Search

Maintaining efficient and stable nitrogen (N) removal in constructed wetlands (CWs) that experience disturbance from their influent pollutant variations is crucial. The ammonium/nitrate (NH4+/NO3−) ratio of influent in CWs often varies widely. The N removal and stability in floating CWs have been found to be enhanced by manipulating plant species diversity. However, whether the positive effects occur in sand-based CWs remains unknown. Here, we established sand-based and hydroponic microcosms to investigate the differences in the responses of N removal and stability to plant species diversity under the disturbance of increasing influent NH4+/NO3− ratio in late period of plant growth. Results indicated that, (1) increasing plant species richness enhanced N removal but did not affect N removal stability in sand-based CWs under disturbance; (2) sand-based CWs had 46% higher average N removal stability than floating CWs, but the stability in floating CWs reached that in sand-based CWs at higher species richness levels; (3) under disturbed conditions, floating CWs with Phragmites australis or Typha latifolia achieved N removal and stability equivalent to those in sand-based CWs. This study indicates that, when treating wastewater with a variable NH4+/NO3− ratio, floating CWs with high plant species richness and specific species can achieve a win-win situation for high and stable N removal and bioenergy production.

Antiphospholipid syndrome (APS) is a systemic autoimmune disease defined by thrombotic or obstetrical events and persistent antiphospholipid antibodies (aPLs). Chemokine-like factor-like MARVEL transmembrane domain-containing family (CMTM) is widely expressed in the immune system and may closely related to APS. This review aimed to systematically summarize the possible effects of CMTM on APS. Publications were collected from PubMed and Web of Science databases up to August 2020. CKLF, CKLFSF, CMTM, antiphospholipid syndrome, immune cells, and immune molecules were used as search criteria. Immune cells, including neutrophil, dendritic cells (DCs), T-cells, B-cells, and inflammatory cytokines, play an important role in the development of APS. Chemokine-like factor 1 (CKLF1) has a chemotactic effect on many cells and can affect the expression of inflammatory cytokines and adhesion molecules through the nuclear factor-kB (NF-kB) pathway or mitogen-activated protein kinase (MARK) pathway. CKLF1 can participate in the maturation of DCs, T lymphocyte activation, and the activation of neutrophils through the MAPK pathway. CMTM1 may act on Annexin A2 by regulating Ca2+ signaling. CMTM2 and CMTM6 are up-regulated in neutrophils of APS patients. Some CMTM family members influence the activation and accumulation of platelets. CMTM3 and CMTM7 are binding partners of B-cell linker protein (BLNK), thereby linking B cell receptor (BCR) and activating BLNK-mediated signal transduction in B cells. Moreover, CMTM3 and CMTM7 can act on DCs and B-1a cell development, respectively. CMTM may have potential effects on the development of APS by acting on immune cells and immune molecules. Thus, CMTM may act as a novel prognostic factor or immunomodulatory treatment option of APS.

MicroRNA (miRNA), a non-coding single-stranded RNA molecule with 20-23 nucleotides encoded by endogenous genes, plays an essential role in maintaining normal cell function and regulating cell proliferation, differentiation, apoptosis, autophagy, and cell metabolism. The imbalance between miRNA and genes can cause a series of diseases, including malignancies. miRNA-326 (miR-326) is extensively known for its core regulation of various biological processes. This review presents an overview of the highlights of miR-326 in female-related diseases. To understand the impact of miR-326 on female disorders, we search all published studies about miR-326 having a high incidence in female conditions, including cervical cancer, endometrial cancer, breast cancer, intrauterine adhesion, and multiple autoimmune diseases. We aim to learn about the mutual regulation mechanism between miR-326 and related genes and signaling pathways, as well as to elaborate on the value of miR-326 as a potential biomarker and therapeutic target of female diseases. Our results provide reliable evidence and new strategies for treating female tumors and autoimmune diseases.

Sodium-ion hybrid capacitors (SICs) combined two advantages of decent specific power of supercapacitors and specific energy of batteries have drawn much attention. Nevertheless, preparing suitable anodes for SICs is currently a main challenge due to that the large Na+ radius that will lead to a terrible volume expansion and sluggish reaction kinetics. To solve the above issues, we meticulously prepare reduced graphene oxide supporting amorphous NiS2 nanosheets (NiS2/rGO) composite by hydrothermal method. When used as anodes for sodium-ion battery, NiS2/rGO exhibits excellent specific capacity of 343.9 mA h g−1 at 0.1 A g−1 after 50 cycles. The structural evolution and pseudocapacitive contribution are analyzed through ex-situ XRD and CV analysis techniques. Simultaneously, the SICs assembled with biomass-derived porous carbon cathodes and NiS2/rGO anodes display superior specific energy and power with excellent cycling stability. Therefore, NiS2/rGO composite based on amorphous structure is a promising anode to promote the commercialization process of SICs.

