Abstract Since the end of 2019, a highly contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has deprived numerous lives worldwide, called COVID-19. Up to date, omicron is the latest variant of concern, and BA.5 is replacing the BA.2 variant to become the main subtype rampaging worldwide. These subtypes harbor an L452R mutation, which increases their transmissibility among vaccinated people. Current methods for identifying SARS-CoV-2 variants are mainly based on polymerase chain reaction (PCR) followed by gene sequencing, making time-consuming processes and expensive instrumentation indispensable. In this study, we developed a rapid and ultrasensitive electrochemical biosensor to achieve the goals of high sensitivity, the ability of distinguishing the variants, and the direct detection of RNAs from viruses simultaneously. We used electrodes made of MXene-AuNP (gold nanoparticle) composites for improved sensitivity and the CRISPR/Cas13a system for high specificity in detecting the single-base L452R mutation in RNAs and clinical samples. Our biosensor will be an excellent supplement to the RT-qPCR method enabling the early diagnosis and quick distinguishment of SARS-CoV-2 Omicron BA.5 and BA.2 variants and more potential variants that might arise in the future. 

CRISPR-Cas13a-powered electrochemical biosensor for the detection of the L452R mutation in clinical samples of SARS-CoV-2 variants

Gene therapy provides a promising approach in treating cancers with high efficacy and selectivity and few adverse effects. Currently, the development of functional vectors with safety and effectiveness is the intense focus for improving the delivery of nucleic acid drugs for gene therapy. For this purpose, stimuli-responsive nanocarriers displayed strong potential in improving the overall efficiencies of gene therapy and reducing adverse effects via effective protection, prolonged blood circulation, specific tumor accumulation, and controlled release profile of nucleic acid drugs. Besides, synergistic therapy could be achieved when combined with other therapeutic regimens. This review summarizes recent advances in various stimuli-responsive nanocarriers for gene delivery. Particularly, the nanocarriers responding to endogenous stimuli including pH, reactive oxygen species, glutathione, and enzyme, etc., and exogenous stimuli including light, thermo, ultrasound, magnetic field, etc., are introduced. Finally, the future challenges and prospects of stimuli-responsive gene delivery nanocarriers toward potential clinical translation are well discussed. The major objective of this review is to present the biomedical potential of stimuli-responsive gene delivery nanocarriers for cancer therapy and provide guidance for developing novel nanoplatforms that are clinically applicable. 

/pdf/stimuli-responsive-gene-delivery-nanocarriers-for-cancer-3dv2kdv0.pdf

Stimuli-Responsive Gene Delivery Nanocarriers for Cancer Therapy

In the past few decades, 2D layer materials have gradually become a central focus in materials science owing to their uniquely layered structural qualities and good optoelectronic properties. However, in the development of 2D materials, several disadvantages, such as limited types of materials and the inability to synthesize large‐scale materials, severely confine their application. Therefore, further exploration of new materials and preparation methods is necessary to meet technological developmental needs. Organic molecular materials have the advantage of being customizable. Therefore, if organic molecular and 2D materials are combined, the resulting 2D organic materials would have excellent optical and electrical properties. In addition, through this combination, the free design and large‐scale synthesis of 2D materials can be realized in principle. Furthermore, 2D organic materials exhibit excellent properties and unique functionalities along with great potential for developing sensors, biomedicine, and electronics. In this review, 2D organic materials are divided into five categories. The preparation methods and material properties of each class of materials are also described in detail. Notably, to comprehensively understand each material's advantages, the latest research applications for each material are presented in detail and summarized. Finally, the future development and application prospects of 2D organic materials are briefly discussed.

