Biology subjects

Tian, J.

Publications and source records attributed to Tian, J..

At least 73 records · Page 4Linked to original sources

bioRxiv2022

Planting graphene quantum dots in PEGylated nanoparticles for enhanced and multimodal in vivo imaging of tumor

Photoluminescent graphene quantum dots (GQDs) have recently attracted considerable attention for biomedical applications owing to the interesting physicochemical and photophysical properties, and prominent biocompatibility and biosafety. However, although much progress has been achieved in therapy and in vitro bioimaging, broad and crucial in vivo fluorescence bioimaging and synergistically working with other nanomedicine are very challenging and limited. Herein, we in situ implanted GQDs in the PEGylated layer of nanoparticles (NPs) via a bottom-up approach to obtain the NPs (core)-GQDs-PEG multifunctional nanoprobe (NPC-GQDs-PEG), which prolonged the blood circulation of GQDs more than four times and increased the tumor accumulation 7~8 times than GQDs used alone. Under assisted by the flexible microscope, the GQDs were successfully used for in vivo real-time monitoring of local NPs pharmacokinetics, in vivo multimodality imaging, and fluorescence imaging-guided tumor surgery. The approach of implanting GQDs in PEGylated nanomedicine and synergistic working provide a new strategy for in vivo biomedical applications of GQDs.

cancer biology↗

bioRxiv2022

Inside-out tracking and projection mapping for robot-assisted transcranial magnetic stimulation

Transcranial Magnetic Stimulation (TMS) is a neurostimulation technique based on the principle of electromagnetic induction of an electric field in the brain with both research and clinical applications. To produce an optimal neuro-modulatory effect, the TMS coil must be placed on the head and oriented accurately with respect to the region of interest within the brain. A robotic method can enhance the accuracy and facilitate the procedure for TMS coil placement. This work presents two system improvements for robot-assisted TMS (RA-TMS) application. Previous systems have used outside-in tracking method where a stationary external infrared (IR) tracker is used as a reference point to track the head and TMS coil position. This method is prone to losing track of the coil or the head if the IR camera is blocked by the robotic arm during its motion. To address this issue, we implemented an inside-out tracking method by mounting a portable IR camera on the robot end-effector. This method guarantees that the line of sight of the IR camera is not obscured by the robotic arm at any time during its motion. We also integrated a portable projection mapping device (PPMD) into the RA-TMS system to provide visual guidance during TMS application. PPMD can track the head via an IR tracker, and can project a planned contact point of the TMS coil on the head or overlay the underlying brain anatomy in real-time.

bioengineering↗

bioRxiv2022

JQ-1 ameliorates schistosomiasis liver granuloma in mice by suppressing male and female reproductive systems and egg development of Schistosoma japonicum

