The cGAS-STING pathway in viral infections: a promising link between inflammation, oxidative stress and autophagy.

The host defence responses play vital roles in viral infection and are regulated by complex interactive networks. The host immune system recognizes viral pathogens through the interaction of pattern-recognition receptors (PRRs) with pathogen-associated molecular patterns (PAMPs). As a PRR mainly in the cytoplasm, cyclic GMP-AMP synthase (cGAS) senses and binds virus DNA and subsequently activates stimulator of interferon genes (STING) to trigger a series of intracellular signalling cascades to defend against invading pathogenic microorganisms. Integrated omic and functional analyses identify the cGAS-STING pathway regulating various host cellular responses and controlling viral infections. Aside from its most common function in regulating inflammation and type I interferon, a growing body of evidence suggests that the cGAS-STING signalling axis is closely associated with a series of cellular responses, such as oxidative stress, autophagy, and endoplasmic reticulum stress, which have major impacts on physiological homeostasis. Interestingly, these host cellular responses play dual roles in the regulation of the cGAS-STING signalling axis and the clearance of viruses. Here, we outline recent insights into cGAS-STING in regulating type I interferon, inflammation, oxidative stress, autophagy and endoplasmic reticulum stress and discuss their interactions with viral infections. A detailed understanding of the cGAS-STING-mediated potential antiviral effects contributes to revealing the pathogenesis of certain viruses and sheds light on effective solutions for antiviral therapy.

3D Printed Conductive Hydrogel Patch Incorporated with MSC@GO for Efficient Myocardial Infarction Repair.

Myocardial infarction (MI) results in an impaired heart function. Conductive hydrogel patch-based therapy has been considered as a promising strategy for cardiac repair after MI. In our study, we fabricated a three-dimensional (3D) printed conductive hydrogel patch made of fibrinogen scaffolds and mesenchymal stem cells (MSCs) combined with graphene oxide (GO) flakes (MSC@GO), capitalizing on GO's excellent mechanical property and electrical conductivity. The MSC@GO hydrogel patch can be attached to the epicardium via adhesion to provide strong electrical integration with infarcted hearts, as well as mechanical and regeneration support for the infarcted area, thereby up-regulating the expression of connexin 43 (Cx43) and resulting in effective MI repair in vivo. In addition, MI also triggers apoptosis and damage of cardiomyocytes (CMs), hindering the normal repair of the infarcted heart. GO flakes exhibit a protective effect against the apoptosis of implanted MSCs. In the mouse model of MI, MSC@GO hydrogel patch implantation supported cardiac repair by reducing cell apoptosis, promoting gap connexin protein Cx43 expression, and then boosting cardiac function. Together, this study demonstrated that the conductive hydrogel patch has versatile conductivity and mechanical support function and could therefore be a promising candidate for heart repair.

Corrigendum: Transcriptome analyses reveal photosynthesis-related genes involved in photosynthetic regulation under low temperature stress in Lavandula angustifolia Mill.

[This corrects the article DOI: 10.3389/fpls.2023.1268666.].

Transcriptome analyses reveal photosynthesis-related genes involved in photosynthetic regulation under low temperature stress in Lavandula angustifolia Mill.

In order to reveal the mechanisms of photosynthetic regulation of Lavandula angustifolia Mill. under low temperature stress, photosynthesis-related genes were screened and the molecular mechanism were analyzed for this species growing in Harbin, northeast of China. RNA-seq technique and photosynthetic physiology measurement were performed under 20°C, 10°C, and 0°C in this study. The results showed that the observing modified rectangular hyperbola mode could accurately reflect the light-response processes under low temperature stress and the low temperature reduced the light energy utilization of L. angustifolia. The stomatal conductance decreased with the temperature dropping, which was associated with the up-regulation of LaBAM1s, LaMPK4-1 and LaMMK2. The up-regulation of LaMPK4-1 and LaMMK2 was beneficial for ROS scavenging. The improvement of cold resistance in L. angustifolia was related to the up-regulated expression of LaFBA and LaOMTs and down-regulated expression of LaGAPAs, LaGOX, and LaTKL1s with the temperature decreasing. The up-expression of LaPSY at 10°C than it at 20°C could protect the photosynthetic organs from oxidative damage. Moreover, the photosynthetic rates at 10°C and 0°C were close to the measured values, which was related to the interactions of RCA with SBPase and Rubisco with SBPase. These findings could provide a theoretical reference for further exploring the cold tolerance mechanism of L. angustifolia, as an important aromatic plant resource, and promoting its cultivation and distribution in the northeast of China.