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/advs.202203889

2D Organic Materials: Status and Challenges

Infectious pathogens cause severe human illnesses and great deaths per year worldwide. Rapid, sensitive, and accurate detection of pathogens is of great importance for preventing infectious diseases caused by pathogens and optimizing medical healthcare systems. Inspired by a microbial defense system (i.e., CRISPR/ CRISPR-associated proteins (Cas) system, an adaptive immune system for protecting microorganisms from being attacked by invading species), a great many new biosensors have been successfully developed and widely applied in the detection of infectious viruses and pathogenic bacteria. Moreover, advanced nanotechnologies have also been integrated into these biosensors to improve their detection stability, sensitivity, and accuracy. In this review, the recent advance in CRISPR/Cas systems-based nano/biosensors and their applications in the detection of infectious viruses and pathogenic bacteria are comprehensively reviewed. First of all, the categories and working principles of CRISPR/Cas systems for establishing the nano/biosensors are simply introduced. Then, the design and construction of CRISPR/Cas systems-based nano/biosensors are comprehensively discussed. In the end, attentions are focused on the applications of CRISPR/Cas systems-based nano/biosensors in the detection of infectious viruses and pathogenic bacteria. Impressively, the remaining opportunities and challenges for the further design and development of CRISPR/Cas system-based nano/biosensors and their promising applications are proposed. 

CRISPR/Cas Systems‐Inspired Nano/Biosensors for Detecting Infectious Viruses and Pathogenic Bacteria

Abstract Early lung cancer screening by computed tomography is hampered by pulmonary nodules caused by massive COVID‐19 infections, necessitating an ultrasensitive approach for the early diagnosis of lung cancers at the single‐base level from circular tumor DNAs (ctDNAs). This study introduces an approach that merges DNA origami and DNA scissors technologies in a framework of surface plasmon resonance (SPR) biosensors. By combining the precision of DNA origami probes with the inherent single‐base resolution of DNA scissors, this method systematically addresses the limitations of conventional SPR techniques, resulting in enhanced detection accuracy. The synergistic interplay between DNA scissors and DNA origami enables the SPR biosensors to achieve unprecedented levels of sensitivity, precision, and practical utility. This efficacy allows the precise identification of mutations, demonstrated here by detection of the T790M mutation in the EGFR gene and the G12C mutation in the KRAS gene of non‐small cell lung cancer patients. With this technique, single‐base resolution as well as near zeptomolar‐level sensitivity is achieved. As a result, this discovery holds significant potential to advance the field of precision diagnostics. 

Ultrasensitive DNA Origami Plasmon Sensor for Accurate Detection in Circulating Tumor DNAs

As stretchable conductive materials, ionogels have gained increasing attention. However, it still remains crucial to integrate multiple functions including mechanically robust, room temperature self-healing capacity, facile processing, and recyclability into an ionogel-based device with high potential for applications such as soft robots, electronic skins, and wearable electronics. Herein, inspired by the structure of spider silk, a multilevel hydrogen bonding strategy to effectively produce multi-functional ionogels is proposed with a combination of the desirable properties. The ionogels are synthesized based on N-isopropylacrylamide (NIPAM), N, N-dimethylacrylamide (DMA), and ionic liquids (ILs) 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([EMI][TFSI]). The synergistic hydrogen bonding interactions between PNIPAM chains, PDMA chains, and ILs endow the ionogels with improved mechanical strength along with fast self-healing ability at ambient conditions. Furthermore, the synthesized ionogels show great capability for the continuous fabrication of the ionogel-based fibers using the melt-spinning process. The ionogel fibers exhibit spider-silk-like features with hysteresis behavior, indicating their excellent energy dissipation performance. Moreover, an interwoven network of ionogel fibers with strain and thermal sensing performance can accurately sense the location of objects. In addition, the ionogels show great recyclability and processability into different shapes using 3D printing. This work provides a new strategy to design superior ionogels for diverse applications.

Spider-Silk-Inspired Tough, Self-Healing, and Melt-Spinnable Ionogels.

