How variable progenitor clones construct a largely invariant neocortex.

The neocortex contains a vast collection of diverse neurons organized into distinct layers. While nearly all neocortical neurons are generated by radial glial progenitors (RGPs), it remains largely unclear how a complex yet organized neocortex is constructed reliably and robustly. Here, we show that the division behavior and neuronal output of RGPs are highly constrained with patterned variabilities to support the reliable and robust construction of the mouse neocortex. The neurogenic process of RGPs can be well-approximated by a consistent Poisson-like process unfolding over time, producing deep to superficial layer neurons progressively. The exact neuronal outputs regarding layer occupation are variable; yet, this variability is constrained systematically to support all layer formation, largely reflecting the variable intermediate progenitor generation and RGP neurogenic entry and exit timing differences. Together, these results define the fundamental features of neocortical neurogenesis with a balanced reliability and variability for the construction of the complex neocortex.

Enhanced sensitivity and accuracy via gold nanoparticles based multi-line lateral flow immunoassay strip for Salmonella typhimurium detection in milk and orange juice.

Food borne pathogens threaten food safety and affect human health. The lateral flow immunoassays (LFIAs) are widely concerned because of simplicity, low cost and user friendliness, and have broad application prospects in pathogen detection. However, the sensitivity of LFIAs is limited. Herein, multi-line LFIAs are introduced into pathogen detection for the first time. Compared with traditional single-line LFIAs, the overall signal strength of multi-line LFIAs has been significantly improved. It is particularly noteworthy that multi-line LFIAs detection accuracy of 103 CFU/mL pathogen has been improved by about 55%. The proposed multi-line LFIAs reduce the possibility of judging a positive result as a false negative result. The LFIAs strip was validated in real samples of milk and orange juice. This strategy has great potential for rapid detection of pathogens in real samples, and provides new insights for improving the accuracy and sensitivity of LFIAs strips.

High extinction coefficient material combined with multi-line lateral flow immunoassay strip for ultrasensitive detection of bacteria.

Lateral flow immunoassay strips (LFIAs) are a reliable and point-of-care detection method for rapid monitoring of bacteria, but their sensitivity was limited by the low extinction coefficient of colloidal gold nanoparticles (Au NPs) and low capture efficiency of test-line. In this study, polydopamine nanoparticles (PDA NPs) were employed to replace Au NPs, due to their high extinction coefficient. And the amount of test-line was increased to 5 for further improving the efficiency of bacteria capture. Thus, under visual observation, the detection limits of PDA-based LFIAs (102 CFU/mL) were about 2 orders of magnitude lower than Au-based LFIAs (104 CFU/mL). Furthermore, the invisible signal could be collected by Image J and the detection limit can reach 10 CFU/mL. The proposed test strips were successfully applied for the quantitative, accurate, and rapid screening of E. coli in food samples. This study provided a universal approach to enhance the sensitivity of bacteria LFIAs.

Ultrasensitive visual detection of the food-borne pathogen via MOF encapsulated enzyme.

Various methods have been made to achieve sensitive detection (10 CFU/mL) of Escherichia coli O157:H7 (E. coli) in real samples, however, they are complex, time-consuming, or instrument-dependent. Enzyme-catalyzed reactions are one of the most efficient methods to amplify signals for sensitive detection. ZIF-8 owning stability, porosity, and high specific area are suitable for embedding enzymes which can effectively protect enzyme activity and thus improve detection sensitivity. Herein, a simple visual assay of E. coli with the limits of detection of 1 CFU/mL was developed based on this stable enzyme-catalyzed amplified system. A microbial safety test of milk, orange juice, seawater, cosmetic, and hydrolyzed yeast protein, was successfully performed with the limits of detection of 10 CFU/mL by the naked eye. And this bioassay possessed high selectivity and stability making the developed detection method practically promising.

Seed-mediated strategy for synthesis of enzyme-encapsulated metal-organic frameworks with enhanced enzyme activity.

Encapsulation of enzymes into metal-organic frameworks (enzyme@MOF) can improve the stability of enzymes. Most present synthesis methods of enzyme@MOF rely on the complex modification of enzymes or the natural negative surface charge of enzymes to promote the synthesis of enzyme@MOF. Despite extensive efforts, it remains challenging to develop a surface charge-independent and convenient strategy to encapsulate various enzymes into MOF efficiently. In this study, we proposed a convenient seed-mediated strategy for efficient synthesis of enzyme@MOF from the perspective of MOF formation. The seed, acting as nuclei, makes the slow nucleation stage skipped, leading to the efficient synthesis of enzyme@MOF. The successful encapsulation of several proteins demonstrated the feasibility and advantages of the seed-mediated strategy. Moreover, the resulting composite, cytochrome (Cyt c) encapsulated in ZIF-8, exhibited a 5.6-fold increase in bioactivity compared to free Cyt c. The seed-mediated strategy provides an efficient, enzyme surface charge-independent, and non-modified method for the synthesis of enzyme@MOF biomaterials, which warrants further exploration and application in diverse fields.

