Regulation of Keap1-Nrf2 signaling in health and diseases.

Nuclear factor erythroid 2-related factor 2 (Nrf2) functions as a central regulator in modulating the activities of diverse antioxidant enzymes, maintaining cellular redox balance, and responding to oxidative stress (OS). Kelch-like ECH-associated protein 1 (Keap1) serves as a principal negative modulator in controlling the expression of detoxification and antioxidant genes. It is widely accepted that OS plays a pivotal role in the pathogenesis of various diseases. When OS occurs, leading to inflammatory infiltration of neutrophils, increased secretion of proteases, and the generation of large quantities of reactive oxygen radicals (ROS). These ROS can oxidize or disrupt DNA, lipids, and proteins either directly or indirectly. They also cause gene mutations, lipid peroxidation, and protein denaturation, all of which can result in disease. The Keap1-Nrf2 signaling pathway regulates the balance between oxidants and antioxidants in vivo, maintains the stability of the intracellular environment, and promotes cell growth and repair. However, the antioxidant properties of the Keap1-Nrf2 signaling pathway are reduced in disease. This review overviews the mechanisms of OS generation, the biological properties of Keap1-Nrf2, and the regulatory role of its pathway in health and disease, to explore therapeutic strategies for the Keap1-Nrf2 signaling pathway in different diseases.

Protein Editing using a Concerted Transposition Reaction.

Protein engineering through the chemical or enzymatic ligation of polypeptide fragments has proven enormously powerful for studying countless biochemical processes in vitro. In general, this strategy necessitates a protein folding step following ligation of the unstructured fragments, a requirement that constrains the types of systems amenable to the approach. Here, we report an in vitro strategy that allows internal regions of target proteins to be replaced in a single operation. Conceptually, our system is analogous to a DNA transposition reaction, but employs orthogonal pairs of split inteins to swap out a designated region of a host protein with an exogenous molecular cassette. We show using isotopic labeling experiments that this 'protein transposition' reaction is concerted when the kinetics for the embedded intein pairs are suitably matched. Critically, this feature allows for efficient manipulation of protein primary structure in the context of a native fold. The utility of this method is illustrated using several protein systems including the multisubunit chromatin remodeling complex, ACF, where we also show protein transposition can occur in situ within the cell nucleus. By carrying out a molecular 'cut and paste' on a protein or protein complex under native folding conditions, our approach dramatically expands the scope of protein semisynthesis.

Microfluidic Printing of Vertically-Oriented Nanosheets/MOFs Hetero-Interface for Intensive Pseudocapacitive Storage.

Efficient manufacture of electroactive vertically-oriented nanosheets with enhanced electrolyte mass diffusion and strong interfacial redox dynamics is critical for realizing high energy density of miniature supercapacitor (SC), but still challenging. Herein, microfluidic droplet printing is developed to controllably construct vertically-oriented graphene/ZIF-67 hetero-microsphere (VAGS/ZIF-67), where the ZIF-67 is coordinately grown on vertically-oriented graphene framework via Co─O─C bonds. The VAGS/ZIF-67 shows ordered porous channel, high electroactivity and strong interfacial interaction, providing rapid electrolyte diffusion dynamics and high faradaic capacitance in KOH solution (1674 F g-1 , 1004 C g-1 ), which are verified by computational fluid dynamics (CFD) and density functional theory (DFT). Moreover, the VAGS/ZIF-67 based SC exhibits large energy density (100 Wh kg-1 ), excellent durability (10 000 cycles and high/low temperature), and robust power-supply applications in portable electronics.

A Novel Bubble-based Microreactor for Enhanced Mass Transfer Dynamics toward Efficient Electrocatalytic Nitrogen Reduction.

Electrocatalytic nitrogen reduction reaction (eNRR) is a promising method for sustainable ammonia production. Although the majority of studies on the eNRR are devoted to developing efficient electrocatalysts, it is critical to study the influence of mass transfer because of the poor N2 transfer efficiency. Herein, a novel bubble-based microreactor (BBMR) is proposed that efficiently promotes the mass transfer behavior during the eNRR using microfluidic strategies. The BBMR possesses abundant triphasic interfaces and provides spatial confinement and accurate potential control, ensuring rapid mass transfer dynamics and improved eNRR performance, as confirmed by experimental and simulation studies. The ammonia yield of the reaction over Ag nanoparticles can be enhanced to 31.35 µg h-1 mgcat. -1, which is twice that of the H-cell. Excellent improvements are also achieved using Ru/C and Fe/g-CN catalysts, with 5.0 and 8.5 times increase in ammonia yield, respectively. This work further demonstrates the significant effect of mass transfer on the eNRR performance and provides an effective strategy for process enhancement through electrode design.

