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Abstract Achieving high selectivity of Li+ and Mg2+ is of paramount importance for effective lithium extraction from brines, and nanofiltration (NF) membrane plays a critical role in this process. The key to achieving high selectivity lies in the on-demand design of NF membrane pores in accordance with the size difference between Li+ and Mg2+ ions, but this poses a huge challenge for traditional NF membranes and difficult to be realized. In this work, we report the fabrication of polyamide (PA) NF membranes with ultra-high Li+/Mg2+ selectivity by modifying the interfacial polymerization (IP) process between piperazine (PIP) and trimesoyl chloride (TMC) with an oil-soluble surfactant that forms a monolayer at oil/water interface, referred to as OSARIP. The OSARIP benefits to regulate the membrane pores so that all of them are smaller than Mg2+ ions. Under the solely size sieving effect, an exceptional Mg2+ rejection rate of over 99.9% is achieved. This results in an exceptionally high Li+/Mg2+ selectivity, which is one to two orders of magnitude higher than all the currently reported pressure-driven membranes, and even higher than the microporous framework materials, including COFs, MOFs, and POPs. The large enhancement of ion separation performance of NF membranes may innovate the current lithium extraction process and greatly improve the lithium extraction efficiency.

Abstract In mammals, the production of mature oocytes necessitates rigorous regulation of the discontinuous meiotic cell-cycle progression at both the transcriptional and post-transcriptional levels. However, the factors underlying this sophisticated but explicit process remain largely unclear. Here we characterize the function of N-acetyltransferase 10 (Nat10), a writer for N4-acetylcytidine (ac4C) on RNA molecules, in mouse oocyte development. We provide genetic evidence that Nat10 is essential for oocyte meiotic prophase I progression, oocyte growth and maturation by sculpting the maternal transcriptome through timely degradation of poly(A) tail mRNAs. This is achieved through the ac4C deposition on the key CCR4-NOT complex transcripts. Importantly, we devise a method for examining the poly(A) tail length (PAT), termed Hairpin Adaptor-poly(A) tail length (HA-PAT), which outperforms conventional methods in terms of cost, sensitivity, and efficiency. In summary, these findings provide genetic evidence that unveils the indispensable role of maternal Nat10 in oocyte development.

Abstract Polymer membranes have been used extensively for Angstrom-scale separation of solutes and molecules. However, the pore size of most polymer membranes has been considered an intrinsic membrane property that cannot be adjusted in operation by applied stimuli. In this work, we show that the pore size of an electrically conductive polyamide membrane can be modulated by an applied voltage in the presence of electrolyte via a mechanism called electrically induced osmotic swelling. Under applied voltage, the highly charged polyamide layer concentrates counter ions in the polymer network via Donnan equilibrium and creates a sizeable osmotic pressure to enlarge the free volume and the effective pore size. The relation between membrane potential and pore size can be quantitatively described using the extended Flory-Rehner theory with Donnan equilibrium. The ability to regulate pore size via applied voltage enables operando modulation of precise molecular separation in-situ. This study demonstrates the amazing capability of electro-regulation of membrane pore size at the Angstrom scale and unveils an important but previously overlooked mechanism of membrane-water-solute interactions.

The relationships between soil eco-enzymatic stoichiometry and substrate stoichiometry could be used to explain nutrient cycling processes regulated by microbial biomass stoichiometry. But what are the relationships between the stoichiometry of resources, microorganisms, and enzymes? We do not have a clear understanding yet, particularly in the different stages of litter decomposition. By analyzing the response of extracellular enzymatic stoichiometry to the imbalance between microbial and substrate stoichiometry, we explore the microbial-mediated litter transformation and microbial adaptation mechanisms in the transformation interface soil (TIS) layer. The results showed that soil microbial metabolism was limited by C and P during decomposition, peaking in the transition (middle) stage and then gradually decreasing. According to the judgment of microbial homeostasis (effect of substrate stoichiometry on microbial biomass stoichiometry), the microbial communities shift from homeostatic in the early stage to non-homeostatic in the middle stage and then return to homeostasis in the later stage. During the litter decomposition, the non-homeostatic period corresponded to the transition stage. That means severe microbial metabolic limitation is a potential determinant of microbial homeostasis. Soil microorganisms adapt and alleviate microbial metabolic limitations by adjusting extracellular enzyme activity and microbial non-homeostatic behavior when the available resources fail to satisfy microbial requirements.