Highly stretchable composites based on cellulose.

Cellulose is a kind of natural polymer with good biocompatibility, biodegradability, non-toxicity, low cost and other advantages, which has been widely used in many fields, such as energy, biological scaffolds, medicine, paper making, cosmetics, and template materials. Based on this, how to use cellulose to construct stretchable composites to meet the needs of different fields has attracted widespread attention. In this review, we have described the applications of cellulose-based stretchable composites, including sensor applications, energy applications, bionic and medical materials applications, fabric applications, and packaging applications. Finally, the future development of stretchable composites based on cellulose is discussed.

Immunoassay for foodborne pathogenic bacteria using magnetic composites Ab@Fe3O4, signal composites Ap@PtNp, and thermometer readings.

A point-of-care (POC) immunoassay was established for the sensitive and rapid detection of pathogenic Escherichia coli O157:H7, using magnetic Fe3O4 organic-inorganic composites (Ab@Fe3O4) for immunomagnetic separation, nanozyme platinum nanoparticle (PtNp) organic-inorganic composites (Ap@PtNp) for signal amplification, and thermometer readings. Antibodies and Fe3O4 were incubated in Cu2+ phosphate buffer to synthesize the magnetic composite Ab@Fe3O4 with antibodies, to specifically capture E. coli O157:H7. Antimicrobial peptides and PtNp were incubated in Cu2+ phosphate buffer to synthesize the signal composites Ap@PtNp with antimicrobial peptides (magainin I), recognizing and labeling E. coli O157:H7. In the presence of E. coli O157:H7, magnetic microcomposites targeted bacteria and signal microcomposites to form the sandwich structure: Ab@Fe3O4-bacteria-Ap@PtNp for magnetic separation. Ap@PtNp of signal composites catalyzed H2O2 to generate thermo-signals (temperature rise), which were determined by a thermometer. This point-of-care bioassay detected E. coli O157:H7 in the linear range of 101-107 CFU mL-1 and with a detection limit of 14 CFU mL-1. One-pot process magnetic Fe3O4 organic-inorganic composites (Ab@Fe3O4, magnetic microcomposites, MMC) for immunomagnetic separation and nanozyme platinum nanoparticle (PtNp) organic-inorganic composites (Ap@PtNp, signal microcomposites, SMC) were used as signal amplification and thermometer readings for E. coli O157:H7 detection.

Ferrocene-functionalized nanocomposites as signal amplification probes for electrochemical immunoassay of Salmonella typhimurium.

An electrochemical immunosensor based on ferrocene (Fc)-functionalized nanocomposites was fabricated as an efficient electroactive signal probe to amplify electrochemical signals for Salmonella typhimurium detection. The electrochemical signal amplification probe was constructed by encapsulating ferrocene into S. typhimurium-specific antimicrobial peptides Magainin I (MI)-Cu3(PO4)2 organic-inorganic nanocomposites (Fc@MI) through a one-step process. Magnetic beads (MBs) coupled with antibody were used as capture ingredient for target magnetic separation, and Fc@MI nanoparticles were used as signal labels in the immunoassays. The sandwich of MBs-target-Fc@MI assay was performed using a screen-printed carbon electrode as transducer surface. The immunosensor platform presents a low limit of detection (LOD) of 3 CFU·mL-1 and a linear range from 10 to 107 CFU·mL-1, with good specificity and precision, and was successfully applied for S. typhimurium detection in milk. Graphical abstract One-pot process antimicrobial peptides Magainin I-Cu3(PO4)2 organic-inorganic nanocomposites (Fc@MI) were used as ideal electrochemical signal label, integrating both essential functions of biological recognition and signal amplification. Screen-printed carbon electrode (SPCE) was used as the electrochemical system for Salmonella typhimurium detection.

An electrochemical biosensor based on methylene blue-loaded nanocomposites as signal-amplifying tags to detect pathogenic bacteria.

