Designable Nanoadaptor for Enhanced Recognition of Natural Killer Cell to Tumor via Bio-orthogonal Click Reaction.

Highly efficient recognition of cancer cells by immune cells is important for successful therapeutic-cell-based cancer immunotherapy. Herein, we present a facile NIR-II nanoadaptor [hyaluronic acid (HA)/dibenzocyclooctyne (DBCO)-Au:Ag2Te quantum dots (QDs)] for enhancing the tumor recognition and binding ability of natural killer (NK) cells via a bio-orthogonal click reaction in vivo. The Nanoadaptor possesses superior tumor-targeting capacity, facilitating the accumulation of the chemical receptor DBCO at the tumor sites. Subsequently, the enrichment of DBCO on tumor cell surfaces provides multivalent recognition sites for capturing pretreated azide engineered NK92 cells (NK92-N3) through an efficient click reaction, thereby significantly enhancing the therapeutical efficiency. The dynamic process of nanoadaptor-mediated recognition of NK cells to tumor cells could be vividly observed using multiplexed NIR-II fluorescence imaging in a mouse model of lung cancer. Such a nanoadaptor strategy can be extended to other therapeutic cellular systems and holds promise for future clinical applications.

Programmed Remodeling of the Tumor Milieu to Enhance NK Cell Immunotherapy Combined with Chemotherapy for Pancreatic Cancer.

Natural killer (NK) cell-based adoptive immunotherapy has demonstrated encouraging therapeutic effects in clinical trials for hematological cancers. However, the effectiveness of treatment for solid tumors remains a challenge due to insufficient recruitment and infiltration of NK cells into tumor tissues. Herein, a programmed nanoremodeler (DAS@P/H/pp) is designed to remodel dense physical stromal barriers and for dysregulation of the chemokine of the tumor environment to enhance the recruitment and infiltration of NK cells in tumors. The DAS@P/H/pp is triggered by the acidic tumor environment, resulting in charge reversal and subsequent hyaluronidase (HAase) release. HAase effectively degrades the extracellular matrix, promoting the delivery of immunoregulatory molecules and chemotherapy drugs into deep tumor tissues. In mouse models of pancreatic cancer, this nanomediated strategy for the programmed remodeling of the tumor microenvironment significantly boosts the recruitment of NK92 cells and their tumor cell-killing capabilities under the supervision of multiplexed near-infrared-II fluorescence.

Spatiotemporally Controlled Photolabeling of Genetically Unmodified Proteins in Live Cells.

Selective labeling of the protein of interest (POI) in genetically unmodified live cells is crucial for understanding protein functions and kinetics in their natural habitat. In particular, spatiotemporally controlled installation of the labels on a POI under light control without affecting their original activity is in high demand but is a tremendous challenge. Here, we describe a novel ligand-directed photoclick strategy for spatiotemporally controlled labeling of endogenous proteins in live cells. It was realized with a designer labeling reagent skillfully integrating the photochemistries of 2-nitrophenylpropyloxycarbonyl and 3-hydroxymethyl-2-naphthol with an affinity ligand. Highly electrophilic ortho-naphthoquinone methide was photochemically released and underwent a proximity coupling reaction with nucleophilic amino acid residues on the POI in live cells. With fluorescein as a marker, this photoclick strategy enables time-resolved labeling of carbonic anhydrase subtypes localized either on the cell membrane or in the cytoplasm and a discriminable visualization of their metabolic kinetics. Given the versatility underlined by facilely tethering other functional entities (e.g., biotin, a peptide short chain) via acylation or (in cell) Huisgen cycloaddition, this affinity-driven photoclick chemistry opens up enormous opportunities for discovering dynamic functions and mechanistic interrogation of endogenous proteins in live cells.

Ni─Co─O─S Derived Catalysts on Hierarchical N-doped Carbon Supports with Strong Interfacial Interactions for Improved Hybrid Water Splitting Performance.

Simultaneously improving electrochemical activity and stability is a long-term goal for water splitting. Herein, hierarchical N-doped carbon nanotubes on carbon nanowires derived from PPy are grown on carbon cloth, serving as a support for NiCo oxides/sulfides. The hierarchical electrodes annealed in N2 or H2/N2 display improved intrinsic activity and stability for hydrogen evolution reaction (HER) and glucose oxidation reaction. Compared with Pt/C||Ir/C in alkaline media, the glucose electrolysis assembled with electrodes exhibits a cell voltage of 1.38 V at 10 mA cm-2, durability for >12 h at 50 mA cm-2, and resistance to glucose/gluconic acid poisoning. In addition, electrocatalysts can also be applied in ethanol oxidation reactions. Systematic characterizations reveal the strong interactions between NiCo and N-doped carbon support-induced partial charge transfer at the interface and regulate the local electronic structure of active sites. Density functional theory calculations demonstrate that the synergistic effect between N-doped carbon supports, metallic NiCo, and NiCo oxides/sulfides optimize the adsorption energy of H2O and the H* free energy for HER. The energy barrier of the dehydrogenation of glucose effectively decreased. This work will attract attention to the role of metal-support interactions in enhancing the intrinsic activity and stability of electrocatalysts.

