Size-matching compositing nanoprobe of AIE-type gold nanocluster supramolecular nanogels wrapped by hypergravity-tailored MnO2 nanosheets for cellular glutathione detection.

Compositing has been the main approach for material creation via wisely combining material components with different properties. MnO2 nanosheets (MNSs) with thin 2 D morphology are usually applied to composite molecules or nanomaterials for biosensing and bioimaging applications. However, such composition is actually structurally unmatched, albeit performance matching. Here, a series of benefits merely on the basis of structural match have been unearthed via tailoring MNSs with four sizes by synthesis under controllable hypergravity field. The classical fluorophore-quencher couple was utilized as the subject model, where the soft supramolecular nanogels based on aggregation-induced emission (AIE)-active gold nanoclusters were wrapped by MNSs of strong absorption. By comparative study of one-on-one wrapping and one-to-many encapsulation with geometrical selection of different MNSs, we found that the one-on-one wrapping model protected weakly-bonded nanogels from combination-induced distortion and strengthened nanogel networks via endowing exoskeleton. Besides, wrapping pattern and size-match significantly enhanced the quenching efficiency of MNSs towards the emissive nanogels. More importantly, the well-wrapped nanocomposites had considerable enhanced biological compatibility with much lower cytotoxicity and higher transfection capacity than the untailored MNSs composite and could serve as cellular glutathione detection.

Protein-Directed Au(0)-Rich Gold Nanoclusters as Ratiometric Luminescence Sensors for Auric Ions via Comproportionation-Induced Emission Enhancement.

Gold nanoclusters (Au NCs) are widely used as fluorescent probes in biomedical sensing and imaging due to their versatile optical properties and low cytotoxicity. Surface engineering of gold nanoclusters (Au NCs) aims to design a surface with versatile physicochemical performances, but previous investigations have primarily focused on the acquisition of the "brightest" species. This has resulted in other types of Au NC being neglected. In the present study, our group prepared a series of Au NCs that were rich in surface Au(0), using the "aged" form of bovine serum albumin (BSA) via controlling the pH during synthesis. We found that slight increases of alkalinity during synthesis over that which produced Au NCs with the most intensive photoluminescence generated the "darkest" Au NCs, which exhibited the strongest absorption. These Au NCs included more Au atoms and had a higher Au(0) content. Furthermore, the addition of Au3+ quenched the emission of the "brightest" Au NCs, but increased that of the "darkest" Au NCs. The increased Au(I) proportion observed in the Au3+-treated "darkest" Au NCs resulted in a novel comproportionation-induced emission enhancement effect, which we utilized to construct a "turn-on" ratiometric sensor for toxic Au3+. The addition of Au3+ generated simultaneous, opposite effects on blue-emissive diTyr BSA residues and red-emissive Au NCs. After optimization, we successfully constructed ratiometric sensors for Au3+ with high sensitivity, selectivity, and accuracy. This study will inspire a new pathway to redesign the protein-framed Au NCs and analytical methodology via comproportionation chemistry.

Rational Design of ZIF-8 for Constructing Luminescent Biosensors with Glucose Oxidase and AIE-Type Gold Nanoclusters.

The development of modern technologies has acclimatized biosensors to complicated applicable scenarios with integrated properties as a whole instead of the pursuit of a single-point breakthrough. Here, we targeted a few concerns in the development of enzyme-based biosensors, including stability, analyte enrichment, and signal transduction, and developed a general biosensing model utilizing enzymes, aggregation-induced emission (AIE) luminogens, and stimuli-responsive framework materials as the units. We propose such proof-of-concept of glucose biosensors by coencapsulating glucose oxidase and AIE-type gold nanoclusters into acid-sensitive zeolite imidazolate framework (ZIF)-8 nanocrystals. The acid-activated degradation of ZIF-8 bridges the molecular signals produced by the enzyme-catalytic reaction of glucose and the photon signals generated by ZIF-8-induced AIE effects of gold nanoclusters, resulting in the "turn-off" model nanoprobes for glucose detection with high selectivity. After embedding the nanoprobes into hollow-out tapes, the formed paper biosensors can conveniently detect glucose with the help of a smartphone.

Portable point-of-care diagnostic devices: an updated review.

