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Sensitive and specific blood-based assays for the detection of pulmonary and extrapulmonary tuberculosis would reduce mortality associated with missed diagnoses, particularly in children. Here we report a nanoparticle-enhanced immunoassay read by dark-field microscopy that detects twoMycobacterium tuberculosisvirulence factors (the glycolipid lipoarabinomannan and its carrier protein) on the surface of circulating extracellular vesicles. In a cohort study of 147 hospitalized and severely immunosuppressed children living with HIV, the assay detected 58 of the 78 (74%) cases of paediatric tuberculosis, 48 of the 66 (73%) cases that were missed by microbiological assays, and 8 out of 10 (80%) cases undiagnosed during the study. It also distinguished tuberculosis from latent-tuberculosis infections in non-human primates. We adapted the assay to make it portable and operable by a smartphone. With further development, the assay may facilitate the detection of tuberculosis at the point of care, particularly in resource-limited settings.

Sensitive detection of extracellular vesicles (EVs) as emerging biomarkers has shown great promises for disease diagnosis. Plasmonic metal nanostructures conjugated with molecules that bind specific biomarker targets are widely used for EVs sensing but involve tradeoffs between particle-size-dependent signal intensity and conjugation efficiency. One solution to this problem would be to induce nucleation on nanoparticles that have successfully bound a target biomarker to permit in situ nanoparticle growth for signal amplification, but approaches that are evaluated to date require harsh conditions or lack nucleation specificity, prohibiting their effective use with most biological specimens. This study describes a one-step in situ strategy to induce monocrystalline copper shell growth on gold nanorod probes without decreasing signal by disrupting probe-target interactions or lipid bilayer integrity to enable EV biomarker detections. This approach increases the detected nanoparticle signal about two orders of magnitude after a 10 min copper nanoshell growth reaction. This has significant implications for improved disease detection, as indicated by the ability of a novel immunoassay using this approach to detect low abundance EVs carrying a pathogen-derived biomarker, after their direct capture from serum, to facilitate the diagnosis of tuberculosis cases in a diagnostically challenging pediatric cohort.

Exosomes are abundantly secreted by most cells that carry membrane and cytosolic factors that can reflect the physiologic state of their source cells and thus have strong potential to serve as biomarkers for early diagnosis, disease staging, and treatment monitoring. However, traditional diagnostic or prognostic applications that might use exosomes are hindered by the lack of rapid and sensitive assays that can exploit their biological information. An array of assay approaches have been developed to address this deficit, including those that integrate immunoassays with nanoplasmonic sensors to measure changes in optical refractive indexes in response to the binding of low concentrations of their targeted molecules. These sensors take advantage of enhanced and tunable interactions between the electron clouds of nanoplasmonic particles and structures and incident electromagnetic radiation to enable isolation-free and ultrasensitive quantification of disease-associated exosome biomarkers present in complex biological samples. These unique advantages make nanoplasmonic sensing one of the most competitive approaches available for clinical applications and point-of-care tests that evaluate exosome-based biomarkers. This review will briefly summarize the origin and clinical utility of exosomes and the limitations of current isolation and analysis approaches before reviewing the specific advantages and limitations of nanoplasmonic sensing devices and indicating what additional developments are necessary to allow the translation of these approaches into clinical applications.