An electrochemical biosensor for Staphylococcus aureus detection based on a multilevel surface 3D micro/nanostructure.

Detection of pathogens is one of the key concerns for hospitals, the food industry, water suppliers, or other environmental engineering practices because pathogens can cause a wide range of infectious risks. Staphylococcus aureus (S. aureus) is one of the most common pathogens that are hazardous to human health and its existence is an important index to the safety of food, environmental sanitation, or medical products. In this study, we prepared an electrode with designed surface multilevel 3D micro/nano protrusions for facile and efficient S. aureus detection. The existence of these multilevel protrusions enhanced the adsorption of S. aureus. Hence, the detection limit could be as low as 10 CFU mL-1. Furthermore, the electrode was also successfully used to detect S. aureus in actual samples, such as milk and artificial human tissue fluid. It was found that the recovery of the reported approach showed no significant difference from that of the traditional plate count method. However, compared with the plate count method, the detection process of our approach is much more time-saving and easy-operating. These advantages of the approach we report, such as high sensitivity, reliability, quickness, and user-friendliness, make it a potential platform for detecting S. aureus in relation to the food industry and clinical diagnosis.

Unexcited Light Source Imaging for Biomedical Applications.

Optical imaging has a wide range of applications in the biomedical field, allowing the visualization of physiological processes and helping in the diagnosis and treatment of diseases. Unexcited light source imaging technologies, such as chemiluminescence imaging, bioluminescence imaging and afterglow imaging have attracted great attention in recent years because of the absence of excitation light interference in their application and the advantages of high sensitivity and high signal-to-noise ratio. In this review, the latest advances in unexcited light source imaging technology for biomedical applications are highlighted. The design strategies of unexcited light source luminescent probes in improving luminescence brightness, penetration depth, quantum yield and targeting, and their applications in inflammation imaging, tumor imaging, liver and kidney injury imaging and bacterial infection imaging are introduced in detail. The research progress and future prospects of unexcited light source imaging for medical applications are further discussed.

Gaucher disease in a patient with membranoproliferative glomerulonephritis: case report.

BACKGROUND: Gaucher disease (GD) is a rare autosomal recessive inherited, lysosomal storage disoder that involves liver, spleen, lung, bone, bone marrow even central nervous. However, GD associated membranoproliferative glomerulonephritis (MPGN) is seldom reported. CASE PRESENTATION: Here we described a case of 35-year-old man suffering from GD with hepatosplenomegaly, ascites, bone destruction, myelofibrosis and MPGN. Renal biopsy revealed MPGN and Gaucher cells presented in the glomeruli capillaries. ß-glucosidase activity was 1.95nmol/1 h/mg and gene detection demonstrated that one homozygous pathogenic variant Leu483Pro in GBA. He received the treatment of oral prednisone and mycophenolate mofetil and his ascites and renal outcomes had been significantly improved. CONCLUSIONS: Therapy of prednisone and mycophenolate mofetil may be an optional choice for patients with Gaucher disease who have no opportunity to use enzyme treatment.

Research Status and Prospect of Non-Viral Vectors Based on siRNA: A Review.

Gene therapy has attracted much attention because of its unique mechanism of action, non-toxicity, and good tolerance, which can kill cancer cells without damaging healthy tissues. siRNA-based gene therapy can downregulate, enhance, or correct gene expression by introducing some nucleic acid into patient tissues. Routine treatment of hemophilia requires frequent intravenous injections of missing clotting protein. The high cost of combined therapy causes most patients to lack the best treatment resources. siRNA therapy has the potential of lasting treatment and even curing diseases. Compared with traditional surgery and chemotherapy, siRNA has fewer side effects and less damage to normal cells. The available therapies for degenerative diseases can only alleviate the symptoms of patients, while siRNA therapy drugs can upregulate gene expression, modify epigenetic changes, and stop the disease. In addition, siRNA also plays an important role in cardiovascular diseases, gastrointestinal diseases, and hepatitis B. However, free siRNA is easily degraded by nuclease and has a short half-life in the blood. Research has found that siRNA can be delivered to specific cells through appropriate vector selection and design to improve the therapeutic effect. The application of viral vectors is limited because of their high immunogenicity and low capacity, while non-viral vectors are widely used because of their low immunogenicity, low production cost, and high safety. This paper reviews the common non-viral vectors in recent years and introduces their advantages and disadvantages, as well as the latest application examples.