Separating molecules or ions with sub-Angstrom scale precision is important but technically challenging. Here, the authors demonstrate that precise solute-solute separation can be achieved using polyamide membranes formed via surfactant-assembly regulated interfacial polymerization.

Pancreatic ductal adenocarcinoma (PAAD) is one of the most common malignant tumors in digestive system. To find the new therapeutic targets and explore potential mechanisms underlying PAAD, the bioinformatics has been performed in our study. The PAAD gene expression profile GSE28735 was chosen to analyze the differentially expressed genes (DEGs) between PAAD carcinoma tissues and normal adjacent tissues from 45 patients with PAAD. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed using Database for Annotation, Visualization and Integrated Discovery (DAVID). Moreover, a protein-protein interaction (PPI) network was also constructed to help us screen the top 20 hub genes in this profile and demonstrated the underlying interactions among them. The Gene Expression Profiling Interactive Analysis (GEPIA) was further performed in order to valid the mRNA levels of top5 up-regulated and top5 down-regualted DEGs, apart from exploring their association with survival rate as well as tumor stage. Finally, Q-PCR was further employed to valid the top5 up-regulated and top5 down-regulated genes in patients with PAAD. In our study, there were a total of 444 DEGs captured (271 up-regulated genes and 173 down-regulated genes). Among these DEGs, the top5 up-regulated genes were CEACAM5, SLC6A14, LAMC2, GALNT5 and TSPAN1 while the top5 down-regulated genes were GP2, CTRC, IAPP, PNLIPRP2 and PNLIPRP1. GO analysis disclosed that the DEGs were predominantly enriched in cell adhesion, lipid metabolism, integrin binding, proteolysis and calcium ion binding. KEGG analysis disclosed that the enriched pathway included pancreatic secretion, protein digestion and absorption, fat digestion and absorption, ECM-receptor interaction, focal adhesion and PI3K-Akt signaling pathway. Survival analysis unveiled that the high expression levels of SLC6A14, GALNT5 and TSPAN1 may correlate with the poor prognosis while high expression levels of IAPP may contribute to a better prognosis in patients with PAAD. Additionally, the levels of CEACAM5, SLC6A14, LAMC2 and GALNT5 were also associated with tumor stage. Furthermore, according to the connectivity degree of these DEGs, we selected the top20 hub genes, namely ALB, FN1, EGF, MMP9, COL1A1, COL3A1, FBN1, CXCL12, POSTIN, BGN, VCAN, THBS2, KRT19, MET, MMP14, COL5A2, GCG, MUC1, MMP1 and CPB1, which were expected to be promising therapeutic targets in PAAD. Collectively, our bioinformatics analysis showed that DEGs and hub genes may be defined as new biomarkers for diagnosis and for guiding the therapeutic strategies of PAAD.

To claim the features of nontumor tissue in gastric cancer patients, especially in those who have undergone gastrectomy, and to identify the molecular subtypes, we collected the immunogenic and hallmark gene sets from gene set enrichment analysis. The activity changes of these gene sets between tumor (375) and nontumor (32) tissues acquired from the Cancer Genome Atlas (TCGA-STAD) were calculated, and the novel molecular subtypes were delineated. Subsequently, prognostic gene sets were determined using least absolute shrinkage and selection operator (lasso) regression prognostic method. In addition, functional analysis was conducted. Totally, three subtypes were constructed in the present study, and there were differences in survival among three groups. Functional analysis showed genes from normal gene set were related to cell adhesion, and genes from tumor gene set were associated with focal adhesion, PI3K-Akt signaling pathway, regulation of actin cytoskeleton, and VEGF signaling pathway. Our study created lasting value beyond molecular subtypes and underscored the significance of normal tissues in gastric cancer development, which drawn a novel prognostic model for gastric treatment.

