Constrained C2 adsorbate orientation enables CO-to-acetate electroreduction.

The carbon dioxide and carbon monoxide electroreduction reactions, when powered using low-carbon electricity, offer pathways to the decarbonization of chemical manufacture1,2. Copper (Cu) is relied on today for carbon-carbon coupling, in which it produces mixtures of more than ten C2+ chemicals3-6: a long-standing challenge lies in achieving selectivity to a single principal C2+ product7-9. Acetate is one such C2 compound on the path to the large but fossil-derived acetic acid market. Here we pursued dispersing a low concentration of Cu atoms in a host metal to favour the stabilization of ketenes10-chemical intermediates that are bound in monodentate fashion to the electrocatalyst. We synthesize Cu-in-Ag dilute (about 1 atomic per cent of Cu) alloy materials that we find to be highly selective for acetate electrosynthesis from CO at high *CO coverage, implemented at 10 atm pressure. Operando X-ray absorption spectroscopy indicates in situ-generated Cu clusters consisting of <4 atoms as active sites. We report a 12:1 ratio, an order of magnitude increase compared to the best previous reports, in the selectivity for acetate relative to all other products observed from the carbon monoxide electroreduction reaction. Combining catalyst design and reactor engineering, we achieve a CO-to-acetate Faradaic efficiency of 91% and report a Faradaic efficiency of 85% with an 820-h operating time. High selectivity benefits energy efficiency and downstream separation across all carbon-based electrochemical transformations, highlighting the importance of maximizing the Faradaic efficiency towards a single C2+ product11.

[Advance of research on endoplasmic reticulum stress and genetic epilepsy].

Epilepsies are a group of chronic neurological disorders characterized by spontaneous recurrent seizures caused by abnormal synchronous firing of neurons and transient brain dysfunction. The underlying mechanisms are complex and not yet fully understood. Endoplasmic reticulum (ER) stress, as a condition of excessive accumulation of unfolded and/or misfolded proteins in the ER lumen, has been considered as a pathophysiological mechanism of epilepsy in recent years. ER stress can enhance the protein processing capacity of the ER to restore protein homeostasis through unfolded protein response, which may inhibit protein translation and promote misfolded protein degradation through the ubiquitin-proteasome system. However, persistent ER stress can also cause neuronal apoptosis and loss, which may aggravate the brain damage and epilepsy. This review has summarized the role of ER stress in the pathogenesis of genetic epilepsy.

Bromodomain containing 4 transcriptionally activated Deltex E3 ubiquitin ligase 2 contributes to glioma progression and predicts an unfavorable prognosis.

Background: Glioblastoma multiforme (GBM) is the most common type of glioma, and the most aggressive brain malignancy in adults. This study sought to identify novel survival-status related markers, and examine their function in glioma. Methods: The gene expression, survival heatmaps, and Kaplan-Meier survival plots of the genes were analyzed by using gene expression profiling interactive analysis (GEPIA) dataset, Linked Omics. The single-cell data analysis and tumor immune infiltration analysis was conducted by Tumor Immune Estimation Resource (TIMER) dataset. DBTRG and U251 cells with silenced Deltex E3 ubiquitin ligase 2 (DTX2) expression were constructed and used for Cell Counting Kit 8 (CCK-8), and wound healing assay in vitro. Chromatin immunoprecipitation sequencing (ChIP-seq) analysis was used to explore the histone activation marks and transcription factors DTX2 promoter. Dual-luciferase assays were carried out to detect the luciferase activities of bromodomain containing 4 (BRD4) binding to DTX2. Results: We first conducted a survival-status analysis to identify survival status-related genes in The Cancer Genome Atlas GBM and low-grade glioma data sets. A subsequent analysis identified 3 novel prognostic biomarkers; that is, DTX2, cytochrome P450 oxidoreductase, and Williams-Beuren syndrome chromosomal region 16 protein. In the validation Chinese Glioma Genome Atlas data sets, DTX2 showed the best performance, and was examined in a further analysis. Next, 3 short-hairpin ribonucleic acids were designed to silence DTX2 expression, and CCK-8 and wound-healing assays were applied to study the function of DTX2. We found that DTX2-silenced glioma cells exhibited a significant decrease in their growth and migration capabilities. Finally, the molecular basis for increased DTX2 in glioma was investigated via ChIP-Seq analysis and luciferase assays. The analysis revealed that DTX2 was transcriptionally activated by BRD4. Conclusions: In conclusion, BRD4 transcriptionally activates DTX2, contributes to glioma progression, predicts an unfavorable prognosis, and could provide new options for glioma prognosis prediction and treatment.

Hypomethylation-induced prognostic marker zinc finger DHHC-type palmitoyltransferase 12 contributes to glioblastoma progression.