BACKGROUND AND PURPOSE Microglia-related inflammation is associated with the pathology of Parkinson's disease. Functional voltage-gated sodium channels (VGSCs) are involved in regulating microglial function. Here, we aim to investigate the effects of scorpion venom heat-resistant synthesized peptide (SVHRSP) on 6-hydroxydopamine (6-OHDA)-induced Parkinson's disease-like mouse model and reveal its underlying mechanism. EXPERIMENTAL APPROACH Unilateral brain injection of 6-OHDA was performed to establish Parkinson's disease mouse model. After behaviour test, brain tissues were collected for morphological analysis and protein/gene expression examination. Primary microglia culture was used to investigate the role of sodium channel Nav 1.6 in the regulation of microglia inflammation by SVHRSP. KEY RESULTS SVHRSP treatment attenuated motor deficits, dopamine neuron degeneration, activation of glial cells and expression of pro-inflammatory cytokines induced by 6-OHDA lesion. Primary microglia activation and the production of pro-inflammatory cytokines induced by lipopolysaccharide (LPS) were also suppressed by SVHRSP treatment. In addition, SVHRSP could inhibit mitogen-activated protein kinases (MAPKs) pathway, which plays pivotal roles in the pro-inflammatory response. Notably, SVHRSP treatment suppressed the overexpression of microglial Nav 1.6 induced by 6-OHDA and LPS. Finally, it was shown that the anti-inflammatory effect of SVHRSP in microglia was Nav 1.6 dependent and was related to suppression of sodium current and probably the consequent Na+ /Ca2+ exchange. CONCLUSIONS AND IMPLICATIONS SVHRSP might inhibit neuroinflammation and protect dopamine neurons via down-regulating microglial Nav 1.6 and subsequently suppressing intracellular Ca2+ accumulation to attenuate the activation of MAPKs signalling pathway in microglia.

We and others previously reported increased signaling through the Prostaglandin E3 Receptor (EP3), a G protein-coupled receptor (GPCR) for the arachidonic acid metabolite, prostaglandin E2 (PGE2), is associated with {beta}-cell dysfunction of type 2 diabetes (T2D). Yet, the relationship between PGE2 production and signaling and {beta}-cell function during the progression to T2D remains unclear. In this work, we assessed gene expression from a panel of cadaveric human islets from 40 non-diabetic donors with BMI values spanning the spectrum from lean to high-risk obesity. Interleukin-6 (gene symbol: IL6) and cyclooxygenase-2 (COX-2) (gene symbol: PTGS2) mRNA levels were positively correlated with donor body mass index (BMI), while EP3 (gene symbol: PTGER3) was not. IL6 was itself strongly correlated with PTGS2 and all but one of the other PGE2 synthetic pathway genes tested. About half of the islet preparations were used in glucose-stimulated- and incretin-potentiated insulin secretion assays using an EP3-specific antagonist, confirming functionally-relevant up-regulation of PGE2 production. Islets from obese donors showed no inherent {beta}-cell dysfunction and were at least equally as glucose- and incretin-responsive as islets from non-obese donors. Furthermore, insulin content, a marker of islet size known to be associated with donor BMI, was also significantly and positively correlated with islet PTGS2 expression. We conclude up-regulated islet PGE2 production and signaling may be a necessary part of the {beta}-cell adaption response, compensating for obesity and insulin resistance. Analysis of plasma PGE2 metabolite levels from a clinical cohort reveal these findings are not in conflict with the concept of further elevations in PGE2 production contributing to T2D-related {beta}-cell dysfunction where islet EP3 expression has also been up-regulated. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=126 HEIGHT=200 SRC="FIGDIR/small/429205v1_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@14056a7org.highwire.dtl.DTLVardef@f8fcf1org.highwire.dtl.DTLVardef@a66915org.highwire.dtl.DTLVardef@13ce208_HPS_FORMAT_FIGEXP M_FIG C_FIG

Sodium-ion hybrid capacitors (SICs) as promising energy conversion and storage devices have exhibited excellent specific energy, high specific power, and good cycling life. Nevertheless, anode materials for SICs suffer from terrible volume expansion and sluggish reaction kinetics owing to the larger radius of sodium-ion. To find suitable anode materials, we design and prepare reduced graphene oxide-supported CoS2 nanoparticles (CoS2/rGO) with high electrochemical performance through a facile hydrothermal method. When tested as anode materials, the specific capacity of CoS2/rGO delivers 529.3 and 1168.6 mA h g−1 in the process of the 1st charge and discharge, respectively. Moreover, the specific capacity retention is up to 214.8 mA h g−1 at 100 mA g−1 over 100 cycles. In order to explore the practical application of CoS2/rGO, SICs are assembled by biomass-derived porous carbon cathodes and CoS2/rGO anodes, which displays remarkable specific energy of 112.6, 103.75, 91.29, 70.34, 47.45 W h kg−1 under specific power 225, 449.82, 899.86, 1350, 2689.3 W kg−1, respectively, benefiting from the high pseudocapacitive performance of CoS2/rGO anodes and outstanding specific capacity of biomass-derived porous carbon cathodes.

Objectives To investigate the role of miR-142-3p in the bleomycin-induced idiopathic pulmonary fibrosis (IPF) mouse model and elucidate its targets. Methods In vitro model: Alveolar epithelial cells (AECs) were isolated and treated with bleomycin (50 µg/mL) or PBS for 12 h. In vivo model: Bleomycin (5 mg/kg) was injected into the trachea under anesthesia and aseptic conditions, and controls were treated with equal saline. After the completion of modeling, proteins and RNA were extracted. p53/NF-κB signaling factors were evaluated by western blot or immunohistochemistry. IL-1β and MMP-9 levels were measured by ELISA. The lentiviral transfection technique was used to overexpress miR-142-3p. Results In IPF, miR-142-3p was identified to play a negative regulatory role in lung epithelial cell senescence. Bleomycin treatment significantly reduced miR-142-3p expression in a concentration-dependent manner in vitro. miR-142-3p overexpression inhibited bleomycin-induced cellular senescence in vivo. In particular, miR-142-3p negatively regulated collagen deposition in pulmonary fibrosis by regulating p53/NF-κB expression. Conclusion MiR-142-3p plays an important role in the development of IPF by negatively regulating the p53/NF-κB network.

