TonEBP: A Key Transcription Factor in Microglia Following Intracerebral Hemorrhage Induced-Neuroinflammation.

Transcription factors within microglia contribute to the inflammatory response following intracerebral hemorrhage (ICH). Therefore, we employed bioinformatics screening to identify the potential transcription factor tonicity-responsive enhancer-binding protein (TonEBP) within microglia. Inflammatory stimuli can provoke an elevated expression of TonEBP in microglia. Nevertheless, the expression and function of microglial TonEBP in ICH-induced neuroinflammation remain ambiguous. In our recent research, we discovered that ICH instigated an increased TonEBP in microglia in both human and mouse peri-hematoma brain tissues. Furthermore, our results indicated that TonEBP knockdown mitigates lipopolysaccharide (LPS)-induced inflammation and the activation of NF-κB signaling in microglia. In order to more deeply comprehend the underlying molecular mechanisms of how TonEBP modulates the inflammatory response, we sequenced the transcriptomes of TonEBP-deficient cells and sought potential downstream target genes of TonEBP, such as Pellino-1 (PELI1). PELI has been previously reported to mediate nuclear factor-κB (NF-κB) signaling. Through the utilization of CUT & RUN, a dual-luciferase reporter, and qPCR, we confirmed that TonEBP is the transcription factor of Peli1, binding to the Peli1 promoter. In summary, TonEBP may enhance the LPS-induced inflammation and activation of NF-κB signaling via PELI1.

Ternary alloy (FeCoNi) nanoparticles supported on hollow porous carbon with defects for enhanced oxygen evolution reaction.

Low-cost non-noble metal nanoparticles are promising electrocatalysts that can catalyze oxygen evolution reaction (OER). Various factors such as poor activity and stability hinder the practical applications of these materials. The electroactivity and durability of the electrocatalysts can be improved by optimizing the morphology and composition of the materials. Herein, we report the successful synthesis of hollow porous carbon (HPC) catalysts loaded with ternary alloy (FeCoNi) nanoparticles (HPC-FeCoNi) for efficient OER. HPC is firstly synthesized by a facile carbon deposition method using the hierarchical porous zeolite ZSM-5 as the hard template. Numerous defects are generated on the carbon shell during the removal of zeolite template. Subsequently, FeCoNi alloy nanoparticles are supported on HPC by a sequence of impregnation and H2 reduction processes. The synergistic effect between carbon defects and FeCoNi alloy nanoparticles endows the catalyst with an excellent OER performance (low overpotential of 219 mV; Tafel slope of 60.1 mV dec-1) in a solution of KOH (1 M). A stable potential is maintained during the continuous operation over 72 h. The designed HPC-FeCoNi presents a platform for the development of electrocatalysts that can be potentially applied for industrial OER.

Identification of epidermal growth factor receptor as an immune-related biomarker in epilepsy using multi-transcriptome data.

Background: Epilepsy is a chronic disease that is characterized by transient brain dysfunction caused by an abrupt abnormal neuronal discharge. Recent studies have indicated that the pathways related to inflammation and innate immunity play significant roles in the pathogenesis of epilepsy, suggesting an interrelationship between immunity and inflammatory processes and epilepsy. However, the immune-related mechanisms are still not precisely understood; therefore, this study aimed to explore the immune-related mechanisms in epilepsy disorders, highlight the role of immune cells at the molecular level in epilepsy, and provide therapeutic targets for patients with epilepsy. Methods: Brain tissue samples from healthy and epileptic individuals were collected for transcriptome sequencing to identify differentially expressed genes (DEGs) and differentially expressed (DE)-long coding RNAs (lncRNAs). Based on interactions from the miRcode, starBase2.0, miRDB, miRTarBase, TargetScan, and ENCORI databases, a lncRNA-associated competitive endogenous RNA (ceRNA) network was created. Gene ontology and the Kyoto encyclopedia of genes analyses established that the genes in the ceRNA network were mainly enriched in immune-related pathways. Immune cell infiltration, screening, and protein-protein interaction analyses of the immune-related ceRNAs, and correlation analysis between immune-related core messenger RNA (mRNA) and immune cells were also performed. Results: Nine hub genes (EGFR, GRB2, KRAS, FOS, ESR1, MAPK1, MAPK14, MAPK8, and PPARG) were obtained. Also, 38 lncRNAs, one miRNA (hsa-miR-27a-3p), and one mRNA (EGFR) comprised the final core ceRNA network. Mast cells, plasmacytoid dendritic cells, and immature dendritic cells all showed positive correlations with EGFR, while Cluster of differentiation 56 dim natural killer cells (CD56dim natural killer cells) showed negative correlations. Finally, we employed an epilepsy mouse model to validate EGFR, which is consistent with disease progression. Conclusions: In conclusion, the pathophysiology of epilepsy was correlated with EGFR. Thus, EGFR could be a novel biomarker of juvenile focal epilepsies, and our findings provide promising therapeutic targets for epilepsy.