Frontier and hotspot evolution in Brugada syndrome: A bibliometric analysis from 2002 to 2022.

BACKGROUND: Brugada syndrome (BrS) is a genetic disorder characterized by a typical electrocardiogram pattern and predisposition to arrhythmias and sudden cardiac death. Despite our considerably evolved understanding of BrS, no bibliometrics have been performed in this research field. We aimed to analyze and visualize the characteristics of the scientific outputs, topical evolutions, and research trends of BrS over the past 2 decades using bibliometric analysis. METHODS: The literature associated with BrS was retrieved from the Science Citation Index Expanded of the Web of Science Core Collection database. Acquired data were then visually analyzed using CiteSpace and VOSviewer. RESULTS: 3042 qualifying records were included in the final analysis. The publication outputs increased over time. The United States was the leading country in the BrS research. The University of Amsterdam (Netherlands) was the most prolific and influential institution. Pedro Brugada, Arthur Wilde, and Charles Antzelevitch exerted notable publication impact and made the most significant contributions in the field of BrS. Heart Rhythm had the highest outputs and Circulation was the most influential journal. Bundle branch block, ST-segment elevation, mechanism, management, right precordial lead, and guideline were the keywords with the strongest citation burst. CONCLUSION: Research on BrS is prosperous. Keywords and co-citation analysis revealed that the mechanism, diagnosis, risk stratification, and management of BrS were the research hotspots. Besides, the underlying pathophysiology, novel therapies, and personalized risk assessment might be the emerging trends of future research.

A critical review of adsorption isotherm models for aqueous contaminants: Curve characteristics, site energy distribution and common controversies.

The quantitative description of the equilibrium data by the isotherm models is an indispensable link in adsorption studies. The previous review papers focus on the underlying assumptions, fitting methods, error functions and practical applications of the isotherm models, usually ignoring their curve characteristics, selection criteria and common controversies. The main contents of this review include: (i) effect of the model parameters on the isotherm curves; (ii) determination of the site energy distribution; (iii) selection criteria of the isotherm models; and (iv) elimination of some common controversies. It is of great significance to reveal the curve characteristics for selecting a proper isotherm model. The site energy distribution is conducive to understanding the physicochemical properties of the adsorbent surface. The complete isotherm is recommended to be correlated with the experimental data. The model parameter qmax should be cautiously adopted for comparison of the adsorbent performance. The residual plot can be used to diagnose the fitting quality of the isotherm models further. This review also addresses some common mistakes and controversies and thereby avoids their propagation in future publications.

Influenza A Virus Infection Reactivates Human Endogenous Retroviruses Associated with Modulation of Antiviral Immunity.

Human endogenous retrovirus (HERVs), normally silenced by methylation or mutations, can be reactivated by multiple environmental factors, including infections with exogenous viruses. In this work, we investigated the transcriptional activity of HERVs in human A549 cells infected by two wild-type (PR8M, SC35M) and one mutated (SC35MΔNS1) strains of Influenza A virus (IAVs). We found that the majority of differentially expressed HERVs (DEHERVS) and genes (DEGs) were up-regulated in the infected cells, with the most significantly enriched biological processes associated with the genes differentially expressed exclusively in SC35MΔNS1 being linked to the immune system. Most DEHERVs in PR8M and SC35M are mammalian apparent LTR retrotransposons, while in SC35MΔNS1, more HERV loci from the HERVW9 group were differentially expressed. Furthermore, up-regulated pairs of HERVs and genes in close chromosomal proximity to each other tended to be associated with immune responses, which implies that specific HERV groups might have the potential to trigger specific gene networks and influence host immunological pathways.

Epidemiology of Campus Football Injuries in Ningxia, China: Occurrence, Causes, and Management.