This paper provides the first systematic micro-level evidences on the effectiveness of anti-corruption campaign in disciplining public officials and its impact on income distribution. Based on China Household Income Project (CHIP) survey data 2007 and 2013, we found that party and government officials had significant hidden income and the public–private earnings gap was as high as 8% before the campaign. However, the hidden income become not significant and the earnings gap declined to [Formula: see text]18% in this post-campaign period. The regions inspected by central anti-corruption inspection groups experience larger public earnings penalties compared to the other regions. Overall, our findings suggest that the privilege of public officials declined sharply during this anti-corruption campaign.

Heme oxygenase-1 (HO-1) is a vital enzyme in humans that primarily regulates free heme concentrations. The overexpression of HO-1 is commonly associated with cardiovascular and neurodegenerative diseases including atherosclerosis and ischemic stroke. Currently, there are no known chemical probes to detect HO-1 activity, limiting its potential as an early diagnostic/prognostic marker in these serious diseases. Reported here are the design, synthesis, and photophysical and biological characterization of a coumarin–porphyrin FRET break-apart probe to detect HO-1 activity, Fe–L1. We designed Fe–L1 to “break-apart” upon HO-1-catalyzed porphyrin degradation, perturbing the efficient FRET mechanism from a coumarin donor to a porphyrin acceptor fluorophore. Analysis of HO-1 activity using Escherichia coli lysates overexpressing hHO-1 found that a 6-fold increase in emission intensity at 383 nm was observed following incubation with NADPH. The identities of the degradation products following catabolism were confirmed by MALDI-MS and LC–MS, showing that porphyrin catabolism was regioselective at the α-position. Finally, through the analysis of Fe–L2, we have shown that close structural analogues of heme are required to maintain HO-1 activity. It is anticipated that this work will act as a foundation to design and develop new probes for HO-1 activity in the future, moving toward applications of live fluorescent imaging.

A composite Mn-Cu-Ce tri-metal oxide supported on γ-Al2O3 (Mn-Cu-Ce/Al2O3) catalyst was prepared by an impregnation-calcination method and investigated in the catalytic ozonation treatment of real coal chemical wastewater (CCW). The catalyst was characterized by XRD, SEM, TEM, XRF, BET, and XPS techniques. The results showed that Mn, Cu, and Ce metal oxides were evenly distributed on the Al2O3 surface and the catalyst maintained a large surface area and a high pore volume compared with the pristine Al2O3. The synergy between Mn, Cu, and Ce oxides greatly enriched the catalytic active sites and enhanced the ozonation performance. The catalytic ozonation process with Mn-Cu-Ce/Al2O3 increased the removal rate of total organic carbon (TOC) by 31.6% compared with ozonation alone. The ketones, aromatic compounds, phenols, and nitrogen-containing heterocyclic compounds in CCW have been effectively degraded and mineralized by Mn-Cu-Ce/Al2O3 catalytic ozonation process, and its biodegradability has also been significantly improved. The experimental results of ∙OH scavengers revealed that the mechanism of Mn-Cu-Ce/Al2O3 catalytic ozonation was to promote the generation of ∙OH radicals. The catalytic activity of Mn-Cu-Ce/Al2O3 was only a slight decrease in six consecutive catalytic ozonation treatments, showing good stability. Therefore, Mn-Cu-Ce/Al2O3 can be used as a candidate catalyst for the advanced treatment of refractory organic wastewaters upon catalytic ozonation.

Background Many recent studies have shown that miRNAs play important roles in the regulation of animal reproduction, including seasonal reproduction. The pineal gland is a crucial hub in the regulation of seasonal reproduction. However, little is known about the expression characteristics of pineal miRNAs in different reproductive seasons (anestrus and breeding season). Therefore, the expression profiles and regulatory roles of ovine pineal miRNAs were investigated during different reproductive stages using Solexa sequencing technology and dual luciferase reporter assays. Results A total of 427 miRNAs were identified in the sheep pineal gland. Significant differences in miRNA expression were demonstrated between anestrus and the breeding season in terms of the frequency distributions of miRNA lengths, number of expressed miRNAs, and specifically and highly expressed miRNAs in each reproductive stage. KEGG analysis of the differentially expressed (DE) miRNAs between anestrus and the breeding season indicated that they are significantly enriched in pathways related to protein synthesis, secretion and uptake. Furthermore, transcriptome analysis revealed that many target genes of DE miRNAs in the ribosome pathway showed relatively low expression in the breeding season. On the other hand, analyses combining miRNA-gene expression data with target relationship validation in vitro implied that miR-89 may participate in the negative regulation of aralkylamine N-acetyltransferase (AANAT) mRNA expression by targeting its 3’UTR at a unique binding site. Conclusions Our results provide new insights into the expression characteristics of sheep pineal miRNAs at different reproductive stages and into the negative regulatory effects of pineal miRNAs on AANAT mRNA expression.

