A transient brain endothelial translatome response to endotoxin is associated with mild cognitive changes post-shock in young mice.

Sepsis-associated encephalopathy (SAE) is a common manifestation in septic patients that is associated with increased risk of long-term cognitive impairment. SAE is driven, at least in part, by brain endothelial dysfunction in response to systemic cytokine signaling. However, the mechanisms driving SAE and its consequences remain largely unknown. Here, we performed translating ribosome affinity purification and RNA-sequencing (TRAP-seq) from the brain endothelium to determine the transcriptional changes after an acute endotoxemic (LPS) challenge. LPS induced a strong acute transcriptional response in the brain endothelium that partially correlates with the whole brain transcriptional response and suggested an endothelial-specific hypoxia response. Consistent with a crucial role for IL-6, loss of the main regulator of this pathway, SOCS3, leads to a broadening of the population of genes responsive to LPS, suggesting that an overactivation of the IL-6/JAK/STAT3 pathway leads to an increased transcriptional response that could explain our prior findings of severe brain injury in these mice. To identify any potential sequelae of this acute response, we performed brain TRAP-seq following a battery of behavioral tests in mice after apparent recovery. We found that the transcriptional response returns to baseline within days post-challenge. Despite the transient nature of the response, we observed that mice that recovered from the endotoxemic shock showed mild, sex-dependent cognitive impairment, suggesting that the acute brain injury led to sustained, non-transcriptional effects. A better understanding of the transcriptional and non-transcriptional changes in response to shock is needed in order to prevent and/or revert the devastating consequences of septic shock.

Helical vasculogenesis driven by cell chirality.

The cellular helical structure is well known for its crucial role in development and disease. Nevertheless, the underlying mechanism governing this phenomenon remains largely unexplored, particularly in recapitulating it in well-controlled engineering systems. Leveraging advanced microfluidics, we present compelling evidence of the spontaneous emergence of helical endothelial tubes exhibiting robust right-handedness governed by inherent cell chirality. To strengthen our findings, we identify a consistent bias toward the same chirality in mouse vascular tissues. Manipulating endothelial cell chirality using small-molecule drugs produces a dose-dependent reversal of the handedness in engineered vessels, accompanied by non-monotonic changes in vascular permeability. Moreover, our three-dimensional cell vertex model provides biomechanical insights into the chiral morphogenesis process, highlighting the role of cellular torque and tissue fluidity in its regulation. Our study unravels an intriguing mechanism underlying vascular chiral morphogenesis, shedding light on the broader implications and distinctive perspectives of tubulogenesis within biological systems.

Shock drives a STAT3 and JunB-mediated coordinated transcriptional and DNA methylation response in the endothelium.

Endothelial dysfunction is a crucial factor in promoting organ failure during septic shock. However, the underlying mechanisms are unknown. Here, we show that kidney injury after lipopolysaccharide (LPS) insult leads to strong endothelial transcriptional and epigenetic responses. Furthermore, SOCS3 loss leads to an aggravation of the responses, demonstrating a causal role for the STAT3-SOCS3 signaling axis in the acute endothelial response to LPS. Experiments in cultured endothelial cells demonstrate that IL-6 mediates this response. Furthermore, bioinformatics analysis of in vivo and in vitro transcriptomics and epigenetics suggests a role for STAT, AP1 and interferon regulatory family (IRF) transcription factors. Knockdown of STAT3 or the AP1 member JunB partially prevents the changes in gene expression, demonstrating a role for these transcription factors. In conclusion, endothelial cells respond with a coordinated response that depends on overactivated IL-6 signaling via STAT3, JunB and possibly other transcription factors. Our findings provide evidence for a critical role of IL-6 signaling in regulating shock-induced epigenetic changes and sustained endothelial activation, offering a new therapeutic target to limit vascular dysfunction.

First-principles investigation on multi-magnesium sulfide and magnesium sulfide clusters in magnesium-sulfide batteries.