Background: Platelet-to-lymphocyte ratio (PLR) is reported to be related to the outcome of intensive care unit (ICU) patients. However, little is known about their associations with prognosis in newborn patients in neonatal ICU (NICU). The aim of the present study was to investigate the prognostic significance of the PLR for newborn patients in the NICU. Methods: Data on newborn patients in the NICU were extracted from the Multiparameter Intelligent Monitoring in Intensive Care III (MIMIC III) database. The initial PLR value of blood examinations within 24 h was analyzed. Spearman's correlation was used to analyze the association of PLR with the length of hospital and ICU stays. The chi-square test was used to analyze the association of PLR with mortality rate. Multivariable logistic regression was used to determine whether the PLR was an independent prognostic factor of mortality. The area under the receiver operating characteristic (ROC) curve was used to assess the predictive ability of models combining PLR with other variables. Results: In total, 5240 patients were enrolled. PLR was negatively associated with length of hospital stay and ICU stay (hospital stay: ρ = −0.416, p < 0.0001; ICU stay: ρ = −0.442, p < 0.0001). PLR was significantly correlated with hospital mortality (p < 0.0001). Lower PLR was associated with higher hospital mortality (OR = 0.85, 95% CI = 0.75–0.95, p = 0.005) and 90-day mortality (OR = 0.85, 95% CI = 0.76–0.96, p = 0.010). The prognostic predictive ability of models combining PLR with other variables for hospital mortality was good (AUC for Model 1 = 0.804, 95% CI = 0.73–0.88, p < 0.0001; AUC for Model 2 = 0.964, 95% CI = 0.95–0.98, p < 0.0001). Conclusion: PLR is a novel independent risk factor for newborn patients in the NICU.

Summary: It is of great importance and practical value to develop a facile and operable surface treatment method of materials with excellent antipollution and antiadhesion property, but still a huge challenge. In this work, a series of pseudo-zwitterions are prepared from electrostatic assembly of cationic polyethyleneimine and anionic phosphonic clusters. These pseudo-zwitterionic assemblies provide a strong hydration through electrostatic interaction with water and in turn create a barrier against oil foulants, leading to a nearly zero crude oil adhesion force. The pseudo-zwitterions-decorated surfaces exhibit exceptional water-cleanable oil-repellent property, even when they are completely dried and without prehydration before fouled by crude oil. While using these pseudo-zwitterions-modified polymeric membranes for separating surfactant stabilized oil-in-water emulsion, less than 10% decline of permeating flux is observed throughout a 2-h continuous separation experiment, showing excellent emulsion separation ability and antipollution performance for high viscous oil.

Background/Aims: Apocynin, a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor, has been identified as a potential neuroprotectant. In this study, we aimed to investigate the protective effect of apocynin against cobalt chloride (CoCl2)-induced pheochromocytoma (PC12) cell apoptosis. Methods: The PC12 cell culture was pretreated with apocynin and/or SB203580 (p38 mitogen-activated protein kinase [p38-MAPK] inhibitor) at different time points prior to CoCl2 incubation. The cell viability, apoptosis rate, DAN damage, and antioxidant activity were detected using cell counting kit-8 (CCK-8), flow cytometry, enzyme-linked immunosorbent assay (ELISA), and comet assay respectively. The protein and mRNA expressions of p38-MAPK and caspase-3 in the cells were measured by qRT-PCR and Western blotting. Results: Apocynin inhibited CoCl2-mediated apoptosis, reduced oxidative stress, and down-regulated the expression of p38-MAPK and caspase-3. Conclusions: Our findings show that apocynin attenuated CoCl2-induced apoptosis by potently restraining p38-MAPK-caspase-3 signaling pathway in PC12 cells, suggesting that apocynin may be a potent prophylactic reagent against CoCl2-mediated PC12 cell apoptosis.

Nanofiltration membranes are important for water desalination technologies, but designing membranes that achieve both high permeance and high salt rejection remains challenging. Here, the authors use sacrificial nanoparticles in the membrane fabrication process, leading to crumpled structures with ultrahigh permeance.