A sandwich-type electrochemical biosensor was successfully constructed for the sensitive detection of pathogenic bacteria. In this biosensor platform, methylene blue (MB) organic-inorganic nanocomposites (MB@MI) were synthesized from magainin I (MI, antimicrobial peptide specific to Escherichia coli O157:H7), Cu3(PO4)2 and MB via a one-pot method, and were explored as a novel electrochemical signal label of biosensors generating amplified electrochemical signals by differential pulse voltammetry (DPV). E. coli O157:H7 specifically sandwich bound to the aptamers on the electrode surface and MB@MI nanocomposites, and the changes in the current signal generated on the electrode surface were used for the quantitative determination of E. coli O157:H7. Under optimum conditions, the proposed biosensor showed excellent performance with a wide linear range of 102-107 CFU mL-1 and a low detection limit of 32 CFU mL-1, featuring favorable selectivity, repeatability and stability. According to the experiments conducted on real samples, the proposed approach is capable of detecting pathogenic bacteria in clinical diagnostics.

Advances in Portable Visual Detection of Pathogenic Bacteria.

Food safety and regulation of consumer welfare are of great concern, so it is necessary to be able to detect pathogenic bacteria quickly and effectively. Although traditional methods of pathogen detection are reliable and widely used, the detection and analysis processes are cumbersome and time-consuming, which is not conducive to fast assays in the field. New detection strategies have emerged in recent years, especially point-of-care testing (POCT) methods, which do not rely on the laboratory and have become an important development direction for pathogen detection. Many visual detection schemes have been developed that integrate portable glucose meters (PGMs), test strips, smartphones, and other portable devices. Importantly, portable and ultrasensitive biosensors have vast promise in detecting pathogens, as they can be suitable tools for clinical diagnosis and the regulation of food safety. This Review focuses on the latest advances in portable device-based methods for visual detection of pathogens, evaluating their advantages and disadvantages.

Immunoassay for pathogenic bacteria using platinum nanoparticles and a hand-held hydrogen detector as transducer. Application to the detection of Escherichia coli O157:H7.

An innovative approach is presented for portable and sensitive detection of pathogenic bacteria. A novel synthetic hybrid nanocomposite encapsulating platinum nanoparticles, as a highly efficient catalyst, catalyzes the hydrolysis of the ammonia-borane complex to generate hydrogen gas. The nanocomposites are used as a label for immunoassays. A portable hand-held hydrogen detector combined with nanocomposite-induced signal conversion was applied for point-of-care testing of pathogenic bacteria. A hand-held hydrogen detector was used as the transducer. Escherichia coli O157:H7 (E. coli O157: H7), as detection target, formed a sandwich structure with magnetic beads and hybrid nanocomposites. Magnetic beads were used for separation of the sandwich structure, and hybrid nanocomposites as catalysts to catalyze the generation of hydrogen from ammonia-borane. The generated hydrogen was detected by a hydrogen detector using an electrochemical method. E. coli O157:H7 has a detection limit of 10 CFU·mL-1. The immunosensor made the hand-held hydrogen detector a point-of-care meter to be used outdoors for the detection and quantification of targets beyond hydrogen. Graphical abstract Schematic presentation of one-pot synthetic peptide-Cu3(PO4)2 hybrid nanocomposites embedded PtNPs (PPNs), encapsulating many Pt particles. The PPNs acts as an ideal immunoprobe for hand-held H2 detector signal readouts, by transforming pathogenic bacteria recognition events into H2 signals.

Disposable syringe-based visual immunotest for pathogenic bacteria based on the catalase mimicking activity of platinum nanoparticle-concanavalin A hybrid nanoflowers.

Disposable syringes were used in a novel point-of-care visual test for detecting pathogenic bacteria (Escherichia coli O157:H7 and Salmonella typhimurium). Hybrid nanoflowers composed of platinum nanoparticles and concanavalin A (Pt-nanoflowers) were prepared through a one-pot reaction and were found to be viable catalase mimics. They catalyze the decomposition of hydrogen peroxide (H2O2) to generate O2. When used as labels in immunoassays, they integrate both the functions of biological recognition and signal amplification. The disposable syringe pressure readout was combined with Pt-nanoflower signal conversion and successfully applied to a visual bacteria detection scheme. Both Escherichia coli O157:H7 and Salmonella typhimurium can be quantified with detection limits of as low as 15 and 7 CFU·mL-1, respectively. Graphical abstract One-pot synthetic platinum nanoparticle (PtNP)-concanavalin A hybrid nanoflowers (Pt-nanoflowers), have been used as ideal signal labels for immunoassays and integrating both essential functions of biological recognition and signal amplification. Disposable syringes were used as a readout to detect pathogenic bacteria.

