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Comprehensive Summary: Electrochemical sensing faces huge challenges in characterizing the transient release of biochemical molecules from deformed cells, due to the severely mechanical mismatch between rigid electrodes and soft cells. In recent years, the emergence of stretchable electrochemical sensors has made a breakthrough by complying with the deformation of living cells and simultaneous monitoring of mechanically evoked biochemical signals. This review first summarizes two fundamental strategies for the fabrication of stretchable electrodes from the points of structure and material. Next, recent progresses in construction of functionalized interface to improve the performance of stretchable electrochemical sensors are presented. Then, the application of stretchable electrochemical sensors in real‐time monitoring of biomolecules released by mechanically sensitive cells is introduced. Finally, some perspectives and challenges of stretchable electrochemical sensors regarding cell detection are discussed. What is the favorite and original chemistry developed in your research group? The design and construction of electrochemical sensing platform for real‐time monitoring of life activities. What is the most important personality for scientific research? Innovative spirit, strong curiosity and persistence. How do you supervise your students? Encourage students to think much and eager to innovate. What are your hobbies? I like music and playing badminton. Who influences you mostly in your life? My family and collaborators. Could you please give us some advices on improving Chinese Journal of Chemistry? Focusing on the originality of the manuscript. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: In vivo monitoring of bioelectrical and biochemical signals with implanted electrodes has received great interest over the past decades. However, this faces huge challenges because of the severe mechanical mismatch between conventional rigid electrodes and soft biological tissues. In recent years, the emergence of flexible and stretchable electrodes offers seamless and conformable biological‐electronic interfaces and has demonstrated significant advantages for in vivo electrochemical and electrophysiological monitoring. This review first summarizes the strategies for electrode fabrication from the point of substrate and conductive materials. Next, recent progress in electrode functionalization for improved performance is presented. Then, the advances of flexible and stretchable electrodes in exploring bioelectrical and biochemical signals are introduced. Finally, we present some challenges and perspectives ranging from electrode fabrication to application. Key Scientists: In 2001, a seminal work by Kipke et al. first showed flexible polyimide‐based intracortical electrode arrays.[1] This electrode was further expanded to 252‐channel using microelectromechanical systems technology by Stieglitz et al. in 2009 and achieved large‐scale cortical recordings.[2] Later, Lieber et al. created mesh electronics that allow for seamless and minimally invasive three‐dimensional interpenetration with nerve tissues, opening up unique applications for flexible electronics.[3] Subsequently, Rogers et al. described bioresorbable electronics for transient electrical activity recordings in 2016.[4] And Frank et al. proposed polymer electrode arrays capable of resolving single neurons in 2019.[5] It wasn't until 2020 that a significant breakthrough in biochemical signals monitoring by Peng et al. demonstrated functionalized carbon nanotube fibre bundles for multiple disease biomarkers monitoring.[6] Later on, Mooney et al. established the first fully viscoelastic electrode arrays for neural recordings from the brain and heart in 2021.[7] Recently, Bao et al. presented tissue‐mimicking, stretchable neurotransmitter interfaces for monitoring the brain and gut.[8] [ABSTRACT FROM AUTHOR]

The indexing Sub-Vector Distance (iSYD) based feature matching algorithm has good search accuracy and efficiency in feature matching of high dimensional vector, but the computational complexity of this algorithm is still high and it is limited in practical applications. Aiming at this problem, we introduce a key dimension selection method to improve the iSYD based feature matching algorithm. This method first divides the feature vector into several sub vectors, and selects some sub vectors to replace the original ones; then we create the index value for the feature vector, and search the nearest neighbor point according to the index value. This method can effectively differentiate the vectors with smaller similarity, and it can further reduce the search scope of the nearest neighbor. Experimental results show that the improved iSVD based feature matching algorithm has good search accuracy, and meanwhile improves the matching accuracy and shortens the time of matching, thus having a good practicability. [ABSTRACT FROM AUTHOR]