Background/Aims: Vibrio vulnificus (V. vulnificus) is a Gram-negative marine bacterium that can cause life-threatening primary septicemia, especially in the innate immune system. But how V. vulnificus affects and acts on dendritic cells (DC) is not well understood. The aim of the present study is to investigate [Ca2+]i change and the expression of the mTor-STAT3-Bcl-2 signaling pathway in V. vulnificus B2-induced DC apoptosis, and explore the protective effect of ethylenediaminetetraacetic acid (EDTA) against DC apoptosis in a V. vulnificus B2 and DC2.4 cell coculture infection model, using EDTA as an intervenient. Methods: The apoptosis rate, [Ca2+]i, and the expression of STAT3, m-Tor and Bcl-2 were detected by cytometry, Fluo-8-AM and Western blotting respectively. Results: The results demonstrated that EDTA inhibited the increase of [Ca2+]i, upregulated the expression of m-Tor-STAT3-Bcl-2 signaling pathway, and protected DC against V. vulnificus B2-induced apoptosis. Conclusions: EDTA inhibits V. Vulnificus-induced DC apoptosis by lowering [Ca2+]i via m-Tor-STAT3-Bcl-2 signaling pathway.

Background/Aims: Hyperuricemia is part of the metabolic-syndrome cluster of abdominal obesity, impaired glucose tolerance, insulin resistance, dyslipidemia, and hypertension. Monocytes/macrophages are critical in the development of metabolic syndrome, including gout, obesity and atherosclerosis. However, how high uric acid (HUA) exposure affects monocyte/macrophage function remains unclear. In this study, we investigated the molecular mechanism of HUA exposure in monocytes/macrophages and its impact on oxidized low-density lipoprotein (oxLDL)-induced foam-cell formation in a human monocytic cell line, THP-1. Methods: We primed THP-1 cells with phorbol-12-myristate-13-acetate (PMA) for differentiation, then exposed cells to HUA and detected the production of reactive oxygen species (ROS) and analyzed the level of phospho-AMPKα. THP-1 cells were pre-incubated with Compound C, an AMPK inhibitor, or N-acetyl-L-cysteine (NAC), a ROS scavenger, or HUA before PMA, to assess CD68 expression and phospho-AMPKα level. PMA-primed THP-1 cells were pre-treated with oxLDL before Compound C and HUA treatment. Western blot analysis was used to examine the levels of phospho-AMPKα, CD68, ABCG1, ABCA1, cyclooxygenase-2 (COX-2) and NF-κB (p65). Flow cytometry was used to assess ROS production and CD68 expression in live cells. Oil-red O staining was used to observe oxLDL uptake in cells. Results: HUA treatment increased ROS production in PMA-primed THP-1 cells; NAC blocked HUA-induced oxidative stress. HUA treatment time-dependently increased phospho-AMPKα level in PMA-primed THP-1 cells. The HUA-induced oxidative stress increased phospho-AMPKα levels, which was blocked by NAC. HUA treatment impaired CD68 expression during cell differentiation by activating the AMPK pathway, which was reversed by Compound C treatment. Finally, HUA treatment inhibited oxLDL uptake in the formation of foam cells in THP-1 cells, which was blocked by Compound C treatment. HUA treatment significantly increased the expression of ABCG1 and reversed the oxLDL-reduced ABCG1 expression but did not affect the expression of ABCA1, NF-κB (p65) or COX-2. Conclusions: HUA exposure activated the ROS-AMPK pathway, impaired CD68 expression, and inhibited oxLDL-induced foam-cell formation in a human monocytic cell line, THP-1.

AMP-activated protein kinase (AMPK) is a central metabolic sensor and plays an important role in regulating glucose, lipid and cholesterol metabolism. Therefore, AMPK is a key therapeutic target in diabetes. Recent pilot studies have suggested that diabetes drugs may reduce the risk of cancer by affecting the AMPK pathway. However, the association between AMPK and the proliferation of hepatocellular carcinoma (HCC) is unknown. In this study, we investigated the relationship between AMPK activity and the proliferation of HCC in cell lines, nude mice and human clinic samples. We first investigated the relationship between AMPK activity and cell proliferation in two HCC cell lines, PLC/PRF/5 and HepG2, by two AMPK activators, 5-aminoimidazole-4-carboxamide-1-h-D-ribofuranoside (AICAR) and metformain. AICAR and metformin treatment significantly inhibited the proliferation of HCC cells and induced cell cycle arrest at G1-S checkpoint. We then observed that metformin abrogated the growth of HCC xenografts in nude mice. The clinical pathology of AMPK activity in HCC, including cell proliferation, differential grade, tumor size and microvessel density, was studied by using 30 clinical tissue samples. In HCC tissue samples, phosphorylated AMPK was expressed mainly in cytoplasm. AMPK activity decreased significantly in HCC in comparison with paracancerous liver tissues (P