Objective: By 2022, the Chinese government intends to have more than 30 million primary-, middle- and high-school children and adolescents regularly participate in campus football. In contrast, epidemiology of campus football injuries is completely missing. The goal of this descriptive epidemiological study was to determine the current state of campus football injuries and then to recommend appropriate prevention and management strategies. Methods: This retrospective epidemiological study conducted a survey of students, physical education and football teachers in primary, middle and high schools in the Ningxia Autonomous Region to determine the campus football injuries that occurred throughout the preceding 12-month period. The survey comprised questions on demographic characteristics, the occurrence, causes, and management of campus football injuries. Results: A total of 1,285 students and 200 teachers returned eligible surveys. 25.7% of students had encountered injury accidents while participating in campus football activities. 31.3% of high school students, 23.8% of middle school students, and 19.2% of primary school students have sustained injuries. Football competition, accounting for 45.4% of all injuries, is the leading cause of injury. Football class teaching, which accounted for 3.0% of all injuries, had the lowest injury rate of any campus football activity. Students and teachers reported that a lack of safety awareness and injury prevention education were the primary causes of injuries. Only 18.7% and 11.4% of students are familiar with first aid basics and cardiopulmonary resuscitation, respectively. 10.6% and 7.5% of students lack any first aid basics and skills, respectively. 43.9% of students lack insurance coverage for athletic injuries. 62.5% and 38.5% of teachers reported that schools lack first aid training and an emergency plan for injuries, respectively. Conclusion: Students in Ningxia's campus football programs have a high injury risk. Injury prevention and management strategies lag significantly behind the mainstream nationwide promotion of campus football in China.

Synthesis of Oriented Hexasomes and Asymmetric Nucleosomes Using a Template Editing Process.

Nucleosomes, the structural building blocks of chromatin, possess 2-fold pseudo symmetry which can be broken through differential modification or removal of one copy of a pair of sister histones. The resultant asymmetric nucleosomes and hexasomes have been implicated in gene regulation, yet the use of these noncanonical substrates in chromatin biochemistry is limited, owing to the lack of efficient methods for their preparation. Here, we report a strategy that allows the orientation of these asymmetric species to be tightly controlled relative to the underlying DNA sequence. Our approach is based on the use of truncated DNA templates to assemble oriented hexasomes followed by DNA ligation and, in the case of asymmetric nucleosomes, addition of the missing heterotypic histones. We show that this approach is compatible with multiple nucleosome positioning sequences, allowing the generation of desymmetrized mononucleosomes and oligonucleosomes with varied DNA overhangs and heterotypic histone H2A/H2B dimer compositions. Using this technology, we examine the functional consequences of asymmetry on BRG1/BRM associated factor (BAF) complex-mediated chromatin remodeling. Our results indicate that cancer-associated histone mutations can reprogram the inherent activity of BAF chromatin remodeling to induce aberrant chromatin structure.

Chromatin landscape signals differentially dictate the activities of mSWI/SNF family complexes.

Mammalian SWI/SNF (mSWI/SNF) adenosine triphosphate-dependent chromatin remodelers modulate genomic architecture and gene expression and are frequently mutated in disease. However, the specific chromatin features that govern their nucleosome binding and remodeling activities remain unknown. We subjected endogenously purified mSWI/SNF complexes and their constituent assembly modules to a diverse library of DNA-barcoded mononucleosomes, performing more than 25,000 binding and remodeling measurements. Here, we define histone modification-, variant-, and mutation-specific effects, alone and in combination, on mSWI/SNF activities and chromatin interactions. Further, we identify the combinatorial contributions of complex module components, reader domains, and nucleosome engagement properties to the localization of complexes to selectively permissive chromatin states. These findings uncover principles that shape the genomic binding and activity of a major chromatin remodeler complex family.

Deeper Insights into the Bohart-Adams Model in a Fixed-Bed Column.