Exocytosis involving the fusion of intracellular vesicles with cell membrane, is thought to be modulated by the mechanical cues in the microenvironment. Single‐cell electrochemistry can offer unique information about the quantification and kinetics of exocytotic events; however, the effects of mechanical force on vesicular release have been poorly explored. Herein, we developed a stretchable microelectrode with excellent electrochemical stability under mechanical deformation by microfabrication of functionalized poly(3,4‐ethylenedioxythiophene) conductive ink, which achieved real‐time quantitation of strain‐induced vesicular exocytosis from a single cell for the first time. We found that mechanical strain could cause calcium influx via the activation of Piezo1 channels in chromaffin cell, initiating the vesicular exocytosis process. Interestingly, mechanical strain increases the amount of catecholamines released by accelerating the opening and prolonging the closing of fusion pore during exocytosis. This work is expected to provide revealing insights into the regulatory effects of mechanical stimuli on vesicular exocytosis. [ABSTRACT FROM AUTHOR]

Exocytosis involving the fusion of intracellular vesicles with cell membrane, is thought to be modulated by the mechanical cues in the microenvironment. Single‐cell electrochemistry can offer unique information about the quantification and kinetics of exocytotic events; however, the effects of mechanical force on vesicular release have been poorly explored. Herein, we developed a stretchable microelectrode with excellent electrochemical stability under mechanical deformation by microfabrication of functionalized poly(3,4‐ethylenedioxythiophene) conductive ink, which achieved real‐time quantitation of strain‐induced vesicular exocytosis from a single cell for the first time. We found that mechanical strain could cause calcium influx via the activation of Piezo1 channels in chromaffin cell, initiating the vesicular exocytosis process. Interestingly, mechanical strain increases the amount of catecholamines released by accelerating the opening and prolonging the closing of fusion pore during exocytosis. This work is expected to provide revealing insights into the regulatory effects of mechanical stimuli on vesicular exocytosis. [ABSTRACT FROM AUTHOR]

In the field of three‐dimensional (3D) cell culture and tissue engineering, great advance focusing on functionalized materials and desirable culture systems has been made to mimic the natural environment of cells in vivo. Mechanical loading is one of the critical factors that affect cell/tissue behaviors and metabolic activities, but the reported models or detection methods offer little direct and real‐time information about mechanically induced cell responses. Herein, for the first time, a stretchable and multifunctional platform integrating 3D cell culture, mechanical loading, and electrochemical sensing is developed by immobilization of biomimetic peptide linked gold nanotubes on porous and elastic polydimethylsiloxane. The 3D scaffold demonstrates very good compatibility, excellent stretchability, and stable electrochemical sensing performance. This allows mimicking the articular cartilage and investigating its mechanotransduction by 3D culture, mechanical stretching of chondrocytes, and synchronously real‐time monitoring of stretch‐induced signaling molecules. The results disclose a previously unclear mechanotransduction pathway in chondrocytes that mechanical loading can rapidly activate nitric oxide signaling within seconds. This indicates the promising potential of the stretchable 3D sensing in exploring the mechanotransduction in 3D cellular systems and engineered tissues. [ABSTRACT FROM AUTHOR]

In the field of three‐dimensional (3D) cell culture and tissue engineering, great advance focusing on functionalized materials and desirable culture systems has been made to mimic the natural environment of cells in vivo. Mechanical loading is one of the critical factors that affect cell/tissue behaviors and metabolic activities, but the reported models or detection methods offer little direct and real‐time information about mechanically induced cell responses. Herein, for the first time, a stretchable and multifunctional platform integrating 3D cell culture, mechanical loading, and electrochemical sensing is developed by immobilization of biomimetic peptide linked gold nanotubes on porous and elastic polydimethylsiloxane. The 3D scaffold demonstrates very good compatibility, excellent stretchability, and stable electrochemical sensing performance. This allows mimicking the articular cartilage and investigating its mechanotransduction by 3D culture, mechanical stretching of chondrocytes, and synchronously real‐time monitoring of stretch‐induced signaling molecules. The results disclose a previously unclear mechanotransduction pathway in chondrocytes that mechanical loading can rapidly activate nitric oxide signaling within seconds. This indicates the promising potential of the stretchable 3D sensing in exploring the mechanotransduction in 3D cellular systems and engineered tissues. [ABSTRACT FROM AUTHOR]