This paper presents the analyses of toppling response of layered reverse-dip slopes under the influence of geometric factors of slope angle, strata thickness and dip. The toppling response of reverse-dip slopes under different geometric factors is obtained by using the discrete element code UDEC. Then, a prediction model for toppling deformation is developed by utilizing support vector machine and the toppling-prone combinations of these geometric factors are determined from a total of 120 samples of reverse-dip slopes. The study has shown that the geometric model is a quarter of a spheroid with a slope angle of 80°, a strata dip of 80°, and a strata thickness of 0.19 m as the center. The length of the long equatorial radius of the spheroid is 31° (strata dip axial), that of the short equatorial radius is 21° (slope angle axial), and the polar radius is 0.075 m (strata thickness axial). And the ratio of long equatorial radius, short equatorial radius, and polar radius is 2.48:1.68:1.00.

Sodium-ion capacitors (SICs) with extensive resources and high specific energy–power characteristics have emerged as an advanced energy storage device for large-scale application. However, the heavier molar mass and larger radius of sodium ions slacken the reaction kinetics of anode materials for SICs. In order to further improve the kinetics of anode materials, we have synthesized mixed bimetallic sulfides embedded on reduced graphene oxide (SnS2/ZnS-RGO) with abundant heterostructure and phase boundaries by a viable hydrothermal method. SnS2/ZnS-RGO composites express a good synergistic effect such as large surface area of RGO for pseudocapacitive charge storage, mixed metal ion reaction for ultrahigh capacity, and abundant phase boundaries for superior Na-ion diffusion rate. With the particular structure, the optimized SnS2/ZnS-RGO-180 deliver the reversible specific capacity as high as 396.6 mA h g−1 over 100 cycles with almost 100% Coulombic efficiency and exhibit outstanding rate capability of 136.8 mA h g−1 at 5 A g−1. Impressively, the SICs by using SnS2/ZnS-RGO-180 as anodes and the peanut shell–derived porous carbon materials as cathodes display a specific energy of 145.6 W h kg−1 at a specific power of 2250 W kg−1 and a capacity retention ratio of 100% after 1000 cycles.

At a time when game-based learning has become a research hotspot, this study focused on the competition mechanism in gamified learning, aiming to explore the impact of different competition modes on students’ vocabulary learning effect and learning motivation. A group of 79 sixth grade students from China were randomly assigned to a non-competitive class, an individual competition class, and an inter-group competition class. The experiment was conducted in an English vocabulary course, and the game competition was carried out using the Quizlet Live game platform. The results indicated that: (1) the vocabulary learning effect and motivation of students in the competitive classes (individual competition and inter-group competition) were better than those in the non-competitive class; (2) the learning effect of students in the inter-group competitive class outperformed that of the individual competitive class, but there was no significant difference in learning motivation. Through the qualitative analysis of the students’ interviews, it was found that the results of inter-group competition may be related to the student’s perception of learning and emotional support. The findings of this study can provide relevant support for the subsequent game-based learning design.

Neurodegenerative diseases are a class of disorders linked to the formation in the nervous system of fibrillar protein aggregates called amyloids. This aggregation process is affected by a variety of post-translational modifications, whose specific mechanisms are not fully understood yet. Emerging chemical mutagenesis technology is currently striving to address the challenge of introducing protein post-translational modifications, while maintaining proteins stable and soluble during the modification reaction. Several amyloidogenic proteins are highly aggregation-prone, and current modification procedures lead to unexpected precipitation of these proteins, affecting their yield and downstream characterization. Here, we present a method for maintaining amyloidogenic proteins soluble during chemical mutagenesis. As proof-of-principle, we applied our method to mimic the phosphorylation of the serine 26 and the acetylation of the lysine 28 of the 40-residue long variant of amyloid-β peptide, whose aggregation is linked to Alzheimer’s disease.

Background Airway remodeling in patients with asthma, which leads to a decline in pulmonary function, is likely the result of repeated exacerbations often provoked by aeroallergen exposures. Aeroallegen exposure triggers a stereotypic response orchestrated by growth factor cytokines and other protein mediators. This results in a late-phase allergic reaction characterized by vascular permeability, recruitment of activated leukocytes, and activation of structural cells of the airway. The spectrum of protein mediators and their functions are incompletely understood. Methods Bronchoalveolar lavage fluid (BALF) samples were obtained from 12 volunteers who exhibited robust eosinophilic recruitment following segmental bronchial provocation with allergen (SBP-Ag). We systematically identified and quantified proteins in BALF using high-performance liquid chromatography–high-resolution mass spectrometry (LC–MS/MS) followed by pathway analysis and correlations with airway physiology. Results Pairwise analysis of protein abundance in BALF pre- vs post-SBP-Ag revealed that 55 proteins were upregulated and 103 proteins were downregulated. We observed enrichment of groups of proteins mapping to hemostasis/fibrin clot, platelet activation, lipoprotein assembly, neutrophil degranulation proteins, and acute-phase inflammation-airway remodeling pathways. The abundances of F2 and Fibrinogen γ (FGG) correlated with eosinophil numbers, whereas SERPINA3 negatively correlated with change in FeNO. The coagulation proteins F2 and KNG negatively correlated with FN1 an index of airway remodeling. Interestingly, patients with lower FEV1 showed distinct allergen-induced patterns of 8 BALF proteins, including MUC1, alarmins (HSPB1), and actin polymerization factors. Conclusions Protein abundance of the fibrin formation cascade, platelet activation and remodeling are associated with late-phase leukocyte numbers and markers of remodeling. Patients with lower FEV1 have distinct dynamic responses to allergen.