Schistosomiasis is a serious and widespread parasitic disease caused by infection with Schistosoma japonicum. Because the parasites eggs are primarily responsible for schistosomiasis dissemination and pathogenesis, inhibiting egg production is a potential approach to control the spread and severity of the disease. The bromodomain and extra-terminal (BET) proteins represent promising targets for the development of epigenetic drugs against Schistosoma. JQ-1 is a selective inhibitor of the BET protein family. In the present study, JQ-1 was applied S. japonicum in vitro. By using laser confocal scanning microscopy and EdU incorporation assays, we showed that application of JQ-1 to worms in vitro affected egg laying and the development of both the male and female reproductive systems. JQ-1 also inhibited the expression of the reproductive-related genes SjPlk1 and SjNanos1 in S. japonicum. Mice infected with S. japonicum were treated with JQ-1 during egg granuloma formation. JQ-1 treatment significantly reduced the size of the liver granulomas and levels of serum alanine aminotransferase and aspartate aminotransferase in mice and suppressed both egg laying and the development of male and female S. japonicum reproductive systems in vivo. Moreover, the mRNA expression levels of some proinflammatory cytokines were decreased in the parasites. Our findings suggest that JQ-1 treatment attenuates S. japonicum egg- induced hepatic granuloma due at least in part to suppressing the development of the reproductive system and egg production of S. japonicum. These findings further suggest that JQ-1 or other BET inhibitors warrant additional study as a new approach for the treatment or prevention of schistosomiasis. Author summaryAmong neglected tropical diseases, schistosomiasis is a serious disease caused by infection with the parasite Schistosomiasis japonicum. Treatment of schistosomiasis is currently almost exclusively with praziquantel, which kills mainly adult parasites, with minimal effectiveness against immature schistosomes and eggs. However, the parasites eggs are primarily responsible for schistosomiasis dissemination and pathology. In addition, overuse of praziquantel in epidemic areas has led to drug resistance and a reduced cure rate. Thus, new parasite targets for the development of novel therapeutics are crucial. Here, we evaluated the potential of JQ-1, a bromodomain and extra-terminal protein inhibitor, to suppress the production of S. japonicum eggs. Application of JQ-1 to S. japonicum in vitro decreased the number of mature germ cells, the rates of oviposition, and the number of eggs produced in each male-female pairing. JQ-1 treatment of mice infected with S. japonicum ameliorated hepatic granuloma and decreased serum liver enzymes, suggesting improved liver function. These results indicate that JQ-1 inhibits reproductive development and egg production in S. japonicum, providing supporting evidence that JQ-1 warrants additional study for use as a novel approach in the prevention or treatment of schistosomiasis.

microbiology↗

bioRxiv2022

Genomic insights into the phylogeny and biomass-degrading enzymes of rumen ciliates

Understanding the biodiversity and genetics of the gut microbiome has important implications for host physiology. One underexplored and elusive group is ciliated protozoa, which play crucial roles in regulating gut microbial interactions. Integrating single-cell sequencing and an assembly-and-identification pipeline, we acquired 52 high-quality ciliate genomes of 22 rumen morphospecies for all major abundant clades. With these genomes, we firstly resolved the taxonomic and phylogenetic framework that reclassified them into 19 species spanning 13 genera and reassigned the genus Dasytricha from Isotrichidae to a new family Dasytrichidae. Via extensive horizontal gene transfer and gene family expansion, rumen ciliates possess a broad array of enzymes to synergistically degrade plant and microbial carbohydrates. In particular, [~]80% of the degrading enzymes in Diplodiniinae and Ophryoscolecinae act on plant cell wall, and the high activities of their cellulase, xylanase and lysozyme reflect the potential of ciliate enzymes for biomass-conversion. Additionally, the new ciliate dataset greatly facilitated the rumen metagenomic analyses by allowing [~]12% of reads to be classified.

microbiology↗

bioRxiv2021

Analyses of the Autism-associated Neuroligin-3 R451C Mutation in Human Neurons Reveals a Gain-of-Function Synaptic Mechanism

Mutations in many synaptic genes are associated with autism spectrum disorders (ASDs), suggesting that synaptic dysfunction is a key driver of ASD pathogenesis. Among these mutations, the R451C-substitution in the NLGN3 gene that encodes the postsynaptic adhesion molecule Neuroligin-3 is noteworthy because it was the first specific mutation linked to ASDs. In mice, the corresponding Nlgn3 R451C-knockin mutation recapitulates social interaction deficits of ASD patients and produces synaptic abnormalities, but the impact of the NLGN3 R451C-mutation on human neurons has not been investigated. Here, we generated human knock-in neurons with the NLGN3 R451C-mutation. Strikingly, analyses of NLGN3 R451C-mutant neurons revealed that the R451C-mutation decreased NLGN3 protein levels but enhanced the strength of excitatory synapses without affecting inhibitory synapses. No significant cell death and endoplasmic reticulum stress were detected. Importantly, the augmentation of excitatory transmission was confirmed in vivo with human neurons transplanted into mouse forebrain. Using single-cell RNA-seq experiments with co-cultured excitatory and inhibitory NLGN3 R451C-mutant neurons, we identified differentially expressed genes in relatively mature human neurons that corresponded to synaptic gene expression networks. Moreover, gene ontology and enrichment analyses revealed convergent gene networks associated with ASDs and other mental disorders. Our findings suggest that the NLGN3 R451C-mutation induces a gain-of-function enhancement in excitatory synaptic transmission that may contribute to the pathophysiology of ASDs.