Because of the abundance of magnesium and sulfur and their low cost, the development of magnesium sulfur batteries is very promising. In particular, the battery performance of nanoscale (MgS)n clusters is much better than that of bulk sized MgS. However, the structures, stability, and properties of MgxSy and (MgS)n clusters, which are very important to improve the performance of Mg-S batteries, are still unexplored. Herein, the most stable structures of MgxSy (x = 1-8, y = 1-8) and (MgS)n (n = 1-10) are reliably determined using the structure search method and density functional theory to calculate. According to calculation results, MgS3 and Mg6S8 may not exist in the actual charging and discharging products of magnesium sulfide batteries. The (MgS)n (n ≥ 5) clusters exhibit intriguing cage-like structures, which are favorable for eliminating dangling bonds and enhancing structural stability. Compared to the MgS monomer, each sulfur atom in the clusters is coordinated with more magnesium atoms, thus lengthening the Mg-S bond length and decreasing the Mg-S bond activation energy. Notably, with the increase of dielectric constant of electrolyte solvent, compared to the DME (ε = 7.2), THF (ε = 7.6) and C2H4Cl2 (ε = 10.0), MgxSy and (MgS)n clusters are most stable in the environment of C3H6O (ε = 20.7). It can delay the transformation of magnesium polysulfide to the final product MgS, which is conducive to improving the performance of Mg-S batteries. The predicted characteristic peaks of infrared and Raman spectra provide useful information for in situ experimental investigation. Our work represents a significant step towards understanding (MgS)n clusters and improving the performance of Mg-S batteries.

Cas12a-based one-pot SNP detection with high accuracy.

CRISPR-Cas12a based one-pot detection system has been used in nucleic acid detection and diagnosis. However, it is not sensitive enough to distinguish single nucleotide polymorphisms (SNP), which has greatly restricted its application. To overcome these limitations, we engineered a LbCas12a variant with enhanced sensitivity against SNP, named seCas12a (sensitive Cas12a). SeCas12a-based one-pot SNP detection system is a versatile platform that could use both canonical and non-canonical PAM, and was almost not limited by mutation types to distinguish SNPs located between position 1 to 17. The use of truncated crRNA further improved SNP specificity of seCas12a. Mechanistically, we found only when the cis-cleavage was at low level between 0.01min-1 and 0.0006 min-1, a good signal-to-noise ratio can be achieved in one-pot test. SeCas12a-based one-pot SNP detection system was applied to detect pharmacogenomic SNPs in human clinical samples. Of thirteen donors tested in two different SNPs, the seCas12a mediated one-pot system could faithfully detect the SNPs in 30 min with 100% accuracy.

Alloying effect of Ni-Mo catalyst in hydrogenation of N-ethylcarbazole for hydrogen storage.

Liquid organic hydrogen storage with N-ethylcarbazole (NEC) as a carrier is a very promising method. The use of precious metal hydrogenation catalysts restricts the development in industrial grade. Efficient and low-cost hydrogen storage catalysts are essential for its application. In this work, a Ni-Mo alloy catalyst supported by commercial activated carbon was synthesized by impregnation method, and the Ni-Mo ratio and preparation conditions were optimized. The catalyst was characterized by XRD, XPS, H2-TPR, SEM, and TEM. The results showed that the doping of Mo could dramatically promote the catalytic hydrogenation of N-ethylcarbazole by the Ni-based catalyst. More than 5.75 wt% hydrogenation could be achieved in 4 h using the Ni-Mo catalyst, and the selectivity of the fully hydrogenated product 12H-NEC could be effectively improved. This result reduces the cost of hydrogenation catalysts by more than 90% and makes liquid organic hydrogen storage a scaled possibility.

First-Principles-Based Optimized Design of Fluoride Electrolytes for Sodium-Ion Batteries.

Because of the abundance and low cost of sodium, sodium-ion batteries (SIBs) are next-generation energy storage mediums. Furthermore, SIBs have become an alternative option for large-scale energy storage systems. Because the electrolyte is a critical component of SIBs, fluorination is performed to improve the cycling performance of electrolytes. Based on the first-principles study, we investigated the effects of the type, quantity, and relative position relationships of three fluorinated units, namely -CF1, -CF2, and -CF3, on the cyclic ester molecule ethylene carbonate (EC) and the linear ether molecule 1,2-dimethoxylethane (DME). The optimal fluorination was proposed for EC and DME by studying the bond length, highest occupied molecular orbital, lowest unoccupied lowest orbital, and other relevant parameters. The results revealed that for EC, the optimal fluorination is 4 F fluorination based on four -CF1 units; for DME, CF3CF1CF1-, CF3CF2CF2-, CF3CF1CF2CF3, and CF3CF2CF2CF3, four combinations of three -CF1, -CF2, and -CF3 units are optimal. The designed fluorinated EC and DME exhibited a wide electrochemical stability window and high ionic solvation ability, which overcomes the drawback of conventional solvents and can improve SIB cycling performance.