Tuberculosis remains a leading cause of global mortality, especially for adults and children living with HIV (CLHIV) underdiagnosed by sputum-based assays. Non-sputum-based assays are needed to improve tuberculosis diagnosis and tuberculosis treatment monitoring. Our aim in this study was to determine whether ultrasensitive detection of Mycobacterium tuberculosis cell-free DNA (Mtb-cfDNA) in blood can diagnose tuberculosis and evaluate tuberculosis treatment responses.In this molecular diagnostics study we analysed archived serum from two patient populations evaluated for tuberculosis in Eswatini and Kenya to detect Mtb-cfDNA, analysing serum from all individuals who had both sufficient serum volumes and clear diagnostic results. An optimised CRISPR-mediated tuberculosis (CRISPR-TB) assay was used to detect Mtb-cfDNA in serum at enrolment from adults and children with presumptive tuberculosis and their asymptomatic household contacts, and at enrolment and during tuberculosis treatment from a cohort of symptomatic CLHIV at high risk for tuberculosis, who provided longitudinal serum at enrolment and during tuberculosis treatment.CRISPR-TB identified microbiologically and clinically confirmed tuberculosis cases in the predominantly HIV-negative Eswatini adult cohort with 96% sensitivity (27 [96%] of 28, 95% CI 80-100) and 94% specificity (16 [94%] of 17, 71-100), and with 83% sensitivity (5 [83%] of 6, 36-100) and 95% specificity (21 [95%] of 22, 77-100) in the paediatric cohort, including all six cases of extrapulmonary tuberculosis. In the Kenyan CLHIV cohort, CRISPR-TB detected all (13 [100%] of 13, 75-100) confirmed tuberculosis cases and 85% (39 [85%] of 46, 71-94) of unconfirmed tuberculosis cases diagnosed by non-microbiological clinical findings. CLHIV who were CRISPR-TB positive at enrolment had a 2·4-times higher risk of mortality by 6 months after enrolment. Mtb-cfDNA signal decreased after tuberculosis treatment initiation, with near or complete Mtb-cfDNA clearance by 6 months after tuberculosis treatment initiation.CRISPR-mediated detection of circulating Mtb-cfDNA shows promise to increase the identification of paediatric tuberculosis and HIV-associated tuberculosis, and potential for early diagnosis and rapid monitoring of tuberculosis treatment responses.US Department of Defense, National Institute of Child Health and Human Development, National Institute of Allergy and Infectious Diseases, University of Washington Center for AIDS Research, and the Weatherhead Presidential Endowment fund.

Nonantibiotic small molecule-modified gold nanoparticles (Au NPs) show great potential as an alternative for commercial antibiotics, yet their narrow antibacterial spectrum hinders the wide application in clinics. We observe that Au NPs cofunctionalized with both bovine serum albumin (BSA) and 4,6-diamino-2-pyrimidinethiol (DAPT) can generate conjugates (Au_DAPT_BSA) with progressive antimicrobial activities, including decreased minimal inhibitory concentration against Gram-negative bacteria and extended antibacterial spectrum against Gram-positive bacteria compared with DAPT-capped Au NPs (Au_DAPT). Au_DAPT_BSA induces no drug resistance and can significantly decrease the number of bacteria in the biofilms formed by Pseudomonas aeruginosa and Staphylococcus aureus. In addition, Au_DAPT_BSA exhibit in vivo healing efficiency for mice with subcutaneous abscesses caused by clinically isolated, multidrug resistant Escherichia coli or S. aureus without inducing detectable toxicity to the mammalian cells/animals. Our findings provide a new strategy for strengthening nanomaterial-based bactericides such as Au NPs, especially against drug-resistant bacterial infections.

We develop an ultrasensitive T2-mediated immunosensor based on the coordination chemistry and Cu(I)-catalyzed 1,3-dipolar cycloaddition of azide andalkyne (CuAAC) and apply it for the detection of pesticide residues. We functionalize polyglutamic acid (PGA) on polystyrene to form a brush-like nanostructure that has a large loading capacity of Cu(II) through the coordination chemistry between PGA and Cu(II). Such a brush-like nanostructure could be used to chelate Cu(II) to modulate the CuAAC between azide-functionalized 1000 nm polystyrene (PS1000) and alkyne-functionalized 30 nm magnetic nanoparticles (MNP30), and the MNP30-PS1000 conjugate as a product of CuAAC can act as a magnetic probe in this T2-based immunosensor. This click chemistry and coordination chemistry-mediated immunosensor allows for an ultrasensitive detection for chlorpyrifos residue (0.022 ng/mL), a 58-fold enhancement compared with that of enzyme-linked immunosorbent assay (1.28 ng/mL), providing a promising platform for detection of trace small molecules.

One major frustration in developing antibiotics is that bacteria can quickly develop resistance that would require an entirely new cycle of research and clinical testing to overcome. Although plenty of bactericidal nanomaterials have been developed against increasingly severe superbugs, few reports have studied the resistance to these nanomaterials. Herein, we show that antibacterial 4,6-diamino-2-pyrimidine thiol (DAPT)-capped gold nanoparticles (AuDAPTs) can induce a 16-fold increased minimum inhibitory concentration (MIC) of E. coli only after very long term exposure (183 days), without developing cross-resistance to commercialized antibiotics. Strikingly, we recovered the bactericidal activities of AuDAPTs to the resistant strain by tuning the sizes of AuDAPTs without employing new chemicals. Such slow, easy-to-handle resistance induced by AuDAPTs is unprecedented compared to traditional antibiotics or other nanomaterials. In addition to the novel antibacterial activities and biocompatibilities, our approach will accelerate the development of gold nanomaterial-based therapeutics against multi-drug-resistant (MDR) bacterial infections.