Background: Glioma is the most common intracranial primary malignancy, characterized by abnormal signal transductions caused by transcriptional and post-transcriptional regulators. Studies show the palmitoylation of oncoproteins and tumor suppressors participate in cancer progression, while studies of protein S-palmitoyltransferases in glioma are limited. A systematic analysis of zinc finger DHHC-type palmitoyltransferases (ZDHHC) in glioma is still lacking. Methods: A prognostic heatmap and Kaplan-Meier overall survival plot of 24 members of the ZDHHC family in pan-cancer created. The expression and prognostic significance of ZDHHC12 was analyzed by using Gene Expression Profiling Interactive Analysis (GEPIA) and PrognoScan. DBTRG and U251 cells with silenced ZDHHC12 expression were constructed and used for cell counting kit-8 (CCK-8), Transwell assay and wound healing assay in vitro. Results: Here, we first conducted expression and prognostic analyses of 24 ZDHHCs from The Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA), and other glioma datasets. We found ZDHHC12 to be the only unfavorable prognostic marker in glioma. The function of ZDHHC12 in glioma was then investigated with loss-of-function strategies and in vitro cell assays. Results showed that ZDHHC12 knockdown remarkably reduced the growth, migration, and invasion capabilities in DBTRG and U251 cell lines, suggesting that ZDHHC12 may contribute to malignant behavior in glioma cells. Finally, the molecular basis for ZDHHC12 expression in glioma was analyzed, and DNA hypomethylation was found to be responsible for increased ZDHHC12 mRNA expression and related prognoses. Conclusions: ZDHHC12 positively promoted the proliferation and migration of glioma cells. Decreased DNA methylation may lead to increased ZDHHC12 expression in gliomas. This study may deepen the understanding of glioma progression and therapeutics.

CRISPR screening of E3 ubiquitin ligases reveals Ring Finger Protein 185 as a novel tumor suppressor in glioblastoma repressed by promoter hypermethylation and miR-587.

Glioblastoma (GBM) is the most common and aggressive malignant primary brain tumor. E3 ligases play important functions in glioma pathogenesis. CRISPR system offers a powerful platform for genome manipulation, while the screen of E3 ligases in GBM still remains to be explored. Here, we first constructed an E3 ligase small guide RNA (sgRNAs) library for glioma cells growth screening. After four passages, 299 significantly enriched or lost genes (SELGs) were compared with the initial state. Then the clinical significance of SELGs were validated and analyzed with TCGA glioblastoma and CGGA datasets. As RNF185 showed lost signal, decreased expression and favorable prognostic significance, we chose RNF185 for functional analysis. In vitro overexpressed cellular phenotype showed that RNF185 was a tumor suppressor in two glioma cell lines. Finally, the molecular mechanism of decreased RNF185 expression was investigated and increased miR-587 expression and DNA hypermethylation was evaluated. This study would provide a link between the molecular basis and glioblastoma pathogenesis, and a novel perspective for glioblastoma treatment.

Chemical and morphological defenses of Pseudo-nitzschia multiseries in response to zooplankton grazing.

Pseudo-nitzschia species frequently blooms in coastal waters, and some species are able to produce the toxin domoic acid (DA), hereby causing harm to the marine ecosystem and humans. Laboratory studies were conducted to investigate the influence of different levels of grazing pressure on the morphological and chemical response (in terms of cellular DA production) of Pseudo-nitzschia. Subsequently, zooplankton grazer responses to these defenses were examined. The cellular DA content of P. multiseries ranged from 0.11-0.27 pg cell-1 without grazers, and increased up to 44% with the presence of grazers (Artemia nauplii) and with grazer concentration. Grazing also affected the density of P. multiseries chains and average chain length which became ~25% higher and ~8% longer, respectively, than without grazers. These effects could either be caused by size-dependent grazing or by grazer-cue-induced effects on chain formation. A negative correlation between cellular DA content in P. multiseries and clearance and/or ingestion rates of Artemia nauplii indicate that DA might have a negative effect on the grazing of Artemia nauplii. Such interaction might result in a decrease in grazing pressure on toxic blooming species, like P. multiseries, and hence potentially a prolonged bloom. This indicates that the interaction between toxic diatoms and grazers may have implications on aquatic food web structure and the progression of Pseudo-nitzschia blooms.

Neuroprotective effects of FK866 against traumatic brain injury: Involvement of p38/ERK pathway.

OBJECTIVE: FK866 is an inhibitor of nicotinamide phosphoribosyltransferase (NAMPT), which exhibits neuroprotective effects in ischemic brain injury. However, in traumatic brain injury (TBI), the role and mechanism of FK866 remain unclear. The present research was aimed to investigate whether FK866 could attenuate TBI and clarified the underlying mechanisms. METHODS: A controlled cortical impact model was established, and FK866 at a dose of 5 mg/kg was administered intraperitoneally at 1 h and 6 h, then twice per day post-TBI until sacrifice. Brain water content, Evans blue dye extravasation, modified neurological severity scores (mNSS), Morris water maze test, enzyme-linked immunosorbent assay (ELISA), immunofluorescence staining, and western blot were performed. RESULTS: The results demonstrated that FK866 significantly mitigated the brain edema, blood-brain barrier (BBB) disruption, and ameliorated the neurological function post-TBI. Moreover, FK866 decreased the number of Iba-1-positive cells, GFAP-positive astrocytes, and AQP4-positive cells. FK866 reduced the protein levels of proinflammatory cytokines and inhibited NF-κB from translocation to the nucleus. FK866 upregulated the expression of Bcl-2, diminished the expression of Bax and caspase 3, and the number of apoptotic cells. Moreover, p38 MAPK and ERK activation were significantly inhibited by FK866. INTERPRETATION: FK866 attenuated TBI-induced neuroinflammation and apoptosis, at least in part, through p38/ERK MAPKs signaling pathway.