Notes on Carex (Cyperaceae) from China (IX): three new species of section Mitratae s.l.

Carexsect.Mitratae s.l. was established by Kükenthal in 1909 and can be distinguished from the closely related sections in having nutlets frequently discoid-annulate at the apex and a persistent style base. Based on field surveys and specimen examination, three new species of sect. Mitratae are described and illustrated here. Carexfatsuaniana was collected from Yunnan and differs from C.truncatigluma in having the utricles nearly glabrous, the nutlets with a ca. 0.5 mm long beak at the apex, the staminate spikes cylindrical, 5-7.5 cm long, 4-5 mm wide, and the pistillate glumes acuminate at the apex. Carexdamingshanica was collected from Guangxi and differs from C.breviscapa and C.rhynchachaenium in having 3 or 4 spikes, the lateral spikes cylindrical, the pistillate glumes, utricles and nutlets all shorter than in the other two species. Carexradicalispicula was collected from Sichuan and differs from C.truncatirostris in having the staminate spikes clavate, 1.5-2 mm wide, the pistillate glumes pale yellow-white, 3-3.2 mm long, acuminate or short-awned at the apex, and the nutlets with 3 angles shallowly constricted at the middle.

NPAS4 Exacerbates Pyroptosis via Transcriptionally Regulating NLRP6 in the Acute Phase of Intracerebral Hemorrhage in Mice.

Intracerebral hemorrhage (ICH) is a severe cerebrovascular disease with a high disability rate and high mortality, and pyroptosis is a type of programmed cell death in the acute phase of ICH. Neuronal Per-Arnt-Sim domain protein 4 (Npas4) is a specific transcription factor highly expressed in the nervous system, yet the role of NPAS4 in ICH-induced pyroptosis is not fully understood. NLR family Pyrin-domain-containing 6 (NLRP6), a new member of the Nod-like receptor family, aggravates pyroptosis via activating cysteine protease-1 (Caspase-1) and Caspase-11. In this study, we found that NPAS4 was upregulated in human and mouse peri-hematoma brain tissues and peaked at approximately 24 h after ICH modeling. Additionally, NPAS4 knockdown improved neurologic dysfunction and brain damage induced by ICH in mice after 24 h. Meanwhile, inhibiting NPAS4 expression reduced the levels of myeloperoxidase (MPO)-positive cells and Caspase-1/TUNEL-double-positive cells and decreased cleaved Caspase-1, cleaved Caspase-11, and N-terminal GSDMD levels. Consistently, NPAS4 overexpression reversed the above alternations after ICH in the mice. Moreover, NPAS4 could interact with the Nlrp6 promoter region (-400--391 bp and -33--24 bp) and activate the transcription of Nlrp6. Altogether, our study demonstrated that NPAS4, as a transcription factor, can exacerbate pyroptosis and transcriptionally activate NLRP6 in the acute phase of intracerebral hemorrhage in mice.

Synergy between endo/exo-glucanases and expansin enhances enzyme adsorption and cellulose conversion.

Effective binding between cellulases and cellulose is essential for enzymatic hydrolysis of lignocellulose. Expansin can loosen the cellulose structure and can enhance the efficiency of cellulase. However, possible synergy between cellulases and expansin is not clear. In this work, the real-time adsorption of exoglucanases (Cel7A) or endoglucanases (Cel7B) with Bacillus subtilis expansin (BsEXLX1) and the enzymatic hydrolysis of cellulose were followed using quartz crystal microbalance with dissipation (QCM-D). Initial adsorption rate, adsorption capacity, and pseudo-steady-state rate of cellulose hydrolysis by Cel7A/Cel7B increased in the presence of BsEXLX1. When injecting Cel7A or Cel7B together with BsEXLX1 at a mass ratio of 1:1, the hydrolysis rate was almost 5 times the rate for Cel7A or Cel7B alone at 25 °C. These results increase our understanding of the real-time synergism between cellulases and expansin on cellulose, as well as the impact of their synergy on the enzymatic hydrolysis of cellulose.