RPA-CRISPR/Cas12a-Based Detection of Haemophilus parasuis.

Haemophilus parasuis (H. parasuis, HPS) is a prominent pathogenic bacterium in pig production. Its infection leads to widespread fibrinous inflammation in various pig tissues and organs, often in conjunction with various respiratory virus infections, and leads to substantial economic losses in the pig industry. Therefore, the rapid diagnosis of this pathogen is of utmost importance. In this study, we used recombinase polymerase amplification (RPA) and clustered regularly interspaced short palindromic repeats (CRISPR) technology to establish a convenient detection and analysis system for H. parasuis that is fast to detect, easy to implement, and accurate to analyze, known as RPA-CRISPR/Cas12a analysis. The process from sample to results can be completed within 1 h with high sensitivity (0.163 pg/µL of DNA template, p < 0.05), which is 104 -fold higher than the common PCR method. The specificity test results show that the RPA-CRISPR/Cas12a analysis of H. parasuis did not react with other common pig pathogens, including Streptococcus suis type II and IX, Actinobacillus pleuropneumoniae, Escherichia coli, Salmonella, Streptococcus suis, and Staphylococcus aureus (p < 0.0001). The RPA-CRISPR/Cas12a assay was applied to 15 serotypes of H. parasuis clinical samples through crude extraction of nucleic acid by boiling method, and all of the samples were successfully identified. It greatly reduces the time and cost of nucleic acid extraction. Moreover, the method allows results to be visualized with blue light. The accurate and convenient detection method could be incorporated into a portable format as point-of-care (POC) diagnostics detection for H. parasuis at the field level.

Nanoscale MOFs in nanomedicine applications: from drug delivery to therapeutic agents.

Metal-organic frameworks (MOFs) hold great promise for widespread applications in biomedicine and nanomedicine. MOFs are one of the most fascinating nanocarriers for drug delivery, benefiting from their high porosity and facile modification. Furthermore, the tailored components of MOFs can be therapeutic agents for various treatments, including drugs as organic ligands of MOFs, active metal as central metal ions of MOFs, and their combinations as carrier-free MOF-based nanodrug. In this review, the advances in delivery systems and applications as therapeutic agents for nanoscale MOF-based materials are summarized. The challenges of MOFs in clinical translation and the future directions in the field of MOFs therapy are also discussed. We hope that more researchers will focus their attention on advancing and translating MOF-based nanodrugs into pre-clinical and clinical applications.

Crash report data analysis for creating scenario-wise, spatio-temporal attention guidance to support computer vision-based perception of fatal crash risks.