The global pandemic caused by the SARS-CoV-2 (COVID) virus indiscriminately impacted people worldwide with unquantifiable and severe impacts on all aspects of our lives, regardless of socioeconomic status. The pandemic brought to light the very real possibility of pathogens changing and shaping the way we live, and our lack of preparedness to deal with viral/bacterial outbreaks. Importantly, the quick detection of pathogens can help prevent and control the spread of disease, making the importance of diagnostic techniques undeniable. Point-of-care diagnostics started as a supplement to standard lab-based diagnostics, and are gradually becoming mainstream. Because of this, and their importance in detecting pathogens (especially in the developing world), their development has accelerated at an unprecedented rate. In this review, we highlight some important and recent examples of point-of-care diagnostics for detecting nucleic acids, proteins, bacteria, and other biomarkers, with the intent of making apparent their positive impact on society and human health.

Projection optical engine design based on tri-color LEDs and digital light processing technology.

Digital light processing (DLP) is currently a cutting-edge technology for desktop projection optical engines. Due to the passive luminescence characteristics, the DLP projection engine needs a few specific illumination optical components for light collimation, homogenization, and color combination, together with a projection lens matching the DLP chip and magnifying the image. In this paper, we propose a design approach that first splits the DLP projection optical engine into individual components for separate design, and then integrates them into a whole system for further verification. For the first step, the collimating lens group is designed for light collection, and the dichroic mirrors are used to fold the light path based on tri-color LED light sources. For the second step, a fly-eye lens and the corresponding relay lens group are designed to achieve uniform illumination on the DMD chip. The third step is to optimize the projection lens group for high-resolution projection display. Based on the design and simulation, the optical efficiency is 63.4% and the uniformity reaches 94.9% on the projection screen. The modulation transfer function (MTF) of the projection lens is higher than 0.4 at 66 lines for the distance of 500∼1500mm, and the distortion is lower than 1%. Simulation results show that the total luminous flux is estimated to reach 224.15 lm when the powers of tri-color LEDs are 21 W, 15.5 W, and 25 W, respectively. A projector prototype is built and tested for further verification, which provides a luminous flux of 220.43 lm and uniformity of 90.22%, respectively. The proposed design, demonstrated by both simulation and experiment, exhibits high feasibility and application potential in state-of-the-art commercial projector design.

Luminescent wearable biosensors based on gold nanocluster networks for "turn-on" detection of Uric acid, glucose and alcohol in sweat.

From the difficulty of awareness of abnormal concentrations of biochemical indexes in people's daily life come wearable sensing technologies. Recently, luminescent wearable biosensors are emerging with simple fabrication, easy use, cost-effectivity and reliability. But several challenges should be taken up, such as availability of varied analytes, high sensitivity, stability of enzymes, photostability, low signal noises and recyclability of sensors. Here, the Luminescent Wearable Sweat Tape (LWST) biosensor is developed via embedding multi-component nanoprobes onto microwell-patterned paper substrates of hollowed-out double-side tapes. The nanoprobes consist of responsive luminophores, enzyme-loaded gold nanocluster (AuNCs) nano-networks, which are wrapped by the switch, MnO2 nanosheets. The responsive luminophores are constructed by 3 substitutable components: enzymes (uricase, GOx and alcohol dehydrogenase) for molecular target recognition, glutathione-protected AuNCs (yellow, red and green) for luminescent signal output and polycations PAH for integration. MnO2 NSs as the switch can quench the emission of the AuNCs but degraded by the reductive product of incorporated enzymes. Thus, targeting analysts (uric acid, glucose and alcohol) can be dose-dependently detected through "turn-on" luminescence approach. After incorporating the nanoprobes into hollow-out tapes, the formed LWST biosensors can detect uric acid, glucose and alcohol in sweat with the help of a smartphone. Subsequently, we primarily apply them into human daily life scenario, sampling from dine parties, and the positive relationships of analyte intakes and the increase of analytes in sweat are significant with individual difference.

Inkjet printing based ultra-small MnO2 nanosheets synthesis for glutathione sensing.

Manganese dioxide (MnO2) with small size is competent in sensing applications, but its synthesis generally adopts templates or in complex ways. Inkjet printing technique with excellent performance offers a versatile tool due to its stability, flexibility, economy. Herein, an inkjet printing method was developed for rapid synthesis of ultra-small MnO2 nanosheets. The findings validated the feasibility of inkjet printing method for MnO2 nanosheets synthesis and achieved the demand of small size and facile mode. Additionally, the limit of detection (LOD) of ultra-small MnO2 nanosheets in glutathione (GSH) sensing achieved 0.26 µM, which was about 40% more sensitive than that of the typical MnO2 nanosheets, enabling the establishment of a rapid and efficient modality for sensitive and selective GSH sensing. By virtue of the inkjet printing approach, the ultra-small MnO2 nanosheets was obtained in a short time without complicated fabricating process. It can be foreseen that the proposed inkjet printing approach would facilitate the application prospects of ultra-small MnO2 nanosheets in diverse fields. Such a facile approach may open new avenues for synthesis of ultra-small or ultrafine nanomaterials.