Fast and sensitive detection of SARS-CoV-2 RNA using suboptimal protospacer adjacent motifs for Cas12a.

CRISPR-based assays for the detection of nucleic acids are highly specific, yet they are not fast, sensitive or easy to use. Here we report a one-step fluorescence assay for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in nasopharyngeal samples, with a sample-to-answer time of less than 20 minutes and a sensitivity comparable to that of quantitative real-time PCR with reverse transcription (RT-qPCR). The assay uses suboptimal protospacer adjacent motifs, allowing for flexibility in the design of CRISPR RNAs and slowing down the kinetics of Cas12a-mediated collateral cleavage of fluorescent DNA reporters and cis cleavage of substrates, which leads to stronger fluorescence owing to the accumulation of amplicons generated by isothermal recombinase polymerase amplification. In a set of 204 nasopharyngeal samples with RT-qPCR cycle thresholds ranging from 18.1 to 35.8, the assay detected SARS-CoV-2 with a sensitivity of 94.2% and a specificity of 100%, without the need for RNA extraction. Rapid and sensitive assays for nucleic acid testing in one pot that allow for flexibility in assay design may aid the development of reliable point-of-care nucleic acid testing.

An improved novel quantum image representation and its experimental test on IBM quantum experience.

Quantum image representation (QIR) is a necessary part of quantum image processing (QIP) and plays an important role in quantum information processing. To address the problems that NCQI cannot handle images with inconsistent horizontal and vertical position sizes and multi-channel image processing, an improved color digital image quantum representation (INCQI) model based on NCQI is proposed in this paper. The INCQI model can process color images and facilitate multi-channel quantum image transformations and transparency information processing of images using auxiliary quantum bits. In addition, the quantum image control circuit was designed based on INCQI. And quantum image preparation experiments were conducted on IBM Quantum Experience (IBMQ) to verify the feasibility and effectiveness of INCQI quantum image preparation. The prepared image information was obtained by quantum measurement in the experiment, and the visualization of quantum information was successfully realized. The research in this paper has some reference value for the research related to QIP.

Endothelial SOCS3 maintains homeostasis and promotes survival in endotoxemic mice.

SOCS3 is the main inhibitor of the JAK/STAT3 pathway. This pathway is activated by interleukin 6 (IL-6), a major mediator of the cytokine storm during shock. To determine its role in the vascular response to shock, we challenged mice lacking SOCS3 in the adult endothelium (SOCS3iEKO) with a nonlethal dose of lipopolysaccharide (LPS). SOCS3iEKO mice died 16-24 hours postinjection after severe kidney failure. Loss of SOCS3 led to an LPS-induced type I IFN-like program and high expression of prothrombotic and proadhesive genes. Consistently, we observed intraluminal leukocyte adhesion and neutrophil extracellular trap-osis (NETosis), as well as retinal venular leukoembolization. Notably, heterozygous mice displayed an intermediate phenotype, suggesting a gene dose effect. In vitro studies were performed to study the role of SOCS3 protein levels in the regulation of the inflammatory response. In human umbilical vein endothelial cells, pulse-chase experiments showed that SOCS3 protein had a half-life less than 20 minutes. Inhibition of SOCS3 ubiquitination and proteasomal degradation led to protein accumulation and a stronger inhibition of IL-6 signaling and barrier function loss. Together, our data demonstrate that the regulation of SOCS3 protein levels is critical to inhibit IL-6-mediated endotheliopathy during shock and provide a promising therapeutic avenue to prevent multiorgan dysfunction through stabilization of endothelial SOCS3.

Chimeric DNA-RNA Guide RNA Designs.