The role of endogenous serotonin (5‐HT) in gastrointestinal motility is still highly controversial. Although electrochemical techniques allow for direct and real‐time recording of biomolecules, the dynamic monitoring of 5‐HT release from elastic and tubular intestine during motor reflexes remains a great challenge because of the specific peristalsis patterns and inevitable passivation of the sensing interface. A stretchable sensor with antifouling and decontamination properties was assembled from gold nanotubes, titanium dioxide nanoparticles, and carbon nanotubes. The sandwich‐like structure endowed the sensor with satisfying mechanical stability and electrochemical performance, high resistance against physical adsorption, and superior efficiency in the photodegradation of biofouling molecules. Insertion of the sensor into the lumen of rat ileum (the last section of the small intestine) successfully mimics intestinal peristalsis, and simultaneous real‐time monitoring of distension‐evoked 5‐HT release was possible for the first time. Our results unambiguously reveal that mechanical distension of the intestine induces endogenous 5‐HT overflow, and 5‐HT level is closely associated with the physiological or pathological states of the intestine. [ABSTRACT FROM AUTHOR]

The role of endogenous serotonin (5‐HT) in gastrointestinal motility is still highly controversial. Although electrochemical techniques allow for direct and real‐time recording of biomolecules, the dynamic monitoring of 5‐HT release from elastic and tubular intestine during motor reflexes remains a great challenge because of the specific peristalsis patterns and inevitable passivation of the sensing interface. A stretchable sensor with antifouling and decontamination properties was assembled from gold nanotubes, titanium dioxide nanoparticles, and carbon nanotubes. The sandwich‐like structure endowed the sensor with satisfying mechanical stability and electrochemical performance, high resistance against physical adsorption, and superior efficiency in the photodegradation of biofouling molecules. Insertion of the sensor into the lumen of rat ileum (the last section of the small intestine) successfully mimics intestinal peristalsis, and simultaneous real‐time monitoring of distension‐evoked 5‐HT release was possible for the first time. Our results unambiguously reveal that mechanical distension of the intestine induces endogenous 5‐HT overflow, and 5‐HT level is closely associated with the physiological or pathological states of the intestine. [ABSTRACT FROM AUTHOR]

Background To investigate fluoroquinolone resistance and associated mechanisms of Shigella sonnei isolates in Jiangsu Province of China between 2002 and 2011. Methods All 337 unduplicated S. sonnei isolates were collected from hospitals in Jiangsu Province from January 2002 to December 2011. Fluoroquinolone susceptibility was characterized by Kirby-Bauer disk diffusion method, and direct nucleotide sequencing of genes of the quinolone resistance determining regions were conducted. Also, the transferable quinolone resistance determinants, including qnrA , qnrB , qnrC , qnrD , qnrS , aac-(6′)-Ib-cr and qepA were amplified by PCR. Results Among 950 Shigella isolates, 337 (35.5%) were identified as S. sonnei , of which 76.6% displayed nalidixic acid resistance and norfloxacin-resistant isolates appeared in 2005-2009, with an average resistance rate of 21.8%. Commonly reported point mutations of Ser83Leu and Asp87Asn/Gly in gyrA and Ser80Ile in parC were detected, with mutation rates of 78.0%, 9.5% and 30.3%, respectively, while no alteration in gyrB or parE were detected. Besides, His211Tyr mutation in gyrA was first reported in a S. sonnei strain in 2009 and two novel mutations in parC were found, of which Met86Trp occurred in another strain in 2009 and Ser129Pro appeared every year except 2011 (28.8%). Plasmid-mediated quinolone resistance determinants were found in 23 isolates and 19 of these isolates were resistant to both nalidixic acid and norfloxacin. qnrB , qnrS , aac-(6′)-Ib-cr and qepA were detected in 1, 7, 14 and 2 S. sonnei strains, relatively, and the most abundant PMQR gene found in this work was aac-(6′)-Ib-cr (4.2%). Interpretation & conclusions S. sonnei became increasingly important as fluoroquinolone-resistant isolates emerged, and further detection on the resistant genes would be useful in the treatment and control of this infection. [ABSTRACT FROM AUTHOR]