neuroscience↗

bioRxiv2021

Tumor Treating Fields Suppression of Ciliogenesis Enhances Temozolomide Toxicity

Tumor Treating Fields (TTFields) are low intensity, alternating intermediate frequency (200kHz) electrical fields that extend survival of glioblastoma patients receiving maintenance temozolomide (TMZ) chemotherapy. How TTFields exert efficacy on cancer over normal cells, or interact with TMZ is unclear. Primary cilia are microtubule-based organelles triggered by extracellular ligands, mechanical and electrical field stimulation, and are capable of promoting cancer growth and TMZ chemoresistance. We found in both low and high grade patient glioma cell lines that TTFields ablated cilia within 24 hours. Halting TTFields treatment led to recovered frequencies of elongated cilia. Cilia on normal primary astrocytes, neurons, and multiciliated/ependymal cells were less affected by TTFields. The TTFields-mediated loss of glioma cilia was partially rescued by chloroquine pretreatment, suggesting the effect is in part due to autophagy activation. We also observed death of ciliated cells during TTFields by live imaging. Notably, TMZ-induced stimulation of ciliogenesis in both adherent cells and gliomaspheres was blocked by TTFields. Moreover, the inhibitory effects of TTFields and TMZ on tumor cell recurrence correlated with the relative timing of TMZ exposure to TTFields and ARL13B+ cilia. Finally, TTFields disrupted cilia in patient tumors treated ex vivo. Our findings suggest TTFields efficacy may depend on the degree of tumor ciliogenesis and relative timing of TMZ treatment.

cancer biology↗

bioRxiv2021

Genome-wide analysis of DNA methylation reveals selection signatures of the grass carp during domestication

With the rapid development of aquaculture, more and more fish species from wild environments are artificially domesticated and cultured. In the process of domestication, the fish develop some adaptations and phenotypic traits, namely selection signatures. However, it is still unclear about the biological process underlying these selection signatures. Here, we used grass carp (Ctenopharyngodon idellus), an aquaculture fish with the largest production worldwide, to detect its selection signatures and investigate the roles of DNA methylation in the emergence of selection signatures during domestication based on whole-genome bisulfite sequencing technology. Our results showed that domesticated grass carp demonstrated four selection signatures, including growth and metabolism, immunity, foraging and learning behaviors, and 38 candidate genes were associated with these traits. 16 of candidate genes, such as IGF-1, GK, GYS1, etc., were found to play major roles in the growth and metabolism. Immunity signature was related to 11 of candidate genes, including MHCI, MHCII, C1QA, etc. The GRM1, TAS1R1 and TAS1R3 genes were essential for the adaptation of domesticated grass carp to commercial feed in artificial rearing condition. The C-FOS, POMC and CBP genes might be responsible for the acquisition of novel feeding habits and contribute to faster growth indirectly by enhancing food intake. These findings would provide new insights to expand our understanding on the role of DNA methylation in shaping physiological phenotypes in fish, and also contribute to efficient breeding of aquaculture stocks and restocking programs.

genetics↗

bioRxiv2021

Spatiotemporal specificity of correlated DNA methylation and gene expression pairs across different human tissues and stages of brain development

