Active Micro-Nano-Collaborative Bioelectronic Device for Advanced Electrophysiological Recording

The development of precise and sensitive electrophysiological recording platforms holds the utmost importance for research in the fields of cardiology and neuroscience.In recent years,active micro/nano-bioelectronic devices have undergone significant advancements,thereby facilitating the study of electrophysiology.The distinctive configuration and exceptional functionality of these active micro-nano-collaborative bioelectronic devices offer the potential for the recording of high-fidelity action potential signals on a large scale.In this paper,we review three-dimensional active nano-transistors and planar active micro-transistors in terms of their applications in electroexcitable cells,focusing on the evaluation of the effects of active micro/nano-bioelectronic devices on electrophysiological signals.Looking forward to the possibilities,challenges,and wide prospects of active micro-nano-devices,we expect to advance their progress to satisfy the demands of theoretical investigations and medical implementations within the domains of cardiology and neuroscience research.

Association of Multiple Urinary Phthalates Metabolites with Diabetes Risk in Elderly Population

As a common environmental endocrine disruptor,phthalate exposure could affect the diabetes risk.However,it remains unclear whether phthalate exposure in the elderly population alters diabetes risk.We conducted a cross-sectional survey to explore the effect of urinary phthalate metabolites on diabetes in the elderly.We conducted a health survey of 200 elderly in northeastern China and measured urinary concentrations of 64 phthalate metabolites.We next evaluated the association between major phthalates and phthalate mixtures and diabetes in the elderly.The least absolute shrinkage and selection operator(LASSO)regression screened for mono(3-carboxypropyl)phthalate(MCPP),monoethyl phthalate(MEP),and mono(2-ethyl-5-hydroxyhexyl)phthalate(MEHHP)as important predictors for diabetes.Weighted quantile sum(WQS)regression and Bayesian Kernel Machine regression(BKMR)models consistently found MEHHP(Weights=51.9%,PIP=0.97)to have the greatest effect on diabetes risk in the elderly.Furthermore,MEHHP was associated with an increased risk of diabetes in the multipollutant logistic regression model(OR=2.148,95%CI:1.255 to 3.677).The overall effect of coexposure to MCPP,MEHHP,and MEP on the risk of diabetes in elderly population was significant and positive.In summary,we found that increased urinary MEHHP levels could increase the risk of diabetes in the elderly population.Co-exposure to MCPP,MEHHP and MEP may increase the risk of diabetes.

Nanodrugs alleviate acute kidney injury: Manipulate RONS at kidney

Currently,there are no clinical drugs available to treat acute kidney injury(AKI).Given the high prevalence and high mortality rate of AKI,the development of drugs to effectively treat AKI is a huge unmet medical need and a research hotspot.Although existing evidence fully demonstrates that reactive oxygen and nitrogen species(RONS)burst at the AKI site is a major contributor to AKI progression,the heterogeneity,complexity,and unique physiological structure of the kidney make most antioxidant and anti-inflammatory small molecule drugs ineffective because of the lack of kidney targeting and side effects.Recently,nanodrugs with intrinsic kidney targeting through the control of size,shape,and surface properties have opened exciting prospects for the treatment of AKI.Many antioxidant nanodrugs have emerged to address the limitations of current AKI treatments.In this review,we systematically summarized for the first time about the emerging nanodrugs that exploit the pathological and physiological features of the kidney to overcome the limitations of traditional small-molecule drugs to achieve high AKI efficacy.First,we analyzed the pathological structural characteristics of AKI and the main pathological mechanism of AKI:hypoxia,harmful substance accumulation-induced RONS burst at the renal site despite the multifactorial initiation and heterogeneity of AKI.Subsequently,we introduced the strategies used to improve renal targeting and reviewed advances of nanodrugs for AKI:nano-RONS-sacrificial agents,antioxidant nanozymes,and nanocarriers for antioxidants and anti-inflammatory drugs.These nanodrugs have demonstrated excellent therapeutic effects,such as greatly reducing oxidative stress damage,restoring renal function,and low side effects.Finally,we discussed the challenges and future directions for translating nanodrugs into clinical AKI treatment.