Many cells in vivo have their inherent motions, which involve numerous biochemical and biophysical signals synergistically regulating cell behavior and function. However, existing methods offer little information about the concurrently chemical and physical responses of dynamically pulsing cells. Here, we report a soft electrode with an electrospun poly(3,4‐ethylenedioxythiophene) (PEDOT)‐based nanomesh to fully comply with spontaneous motions of cells. Moreover, this electrode demonstrated excellent electrical conductivity, electrochemical performance and cellular biocompatibility. Cardiomyocytes cultured thereon exhibited autonomous and rhythmic contractility, and synchronously induced mechanical deformation of the underlying electrode, which allowed real‐time monitoring of nitric oxide release and electrophysiological activity of cardiomyocytes. This work provides a promising way toward recording chemical and electrical signals of biological systems with their natural motions. [ABSTRACT FROM AUTHOR]

Many cells in vivo have their inherent motions, which involve numerous biochemical and biophysical signals synergistically regulating cell behavior and function. However, existing methods offer little information about the concurrently chemical and physical responses of dynamically pulsing cells. Here, we report a soft electrode with an electrospun poly(3,4‐ethylenedioxythiophene) (PEDOT)‐based nanomesh to fully comply with spontaneous motions of cells. Moreover, this electrode demonstrated excellent electrical conductivity, electrochemical performance and cellular biocompatibility. Cardiomyocytes cultured thereon exhibited autonomous and rhythmic contractility, and synchronously induced mechanical deformation of the underlying electrode, which allowed real‐time monitoring of nitric oxide release and electrophysiological activity of cardiomyocytes. This work provides a promising way toward recording chemical and electrical signals of biological systems with their natural motions. [ABSTRACT FROM AUTHOR]

[Display omitted] • We developed a 3D lactate electrochemical sensor by layer-by-layer assembly of carbon nanotubes, Prussian blue nanoparticles and lactate oxidase on a 3D scaffold electrode. • Further, the 3D sensor was integrated with collagen hydrogel with C6 glioma cells seeded therein and allowed the successful real-time monitoring of lactate released from C6 glioma cells, providing an effective detection platform for exploring the biochemical response in 3D cell culture systems. Three-dimensional (3D) cell culture has attracted increasing interest in many fields with the significant advantages in reproducing in vivo cell environment. For the characterization of biochemical information, electrochemical sensing has stood out from other techniques in real-time monitoring of living cells, and made an attempt to integrate with hydrogel for investigating the biological processes in 3D cell culture. However, it is still a challenge for real-time monitoring of cellular metabolites therein for the lack of electrochemical activity, and lactate (the product of aerobic glycolysis) is a typical example of such a predicament. Herein, we developed a 3D enzymatic electrochemical sensor that could be integrated with collagen hydrogel to monitor the lactate levels of cells cultured therein. Specifically, lactate oxidase immobilized on the outer surface of 3D sensor could oxidize lactate with H 2 O 2 as a product, and Prussian blue nanoparticles electrodeposited on carbon nanotubes adsorbed electrode conferred the excellent and stable electrocatalytic performance to H 2 O 2 for lactate detection. Further, the 3D sensor was integrated with collagen hydrogel with C6 glioma cells seeded therein and allowed the successful real-time monitoring of lactate released from C6 glioma cells, providing an effective detection platform for exploring the biochemical response in 3D cell culture systems. [ABSTRACT FROM AUTHOR]