Hemin-incorporated nanoflowers as enzyme mimics for colorimetric detection of foodborne pathogenic bacteria.

Rapid, sensitive and point-of-care detection of foodborne pathogenic bacteria is essential for food safety. In this study, we found that hemin-concanavalin A hybrid nanoflowers (HCH nanoflowers), as solid mimic peroxidase, could catalyze oxidation of 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) diammonium salt (ABTS) in the presence of H2O2 to a green-colored product. HCH nanoflowers, integrating the essential functions of both biological recognition and signal amplification, meet the requirements of signal labels for colorimetric immunoassay of bacteria. In view of the excellent peroxidase mimetic catalytic activity of HCH nanoflowers, a colorimetric biosensing platform was newly constructed and applied for sensitive detection of foodborne Escherichia coli O157:H7 (E. coli O157:H7). The corresponding detection limits was as low as 4.1 CFU/mL with wide linear ranges (101-106 CFU/mL).

Correction to: A pregnancy test strip for detection of pathogenic bacteria by using concanavalin A-human chorionic gonadotropin-Cu3(PO4)2 hybrid nanoflowers, magnetic separation, and smartphone readout.

The published version of this article, unfortunately, contained error. The authors are re-writing to express their sincere apology for a mistake that a mark "10-5, 10-4, 10-3, 10-2, 10-1 CFU•mL-1" in the legend of Fig. 2 was not corrected as "105, 104, 103, 102, 101 CFU•mL-1".

A pregnancy test strip for detection of pathogenic bacteria by using concanavalin A-human chorionic gonadotropin-Cu3(PO4)2 hybrid nanoflowers, magnetic separation, and smartphone readout.

Pregnancy test strips are widely used in daily life. A commercial pregnancy test strip was modified to obtain a point-of-care device for the detection of pathogenic bacteria. Hybrid nanoflowers were prepared from concanavalin A, human chorionic gonadotropin, and Cu3(PO4)2 via a one-pot method. They were used as signaling probes in an off-the-shelf pregnancy test strip. This modified lateral flow immunoassay can detect Escherichia coli O157:H7 with a detection limit of 4 CFU·mL-1, and Salmonella typhimurium with a detection limit of 3 CFU·mL-1. Conceivably, the method has high potential as a portable and cost-effective tool for rapid determination of a wide range of analytes, especially in resource-constrained settings. Graphical abstract Hybrid nanoflower loaded human chorionic gonadotropin (hCG) and concanavalin A (hCG - nanoflowers) were synthesized via a one-pot method and used as signal labels with commercial commercial-off-the-shelf pregnancy test strips to detect pathogenic bacteria targets, thus yielding an easily smartphone readout signal.

Colorimetric detection of microRNA based on DNAzyme and nuclease-assisted catalytic hairpin assembly signal amplification.

Accurate and quantitative analysis of microRNA (miRNA) expression is critical for the diagnostics and theranostics of a disease. Herein, a proof-of-concept of a colorimetric horseradish peroxidase-mimicking DNAzyme (HRP-DNAzyme) biosensor for miRNA assay based on nuclease-assisted catalytic hairpin assembly (CHA) signal amplification was demonstrated. Duplex-specific nuclease (DSN) was employed to cleave the single-stranded DNA (ssDNA) chimeric probe (CP) on the magnetic bead (MB) surface via hybridization of the CP and target miRNA. The regenerated miRNA can cleave a large number of ssDNA CP to produce CHA initiator sequence fragments. The CP consists of two main regions: a target miRNA recognition DNA sequence at the 5' end and a CHA initiator (CI) sequence at the 3' end. The catalyzed assembly process of CHA produces a large amount of G-rich DNA. In the presence of hemin, the G-rich DNA forms G-quadruplex/hemin complex and mimics the horseradish peroxidase activity, which catalyzes a colorimetric reaction. For the proof-of-concept, microRNA-21 (miR-21) was selected as the model target to authenticate this strategy as a versatile assay platform. The proposed strategy allowed quantitation of the sequence specificity of miRNA-21 with a detection limit of 9.2 fM in a dynamic range from 10 fM-1 nM, with an excellent ability to discriminate the differences in miRNAs. Additionally, the miRNA assay in real samples was satisfactory, thereby confirming its applicability. Therefore, this method exhibited a great potential as a miRNA quantification method in biomedical research and clinical diagnosis.