Recognition of high-specificity hERG K+ channel inhibitor-induced arrhythmia in cardiomyocytes by automated template matching

Cardiovascular disease(CVD)is the number one cause of death in humans.Arrhythmia induced by gene mutations,heart disease,or hERG K+channel inhibitors is a serious CVD that can lead to sudden death or heart failure.Conventional cardiomyocyte-based biosensors can record extracellular potentials and mechanical beating signals.However,parameter extraction and examination by the naked eye are the traditional methods for analyzing arrhythmic beats,and it is difficult to achieve automated and efficient arrhythmic recognition with these methods.In this work,we developed a unique automated template matching(ATM)cardiomyocyte beating model to achieve arrhythmic recognition at the single beat level with an interdigitated electrode impedance detection system.The ATM model was established based on a rhythmic template with a data length that was dynamically adjusted to match the data length of the target beat by spline interpolation.The performance of the ATM model under long-term astemizole,droperidol,and sertindole treatment at different doses was determined.The results indicated that the ATM model based on a random rhythmic template of a signal segment obtained after astemizole treatment presented a higher recognition accuracy(100%for astemizole treatment and 99.14%for droperidol and sertindole treatment)than the ATM model based on arrhythmic multitemplates.We believe this highly specific ATM method based on a cardiomyocyte beating model has the potential to be used for arrhythmia screening in the fields of cardiology and pharmacology.

A biosensing system employing nanowell microelectrode arrays to record the intracellular potential of a single cardiomyocyte

Electrophysiological recording is a widely used method to investigate cardiovascular pathology,pharmacology and developmental biology.Microelectrode arrays record the electrical potential of cells in a minimally invasive and highthroughput way.However,commonly used microelectrode arays primarily employ planar microelectrodes and cannot work in applications that require a recording of the intracellular action potential of a single cell.In this study,we proposed a novel measuring method that is able to record the intracellular action potential of a single cardiomyocyte by using a nanowell patterned microelectrode array(NWMEA).The NWMEA consists of five nanoscale wells at the center of each circular planar microelectrode.Biphasic pulse electroporation was applied to the NWMEA to penetrate the cardiomyocyte membrane,and the intracellular action potential was continuously recorded.The intracellular potential recording of cardiomyocytes by the NWMEA measured a potential signal with a higher quality(213.76±25.85%),reduced noise root-mean-square(~33%),and higher signal-to-noise ratio(254.36±12.61%)when compared to those of the extracellular recording.Compared to previously reported nanopillar microelectrodes,the NWMEA could ensure single cell electroporation and acquire high-quality action potential of cardiomyocytes with reduced fabrication processes.This NWMEA-based biosensing system is a promising tool to record the intracellular action potential of a single cell to broaden the usage of microelectrode arrays in electrophysiological investigation.

An insect sclerotization-inspired antifouling armor on biomedical devices combats thrombosis and embedding

Thrombus formation and tissue embedding significantly impair the clinical efficacy and retrievability of temporary interventional medical devices.Herein,we report an insect sclerotization-inspired antifouling armor for tailoring temporary interventional devices with durable resistance to protein adsorption and the following protein-mediated complications.By mimicking the phenol-polyamine chemistry assisted by phenol oxidases during sclerotization,we develop a facile one-step method to crosslink bovine serum albumin(BSA)with oxidized hydrocaffeic acid(HCA),resulting in a stable and universal BSA@HCA armor.Furthermore,the surface of the BSA@HCA armor,enriched with carboxyl groups,supports the secondary grafting of polyethylene glycol(PEG),further enhancing both its antifouling performance and durability.The synergy of robustly immobilized BSA and covalently grafted PEG provide potent resistance to the adhesion of proteins,platelets,and vascular cells in vitro.In ex vivo blood circulation experiment,the armored surface reduces thrombus formation by 95%.Moreover,the antifouling armor retained over 60%of its fouling resistance after 28 days of immersion in PBS.Overall,our armor engineering strategy presents a promising solution for enhancing the antifouling properties and clinical performance of temporary interventional medical devices.