Economy and ecology are two main aspects of human sustainable development. However, a comprehensive analysis of the status and trends of economic and ecological cognition is still lacking. Here, we defined economic and ecological concepts as cultural traits that constitute a complex system representing sustainability ideas. Adopting a linguistic ecology perspective, we analysed the frequency distribution, turnover and innovation rates of 3713 concepts appearing in China’s mainstream newspaper, People’s Daily, from 1946 to 2015. Results reveal that: (1) In the whole historical period, there were more economic concepts than ecological concepts both in amount and category. Economic concepts experienced stronger cultural drift than ecological concepts tested by the neutral model of cultural evolution; (2) popular economic concepts became more diversified, but popular ecological concepts became more uniform; (3) both economic concepts and ecological concepts attained more variation in their own disciplinary domains than in cross-disciplinary domains; and (4) as a platform of both giving information and opinion, a newspaper is subjected to cultural selection, especially reflected in the change in ecological concepts under the context of Chinese ecological civilization construction. We concluded with a discussion of promoting vibrant and resilient ecological knowledge in fostering sustainability activities and behaviours.

As a national development strategy, rural revitalization is of great significance in China’s modern construction, among which cultural revitalization plays a leading role. This paper will discuss the way to explore rural culture from the perspective of user experience. With a focus on such fields as “eating, clothing, housing, travel, and recreation” that are familiar to the general public, it aims to highlight the protection, inheritance, and development of rural culture, and talent training, and promote rural cultural landscapes and immersive experience of farming culture, as well as cultural productization and the extension of cultural connotation to properly satisfy users’ diversified needs and facilitate the national rural revitalization.

To explore humor style and creativity tendency of senior high school students of Tujia, a Chinese ethnic group, and the relation between the two in Chinese ethnic culture, 127 Tujia high school students and 124 Han ones were selected to complete Humor Styles Questionnaire and Creativity Assessment Packet. The study questionnaires were administered in a classroom setting when participants were attending their classes. The results show that: 1) Tujia school students prefer affiliative and self-enhancing humor. Among them, urban male students and rural female students exhibit a greater tendency to engage in self-enhancing humor, while urban female students are relatively weak; first grade senior high school students from the city prefer maladaptive aggressive humor. Between Tujia and Han students, the former ones are more prone to engage in self-enhancing humor and less prone to engage in aggressive humor than their Han counterparts. 2) Creativity tendency of Tujia students is at a good level, especially inquisitiveness and adventure. In terms of overall performance and adventure, Tujia students fare better than the students of Han ethnicity, and then the first-grade students stand out among the Tujia students. 3) There is a significant positive correlation between humor style and creativity tendency in the Tujia groups. The affiliative humor style is associated with higher levels of creativity.

In this work, a modified curing agent (MCA) with a flexible long chain and semi-aromatic amide units was synthesized using M-benzoyl chloride and polyether amine (D-230 and D-400), and then innovatively incorporated into epoxy to prepare a multifunctional epoxy structural adhesive with superior flexibility, damping and durability. It was shown that the strength of the MCA modified epoxy thermosets was 18 MPa, and the elongation at break was significantly improved to 17.9 times higher than that of the control blending samples (D-230, D-230D its damping temperature range was from 24.3 °C to 81.6 °C, suggesting that it was a good damping material. After three stretch–recovery cycles, over 97% of the tensile strength of the MCA modified epoxy was still maintained, indicating that it has good stress fatigue durability. This new multifunctional epoxy adhesive significantly broadened the usage of epoxy and has the potential for use as a high damping adhesive in the automotive and aerospace fields.

The extracellular matrix (ECM) provides an architectural meshwork that surrounds and supports cells. The dysregulation of heavily post-translationally modified ECM proteins directly contributes to various diseases. Mass spectrometry (MS)-based proteomics is an ideal tool to identify ECM proteins and characterize their post-translational modifications, but ECM proteomics remains extremely challenging owing to the extremely low solubility of the ECM. Herein, enabled by effective solubilization of ECM proteins using our recently developed photocleavable surfactant, Azo, we have developed a streamlined ECM proteomic strategy that allows fast tissue decellularization, efficient extraction and enrichment of ECM proteins, and rapid digestion prior to reversed-phase liquid chromatography (RPLC)-MS analysis. A total of 173 and 225 unique ECM proteins from mouse mammary tumors have been identified using 1D and 2D RPLC-MS/MS, respectively. Moreover, 87 (from 1DLC-MS/MS) and 229 (from 2DLC-MS/MS) post-translational modifications of ECM proteins, including glycosylation, phosphorylation, and hydroxylation, were identified and localized. This Azo-enabled ECM proteomics strategy will streamline the analysis of ECM proteins and promote the study of ECM biology.