CRISPR-associated nuclease (Cas) has been widely applied to modify the genomes of various cell types. As RNA-guided endonucleases, Cas enzymes can target different genomic sequences simply by changing the guide sequence of the CRISPR RNA (crRNA) or single guide RNA (sgRNA). Recent studies have demonstrated that DNA-RNA chimeric crRNA or sgRNA can efficiently guide the Cas9 protein for genome editing with reduced off-target effects. This chapter aims to describe a procedure for using chimeric RNA to modify the genomes of mammalian cells.

ResNet-Locust-BN Network-Based Automatic Identification of East Asian Migratory Locust Species and Instars from RGB Images.

Locusts are agricultural pests found in many parts of the world. Developing efficient and accurate locust information acquisition techniques helps in understanding the relation between locust distribution density and structural changes in locust communities. It also helps in understanding the hydrothermal and vegetation growth conditions that affect locusts in their habitats in various parts of the world as well as in providing rapid and accurate warnings on locust plague outbreak. This study is a preliminary attempt to explore whether the batch normalization-based convolutional neural network (CNN) model can be applied used to perform automatic classification of East Asian migratory locust (AM locust), Oxya chinensis (rice locusts), and cotton locusts. In this paper, we present a way of applying the CNN technique to identify species and instars of locusts using the proposed ResNet-Locust-BN model. This model is based on the ResNet architecture and involves introduction of a BatchNorm function before each convolution layer to improve the network's stability, convergence speed, and classification accuracy. Subsequently, locust image data collected in the field were used as input to train the model. By performing comparison experiments of the activation function, initial learning rate, and batch size, we selected ReLU as the preferred activation function. The initial learning rate and batch size were set to 0.1 and 32, respectively. Experiments performed to evaluate the accuracy of the proposed ResNet-Locust-BN model show that the model can effectively distinguish AM locust from rice locusts (93.60% accuracy) and cotton locusts (97.80% accuracy). The model also performed well in identifying the growth status information of AM locusts (third-instar (77.20% accuracy), fifth-instar (88.40% accuracy), and adult (93.80% accuracy)) with an overall accuracy of 90.16%. This is higher than the accuracy scores obtained by using other typical models: AlexNet (73.68%), GoogLeNet (69.12%), ResNet 18 (67.60%), ResNet 50 (80.84%), and VggNet (81.70%). Further, the model has good robustness and fast convergence rate.

Rapid detection of African swine fever virus using Cas12a-based portable paper diagnostics.

African swine fever virus (ASFV) is a dsDNA virus responsible for a severe, highly contagious, and lethal disease affecting both domestic and wild pigs. ASFV has brought enormous economic loss to a number of countries, and effective vaccine and therapy are still lacking. Therefore, a rapid, sensitive, and field-deployable detection of ASFV is important for disease surveillance and control. Herein, we developed a Cas12a-mediated portable paper assay to rapidly and precisely detect ASFV. We identified a robust set of crRNAs that recognized the highly conserved region of essential ASFV genes. The Cas12a-mediated detection assay showed low tolerance for mismatch mutations, and no cross-reactivity against other common swine pathogens. We further developed a paper-based assay to allow instrument-free detection of ASFV. Specifically, we applied gold nanoparticle-antibody conjugate to engineer homemade strips and combined it with Cas12a-mediated ASFV detection. This portable paper, instrument-free diagnostics, faithfully detected ASFV in swine samples, showing comparable sensitivity to the traditionally instrument-dependent qPCR method. Taking together, we developed a highly sensitive, instant, and economic Cas12a-mediated paper diagnostics of ASFV, with a great application potential for monitoring ASFV in the field.

A biocompatible PAA-Cu-MOP hydrogel for wound healing.

Wounds infected by bacteria are dangerous for human beings. However, along with the emergence of new strains and strong bacterial resistance, traditional antibiotics are unable to meet the medical needs for treating bacterial infections. Thus, new antibacterial substances with superior antimicrobial properties are urgently needed. Herein, a hydrogel containing poly acrylic acid (PAA), glycerol and Cu-MOP (named PAA-Cu-MOP hydrogel) is obtained by a facile mixing and ultrasonic procedure for wound healing treatment. This PAA-Cu-MOP hydrogel with high biocompatibility exhibits excellent wound healing behavior and is even better than the one of recombinant human epidermal growth factor. Tissue experiment results reveal that the PAA-Cu-MOP hydrogel accelerates the wound healing process by promoting angiogenesis, stimulating cell proliferation, and up-regulating cell factors.