Biodegradation of di(2-ethylhexyl) phthalate by a new bacterial consortium.

Di(2-ethylhexyl) phthalate (DEHP) with continuous high concentration was used as the sole carbon and energy source to isolate a new bacterial consortium (K1) from agricultural soil covered with plastic film for a long time. Unclassified Comamonadaceae, Achromobacter, and Pseudomonas in K1 were identified as major genera of the consortium by high-throughput sequencing, and unclassified Commanadaceae was first reported to be related to DEHP degradation. Response surface method (RSM) showed that the optimum conditions for K1 to degrade DEHP were 31.4 °C, pH 7.3, and a concentration of 420 mg L-1. K1 maintains normal cell viability and stable DEHP degradation efficiency in the range of 10-3000 mg L-1 DEHP concentration, which is superior to existing research. The biodegradation of DEHP followed first-order kinetics when the initial concentration of DEHP was between 100 and 3,000 mg L-1. GC-MS analysis of different treatment groups showed that DEHP was degraded by the consortium group through the de-esterification pathway, and treatment effect was significantly better than that of the single bacteria treatment group. The subsequent substrate utilization experiment further confirmed that K1 could quickly mineralize DEHP. In addition, K1 has high degradation capacity for the most common phthalate acid esters in the environment.

Oral Administration of Starting Materials for In Vivo Synthesis of Antibacterial Gold Nanoparticles for Curing Remote Infections.

Oral administration is a facile and safe way for medication. However, most of the reported nanomedicines could not be taken orally, partially due to their unsatisfied stability, poor absorbance, or toxicity in the gastrointestinal tract. Here, we demonstrate that we could robustly synthesize gold nanoparticles (GNPs) in vivo by orally administering two starting materials, tetrachloroauric acid and aminophenyl boronic acid (ABA). The ABA-activated GNPs (A-GNPs) synthesized in vivo could be absorbed by the gastrointestinal tract and reach the remote infection lesions such as peritonitis caused by multidrug resistant (MDR) bacteria in mice. The A-GNPs exhibit excellent antibacterial efficacy (MIC, 3 µg/mL), long half-life (16-17 h), effective clearance (residual concentration is near 0 within 72 h), and high biosafety (safe dose/effective dose, 8 times). Our study is a pioneering attempt for synthesizing and taking nanomedicines orally just like preparing and drinking a cocktail.

Degradation of tetracycline wastewater by suspended biochar as carriers in moving bed biofilm reactor.

To improve the removal efficiency of antibiotics in moving bed biofilm reactor, suspended biochar block was prepared by the one-pot process and was used as carriers to construct a reaction device to study the treatment effect of antibiotic wastewater. The characteristics of the hanging biofilm in wastewater were investigated. And the mechanism of biochar as a biological carrier has been studied. The results showed that in the 45-day experiment, the maximum number of biofilms for suspended biochar carriers was twice 3.4 times that of the high-density polyethylene carriers. When 10 mg/L tetracycline was added to the reactor, the removal efficiency of the tetracycline removal rate was 71.85% and the chemical oxygen demand (COD), total nitrogen (TN), and NH4+-N removal efficiency reached to 89.95, 61.91 and 85.47% respectively. Suspension biochar carriers can reduce fluctuations in redox potentials, thereby improving the cellular efficiency of microorganisms. Meanwhile, it inhibits the production of soluble microbial products and extracellular polymers, reduces toxic effects, and enhances the adhesion between microorganisms and carriers. The microbial communities of the two carriers were investigated by high-throughput sequencing techniques. Suspended biochar significantly increased the relative abundance of Hydrogenophaga and Comamonas, and improved the ability of nitrification and denitrification. Comamonas could be responsible for tetracycline degradation.

An Intelligent Graphene-Based Biosensing Device for Cytokine Storm Syndrome Biomarkers Detection in Human Biofluids.