Many efforts to design and screen therapeutics for the current severe acute respiratory syndrome coronavirus (SARS-CoV-2) pandemic have focused on inhibiting viral host cell entry by disrupting ACE2 binding with the SARS-CoV-2 spike protein. This work focuses on the potential to inhibit SARS-CoV-2 entry through a hypothesized α5β1 integrin-based mechanism, and indicates that inhibiting the spike protein interaction with α5β1 integrin (+/- ACE2), and the interaction between α5β1 integrin and ACE2 using a novel molecule ATN-161 represents a promising approach to treat COVID-19., Graphical abstract, Highlights • SARS-CoV-2 Spike protein binds to α5β1 integrin protein as well as human ACE2 / α5β1, facilitating entry into host cells. • ATN-161, an integrin binding peptide, inhibits the interaction between SARS-CoV-2 Spike protein and its host binding partners, with three sites of binding identified via molecular modeling. • ATN-161 inhibits infection in vitro, as well as demonstrates increases in cell viability when administered prophylactically. • ATN-161 is well-studied, with the potential for more rapid introduction into clinical trials than many other compounds currently undergoing preclinical evaluation.

We have developed an alginate hydrogel-embedded capillary sensor (AHCS) for naked eye-based quantification of immunoassay. Alkaline phosphatase (ALP) can modulate gel-sol transformation to increase the permeability of Cu2+-cross-linked alginate hydrogel film in the AHCS, followed by solution exchange into the capillary. Through measuring the length of the liquid phase of the microfluidics in the capillary at a given time, the concentration of the ALP could be quantified with the naked eye. Since ALP is widely applied as a signal reporter for immunoassays, the AHCS could easily accommodate conventional immune sensing platforms. We justify the practicality of AHCS with hepatitis B virus surface antigen (HBsAg) in serum samples and got comparable results with commercialized immunoassay. This AHCS is easy to make and use, effective in cost, and robust in quantification with the naked eye, showing great promise for next generation point-of-care testing.

The increase in antibiotic resistance reported worldwide poses an immediate threat to human health and highlights the need to find novel approaches to inhibit bacterial growth. In this study, we present a series of gold nanoparticles (Au NPs) capped by different N-heterocyclic molecules (N_Au NPs) which can serve as broad-spectrum antibacterial agents. Neither the Au NPs nor N-heterocyclic molecules were toxic to mammalian cells. These N_Au NPs can attach to the surface of bacteria and destroy the bacterial cell wall to induce cell death. Sonochemistry was used to coat Au NPs on the surface of fabrics, which showed superb antimicrobial activity against multi-drug resistant (MDR) bacteria as well as excellent efficacy in inhibiting bacterial biofilms produced by MDR bacteria. Our study provides a novel strategy for preventing the formation of MDR bacterial biofilms in a straightforward, low-cost, and efficient way, which holds promise for broad clinical applications.

The main challenge of paramagnetic ions-mediated magnetic sensors is their relatively low sensitivity. In this study, we observe the amplification of longitudinal relaxation time (T1) signal when Fe2+ transforms into Fe3+ followed by the coordination of potassium thiocyanate (KSCN) and develop a sensitive Fe-T1 sensor based on the coordination chemistry between KSCN and Fe3+ to amplify the T1 signal for detecting a series of targets, such as hydrogen peroxide, glucose, and antigen/antibody. We justify the practicability of our assay by successfully detecting tetracycline in milk samples and hepatitis C virus in clinical samples with satisfactory accuracy. This KSCN-mediated Fe-T1 sensor not only realizes biochemical analysis and immunoassay with higher sensitivity but also retains many advantages of paramagnetic ions-mediated magnetic sensors (good stability and straightforward operation), which holds great promise for the detection of a range of targets of interest in complex samples.