Reducing traffic fatal crashes has been an important mission of transportation. With the rapid development of sensor and Artificial Intelligence (AI) technologies, the computer vision (CV)-based crash anticipation in the near-crash phase is receiving growing attention. The ability to perceive fatal crash risks in an early stage is of paramount importance as well because it can improve the reliability of crash anticipation. Yet this task is challenging because it requires establishing a relationship between the driving scene information that CV can recognize and the fatal crash features that CV will not get until the crash occurrence. Image data with the annotation for directly training a reliable AI model for the early visual perception of fatal crash risks are not abundant. The Fatality Analysis Reporting System (FARS) contains big data on fatal crashes, which is a reliable data source for finding fatal crash clusters and discovering their distribution patterns to tell the association between driving scene characteristics and fatal crash features. To enhance CV's ability to perceive fatal crash risks earlier, this paper develops a data analytics model from fatal crash report data, which is named scenario-wise, spatio-temporal attention guidance. First, the paper identifies five descriptive variables that are sparse and thus allow for decomposing the 5-year (2013-2017) fatal crash dataset to develop scenario-wise attention guidance. Then, an exploratory analysis of location- and time-related descriptive variables suggests dividing fatal crashes into spatially defined groups. A group's temporal distribution pattern is an indicator of the similarity of fatal crashes in the group. Hierarchical clustering and K-means clustering further merge the spatially defined groups into six clusters according to the similarity of their temporal patterns. After that, association rule mining discovers the statistical relationship between the temporal information of driving scenes with fatal crash features, such as the first harmful event and the manner of collisions, for each cluster. The paper illustrates how the developed attention guidance supports the design and implementation of a preliminary CV model that can identify agents of a possibility to involve in fatal crashes from their environmental and context information.

DBSDA : Lowering the Bound of Misclassification Rate for Sparse Linear Discriminant Analysis via Model Debiasing.

Linear discriminant analysis (LDA) is a well-known technique for linear classification, feature extraction, and dimension reduction. To improve the accuracy of LDA under the high dimension low sample size (HDLSS) settings, shrunken estimators, such as Graphical Lasso, can be used to strike a balance between biases and variances. Although the estimator with induced sparsity obtains a faster convergence rate, however, the introduced bias may also degrade the performance. In this paper, we theoretically analyze how the sparsity and the convergence rate of the precision matrix (also known as inverse covariance matrix) estimator would affect the classification accuracy by proposing an analytic model on the upper bound of an LDA misclassification rate. Guided by the model, we propose a novel classifier, DBSDA , which improves classification accuracy through debiasing. Theoretical analysis shows that DBSDA possesses a reduced upper bound of misclassification rate and better asymptotic properties than sparse LDA (SDA). We conduct experiments on both synthetic datasets and real application datasets to confirm the correctness of our theoretical analysis and demonstrate the superiority of DBSDA over LDA, SDA, and other downstream competitors under HDLSS settings.

Freshly-mixed and setting calcium-silicate cements stimulate human dental pulp cells.

OBJECTIVES: To evaluate the effect of the eluates from 3 freshly-mixed and setting hydraulic calcium-silicate cements (hCSCs) on human dental pulp cells (HDPCs) and to examine the effect of a newly developed hCSC containing phosphopullulan (PPL) on HDPCs. METHODS: Human dental pulp cells, previously characterized as mesenchymal stem cells, were used. To collect the eluates, disks occupying the whole surface of a 12-well plate were prepared using an experimental hCSC containing phosphopullulan (GC), Nex-Cem MTA (GC), Biodentine (Septodont) or a zinc-oxide (ZnO) eugenol cement (material-related negative control). Immediately after preparing the disks (non-set), 3ml of Dulbecco's Modified Eagle Medium (DMEM) with 10% fetal bovine serum (FBS) were added. The medium was left in contact with the disks for 24h before being collected. Four different dilutions were prepared (100%, 50%, 25% and 10%) and cell-cytotoxicity, cell-proliferation, cell-migration and odontogenic differentiation were tested. The cell-cytotoxicity and cell-proliferation assays were performed by XTT-colorimetric assay at different time points. The cell-migration ability was tested with the wound-healing assay and the odontogenic differentiation capacity of hCSCs on HDPCs was tested with RT-PCR. RESULTS: Considering all experimental data together, the eluates from 3 freshly-mixed and setting hCSCs appeared not cytotoxic toward HDPCs. Moreover, all three cements stimulated proliferation, migration and odontogenic differentiation of HDPCs. SIGNIFICANCE: The use of freshly-mixed and setting hCSCs is an appropriate approach to test the effect of the materials on human dental pulp cells. The experimental material containing PPL is non-cytotoxic and positively stimulates HDPCs.