DNA methylation (DNAm) that occurs on promoter regions is primarily considered to repress gene expression. Previous studies indicated that DNAm could also show positive correlations with gene expression. Both DNAm and gene expression profiles are known to be tissue- and development-specific. This study aims to investigate how DNAm and gene expression are coordinated across different human tissues and developmental stages, as well as the biological significance of such correlations. By analyzing 2,239 samples with both DNAm and gene expression data in the same human subjects obtained from six published datasets, we evaluated the correlations between gene and CpG pairs (GCPs) at cis-regions and compared significantly correlated GCPs (cGCPs) across different tissues and brains at different age groups. A total of 37,363 cGCPs were identified in the six datasets; approximately 38% of the cGCPs were positively correlated. The majority (>90%) of cGCPs were tissue- or development-specific. We also observed that the correlation direction can be opposite in different tissues and ages. Further analysis highlighted the importance of cGCPs for their cellular functions and potential roles in complex traits and human diseases. For instance, early developmental brain possessed a highly unique set of cGCPs that were associated with neurogenesis and psychiatric disorders. By assessing the epigenetic factors involved in cGCPs, we discovered novel regulatory mechanisms of positive cGCPs distinct from negative cGCPs, which were related to multiple factors, such as H3K27me3, CTCF, and JARD2. The catalog of cGCPs compiled can be used to guide functional interpretation of genetic and epigenetic studies.

genetics↗

bioRxiv2021

Altered O-glycosylation Level of SARS-CoV-2 Spike Protein by Host O-glycosyltransferase Strengthens Its Trimeric Structure

The trimeric spike protein (S) mediates host-cell entry and membrane fusion of SARS-CoV-2. S protein is highly glycosylated, whereas its O-glycosylation is still poorly understood. Herein, we site-specifically examine the O-glycosylation of S protein through a mass spectrometric approach with HCD-triggered-ETD model. We identify 15 high-confidence O-glycosites and at least 10 distinct O-glycan structures on S protein. Peptide microarray assays prove that human ppGalNAc-T6 actively participates in O-glycosylation of S protein. Importantly, the upregulation of ppGalNAc-T6 expression can profoundly enhance the O-glycosylation level by generating new O-glycosites and increasing both O-glycan heterogeneity and intensities. Further molecular dynamics simulations reveal that the O-glycosylation on the protomer-interface regions, which are mainly modified by ppGalNAc-T6, can potentially stabilize the trimeric S protein structure. Our work provides deep molecular insights of how viral infection harnesses the host O-glycosyltransferases to dynamically regulate the O-glycosylation level of the viral envelope protein responsible for membrane fusion.

biochemistry↗

bioRxiv2021

Insulin-like peptide receptor mediated signaling pathways orchestrate regulation of energy homeostasis in the Pacific oyster, Crassostrea gigas

The involvement of insulin/insulin-like growth factor (IIS) signaling pathway in growth regulation of marine invertebrates remains largely unexplored. In this study, we used a fast-growing Pacific oyster (Crassostrea gigas) variety "Haida No.1" as material to unravel the role of IIS system in growth regulation in oysters. Systematic bioinformatics analyses allowed to identify major components of IIS signaling pathway and insulin-like peptide receptor (ILPR) mediated signaling pathways, including PI3K-AKT, RAS-MAPK, and TOR, in C. gigas. Expression levels of the major genes in IIS and its downstream signaling pathways were significantly higher in "Haida No.1" than wild oysters, suggesting their involvement in growth regulation of C. gigas. Expression profiles of IIS and its downstream signaling pathway genes were significantly altered by nutrient abundance and culture temperature. These results suggested that IIS signaling pathway coupled with the ILPR mediated signaling pathways orchestrated energy homeostasis to regulate growth in the Pacific oyster. Research HighlightsO_LIILPR, IRS, IGFBPRP, and IGFALS genes were characterized in the C. gigas. C_LIO_LIMajor genes of IIS signaling pathway were highly expressed in fast-growing C. gigas. C_LIO_LIIIS and downstream pathways participates in energy homeostasis of oysters. C_LIO_LIILPR mediated signaling pathways orchestrate growth regulation in oysters. C_LI

genomics↗

bioRxiv2021

GABA administration limits viral replication and pneumonitis in a mouse model of COVID-19