Although top-down proteomics has emerged as a powerful strategy to characterize proteins in biological systems, the analysis of endogenous membrane proteins remains challenging due to their low solubility, low abundance, and the complexity of the membrane sub-proteome. Here, we report a simple but effective enrichment and separation strategy for top-down proteomics of endogenous membrane proteins enabled by cloud point extraction and multidimensional liquid chromatography coupled to high-resolution mass spectrometry (MS). The cloud point extraction efficiently enriched membrane proteins using a single extraction, eliminating the need for time-consuming ultracentrifugation steps. Subsequently, size-exclusion chromatography (SEC) with an MS-compatible mobile phase (59% water, 40% isopropanol, 1% formic acid) was used to remove the residual surfactant and fractionate intact proteins (6–115 kDa). The fractions were separated further by reversed-phase liquid chromatography (RPLC) coupled with MS for protein characterization. This method was applied to human embryonic kidney cells and cardiac tissue lysates, to enable the identification of 188 and 124 endogenous integral membrane proteins respectively, some with as many as 19 transmembrane domains.

Enterohemorrhagic Escherichia coli (EHEC) is the causative agent of severe diarrheal disease in humans. Cattle are the natural reservoir of EHEC, and approximately 75% of EHEC infections in humans ...

Metabolomics-the endpoint of the omics cascade-is increasingly recognized as a preferred method for understanding the ultimate responses of biological systems to stress. Flow injection electrospray (FIE) mass spectrometry (MS) has advantages for untargeted metabolic fingerprinting due to its simplicity and capability for high-throughput screening but requires a high-resolution mass spectrometer to resolve metabolite features. In this study, we developed and validated a high-throughput and highly reproducible metabolomics platform integrating FIE with ultrahigh-resolution Fourier transform ion cyclotron resonance (FTICR) MS for analysis of both polar and nonpolar metabolite features from plasma samples. FIE-FTICR MS enables high-throughput detection of hundreds of metabolite features in a single mass spectrum without a front-end separation step. Using plasma samples from genetically identical obese mice with or without type 2 diabetes (T2D), we validated the intra and intersample reproducibility of our method and its robustness for simultaneously detecting alterations in both polar and nonpolar metabolite features. Only 5 min is needed to acquire an ultra-high resolution mass spectrum in either a positive or negative ionization mode. Approximately 1000 metabolic features were reproducibly detected and annotated in each mouse plasma group. For significantly altered and highly abundant metabolite features, targeted tandem MS (MS/MS) analyses can be applied to confirm their identity. With this integrated platform, we successfully detected over 300 statistically significant metabolic features in T2D mouse plasma as compared to controls and identified new T2D biomarker candidates. This FIE-FTICR MS-based method is of high throughput and highly reproducible with great promise for metabolomics studies toward a better understanding and diagnosis of human diseases.

Objective People can be categorized into one of four meaning-in-life profiles: High Presence High Search (HPHS), High Presence Low Search (HPLS), Low Presence High Search (LPHS), and Low Presence Low Search (LPLS).The main goal of this study is to provide a theoretical explanation for why Chinese people with different meaning-in-life profiles have different mental health levels than Western people, based on their emotional-cognitive-processing ability. Method We adopted eye-movement analysis and recognition-judgment experimental paradigm concerning absolute-recognition judgment and relative-recognition judgment in our study. Moreover, we applied a multifactor and multilevel mixed-experimental design. We selected 118 participants for the experiments from the 788 Chinese college students who responded. Results Our results showed that HPHS individuals preferred positive-emotion pictures, LPLS individuals preferred negative-emotion pictures, HPLS individuals preferred positive- and neutral-emotion pictures, and LPHS individuals preferred neutral-emotion pictures. Moreover, HPHS individuals were better at accurately processing facial expression from pictures, while LPLS individuals lacked such ability. The fine-processing ability of HPLS and LPHS individuals was lower than that of HPHS yet higher than that of LPLS individuals. Moreover, the features of HPLS individuals were closer to HPHS, while those of LPHS individuals were closer to LPLS. Conclusions Our findings support the hypothesis that meaning-in-life profiles have different immediate processing abilities and preferences regarding facial expression recognition and different emotional-cognitive-processing ability.

In biology, it can be argued that if the genome contains the script for a cell's life cycle, then the proteome constitutes an ensemble cast of actors that brings these instructions to life. Their interactions with each other, co-factors, ligands, substrates, and so on, are key to understanding nearly any biological process. Mass spectrometry is well established as the method of choice to determine protein primary structure and location of post-translational modifications. In recent years, top-down fragmentation of intact proteins has been increasingly combined with ionisation of noncovalent assemblies under non-denaturing conditions, i.e., native mass spectrometry. Sequence, post-translational modifications, ligand/metal binding, protein folding, and complex stoichiometry can thus all be probed directly. Here, we review recent developments in this new and exciting field of research. While this work is written primarily from a mass spectrometry perspective, it is targeted to all bioanalytical scientists who are interested in applying these methods to their own biochemistry and chemical biology research., Top-down mass spectrometry techniques break up native proteins and complexes to reveal all levels of structural information.