The current strategies for nanoelectrode functionalization usually involve sophisticated modification procedures, uncontrollable and unstable modifier assembly, as well as a limited variety of modifiers. To address this issue, we propose a versatile strategy for large‐scale synthesis of biomimetic molecular catalysts (BMCs) modified nanowires (NWs) to construct functionalized electrochemical nanosensors. This design protocol employs an easy, controllable and stable assembly of diverse BMCs‐poly(3,4‐ethylenedioxythiophene) (PEDOT) composites on conductive NWs. The intrinsic catalytic activity of BMCs combined with outstanding electron transfer ability of conductive polymer enables the nanosensors to sensitively and selectively detect various biomolecules. Further application of sulfonated cobalt phthalocyanine functionalized nanosensors achieves real‐time electrochemical monitoring of intracellular glutathione levels and its redox homeostasis in single living cells for the first time. [ABSTRACT FROM AUTHOR]

The current strategies for nanoelectrode functionalization usually involve sophisticated modification procedures, uncontrollable and unstable modifier assembly, as well as a limited variety of modifiers. To address this issue, we propose a versatile strategy for large‐scale synthesis of biomimetic molecular catalysts (BMCs) modified nanowires (NWs) to construct functionalized electrochemical nanosensors. This design protocol employs an easy, controllable and stable assembly of diverse BMCs‐poly(3,4‐ethylenedioxythiophene) (PEDOT) composites on conductive NWs. The intrinsic catalytic activity of BMCs combined with outstanding electron transfer ability of conductive polymer enables the nanosensors to sensitively and selectively detect various biomolecules. Further application of sulfonated cobalt phthalocyanine functionalized nanosensors achieves real‐time electrochemical monitoring of intracellular glutathione levels and its redox homeostasis in single living cells for the first time. [ABSTRACT FROM AUTHOR]

A strategy for one‐pot and large‐scale synthesis of functionalized core–shell nanowires (NWs) to high‐efficiently construct single nanowire electrodes is proposed. Based on the polymerization reaction between 3,4‐ethylenedioxythiophene (EDOT) and noble metal cations, manifold noble metal nanoparticles‐polyEDOT (PEDOT) nanocomposites can be uniformly modified on the surface of any nonconductive NWs. This provides a facile and versatile approach to produce massive number of core–shell NWs with excellent conductivity, adjustable size, and well‐designed properties. Nanoelectrodes manufactured with such core–shell NWs exhibit excellent electrochemical performance and mechanical stability as well as favorable antifouling properties, which are demonstrated by in situ intracellular monitoring of biological molecules (nitric oxide) and unraveling its relevant unclear signaling pathway inside single living cells. [ABSTRACT FROM AUTHOR]

A strategy for one‐pot and large‐scale synthesis of functionalized core–shell nanowires (NWs) to high‐efficiently construct single nanowire electrodes is proposed. Based on the polymerization reaction between 3,4‐ethylenedioxythiophene (EDOT) and noble metal cations, manifold noble metal nanoparticles‐polyEDOT (PEDOT) nanocomposites can be uniformly modified on the surface of any nonconductive NWs. This provides a facile and versatile approach to produce massive number of core–shell NWs with excellent conductivity, adjustable size, and well‐designed properties. Nanoelectrodes manufactured with such core–shell NWs exhibit excellent electrochemical performance and mechanical stability as well as favorable antifouling properties, which are demonstrated by in situ intracellular monitoring of biological molecules (nitric oxide) and unraveling its relevant unclear signaling pathway inside single living cells. [ABSTRACT FROM AUTHOR]

The current strategies for nanoelectrode functionalization usually involve sophisticated modification procedures, uncontrollable and unstable modifier assembly, as well as a limited variety of modifiers. To address this issue, we propose a versatile strategy for large‐scale synthesis of biomimetic molecular catalysts (BMCs) modified nanowires (NWs) to construct functionalized electrochemical nanosensors. This design protocol employs an easy, controllable and stable assembly of diverse BMCs‐poly(3,4‐ethylenedioxythiophene) (PEDOT) composites on conductive NWs. The intrinsic catalytic activity of BMCs combined with outstanding electron transfer ability of conductive polymer enables the nanosensors to sensitively and selectively detect various biomolecules. Further application of sulfonated cobalt phthalocyanine functionalized nanosensors achieves real‐time electrochemical monitoring of intracellular glutathione levels and its redox homeostasis in single living cells for the first time. [ABSTRACT FROM AUTHOR]