Fibers, with over 100 million tons produced each year, have been widely used in various areas. Recent efforts have focused on improving mechanical properties and chemical resistance of fibers via covalent cross-linking. However, the covalently cross-linked polymers are usually insoluble and infusible, and thus fiber fabrication is difficult. Those reported require complex multiple-step preparation processes. Herein, we present a facile and effective strategy to prepare adaptable covalently cross-linked fibers by direct melt spinning of covalent adaptable networks (CANs). At processing temperature, dynamic covalent bonds are reversibly dissociated/associated and the CANs are temporarily disconnected to enable melt spinning; at the service temperature, the dynamic covalent bonds are frozen, and the CANs exhibit favorable structural stability. We demonstrate the efficiency of this strategy via dynamic oxime-urethane based CANs, and successfully prepare adaptable covalently cross-linked fibers with robust mechanical properties (maximum elongation of 2639%, tensile strength of 87.68 MPa, almost complete recovery from an elongation of 800%) and solvent resistance. Application of this technology is demonstrated by an organic solvent resistant and stretchable conductive fiber. 

/pdf/adaptable-covalently-cross-linked-fibers-2vt4jmrt.pdf

Adaptable covalently cross-linked fibers

Respiratory viruses have long been a major cause of a global pandemic, emphasizing the urgent need for high-sensitivity diagnostic tools. Typical PCR technology can only determine the type of virus in the sample, which is unable to detect different variants of the same virus without costly and time-consuming gene sequencing. Here, we introduce a simple, fully enclosed, and highly integrated microfluidic system based on CRISPR/Cas12a and isothermal amplification techniques (LOC-CRISPR) that can specifically identify multiple common respiratory viruses and their variants. The LOC-CRISPR chip integrates viral nucleic acid extraction, recombinant polymerase amplification, and CRISPR/Cas12a cleavage reaction-based detection, contamination-free detection. In addition, the LOC-CRISPR chip was designed for multiplexed detection (two-sample input and ten-result outputs), which can not only detect the presence of SARS-CoV-2, H1N1, H3N2, IVB and HRSV but also differentiate the BA.1, BA.2, and BA.5 variants of SARS-COV-2. For clinical validation, the LOC-CRISPR chip was used to analyze 50 nasopharyngeal swab samples (44 positive and 6 negative) and achieved excellent sensitivity (97.8%) and specificity (100%). This innovative LOC-CRISPR system has the ability to quickly, sensitively, and accurately detect multiple target nucleic acid sequences with single-base mutations, which will further improve the rapid identification and traceability of respiratory viruses infectious diseases.

CRISPR/Cas12a-Assisted isothermal amplification for rapid and specific diagnosis of respiratory virus on an microfluidic platform.

Stretchable conductive fibers play key roles in electronic textiles, which have substantial improvements in terms of flexibility, breathability, and comfort. Compared to most existing electron-conductive fibers, ion-conductive fibers are usually soft, stretchable, and transparent, leading to increasing attention. However, the integration of desirable functions including high transparency, stretchability, conductivity, solvent resistance, self-healing ability, processability, and recyclability remains a challenge to be addressed. In the current research, we proposed a new molecular strategy based on dynamic covalent cross-linking networks to enable continuous melt spinning of the ionogel fiber with the aforementioned properties. As a proof of concept, covalently cross-linked ionogel fibers based on dimethylglyoximeurethane (DOU) groups (DOU-IG fiber) were prepared. The resultant DOU-IG fiber exhibited high transparency (> 93%), tensile strength (0.76 MPa), stretchability (784%), and solvent resistance. Owing to the dynamic of DOU groups, the DOU-IG fiber showed high healing performance using near-infrared light. Taking advantage of DOU-IG fibers, multifunctional ionotronics with the integration of several desirable functionalities including sensor, triboelectric nanogenerator, and electroluminescent display were fabricated and used for motion monitoring, energy harvesting, and human-machine interaction. It is believed that these DOU-IG fibers are promising for fabricating the next generation of electronic textiles and other wearable electronics. This article is protected by copyright. All rights reserved.

Continuous Melt Spinning of Covalently Cross-Linked Self-Healing Ionogel Fibers for Multi-Functional Ionotronics.

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