Rational Design of "Three-in-One" Ratiometric Nanoprobes: Protein-Caged Dityrosine, CdS Quantum Dots, and Gold Nanoclusters.

Recently, multiplexed ratiometric fluorescence sensors for detecting several analytes have received much interest because of their multifunctionality. Here, we fabricate a novel trinity fluorescent nanoprobe in which one small-molecule fluorophore, blue-emissive dityrosine (diTyr) residues, and two nanomaterial fluorophores, green-emissive CdS quantum dots (CdSQDs) and red-emissive gold nanoclusters (AuNCs), are cocaged in a bovine serum albumin (BSA) molecule. The large differences of Stokes shifts among diTyr residues, CdSQDs, and AuNCs ensure their emission at a single excitation wavelength. The nanoprobes can be facilely integrated using two-step synthetic reactions. DiTyr residues and AuNCs are formed and bound to the protein cage through the redox reaction between Au3+ and tyrosine residues of BSA, and the CdSQDs are followed to be conjugated to the modified BSA cage-templated CdS combination reaction. With established benign biocompatibility, the nanoprobes can ratiometrically detect intracellular glutathione by significantly enhancing the green emission of the conjugated CdSQDs. Likewise, the ratiometric sensing of solution alkalinity and tris(2-carboxyethyl)phosphine can be achieved using blue-emitted diTyr residues and red-emitted AuNCs as the responsive units, respectively, and the corresponding other two fluorophores as the reference signals. This study addresses a concept of trinity fluorescence ratiometric sensing system with multiple targets and optional references, which should be a promising pathway to meet the challenges from complexing biochemical environments and multivariate analysis.

Gallic Acid Attenuates Dimethylnitrosamine-Induced Liver Fibrosis by Alteration of Smad Phosphoisoform Signaling in Rats.

Dimethylnitrosamine (DMN) is a potent hepatotoxin, carcinogen, and mutagen. In our previous study, a candidate gallic acid (GA) that widely exists in food and fruit was selected for its capability to alleviate DMN toxicity in vivo. We aimed to investigate the therapeutic potential of GA against DMN-induced liver fibrosis. During the first four weeks, DMN was administered to rats via intraperitoneal injection every other day, except the control group. GA or silymarin was given to rats by gavage once daily from the second to the sixth week. GA significantly reduced liver damage in serum parameters and improved the antioxidant capacity in liver and kidney tissues. Cytokines involved in liver fibrosis were measured at transcriptional and translational levels. These results indicate that GA exhibits robust antioxidant and antifibrosis effects and may be an effective candidate natural medicine for liver fibrosis treatment.

Cystathionine γ-Lyase Deficiency Exacerbates CCl4-Induced Acute Hepatitis and Fibrosis in the Mouse Liver.

AIMS: The present study examined the role of cystathionine γ-lyase (CSE) in carbon tetrachloride (CCl4)-induced liver damage. RESULTS: A CSE gene knock-out and luciferase gene knock-in (KI) mouse model was constructed to study the function of CSE and to trace its expression in living status. CCl4 or lipopolysaccharide markedly downregulated CSE expression in the liver of mice. CSE-deficient mice showed increased serum alanine aminotransferase and aspartate aminotransferase levels, and liver damage after CCl4 challenge, whereas albumin and endogenous hydrogen sulfide (H2S) levels decreased significantly. CSE knockout mice showed increased serum homocysteine levels, upregulation of inflammatory cytokines, and increased autophagy and IκB-α degradation in the liver in response to CCl4 treatment. The increase in pro-inflammatory cytokines, including tumor necrosis factor-alpha in CSE-deficient mice after CCl4 challenge, was accompanied by a significant increase in liver tissue hydroxyproline and α-smooth muscle actin and histopathologic changes in the liver. However, H2S donor pretreatment effectively attenuated most of these imbalances. INNOVATION: Here, a CSE knock-out and luciferase KI mouse model was established for the first time to study the transcriptional regulation of CSE expression in real time in a non-invasive manner, providing information on the effects and potential mechanisms of CSE on CCl4-induced liver injury. CONCLUSION: CSE deficiency increases pro-inflammatory cytokines in the liver and exacerbates acute hepatitis and liver fibrosis by reducing H2S production from L-cysteine in the liver. The present data suggest the potential of an H2S donor for the treatment of liver diseases such as toxic hepatitis and fibrosis. Antioxid. Redox Signal. 27, 133-149.