Despite the availability of vaccines for COVID-19, serious illness and death induced by coronavirus infection will remain a global health burden because of vaccination hesitancy, possible virus mutations, and the appearance of novel coronaviruses. Accordingly, there is a need for new approaches to limit severe illness stemming from coronavirus infections. Cells of the immune system and lung epithelia express receptors for GABA (GABA-Rs), a widely used neurotransmitter within the CNS. GABA-R agonists have anti-inflammatory effects and can limit acute lung injury. We previously showed that GABA treatment effectively reduced disease severity and death rates in mice following infection with a coronavirus (MHV-1) which provides a potentially lethal model of COVID-19. Here, we report that GABA treatment also reduced viral load in the lungs, suggesting that GABA-Rs may provide a new druggable target to limit pulmonary coronavirus replication. Histopathological analysis revealed that GABA treatment reduced lung inflammatory infiltrates and damages. Since GABA is safe for human consumption, inexpensive, and available worldwide, it is a promising candidate to help treat COVID-19.

immunology↗

bioRxiv2021

IRGM/Irgm1 Aggravates Progression of Atherosclerosis by Inducing Macrophage Apoptosis

AimsAtherosclerosis underlies most cardiovascular diseases, among which acute coronary syndrome (ACS) caused by plaque rupture (PR) often leads to death. Immune-related GTPases (IRGM/Irgm1) have been extensively studied in inflammatory diseases, but their role in atherosclerosis is unclear. Determining how IRGM/Irgm1 promotes atherosclerotic plaque vulnerability will provide information for new biomarkers and/or therapeutic targets. Methods and resultsWe identified ruptured and unruptured plaques by optical coherence tomography, and found that serum IRGM was highly expressed in patients with ST-segment elevation myocardial infarction in PR. We used ApoE-/-Irgm1+/+, ApoE-/-Irgm1+/- mice and chimeric mice to establish a model of advanced atherosclerosis. The results of pathological experiments showed that Irgm1 caused plaque necrosis. The ratio of neutral lipids and cholesterol crystals increases, while the content of collagen fibers decreases, aggravating the destabilization of atherosclerotic plaques. In vitro, we used multiple approaches to confirm that Irgm1 promotes macrophage apoptosis by promoting the production of reactive oxygen species and activating the MAPK signaling pathway. ConclusionsIRGM may be a potential risk factor for PR. Mechanistic studies have shown that IRGM/Irgm1 contributes to the formation and rupture of fragile plaques. This is partly mediated by the induction of macrophage apoptosis via the MAPK signaling pathway. IRGM may offer new strategies for early treatment of ACS. Translation viewOur findings indicate that IRGM/Irgm1 contributes to formation and rupture of vulnerable plaques. It suggests that IRGM may provide a new target for the early treatment of ACS.

pathology↗

bioRxiv2020

Regional and age-dependent Effects of Cortical Magnetic Stimulation on Unconstrained Reaching Behavior

BackgroundThe specific and dynamic contributions of premotor and supplementary motor areas to reaching movements in aging humans are not well understood. ObjectiveTo better understand the role of cortical motor regions and age on the control of unconstrained reaches against gravity by neurologically intact, younger and older adults. MethodsDouble pulse transcranial magnetic stimulation (TMS) was applied at locations targeting primary motor cortex (M1), dorsal premotor area (PMA), supplementary motor area (SMA), or dorsolateral prefrontal cortex (DLPFC). Paired stimuli were delivered before or after a visual cue was presented to initiate self-paced right-handed reaches to one of three, vertically oriented target locations. ResultsRegional stimulation effects on movement amplitude were observed both early and late in the reach. PMA stimulation increased reach distance to a greater extent than M1, SMA, and DLPFC stimulation. M1 and PMA stimulation increased deviation from the straight-line path around the time of peak velocity to an extent that was greater than SMA and DLPFC stimulation. Cortical stimulation increased the time that elapsed after, but not before, peak velocity. Despite stronger effects of stimulation on reaches in the younger group, this group had shorter times to reach the target after reaching peak velocity. ConclusionThese results provide support for a role of PMA in visually guided movement after movement initiation. For older subjects, the increased time to arrive at the target after peak velocity despite weaker stimulation effects suggests an age-related reduction in sensorimotor processing flexibility for online control of unconstrained reaching. HighlightsO_LIDorsal premotor area stimulation at any time during the reaction-time period and early reaching affected early reach kinematics at least as much as stimulation of primary motor cortex. C_LIO_LIOlder individuals had more stimulation-related interference in the late components of reaching despite having less early effect of stimulation, suggesting a reduction in flexibility of dynamic motor control due to aging. C_LIO_LIThe antigravity component of unconstrained reaching did not have special aspects for regional cortical effects of stimulation. C_LI