The Bohart-Adams model was one of the most widely used breakthrough models in column experiments. However, it usually provided a poor fit for the modeling of an asymmetric breakthrough curve. This work proposed the n-order Bohart-Adams and fractal-like Bohart-Adams models. The former indicated a nonlinear decay process of the concentration of the adsorbate or residual capacity of the adsorbent, while the latter reflected a diffusion-limited process on the heterogeneous surfaces. The Bohart-Adams and modified Bohart-Adams models were mathematically equivalent. The applicability of the n-order Bohart-Adams and fractal-like Bohart-Adams models was validated by norfloxacin and Cu(II) adsorption in a fixed-bed column. Compared with the Bohart-Adams model, the two new models had better fitting performance with higher R2 and lower χ2 values, and all of the residuals were randomly distributed. The fractal-like Bohart-Adams and modified dose-response models provided the best fitting quality for the adsorption of Cu(II) (R2 = 0.9956 and χ2 = 7.56 × 10-4) and norfloxacin (R2 = 0.9991 and χ2 = 1.37 × 10-4), respectively. This work may provide a practical method for the modeling of the asymmetric breakthrough curves.

Activation of HERV-K(HML-2) disrupts cortical patterning and neuronal differentiation by increasing NTRK3.

The biological function and disease association of human endogenous retroviruses (HERVs) are largely elusive. HERV-K(HML-2) has been associated with neurotoxicity, but there is no clear understanding of its role or mechanistic basis. We addressed the physiological functions of HERV-K(HML-2) in neuronal differentiation using CRISPR engineering to activate or repress its expression levels in a human-pluripotent-stem-cell-based system. We found that elevated HERV-K(HML-2) transcription is detrimental for the development and function of cortical neurons. These effects are cell-type-specific, as dopaminergic neurons are unaffected. Moreover, high HERV-K(HML-2) transcription alters cortical layer formation in forebrain organoids. HERV-K(HML-2) transcriptional activation leads to hyperactivation of NTRK3 expression and other neurodegeneration-related genes. Direct activation of NTRK3 phenotypically resembles HERV-K(HML-2) induction, and reducing NTRK3 levels in context of HERV-K(HML-2) induction restores cortical neuron differentiation. Hence, these findings unravel a cell-type-specific role for HERV-K(HML-2) in cortical neuron development.

Simultaneous removal of nitrate and hydrogen sulfide by autotrophic denitrification in nitrate-contaminated water treatment.

Nitrate contamination is a risk to human health and may cause eutrophication, whereas H2S is an undesirable constituent in biogas. In order to better understand denitrification using gaseous H2S as electron donor, this study investigated denitrification at different molar ratios of sulfur and nitrogen (S/N ratios) and H2S dosages. Although nitrate continued to decrease, a lag in sulfate generation was observed, implying the generation of sulfide oxidizing intermediates, which accumulated even though nitrate was in excess at lower S/N ratios of 0.19 and 0.38. More addition of H2S could result in a longer lag of sulfate generation. Before depletion of dissolved sulfide, denitrification could proceed with little nitrite accumulation. High throughout sequencing analysis identified two major genera, Thiobacillus and Sulfurimonas, that were responsible for autotrophic denitrification. The simultaneous removal of nitrate and H2S using a wide range of concentrations could be achieved.

Stimulation impact of electric currents on heterotrophic denitrifying microbial viability and denitrification performance in high concentration nitrate-contaminated wastewater.

Electric current stimulation has been shown to have a positive influence on heterotrophic denitrifying microbial viability and has the potential to improve wastewater denitrification performance. This study investigated the effects of varying current densities on microbial activity and NO3- removal efficiency under heterotrophic conditions.NO3- removal rate was highest at an applied current density of 400 mA/m2. However, the optimum removal efficiency of total inorganic nitrogen (TIN; 99%) was achieved when the current density was fixed at 200 mA/m2. Accumulation of NH4+-N and NO2--N byproducts were also minimized at this current density. The activity of heterotrophic denitrifying microorganisms was much higher at both 200 and 400 mA/m2. Moreover, the average adenosine-5'-triphosphate (ATP) content (an indicator of cell metabolism) at a current density of 1600 mA/m2 was lower than that under no current, indicating heterotrophic denitrifying microbial activity can be inhibited at high current densities. Hence, direct electrical stimulation on the activity of heterotrophic denitrifying microorganisms in the developed system should be lower than 1600 mA/m2. This study improves the understanding of electric current influence on heterotrophic denitrifying microorganisms and promotes the intelligent application of direct electrical stimulation on wastewater treatment processes.

Research on the treatment of biologically treated landfill leachate by joint electrochemical system.

