide nanoparticles (MoS2 NPs), representative transition metal dichacogenide materials, have great potential as a multifunctional therapeutic agent against various disorders, the present study aimed to investigate whether MoS2 NPs prevents hydrogen peroxide (H2O2)-induced endothelial senescence by modulating autophagic process. Our results showed that pretreatment with MoS2 NPs inhibited H2O2-induced endothelial senescence and improved endothelial functions. Exposure of H2O2 increased p62 level and blocked the fusion of autophagosomes with lysosomes, indicating of impaired autophagic flux in senescent endothelial cells. However, MoS2 NPs pretreatment efficiently suppressed cellular senescence through triggering autophagy and resisting impaired autophagic flux. Furthermore, the genetic inhibition of autophagy by siRNA against Beclin 1 or ATG-5 directly abrogated the protective action of MoS2 NPs on endothelial cells against H2O2-induced senescence.Thus, these results suggested that MoS2 NPs rescue endothelial cells from H2O2-induced senescence by improving autophagic flux, and provide valuable information for the rational design of MoS2-based nanomaterials for therapeutic use in senescence-related diseases.

Visible-Light-Enabled Decarboxylative Sulfonylation of Cinnamic Acids with Sulfonylhydrazides under Transition-Metal-Free Conditions.

Decarboxylative cross-coupling reactions of cinnamic acids with sulfonylhydrazides were explored using oxygen as the sole terminal oxidant, realizing a conceptually novel technology for vinyl sulfone synthesis under the synergistic interactions of visible light irradiation, organic dye-type photocatalyst eosin Y, KI, and Cs2CO3 at room temperature.

Visible-light-promoted syntheses of ß-keto sulfones from alkynes and sulfonylhydrazides.

A variety of functionalized ß-keto sulfones were smoothly prepared through oxysulfonylation of commercially available alkynes with sulfonylhydrazides under the synergistic interactions of visible light irradiation, Ru(bpy)3Cl2 photocatalyst, oxygen, KI, and NaOAc basic additive under very mild reaction conditions.