Abnormal elevated levels of cytokines such as interferon (IFN), interleukin (IL), and tumor necrosis factor (TNF), are considered as one of the prognosis biomarkers for indicating the progression to severe or critical COVID-19. Hence, it is of great significance to develop devices for monitoring their levels in COVID-19 patients, and thus enabling detecting COVID-19 patients that are worsening and to treat them before they become critically ill. Here, an intelligent aptameric dual channel graphene-TWEEN 80 field effect transistor (DGTFET) biosensing device for on-site detection of IFN-γ, TNF-α, and IL-6 within 7 min with limits of detection (LODs) of 476 × 10-15 , 608 × 10-15 , or 611 × 10-15 m respectively in biofluids is presented. Using the customized Android App together with this intelligent device, asymptomatic or mild COVID-19 patients can have a preliminary self-detection of cytokines and get a warning reminder while the condition starts to deteriorate. Also, the device can be fabricated on flexible substrates toward wearable applications for moderate or even critical COVID-19 cases for consistently monitoring cytokines under different deformations. Hence, the intelligent aptameric DGTFET biosensing device is promising to be used for point-of-care applications for monitoring conditions of COVID-19 patients who are in different situations.

Printed Stretchable Liquid Metal Electrode Arrays for In Vivo Neural Recording.

The adoption of neural interfacing into neurological diagnosis is severely hampered by the complex, costly, and error-prone manufacturing methods, requiring new fabrication processes and materials for flexible neural interfacing. Here a strategy for fabricating highly stretchable neural electrode arrays based on screen printing of liquid metal conductors onto polydimethylsiloxane substrates is presented. The screen-printed electrode arrays show a resolution of 50 µm, which is ideally applicable to neural interfaces. The integration of liquid metal-polymer conductor enables the neural electrode arrays to retain stable electrical properties and compliant mechanical performance under a significant (≈108%) strain. Taking advantage of its high biocompatibility, liquid metal electrode arrays exhibit excellent performance for neurite growth and long-term implantation. The stretchable electrode arrays can spontaneously conformally come in touch with the brain surface, and high-throughput electrocorticogram signals are recorded. Based on stretchable electrode arrays, real-time monitoring of epileptiform activities can be provided at different states of seizure. The method reported here offers a new fabrication strategy to manufacture stretchable neural electrodes, with additional potential utility in diagnostic brain-machine interfaces.

The Density of Surface Coating Can Contribute to Different Antibacterial Activities of Gold Nanoparticles.

With the widespread use of antibiotics, the number of complex infection cases caused by unknown pathogens is increasing and novel antibiotics with tunable antibacterial spectra and low toxicity are highly desirable. Herein, we report that, by selecting thiol or amine, two groups with different binding affinities with gold, as anchoring groups, phenylboronic acid can be decorated on gold nanoparticles (AuNPs) with different densities, which contributes to Gram-selective antibacterial activities of the AuNPs. The AuNPs modified with amine- or thiol-tethered phenylboronic acids specifically bind to lipopolysaccharide (LPS, Gram-negative) or lipoteichoic acid (LTA, Gram-positive), respectively. By modifying AuNPs with different ratios of thiol- and amine-tethered phenylboronic acids, the resulting AuNPs show potent and tunable antibacterial activity. The AuNP-based antibacterial agents with optional Gram selectivity are promising for applications in personalized therapy.

Delivery of CRISPR/Cas9 by Novel Strategies for Gene Therapy.

Precise editing of the genome of a living body is a goal pursued by scientists in many fields. In recent years, CRISPR (clustered regularly interspaced short palindromic repeat)/Cas (CRISPR-associated) genome-editing systems have become a revolutionary toolbox for gene editing across various species. However, the low transfection efficiency of the CRISPR/Cas9 system to mammalian cells in vitro and in vivo is a big obstacle hindering wide and deep application. In this review, recently developed delivery strategies for various CRISPR/Cas9 formulations and their applications in treating gene-related diseases are briefly summarized. This review should inspire others to explore more efficient strategies for CRISPR system delivery and gene therapy.

Electrochemiluminescent detection of Escherichia coli O157:H7 based on Ru(bpy)3 2+/ZnO nanorod arrays.

Foodborne pathogens are perpetual threats to human and animal health. Detection of pathogens requires accurate, sensitive, rapid and point-of-care diagnostic assays. In this study, we described a simple and sensitive electrochemiluminescent (ECL) assay to detect the deadly bacteria Escherichia coli O157:H7 by [Formula: see text]-coated ZnO nanorods arrays (NAs). The [Formula: see text]-coated ZnO NAs were fabricated by immobilizing [Formula: see text] on ZnO NAs with a large specific surface area and good conductivity. An [Formula: see text]-2-(dibutylamino)-ethanol (DBAE) system coated on ZnO NAs exhibits high ECL intensity, rapid response and good stability. This system was further developed as an ECL immunosensor used in the detection of E. coli O157:H7. The proposed ECL immunosensor exhibits a broad detection range within the scope of 200-100 000 CFU ml-1 and quite a low detection limit of 143 CFU ml-1. The high specificity, remarkable reproducibility and good stability offer a sensitive, selective, and convenient pathway for detecting E. coli O157:H7 in the field of food safety and clinical diagnosis.