Three Silver Coordination Polymers with Diverse Architectures Constructed from Pyridine Carboxylic Hydrazide Ligands.

A series of silver coordination polymers (CPs) have been synthesized through self-assembly of three pyridinecarboxylic acid hydrazide (p-, m-, o-position) ligands with silver clusters (named Ag1-iah, Ag2-iah, and Ag3-iah). These silver CPs show different one- and two-dimensional topologies including cross-helical chains, planar network, and parallel helical chains for Ag1-iah, Ag2-iah, and Ag3-iah, respectively. The combination of experimental and computational results reveals the critical role in the space distribution of the coordination site of silver clusters and ligands in controlling the silver CPs' dimensionality and packing arrangement and modulating the optical properties and stability. Luminescent investigations reveal that Ag3-iah can selectively detect dichloromethane or trichloromethane in tetrachloromethane. These silver CPs provide a good model to study the influence of the space distribution of the coordination site of ligands on their packing arrangement and properties.

A hollow microshuttle-shaped capsule covalent organic framework for protein adsorption.

Covalent organic frameworks (COFs) are a class of crystalline porous materials utilized in various potential applications. However, the development of hollow-structured COFs with defined morphology is important for their further applications, which is rare. Herein, COF with unique hollow shuttle morphology was prepared by a Schiff condensation reaction between 4-(4-aldehyde phenyl)ethylene (TPE) and tetra-(4-aminophenyl) porphyrin (TAP). A detailed mechanistic investigation reveals that an initial self-assembly followed by a similar inside-out Ostwald ripening process is responsible for the hollow capsule formation. The hollow microshuttle-shaped capsule COF is used for studying hemoglobin adsorption, which shows an uptake of 550.82 mg g-1 of hemoglobin. These studies could foreshadow new avenues for the development of porous materials with defined morphologies for the adsorption of biomolecules.

Trichostatin A inhibits the activation of Hepatic stellate cells by Increasing C/EBP-α Acetylation in vivo and in vitro.

Reversal of activated hepatic stellate cells (HSCs) to a quiescent state and apoptosis of activated HSCs are key elements in the reversion of hepatic fibrosis. CCAAT/enhancer binding protein α (C/EBP-α) has been shown to inhibit HSC activation and promote its apoptosis. This study aims to investigate how C/EBP-α acetylation affects the fate of activated HSCs. Effects of a histone deacetylation inhibitor trichostatin A (TSA) on HSC activation were evaluated in a mouse model of liver fibrosis caused by carbon tetrachloride (CCl4) intoxication. TSA was found to ameliorate CCl4-induced hepatic fibrosis and improve liver function through increasing the protein level and enhancing C/EBP-α acetylation in the mouse liver. C/EBP-α acetylation was determined in HSC lines in the presence or absence of TSA, and the lysine residue K276 was identified as a main acetylation site in C/EBP-α protein. C/EBP-α acetylation increased its stability and protein level, and inhibited HSC activation. The present study demonstrated that C/EBP-α acetylation increases the protein level by inhibiting its ubiquitination-mediated degradation, and may be involved in the fate of activated HSCs. Use of TSA may confer an option in minimizing hepatic fibrosis by suppressing HSC activation, a key process in the initiation and progression of hepatic fibrosis.

A highly selective TPE-based AIE fluorescent probe is developed for the detection of Ag.

The detection of Ag+ in the environment is very important to determine the level of pollution from silver complexes, which have caused various human health problems. Herein, an aggregation-induced emission (AIE) chromophore (tetraphenylethane, TPE) attached to a benzimidazole group (tetra-benzimidazole, TBI-TPE) is synthesized and utilized to detect Ag+ in the environment. The strong chelating effect between the benzimidazole group and Ag+ leads to the formation of aggregates, and strong yellow fluorescence signals were observed after adding Ag+ into a TBI-TPE solution. The stoichiometry of the complex of TBI-TPE and Ag+ was established to be 1 : 2 using photochemical and mass spectra measurements. The detection limit of the Ag+ assay is 90 nM with a linear range from 100 nM to 6 µM. This study provides a facile method to determine Ag+ in real environmental samples with satisfactory results.