We develop a convenient, colorimetric assay (Au/PEI) for rapid iodide (I–) determination that can be prepared facilely by mixing commercially available chemicals including tetrachloroauric acid (HAuCl4) and poly(ether imide) (PEI), and the assay can be carried out directly by adding the samples to the assay without any pretreatment and additional procedure. Au/PEI operates on the principle that I– accelerates the formation of Au NPs, which leads to a visible color change from light yellow to red for naked-eye readout with high specificity. We integrate our assay on solid devices including gel hybrids (Au/PEI/GH) and filter paper (Au/PEI paper) to satisfy the demand of point-of-care testing and justify the practicality by detecting I– in lake water that was supplemented with 10, 20, or 40 μM of I–. Au/PEI/GH with the limit of detection of 0.35 μM can satisfy the detection of drinking water based on the guidelines (1.2 μM) set by the Chinese government, and Au/PEI paper can be used even after 1 year of stor...

Conventional magnetic relaxation switching (MRS) sensor suffers from its relatively low sensitivity when it comes to the analysis of trace small molecules in complicated samples. To meet this challenge, we develop a cascade reaction-mediated magnetic relaxation switching (CR-MRS) sensor, based on the assembly of silver nanoparticles (Ag NPs) and magnetic nanoparticles (MNPs) to improve the sensitivity of conventional MRS. The cascade reaction triggered by alkaline phosphatase generates ascorbic acid, which reduces Ag+ to Ag NPs that can assemble the initially dispersed MNPs to form magnetic/silver nanoassemblies, thus modulating the state of MNPs to result in the change of transverse relaxation time. The formed magnetic/silver nanoassemblies can greatly enhance the state change of MNPs (from dispersed to aggregated) and dramatically improve the sensitivity of traditional MRS sensor, which makes this CR-MRS sensor a promising platform for highly sensitive detection of small molecules in complicated samples.

Multiplexed analysis of molecules with different concentrations requires assays with a tunable detection range. A strategy is outlined that uses click chemistry to assemble horseradish peroxidase in a controlled fashion to generate enzyme assemblies as probes for multiplexed bioassays. This controllable assembly of enzymes on detection antibodies allows for lab-on-a-chip immunoassays with a tunable detection range from pg mL-1 to μg mL-1 . Simultaneous, multiplexed bioassays of clinically relevant inflammatory biomarkers in serum are demonstrated in one lab-on-a-chip format, with a limit of detection of 0.47 pg mL-1 for interleukin-6, 2.6 pg mL-1 for procalcitonin, and 40 ng mL-1 for C-reactive protein. This controlled assembly technique provides a multiplexed platform for simultaneous and quantitative analyses of both low-abundance and high-abundance biomarkers with a broad detection range, which holds great promise as a point-of-care platform for biomedical diagnostics.

Conventional magnetic sensors usually employ Fe-based magnetic materials as signal probes. In this work, we find that Cu(II) is also a useful longitudinal relaxation time (T1) signal-based magnetic probe. We adopt bathocuproinedisulfonic acid disodium salt hydrate (BCS) to chelate Cu(I) and form a stable Cu(I)–BCS complex in aqueous solution and find the significant difference in the T1 value of water protons between Cu(II) aqueous solution and Cu(I)–BCS complex aqueous solution. Redox reaction can convert Cu(II) to Cu(I) followed by the complexation of BCS, which results in apparent change of T1 that can serve as magnetic signal readout, which is the basis of this Cu-T1 sensor. Many redox reactions between Cu(II) and Cu(I) allow this Cu-T1 sensor to not only realize “one-step mode” assay such as ascorbic acid, protein, and alkaline phosphatase but also enable “multi-step mode” immunoassay, such as biomacromolecules and small molecules. This Cu-T1 sensor employs Cu ion as signal readout, providing an alte...

We provide a facile and scalable strategy for preparing gold nanoparticles (AuNPs)-based antibacterial coating on a variety of surfaces through electrostatic self-assembly. AuNPs conjugated with 4,6-diamino-2-pyrimidinethiol (DAPT, not antibacterial by itself), AuDAPT, can form stable coating on different substrates made from polyethylene (PS), polyvinyl chloride (PVC), polypropylene (PP), polyethylene (PE), polydimethylsiloxane (PDMS), and SiO2 in one step. Such a coating can efficiently eradicate pathogenic Gram-negative bacteria and even multidrug-resistant (MDR) mutants without causing any side-effect such as cytotoxicity, hemolysis, coagulation, and inflammation. We show that immobilized AuDAPT, instead of AuDAPT released from the substrate, is responsible for killing the bacteria and that the antimicrobial components do not enter into the environment to cause secondary contamination to breed drug resistance. Advantages for such coating include applicability on a broad range of surfaces, low cost, st...