The relationship between suicidality and major depression is complex. Socio- demography, clinical features, comorbidity, clinical symptoms, and stressful life events are important factors influencing suicide in major depression, but these are not well defined. Thus, the aim of the present study was to assess the associations between the above-mentioned factors and suicide ideation, suicide plan, and suicide attempt in 6008 Han Chinese women with recurrent major depression (MD). Patients with any suicidality had significantly more MD symptoms, a significantly greater number of stressful life events, a positive family history of MD, a greater number of episodes, a significant experience of melancholia, and earlier age of onset. Comorbidity with dysthymia, generalized anxiety disorder (GAD), social phobia, and animal phobia was seen in suicidal patients. The present findings indicate that specific factors act to increase the likelihood of suicide in MD. Our results may help improve the clinical assessment of suicide risk in depressed patients, especially for women.

In this study, we report the emergence of two-dimensional (2D) branching fractal structures (BFS) in the nanoconfinement between the active and the support layer of a thin-film-composite polyamide (TFC-PA) nanofiltration membrane. These BFS are crystal dendrites of NaCl formed when salts are either added to the piperazine solution during the interfacial polymerization process or introduced to the nascently formed TFC-PA membrane before drying. The NaCl dosing concentration and the curing temperature have an impact on the size of the BFS but not on the fractal dimension (~1.76). The BFS can be removed from the TFC-PA membranes by simply dissolving the crystal dendrites in deionized water, and the resulting TFC-PA membranes have substantially higher water fluxes (three-to fourfold) without compromised solute rejection. The flux enhancement is believed to be attributable to the distributed reduction in physical binding between the PA active layer and the support layer, caused by the exertion of crystallization pressure when the BFS formed. This reduced physical binding leads to an increase in the effective area for water transport, which, in turn, results in higher water flux. The BFS-templating method, which includes the interesting characteristics of 2D crystal dendrites, represents a facile, low-cost, and highly practical method of enhancing the performance of the TFC-PA nanofiltration membrane without having to alter the existing infrastructure of membrane fabrication. [ABSTRACT FROM AUTHOR]

Clinical studies have shown hyperuricemia strongly associated with insulin resistance as well as cardiovascular disease. Direct evidence of how high uric acid (HUA) affects insulin resistance in cardiomyocytes, but the pathological mechanism of HUA associated with cardiovascular disease remains to be clarified. We aimed to examine the effect of HUA on insulin sensitivity in cardiomyocytes and on insulin resistance in hyperuricemic mouse model. We exposed primary cardiomyocytes and a rat cardiomyocyte cell line, H9c2 cardiomyocytes, to HUA, then quantified glucose uptake with a fluorescent glucose analog, 2-NBDG, after insulin challenge and detected reactive oxygen species (ROS) production. Western blot analysis was used to examine the levels of insulin receptor (IR), phosphorylated insulin receptor substrate 1 (IRS1, Ser307) and phospho-Akt (Ser473). We monitored the impact of HUA on insulin resistance, insulin signaling and IR, phospho-IRS1 (Ser307) and phospho-Akt levels in myocardial tissue of an acute hyperuricemia mouse model established by potassium oxonate treatment. HUA inhibited insulin-induced glucose uptake in H9c2 and primary cardiomyocytes. It increased ROS production; pretreatment with N-acetyl-L-cysteine (NAC), a ROS scavenger, reversed HUA-inhibited glucose uptake induced by insulin. HUA exposure directly increased the phospho-IRS1 (Ser307) response to insulin and inhibited that of phospho-Akt in H9C2 cardiomyocytes, which was blocked by NAC. Furthermore, the acute hyperuricemic mice model showed impaired glucose tolerance and insulin tolerance accompanied by increased phospho-IRS1 (Ser307) and inhibited phospho-Akt response to insulin in myocardial tissues. HUA inhibited insulin signaling and induced insulin resistance in cardiomyocytes in vitro and in vivo, which is a novel potential mechanism of hyperuricemic-related cardiovascular disease. [ABSTRACT FROM AUTHOR]