neuroscience↗

bioRxiv2020

Normal aging affects unconstrained three-dimensional reaching against gravity with reduced vertical precision and increased co-contraction

Reaching for an object in space forms the basis for many activities of daily living and is important in rehabilitation after stroke and in other neurological and orthopedic conditions. It has been the object of motor control and neuroscience research for over a century, but studies often constrain movement to eliminate the effect of gravity or reduce the degrees of freedom. In some studies, aging has been shown to reduce target accuracy, with a mechanism suggested to be impaired corrective movements. We sought first to explore the changes in control of shoulder and elbow joint movements that occur with aging during performance of reaching movements to different target heights with the normal effects of gravity, unconstrained hand movement, and stable target locations. Three-dimensional kinematic data and electromyography were collected in 14 young (25{+/-}6 years) and 10 older adults (68{+/-}3 years) during second-long reaches to three targets aligned vertically in front of the participants. Older adults took longer to initiate a movement than the young adults and were more variable and inaccurate in their initial and final movements. Target height had greater effect on trajectory curvature variability in older than young adults, with angle variability relative to target position being greater in older adults around the time of peak speed. There were significant age-related differences in use of the multiple degrees of freedom of the upper extremity, with less variability in shoulder abduction in the older group. Muscle activation patterns were similar, except for a higher biceps-triceps co-contraction and tonic levels of some proximal muscle activation. The path length of movements was not affected by age. These results show an age-related deficit in the motor planning and online correction of reaching movements against a predictable force (i.e., gravity). These results will facilitate interpretation of our forthcoming study of transcranial magnetic stimulation effects on the same task in these two populations, and is relevant to any study that seeks to measure the effect of pathological processes on upper extremity motor performance in the elderly.

neuroscience↗

bioRxiv2020

ESCO: single cell expression simulation incorporating gene co-expression

MotivationGene-gene co-expression networks (GCN) are of biological interest for the useful information they provide for understanding gene-gene interactions. The advent of single cell RNA-sequencing allows us to examine more subtle gene co-expression occurring within a cell type. Many imputation and denoising methods have been developed to deal with the technical challenges observed in single cell data; meanwhile, several simulators have been developed for benchmarking and assessing these methods. Most of these simulators, however, either do not incorporate gene co-expression or generate co-expression in an inconvenient manner. ResultsTherefore, with the focus on gene co-expression, we propose a new simulator, ESCO, which adopts the idea of the copula to impose gene co-expression, while preserving the highlights of available simulators, which perform well for simulation of gene expression marginally. Using ESCO, we assess the performance of imputation methods on GCN recovery and find that imputation generally helps GCN recovery when the data are not too sparse, and the ensemble imputation method works best among leading methods. In contrast, imputation fails to help in the presence of an excessive fraction of zero counts, where simple data aggregating methods are a better choice. These findings are further verified with mouse and human brain cell data. AvailabilityThe ESCO implementation is available as R package SplatterESCO (https://github.com/JINJINT/SplatterESCO). Contactroeder@andrew.cmu.edu

genetics↗

bioRxiv2020

Multidimensional face representation in deep convolutional neural network reveals the mechanism underlying AI racism