We report an ultrasensitive, quantitative, and rapid bioluminescent immunosensor (ABS) for point-of-care testing (POCT) of the disease biomarker in clinical samples using double enzymes including alkaline phosphatase (ALP) and luciferase. In the presence of the biomarker, the ALP attached on the surface of immuno-nanocomplex dephosphorylates adenine triphosphate (ATP), subsequently inhibiting the ATP-luciferin-luciferase bioluminescent reaction. The highly sensitive response of ATP (picomolar level) allows for ultrasensitive detection of biomarker via the effective change of the bioluminescence intensity through ALP- and luciferase-catalyzed reactions, which can be quantitatively determined by a portable ATP detector. This ABS fulfills the criteria for POCT that performs sensitive (femtomolar level of biomarkers) and quantitative measurement quickly (less than 1 h) with minimal equipment (portable detector).

Conventional transverse relaxation time (T2)-mediated magnetic resonance sensors (MRS) that utilizing the target-induces state change of magnetic nanoparticles (MNPs) mainly suffer from low sensiti...

We develop an ultrasensitive

We describe an ultra-stable, ultra-robust, straightforward and low-cost approach for the colorimetric detection of H2S with nanocrystalline cellulose (NCC) based on the reaction of H2S with lead acetate. The presence of NCC not only mediates the seed growth of a PbS/NCC complex, but also acts as a stabilizer protecting PbS from precipitation. This stable system is so robust that it can be used to quantitatively detect H2S even after two-year storage.

This study reports a simple, rapid, low-cost, robust, and multiplexed barcoded paper-based assay (BPA) compatible with mobile devices. An inkjet printer and an XYZ dispensing platform were used to realize mass-manufacturing of barcoded paper-based analytical devices (BPADs) with high precision and efficiency. We designed a new group of barcodes and developed an application (APP) for the reading of the new code. The new barcodes possess a 16 times higher coding capacity than the standard Codabar code in our experiment on drug residue detection. The BPA system allows applications in the assays of blood-transmitted infections, drug residues in milk and multiplex nucleic acids. The whole detection process and the readout of the results can be completed within 10 minutes. The limit of detection for enrofloxacin (ENR) (8 ng mL−1) satisfies the requirements of drug residue monitoring. Its high rapidity, simplicity, efficiency and selectivity make the BPA system extremely suitable to be applied in rapid and on-site detection.

The main challenge of paramagnetic ions-mediated magnetic sensors is their relatively low sensitivity. In this study, we observe the amplification of longitudinal relaxation time (T

The colorimetric immunoassay based on gold nanoparticles (AuNPs) can hardly enable simultaneous detection of multiple biomarkers in vastly different concentrations (e.g., pg/mL-μg/mL) because of its narrow dynamic range. In this work, we demonstrate an immunoassay with tunable detection range by using peptide-mediated controlled aggregation of surface modification-free AuNPs. Alkaline phosphatase (ALP) removes the phosphate group of the peptide to yield a positively charged product, which triggers the aggregation of negatively charged AuNPs and the color change of the AuNPs solution from red to blue with naked-eye readout. We design and screen 20 kinds of phosphorylated peptides to obtain a broad and controllable detection range for ALP sensing and apply them for detecting multiple inflammatory biomarkers in clinical samples. Our assay realizes straightforward, multiplexed, and simultaneous detection of multiple clinical biomarkers with tunable detection range (from pg/mL to μg/mL) in the same run and holds great potential for chemical/biochemical analysis.

Chemical regulation of enzyme-mimic activity of nanomaterials is challenging because it requires a precise understanding of the surface chemistry and mechanism, and rationally designed applications. Herein, Ag

Conventional magnetic sensors usually employ Fe-based magnetic materials as signal probes. In this work, we find that Cu(II) is also a useful longitudinal relaxation time (T

Current magnetic relaxation switching (MRS) sensors for detection of trace targets in complex samples still suffer from limitations in terms of relatively low sensitivity and poor stability. To meet this challenge, we develop a longitudinal relaxation time (T

We synthesized ionic liquid (1-ethyl-3-methylimidazolium thiocyanate)-coated gold nanoparticles (IL-Au NPs) using a one-pot method and introduced them in the colorimetric assay for Al3+. IL-Au NPs showed good sensitivity and selectivity. They can determine the concentration of aluminum in vermicelli samples.