Significance Hypertrophic cardiomyopathy (HCM) is a common genetic heart disease and a leading cause of sudden cardiac death in young adults. HCM has been linked to mutations in genes encoding sarcomeric proteins, but how different mutations can result in a similar clinical phenotype is unknown. Analysis of surgical heart tissue samples from HCM patients with severe outflow track obstruction using high-resolution mass spectrometry–based top-down proteomics revealed a common pattern of altered sarcomeric proteoforms across HCM tissues compared to non-failing donor heart tissues. Our data suggest that common pathways are associated with clinical phenotypes in patients diagnosed with obstructive HCM, opening the door for the development of interventions that target the HCM phenotype rather than the individual sarcomeric gene mutation., Hypertrophic cardiomyopathy (HCM) is the most common heritable heart disease. Although the genetic cause of HCM has been linked to mutations in genes encoding sarcomeric proteins, the ability to predict clinical outcomes based on specific mutations in HCM patients is limited. Moreover, how mutations in different sarcomeric proteins can result in highly similar clinical phenotypes remains unknown. Posttranslational modifications (PTMs) and alternative splicing regulate the function of sarcomeric proteins; hence, it is critical to study HCM at the level of proteoforms to gain insights into the mechanisms underlying HCM. Herein, we employed high-resolution mass spectrometry–based top-down proteomics to comprehensively characterize sarcomeric proteoforms in septal myectomy tissues from HCM patients exhibiting severe outflow track obstruction (n = 16) compared to nonfailing donor hearts (n = 16). We observed a complex landscape of sarcomeric proteoforms arising from combinatorial PTMs, alternative splicing, and genetic variation in HCM. A coordinated decrease of phosphorylation in important myofilament and Z-disk proteins with a linear correlation suggests PTM cross-talk in the sarcomere and dysregulation of protein kinase A pathways in HCM. Strikingly, we discovered that the sarcomeric proteoform alterations in the myocardium of HCM patients undergoing septal myectomy were remarkably consistent, regardless of the underlying HCM-causing mutations. This study suggests that the manifestation of severe HCM coalesces at the proteoform level despite distinct genotype, which underscores the importance of molecular characterization of HCM phenotype and presents an opportunity to identify broad-spectrum treatments to mitigate the most severe manifestations of this genetically heterogenous disease.

Metal sulfide is the most promising anode material for sodium storage devices due to its high theoretical capacity and low cost. However, the practical application of metal sulfide is largely hindered by huge capacity fading during the sodiation/desodiation process. Here mixed bimetallic sulfides grown on reduced graphene oxide (MoS2/CoS2-RGO) are prepared via a facile hydrothermal method. MoS2/CoS2-RGO displays a unique 2D structure which provides large specific surface area for pseudocapacitive charge storage, polyvalent ion reaction for ultrahigh capacity, and a heterostructure to high Na-ion diffusion rate. The optimized MoS2/CoS2-RGO shows a considerable reversible capacity of 593.6 mA h g−1 at 100 mA g−1 over 50 cycles and a high rate capability of 215.8 mA h g−1 even at a high specific current of 5000 mA g−1. A reaction kinetics and galvanostatic intermittent titration technique analysis indicates that MoS2/CoS2-RGO possesses fast pseudocapacitive charge storage and high Na-ion diffusion rate, benefiting the kinetics balance between anode and cathode. With this special structure, SICs containing the anode deliver a high specific energy of 152.98 W h kg−1 at 562.5 W kg−1. Similarly, the SIB exhibits a good capacities of 64 mA h g−1 at the high rates of 5C over 100 cycles.

Background Myocardial strain for assessment of hypertrophic cardiomyopathy (HCM) is of importance and may play a role in identifying obstruction in HCM patients. Purpose To evaluate the utility of myocardial strain for detecting left ventricular (LV) outflow tract (LVOT) obstruction in HCM patients based on magnetic resonance tissue tracking. Study type Retrospective. Population In all, 44 adult HCM patients with LVOT obstruction and 108 adult HCM patients without LVOT obstruction. Field strength/sequence 1.5 T; Steady-state free-precession cine sequence; phase-sensitive inversion-prepared segmented gradient echo sequence for late gadolinium enhancement (LGE) imaging. Assessment Strain parameters including the local and global levels of LV myocardium and the subtraction (Sub) of myocardial strain variables between interventricular septal segments (IVSS) and noninterventricular septal segments (NIVSS) were measured for differentiating HCM with obstruction from nonobstruction. Average and maximum LV wall thickness (Average and Maximum LVWT) were also analyzed. Statistical tests Univariate and multivariate logistic regression analysis, area under the receiver operating characteristic (ROC) curve (AUC), intraclass correlation coefficient. Results In multivariate analysis, Average LVWT, Maximum LVWT, and the subtraction of radial peak strain (Sub Radial PS) between NIVSS and IVSS were independently associated with LVOT obstruction. The AUCs were 0.731, 0.840, and 0.890 for Average LVWT, Maximum LVWT, and Sub Radial PS, respectively. Sub Radial PS (cutoff value: 8.1%) demonstrated the highest sensitivity of 75.0% and a high specificity of 87.9% for identifying LVOT; Maximum LVWT (cutoff value: 22.9 mm) showed good sensitivity (72.7%) and specificity (83.3%). Combining Maximum LVWT >22.9 mm and Sub Radial PS > 8.1% achieved a better diagnostic performance (specificity 95.4%, sensitivity 70.5%). Data conclusion Combining Maximum LVWT >22.9 mm and Sub Radial PS >8.1% holds promise for objectively evaluating LVOT obstruction in HCM patients with very high specificity and acceptable sensitivity. Level of evidence 3 TECHNICAL EFFICACY STAGE: 2.