Organoplatinum-Substituted Polyoxometalate Inhibits ß-amyloid Aggregation for Alzheimer's Therapy.

Aggregated ß-amyloid (Aß) is widely considered as a key factor in triggering progressive loss of neuronal function in Alzheimer's disease (AD), so targeting and inhibiting Aß aggregation has been broadly recognized as an efficient therapeutic strategy for curing AD. Herein, we designed and prepared an organic platinum-substituted polyoxometalate, (Me4 N)3 [PW11 O40 (SiC3 H6 NH2 )2 PtCl2 ] (abbreviated as PtII -PW11 ) for inhibiting Aß42 aggregation. The mechanism of inhibition on Aß42 aggregation by PtII -PW11 was attributed to the multiple interactions of PtII -PW11 with Aß42 including coordination interaction of Pt2+ in PtII -PW11 with amino group in Aß42 , electrostatic attraction, hydrogen bonding and van der Waals force. In cell-based assay, PtII -PW11 displayed remarkable neuroprotective effect for Aß42 aggregation-induced cytotoxicity, leading to increase of cell viability from 49 % to 67 % at a dosage of 8 µm. More importantly, the PtII -PW11 greatly reduced Aß deposition and rescued memory loss in APP/PS1 transgenic AD model mice without noticeable cytotoxicity, demonstrating its potential as drugs for AD treatment.

Fuel-Driven Dissipative Self-Assembly of a Supra-Amphiphile in Batch Reactor.

Dissipative self-assembly is an intriguing but challenging research topic in chemistry, materials science, physics, and biology because most functional self-assembly in nature, such as the organization and operation of cells, is actually an out-of-equilibrium system driven by energy dissipation. In this article, we successfully fabricated an I2-responsive supra-amphiphile by a PEGylated poly(amino acid) and realize its dissipative self-assembly in batch reactor by coupling it with the redox reaction between NaIO3 and thiourea, in which I2 is an intermediate product. The formation and dissipative self-assembly of the supra-amphiphile can be repeatedly initiated by adding the mixture of NaIO3 and thiourea, which herein acts as "chemical fuel", while the lifetime of the transient nanostructures formed by the dissipative self-assembly is easily tuned by altering thiourea concentration in the "chemical fuel". Furthermore, as an application demo, the dissipative self-assembly of the supra-amphiphile is examined to control dispersion of multiwalled carbon nanotubes in water, exhibiting a good performance of organic pollutant removal.

Self-Assembly of Chiral Gold Clusters into Crystalline Nanocubes of Exceptional Optical Activity.

Self-assembly of inorganic nanoparticles into ordered structures is of interest in both science and technology because it is expected to generate new properties through collective behavior; however, such nanoparticle assemblies with characteristics distinct from those of individual building blocks are rare. Herein we use atomically precise Au clusters to make ordered assemblies with emerging optical activity. Chiral Au clusters with strong circular dichroism (CD) but free of circularly polarized luminescence (CPL) are synthesized and organized into uniform body-centered cubic (BCC) packing nanocubes. Once the ordered structure is formed, the CD intensity is significantly enhanced and a remarkable CPL response appears. Both experiment and theory calculation disclose that the CPL originates from restricted intramolecular rotation and the ordered stacking of the chiral stabilizers, which are fastened in the crystalline lattices.

Enantioselective circular dichroism sensing of cysteine and glutathione with gold nanorods.

Enantioselective analysis of biological thiols, including cysteine (Cys) and glutathione (GSH), is extremely important because of their unique role in bioentities. Here we demonstrated that the end-to-end assemblies of plasmonic gold nanorods with chiral Cys or GSH can be used as a distinctive chiroptical sensor for reliable determination of the absolute configuration of Cys and GSH at the visible light region. The end-to-end assemblies of Au nanorods induced by Cys or GSH exhibit strong circular dichroism (CD) signals in the region of 500-850 nm, which is attributed to chiral current inside Au nanorods induced by the mixed biothiols. The CD intensity of the assemblies shows good linearity with the amount of Cys and GSH. The limit of detection for Cys and GSH using end-to-end assemblies is at micromolar concentrations. In addition, the sensing system exhibits good selectively toward Cys and GSH in the presence of other amino acids.