Stacked paper skiving paves the way for industrial manufacturing of paper-based analytical devices for barcode assays., This paper shows that stacked sheets of paper preincubated with different biological reagents and skiving them into uniform test paper sheets allow mass manufacturing of multiplexed immunoassay devices and simultaneous detection of multiplex targets that can be read out by a barcode scanner. The thickness of one sheet of paper can form the width of a module for the barcode; when stacked, these sheets of paper can form a series of barcodes representing the targets, depending on the color contrast provided by a colored precipitate of an immunoassay. The uniform thickness of sheets of paper allows high-quality signal readout. The manufacturing method allows highly efficient fabrication of the materials and substrates for a straightforward assay of targets that range from drugs of abuse to biomarkers of blood-transmitted infections. In addition, as a novel alternative to the conventional point-of-care testing method, the paper-based barcode assay system can provide highly efficient, accurate, and objective diagnoses.

We developed a competitive colorimetric nanosensor based on Au@Ag bimetallic nanoparticles for the detection of interleukin-6 (IL-6) in clinical samples. Antibody-conjugated magnetic nanoparticles (MNPs) and polystyrene (PS) microparticles conjugated with both catalase and a secondary antibody can form sandwich structures that enable one-step target enrichment and separation. The catalase on the surface of the PS can catalyze the hydrolysis of hydrogen peroxide (H2O2) to regulate the deposition of Ag+ on the surface of gold nanoparticles (AuNPs), and forms different sizes and amounts of Au@Ag bimetallic nanoparticles (Au@AgNPs) which produce a distinct color signal for readout with the naked eye. Our sensor features high sensitivity, selectivity, reproducibility and anti-interference property as a result of comprehensive parameter optimization. The limit of detection of IL-6 can reach 11 pg mL-1 with the naked eye and 1.2 pg mL-1 by quantitative instrumental analysis. The whole analysis can be finished within 1 h. More importantly, we successfully apply our platform or the detection of IL-6 in clinical samples with better accuracy than conventional enzyme-linked immunosorbent assay (ELISA).

We report a method for the rapid and efficient identification of bacteria making use of five probes having fluorescent characteristics (F-array) and subsequent statistical analysis. Eight kinds of bacteria, including normal and multidrug-resistant bacteria, are differentiated successfully. Our easy-to-perform and time-saving method consists of mixing bacteria and probes, recording fluorescent intensity data by automated flow cytometry, and statistical analysis. No washing steps are required in order to identify the different bacteria simultaneously.

Biochemical analysis assays based on colorimetric methods using gold nanoparticles have many advantages such as high sensitivity, good selectivity, naked-eyes readout and complex instruments free. These methods have good prospects in applications. This review mainly focuses on colorimetric assays applying gold nanoparticles for biomolecules detection.

Bacterial infections, especially multidrug-resistant bacterial infections, are an increasingly serious problem in the field of wound healing. Herein, bacterial cellulose (BC) decorated by 4,6-diamino-2-pyrimidinethiol (DAPT)-modified gold nanoparticles (Au-DAPT NPs) is presented as a dressing (BC-Au-DAPT nanocomposites) for treating bacterially infected wounds. BC-Au-DAPT nanocomposites have better efficacy (measured in terms of reduced minimum inhibition concentration) than most of the antibiotics (cefazolin/sulfamethoxazole) against Gram-negative bacteria, while maintaining excellent physicochemical properties including water uptake capability, mechanical strain, and biocompatibility. On Escherichia coli- or Pseudomonas aeruginosa-infected full-thickness skin wounds on rats, the BC-Au-DAPT nanocomposites inhibit bacterial growth and promote wound repair. Thus, the BC-Au-DAPT nanocomposite system is a promising platform for treating superbug-infected wounds.

This report describes a colorimetric assay for trivalent metal cations (M(3+)) using gold nanoparticles (AuNPs)-modified with oppositely charged thiols that can form intermolecular zwitterionic surfaces. Zwitterionic AuNPs (Zw-AuNPs) are stable in high-salt solutions and well-dispersed in a wide range of pH values. M(3+) including Fe(3+), Al(3+), and Cr(3+) can effectively trigger the aggregation of Zw-AuNPs by interfering with their surface potential, and aggregated AuNPs can be regenerated and recycled by removing M(3+). In our approach, the output signal can be observed by the naked eye within a micromolar (μM) concentration range. Uniquely, our assay is capable of discriminating Fe(3+) from Fe(2+), which is challenging using traditional approaches. More importantly, Zw-AuNPs can be stored stably at room temperature for a long period (3 months) with constant detection performance. Both the cost-effectiveness and the long shelf life make Zw-AuNPs ideal for detecting M(3+) in resource-poor and remote areas.