Real-Time QCM-D Monitoring of the Adsorption-Desorption of Expansin on Lignin.

Expansin has nonhydrolytic disruptive activity and synergistically acts with cellulases to enhance the hydrolysis of cellulose. The adsorption-desorption of expansin on noncellulosic lignin can greatly affect the action of expansin on lignocellulose. In this study, three lignins with different sources (kraft lignin (KL), sodium lignin sulfonate (SLS), and enzymatic hydrolysis lignin (EHL)) were selected as the substrates. The real-time adsorption-desorption of Bacillus subtilis expansin (BsEXLX1) on lignins was monitored using quartz crystal microgravimetry with dissipation (QCM-D). The effects of temperature and Tween 80 on the adsorption-desorption behaviors were also investigated. The results show that BsEXLX1 exhibited high binding ability on lignin and achieved maximum adsorption of 283.2, 273.8, and 266.9 ng cm-2 at 25 °C on KL, SLS, and EHL, respectively. The maximum adsorption decreased to 148.2-192.8 ng cm-2 when the temperature increased from 25 to 45 °C. Moreover, Tween 80 competitively bound to lignin and significantly prevented expansin adsorption. After irreversible adsorption of Tween 80, the maximum adsorption of BsEXLX1 greatly decreased to 33.3, 37.2, and 10.3 ng cm-2 at 25 °C on KL, SLS, and EHL, respectively. Finally, a kinetic model was developed to analyze the adsorption-desorption process of BsEXLX1. BsEXLX1 has a higher adsorption rate constant (kA) and a lower desorption rate constant (kD) on KL than on SLS and EHL. The findings of this study provide useful insights into the adsorption-desorption of expansin on lignin.

Real-time adsorption and action of expansin on cellulose.

BACKGROUND: Biological pretreatment is an environmentally safe method for disrupting recalcitrant structures of lignocellulose and thereby improving their hydrolysis efficiency. Expansin and expansin-like proteins act synergistically with cellulases during hydrolysis. A systematic analysis of the adsorption behavior and mechanism of action of expansin family proteins can provide a basis for the development of highly efficient pretreatment methods for cellulosic substrates using expansins. RESULTS: Adsorption of Bacillus subtilis expansin (BsEXLX1) onto cellulose film under different conditions was monitored in real time using a quartz crystal microbalance with dissipation. A model was established to describe the adsorption of BsEXLX1 onto the film. High temperatures increased the initial adsorption rate while reducing the maximum amount of BsEXLX1 adsorbed onto the cellulose. Non-ionic surfactants (polyethylene glycol 4000 and Tween 80) at low concentrations enhanced BsEXLX1 adsorption; whereas, high concentrations had the opposite effect. However, sodium dodecyl sulfate inhibited adsorption at both low and high concentrations. We also investigated the structural changes of cellulose upon BsEXLX1 adsorption and found that BsEXLX1 adsorption decreased the crystallinity index, disrupted hydrogen bonding, and increased the surface area of cellulose, indicating greater accessibility of the substrate to the protein. CONCLUSIONS: These results increase our understanding of the interaction between expansin and cellulose, and provide evidence for expansin treatment as a promising strategy to enhance enzymatic hydrolysis of lignocellulose.

Real-Time Adsorption of Exo- and Endoglucanases on Cellulose: Effect of pH, Temperature, and Inhibitors.

Effective regulation of cellulase adsorption is key to improving the efficiencies of the two major bottlenecks of lignocellulose hydrolysis and cellulase recovery. In this work, we investigated the effect of inhibitors, pH, and temperature on the adsorption of exo- and endoglucanases (Cel7A and Cel7B, respectively) on cellulose using quartz crystal microgravimetry with dissipation. The addition of glucose and cellobiose can both inhibit the hydrolysis activity of Cel7A, whereas only cellobiose can inhibit that of Cel7B. Notably, the adsorption was favored by acidic conditions (pH ≤ 4.8) and low temperature, whereas alkaline conditions (pH 9 and 10) facilitated enzyme desorption, which is useful to guide the process of cellulase recovery. The adsorption and hydrolysis activity of Cel7A and Cel7B were both higher at 45 °C than at 25 °C. These findings pave the way to effective regulation of cellulase adsorption and thus improve lignocellulose conversion and cellulase recovery.