Molecular markers in ambient organic aerosol (OA) provide highly specific source information. Their traditional quantification is based on offline analysis of filter samples, and the coarse time re...

Top-down mass spectrometry (MS)-based proteomics enable a comprehensive analysis of proteoforms with molecular specificity to achieve a proteome-wide understanding of protein functions. However, the lack of a universal software for top-down proteomics is becoming increasingly recognized as a major barrier, especially for newcomers. Here, we have developed MASH Explorer, a universal, comprehensive, and user-friendly software environment for top-down proteomics. MASH Explorer integrates multiple spectral deconvolution and database search algorithms into a single, universal platform which can process top-down proteomics data from various vendor formats, for the first time. It addresses the urgent need in the rapidly growing top-down proteomics community and is freely available to all users worldwide. With the critical need and tremendous support from the community, we envision that this MASH Explorer software package will play an integral role in advancing top-down proteomics to realize its full potential for biomedical research.

Cancer testis (CT) antigens have received particular attention in cancer immunotherapy. OY-TES-1 is a member of CT antigens. This study was to evaluate OY-TES-1 expression and immunogenicity in hepatocelluar carcinoma (HCC). OY-TES-1 mRNA expression was detected in 56 HCC tissues and 5 normal liver tissues by reverse transcriptase PCR (RT-PCR). Of the 56 cases of HCC tissues tested, 37 cases had tumor and matched adjacent non-cancer tissues and were subjected to both RT-PCR and quantitative real-time PCR. OY-TES-1 protein was subsequently observed on a panel of tissue microarrays. Sera from patients were tested for OY-TES-1 antibody by ELISA. To identify OY-TES-1 capable of inducing cellular immune response, OY-TES-1 protein was used to sensitize dentritic cells and the cytotoxicity effect was measured in vitro. The results showed that OY-TES-1 mRNA was highly expressed in 41 of the 56 (73.21%) HCC tissues, whereas none in 5 normal liver tissues. OY-TES-1 mRNA was frequently expressed not only in HCC tissues (72.97%, 27/37), but also in paired adjacent non-cancer tissues (64.86%, 24/37). But the mean expression level of OY-TES-1 mRNA in HCC tissues was significantly higher than that in adjacent non-cancer tissues (0.76854 vs. 0.09834, P=0.021). Immunohistochemistry showed that OY-TES-1 protein expression was detected in 6 of the 49 cases of HCC tissues, and absent in 9 cases of normal liver and 6 cases of cirrhosis tissues. Seropositivity was detected in 10 of the 45 HCC patients, but not detected in 17 cirrhosis patients and 76 healthy donors. The specific cytotoxic T cells elicited by OY-TES-1 could kill HLA-A2+ HCC cell line which expressed OY-TES-1. The target lysis was mainly HLA class I -dependent and could be blocked by antibodies against monomorphic HLA class I but not HLA class II molecule. In summary, OY-TES-1 expression is up-regulated in HCC tissues and can be recognized by humoral and cellular responses, which suggests that OY-TES-1 is an attractive target for tumor immunotherapy in HCC.

As wastewater treatment systems that strengthen natural processes, constructed wetlands provide both ecosystem services and disservices. Manipulating both the physical and ecological structures of constructed wetlands has been the key to improve ecosystem services while reducing disservices. Herein, an experiment using simulated constructed wetlands was conducted to explore the effect of two different substrate sizes (fine sand or coarse sand), plant richness (1, 3, or 4 species), and plant species identity on ecosystem services. Results indicated that (1) only in microcosms with coarse sand, species richness enhanced nitrogen removal efficiency while reduced nitrous oxide emissions and that (2) the presence of Phalaris arundinacea increased nitrogen removal rate, and the presence of Rumex japonicus or Oenanthe javanica decreased nitrous oxide emissions; (3) however, the net ecosystem services (nitrogen removal, greenhouse gas emissions, biofuel production) of microcosms with fine sand were higher than those of microcosms with coarse sand, and (4) interestingly, there was no difference in net ecosystem services between microcosms with coarse sand (1033 yuan ha−1 day−1; 1 yuan ≈ 0.14 USD) and those with fine sand (1071 yuan ha−1 day−1) for the four-species mixtures. Hence, in practice, ensuring plant species richness with appropriate species in microcosms with coarse sand can improve ecosystem services to a level equal to that of microcosms with fine sand and help to prevent constructed wetlands from clogging.

The effects of minor Sc and Zr additions on the mechanical properties and microstructure evolution of Al−Zn−Mg−Cu alloys were studied using tensile tests, scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The ultimate tensile strength of the peak-aged Al−Zn−Mg−Cu alloy is improved by about 105 MPa with the addition of 0.10% Zr. An increase of about 133 MPa is observed with the joint addition of 0.07% Sc and 0.07% Zr. For the alloys modified with the minor addition of Sc and Zr (0.14%), the main strengthening mechanisms of minor addition of Sc and Zr are fine-grain strengthening, sub-structure strengthening and the Orowan strengthening mechanism produced by the Al3(Sc,Zr) and Al3Zr dispersoids. The volume of Al3Zr particles is less than that of Al3(Sc,Zr) particles, but the distribution of Al3(Sc,Zr) particles is more dispersed throughout the matrix leading to pinning the dislocations motion and restraining the recrystallization more effectively.