Controlling phosphorylation processes of proteins is a facile way for manipulating cell fates. Herein, a synergistic therapeutic strategy utilizing a near-infrared (NIR)-responsive nanocatalyst (NC) complex is presented, which is comprised of photoactive NC and protein phosphatase 2A (PP2A), to synergistically inhibit hyperphosphorylation of mitogen-activated protein kinase (MAPK) pathway for cancer therapy, as an example of many biological processes this approach can apply to. NIR-triggered release of PP2A specially dephosphorylates and inactivates mitogen-activated protein kinase kinase (MAP2K, also known as MEK) and extracellular regulated protein kinases (ERK) in the MAPK pathway, meanwhile, the NIR-triggered activation of NC decreases the level of intracellular adenosine triphosphate to attenuate protein phosphorylation of MEK and ERK. The synergistic therapeutics effectively suppress melanoma progression by inhibiting hyperphosphorylation of the MAPK pathway. In addition, the nanocatalyst complex reduces the risk of drug-resistance through inhibiting a rebound of RAS-GTP. The NIR-responsive nanocatalyst complex paves a novel way for cancer therapeutics.

Chemical regulation of enzyme-mimic activity of nanomaterials is challenging because it requires a precise understanding of the surface chemistry and mechanism, and rationally designed applications. Herein, Ag+ -gated peroxidase activity is demonstrated by successfully modulating surface chemistry of cetyltrimethylammonium bromide-capped gold nanoparticles (CTAB-AuNPs). A surface blocking effect of long-chain molecules on surfaces of AuNPs that inhibit peroxidase activity of AuNPs is found. Ag+ ions can selectively bind on the surfaces of AuNPs and competitively destroy CTAB membrane forming Ag+ @CTAB-AuNPs complexes to result in enhanced peroxidase activity. Ag+ @CTAB-AuNPs show the highest peroxidase activity compared to similar-sized citrate-capped and ascorbic acid-capped AuNPs. Ag+ @CTAB-AuNPs can potentially develop into analyte-responsive systems and exhibit advantages in the optical sensing field. For example, the Ag+ @CTAB-AuNPs system shows an enhanced sensitivity and selectivity for acetylcholinesterase activity sensing compared to other methods.

The boom of nanotechnology has yielded exciting developments in designing new kinds of colorimetric immunoassays. These nanomaterial-associated immunoassays have shown great potential for clinical translation and a number of them have already been implemented for testing patient samples from the clinics. Different from most reviews where researchers typically focus on a specific type of nanomaterial or describe assays based on the types of materials, we classify these assays by the function of nanomaterials, focusing on reviewing the distinct phenomenon of nanomaterials and how these properties are utilized to overcome limitations faced by traditional colorimetric immunoassays. We also discuss the challenges and give our perspectives in this field.

We report a method for rapid, effective detection of both Cr(iii) and Cr(vi) (in the form of Cr(3+) and Cr2O7(2-), the main species of chromium in the natural environment) by making use of meso-2,3-dimercaptosuccinic acid (DMSA)-functionalized gold nanoparticles (Au NPs). The limit of detection (LOD) is 10 nM with the naked eye and the assay can be applied in detecting chromium in polluted soil from Yun-Nan Province in Southwest China. We use density functional theory to calculate the change of the Gibbs free energy (ΔG) of the interactions between the DMSA-Au NP system and various metal ions, which shows that DMSA-Au NPs have high specificity for both Cr(3+) and Cr2O7(2-).

Accurate wind power forecasting is significant for safe dispatching and stable operation of power system. In this paper, based on the wind speed distribution characteristics in wind farm, a novel approach for wind power real-time forecasting is proposed. Firstly, the space distribution characteristics of wind speed were analysed greatly. Then, WTGs (Wind Turbine Group) were divided into several groups with grouping model method based on SCCF (Sample Cross Correlation Function, SCCF), and the turbines of approximately identically-distributed were divided into the same group. Finally, the direct multi-step forecasting of grouped wind power was carried out with radial basis function neural network, then the whole power of wind farm was obtained by superposition. The simulation results for real data of wind farm at two typical areas in China, coastal areas and North China, show that the prediction accuracy is improved and the prediction computation is significantly reduced with the presented