Biologically treated landfill leachate (BTLL) is typically characterized by significantly high amount of total nitrogen (TN) and chemical oxygen demand (COD), and it has low biodegradability. In this study, a joint electrochemical system (JES) composed of iron anode reactor (IAR) and Ti/RuO2 anode reactor (TAR) was constructed to remove both TN and COD from BTLL and improve its biodegradability. The IAR and TAR with the same structure but using different anodes. As a result, JES could simultaneously remove COD and TN by 90.9 ±â€¯0.3% and 90.2 ±â€¯1.0%, respectively. Reduction of nitrite-N by Cu/Zn cathode in IAR and oxidation of ammonium-N by active chlorine in TAR were the major pathways for TN removal, while the COD could be removed by coagulation of iron flocs and oxidation by hydroxyl radicals and active chlorine. Fluorescence spectrum and parallel factor analysis showed that the main components of organics in BTLL were humic-like substances, fulvic-like substances, and soluble microbial degradation products. Humic-like substances were particularly removed by JES, and the remaining organics after electrolysis were some alkanes (e.g., heptane and nonane). Furthermore, decrease in molecular weight and aromaticity and increase in biodegradable substances indicated that the biodegradability of BTLL was effectively improved by the JES. The developed JES is a promising approach for application in the BTLL treatment.

Tuning the Mechanical Properties of a DNA Hydrogel in Three Phases Based on ATP Aptamer.

By integrating ATP aptamer into the linker DNA, a novel DNA hydrogel was designed, with mechanical properties that could be tuned into three phases. Based on the unique interaction between ATP and its aptamer, the mechanical strength of the hydrogel increased from 204 Pa to 380 Pa after adding ATP. Furthermore, with the addition of the complementary sequence to the ATP aptamer, the mechanical strength could be increased to 570 Pa.

Impact of electro-stimulation on denitrifying bacterial growth and analysis of bacterial growth kinetics using a modified Gompertz model in a bio-electrochemical denitrification reactor.

This study aimed to investigate the effect of electro-stimulation on denitrifying bacterial growth in a bio-electrochemical reactor, and the growth were modeled using modified Gompertz model under different current densities at three C/Ns. It was found that the similar optimum current density of 250mA/m2 was obtained at C/N=0.75, 1.00 and 1.25, correspondingly the maximum nitrate removal efficiencies were 98.0%, 99.2% and 99.9%. Moreover, ATP content and cell membrane permeability of denitrifying bacteria were significantly increased at optimum current density. Furthermore, modified Gompertz model fitted well with the microbial growth curves, and the highest maximum growth rates (µmax) and shorter lag time were obtained at the optimum current density for all C/Ns. This study demonstrated that the modified Gompertz model could be used for describing microbial growth under different current densities and C/Ns in a bio-electrochemical denitrification reactor, and it provided an alternative for improving the performance of denitrification process.

Effect of electro-stimulation on activity of heterotrophic denitrifying bacteria and denitrification performance.

The effects of electro-stimulation on heterotrophic denitrifying bacterial activity and nitrate removal were investigated using a bench-scale bio-electrochemical reactor in this study. Results showed that the maximum nitrate removal efficiency was 100% at the optimum current density of 200mA/m(2), at which low nitrite production and high ATP aggregate level were obtained. The activity of denitrifying bacteria was highest at the range densities of 200-250mA/m(2), although the terminative pH increased to 8.62 at 200mA/m(2) and 9.63 at 250mA/m(2). This demonstrates that suitable current densities could improve the activity of denitrifying bacteria. Therefore, this study provides a number of useful information to improve the bio-electrochemical reactor designs and promote the removal efficiency of pollutants.

Imprecise intron losses are less frequent than precise intron losses but are not rare in plants.

UNLABELLED: In this study, we identified 19 intron losses, including 11 precise intron losses (PILs), six imprecise intron losses (IILs), one de-exonization, and one exon deletion in tomato and potato, and 17 IILs in Arabidopsis thaliana. Comparative analysis of related genomes confirmed that all of the IILs have been fixed during evolution. Consistent with previous studies, our results indicate that PILs are a major type of intron loss. However, at least in plants, IILs are unlikely to be as rare as previously reported. REVIEWERS: This article was reviewed by Jun Yu and Zhang Zhang. For complete reviews, see the Reviewers' Reports section.