The increasingly popular application of AI runs the risks of amplifying social bias, such as classifying non-white faces to animals. Recent research has attributed the bias largely to data for training. However, the underlying mechanism is little known, and therefore strategies to rectify the bias are unresolved. Here we examined a typical deep convolutional neural network (DCNN), VGG-Face, which was trained with a face dataset consisting of more white faces than black and Asian faces. The transfer learning result showed significantly better performance in identifying white faces, just like the well-known social bias in human, the other-race effect (ORE). To test whether the effect resulted from the imbalance of face images, we retrained the VGG-Face with a dataset containing more Asian faces, and found a reverse ORE that the newly-trained VGG-Face preferred Asian faces over white faces in identification accuracy. In addition, when the number of Asian faces and white faces were matched in the dataset, the DCNN did not show any bias. To further examine how imbalanced image input led to the ORE, we performed the representational similarity analysis on VGG-Faces activation. We found that when the dataset contained more white faces, the representation of white faces was more distinct, indexed by smaller ingroup similarity and larger representational Euclidean distance. That is, white faces were scattered more sparsely in the representational face space of the VGG-Face than the other faces. Importantly, the distinctiveness of faces was positively correlated with the identification accuracy, which explained the ORE observed in the VGG-Face. In sum, our study revealed the mechanism underlying the ORE in DCNNs, which provides a novel approach of study AI ethics. In addition, the face multidimensional representation theory discovered in human was found also applicable to DCNNs, advocating future studies to apply more cognitive theories to understand DCNNs behavior.

neuroscience↗

bioRxiv2020

Flexible and transparent silver nanowire structures for multifunctional electrical and optical biointerfacing

Transparent microelectrodes have recently emerged as a promising approach to combine electrophysiology with optophysiology for multifunctional biointerfacing. High-performance flexible platforms that allow seamless integration with soft tissue systems for such applications are urgently needed. Here, silver nanowires (Ag NWs)-based transparent microelectrodes and interconnects are designed to meet this demand. The Ag NWs percolating networks are patterned on flexible polymer substrates using an innovative photolithography-based solution-processing technique. The resulting nanowire networks exhibit a high average optical transparency of 76.1-90.0% over the visible spectrum, low normalized electrochemical impedance of 3.4-15 {Omega} cm2 at 1 kHz which is even better than those of opaque solid Ag films, superior sheet resistance of 11-25 {Omega} sq-1, excellent mechanical stability up to 10,000 bending cycles, good biocompatibility and chemical stability. Studies on Langendorff-perfused mouse and rat hearts demonstrate that the Ag NWs microelectrodes enable high-fidelity real-time monitoring of heart rhythm during co-localized optogenetic pacing and optical mapping with negligible light-induced electrical artifacts. This proof-of-concept work illustrates that the solution-processed, transparent, and flexible Ag NWs networks are a promising candidate for the next-generation of large-area multifunctional biointerfaces for interrogating complex biological systems in basic and translational research.

bioengineering↗

bioRxiv2020

GABA administration prevents severe illness and death following coronavirus infection in mice

There is an urgent need for new treatments to prevent and ameliorate severe illness and death induced by SARS-CoV-2 infection in COVID-19 patients. The coronavirus mouse hepatitis virus (MHV)-1 causes pneumonitis in mice which shares many pathological characteristics with human SARS-CoV infection. Previous studies have shown that the amino acid gamma-aminobutyric acid (GABA) has anti-inflammatory effects. We tested whether oral treatment with GABA could modulate the MHV-1 induced pneumonitis in susceptible A/J mice. As expected, MHV-1-inoculated control mice became severely ill (as measured by weight loss, clinical score, and the ratio of lung weight to body weight) and >60% of them succumbed to the infection. In contrast, mice that received GABA immediately after MHV-1 inoculation became only mildly ill and all of them recovered. When GABA treatment was initiated after the appearance of illness (3 days post-MHV-1 infection), we again observed that GABA treatment significantly reduced the severity of illness and greatly increased the frequency of recovery. Therefore, the engagement of GABA receptors (GABA-Rs) prevented the MHV-1 infection-induced severe pneumonitis and death in mice. Given that GABA-R agonists, like GABA and homotaurine, are safe for human consumption, stable, inexpensive, and available worldwide, they are promising candidates to help prevent severe illness stemming from SARS-CoV-2 infection and other coronavirus strains.

immunology↗