Water-oil dual-channels enabled exceptional anti-fouling performances for separation of emulsified oil pollutant.

Oil contamination has been an increasingly concerned environmental issue due to the large quantity of oily wastewater discharged by the industry. The extreme wettability-enabled single-channel separation strategy guarantees efficient separation of oil pollutant from wastewater. However, the ultra-high selective permeability forces the intercepted oil pollutant to form a blocking layer, which weakens the separation capability and slows the kinetics of permeable phase. As a consequence, the single-channel separation strategy fails to maintain a stable flux for a long-term separation process. Herein, we reported a brand-new water-oil dual-channels strategy for accomplishing an ultra-stable long-term separation of emulsified oil pollutant from oil-in-water nano-emulsion by engineering two drastically opposite extreme wettabilities (i.e. superhydrophilicity and superhydrophobicity) to build the water-oil dual-channels. The strategy established the superwetting transport channels to permit water and oil pollutant to permeate through their own channel. In this way, the generation of intercepted oil pollutant was prevented, which guaranteed an exceptional long-lasting (20 h) anti-fouling performance for successful achievement of an ultra-stable separation of oil contamination from oil-in-water nano-emulsion with high flux retention and high separation efficiency. Therefore, our investigations provided a new route for realizing ultra-stable long-term separation of emulsified oil pollutant from wastewater.

Improved CEEMDAN, GA, and SVR Model for Oil Price Forecasting.

Accurate prediction of crude oil prices (COPs) is a challenge for academia and industry. Therefore, the present research developed a new CEEMDAN-GA-SVR hybrid model to predict COPs, incorporating complete ensemble empirical mode decomposition with adaptive noise (CEEMDAN), a genetic algorithm (GA), and support vector regression machine (SVR). First, our team utilized CEEMDAN to realize the decomposition of a raw series of COPs into a group of comparatively simpler subseries. Second, SVR was utilized to predict values for every decomposed subseries separately. Owing to the intricate parametric settings of SVR, GA was employed to achieve the parametric optimisation of SVR during forecast. Then, our team assembled the forecasted values of the entire subseries as the forecasted values of the CEEMDAN-GA-SVR model. After a series of experiments and comparison of the results, we discovered that the CEEMDAN-GA-SVR model remarkably outperformed single and ensemble benchmark models, as displayed by a case study finished based on a time series of weekly Brent COPs.

Collagen fiber membrane as multi-functional support enabled rational design of ultrahigh-flux separation membrane for the remediation of oil contamination in water.

Membrane separation is a promising approach for the remediation of oil contamination in water. High-flux separation of membrane relies on the rational design of ultrathin active layer to significantly reduce mass transfer distance for achieving high separation flux, while the ultrathin active layer is usually fragile with poor mechanical strength, which has to be supported on a support. Herein, we employed collagen fiber membrane (CFM) as multi-functional support for the in-situ growth of polyacrylonitrile (PAN) layer by electrospinning to prepare the high-performance PAN/CFM composite membrane. Due to the amphiphilic nature and strong capillary effect, CFM played the role as multi-functional support to provide separation effectiveness and boosted separation flux. The PAN/CFM composite membrane enabled ultrahigh separation flux (e.g., 51751.59 L m-2 h-1 bar-1) to a variety of oil-in-water emulsion, which was one order of magnitude higher than that of commercial polyethersulfone membrane and 1.86-fold to that of cellulose acetate membrane. Furthermore, the PAN/CFM composite membrane retained high separation flux (e.g., 11046.97 L m-2 h-1 bar-1) during the 5th separation cycle, providing appreciable anti-fouling capability. Therefore, our findings provided a promising way to effectively resolve the problem of oil contamination in water.

Identifying potential thyroid hormone disrupting effects among diphenyl ether structure pesticides and their metabolites in silico.

The environmental and dietary pesticide exposures can cause thyroid hormones (THs) disorders, which are associated with the high incidence of thyroid diseases worldwide. The structures of diphenyl ether pesticides and their metabolites are very similar to the structure of THs. Based on this, in silico molecular simulation approaches were used to predict, screen, evaluate and identify the binding interactions of 98 diphenyl ether structure pesticides and their metabolites (DEPMs) with 10 THs related proteins in the study. The research results indicated that these DEPMs such as fluoroglycofen (FOG), rafoxanide, diclofop, ethoxyfen and difenopenten were considered to have the greater potentials to interfere with the related proteins of THs biosynthesis, blood transport, receptor binding and metabolism. And FOG can interact with thyroid hormone receptor beta (TRß) to form non-bond interactions. Furthermore, the results of molecular dynamics simulations showed that there were strong and stable interactions between FOG and TRß. These results suggested that the herbicide FOG was likely to disturb THs nuclear receptor. And benzene rings and hydrophobic groups might be the characteristic chemical functional groups for DEPMs to disrupt TRß. The relevant results of this study can be used to provide references for environmental toxicology evaluation, food safety risk assessment, and formulation and revision of pesticides and their metabolites residue limits in agricultural products and food.

Biomimetic α-selective ribosylation enables two-step modular synthesis of biologically important ADP-ribosylated peptides.

The α-type ADP-ribosylated peptides represent a class of important molecular tools in the field of protein ADP-ribosylation, however, they are difficult to access because of their inherent complicated structures and the lack of effective synthetic tools. In this paper, we present a biomimetic α-selective ribosylation reaction to synthesize a key intermediate, α-ADP-ribosyl azide, directly from native ß-nicotinamide adenine dinucleotide in a clean ionic liquid system. This reaction in tandem with click chemistry then offers a two-step modular synthesis of α-ADP-ribosylated peptides. These syntheses can be performed open air in eppendorf tubes, without the need for specialized instruments or training. Importantly, we demonstrate that the synthesized α-ADP-ribosylated peptides show high binding affinity and desirable stability for enriching protein partners, and reactivity in post-stage poly ADP-ribosylations. Owing to their simple chemistry and multidimensional bio-applications, the presented methods may provide a powerful platform to produce general molecular tools for the study of protein ADP-ribosylation.

Structure-guided development of YEATS domain inhibitors by targeting π-π-π stacking.

Chemical probes of epigenetic 'readers' of histone post-translational modifications (PTMs) have become powerful tools for mechanistic and functional studies of their target proteins in normal physiology and disease pathogenesis. Here we report the development of the first class of chemical probes of YEATS domains, newly identified 'readers' of histone lysine acetylation (Kac) and crotonylation (Kcr). Guided by the structural analysis of a YEATS-Kcr complex, we developed a series of peptide-based inhibitors of YEATS domains by targeting a unique π-π-π stacking interaction at the proteins' Kcr recognition site. Further structure optimization resulted in the selective inhibitors preferentially binding to individual YEATS-containing proteins including AF9 and ENL with submicromolar affinities. We demonstrate that one of the ENL YEATS-selective inhibitors, XL-13m, engages with endogenous ENL, perturbs the recruitment of ENL onto chromatin, and synergizes the BET and DOT1L inhibition-induced downregulation of oncogenes in MLL-rearranged acute leukemia.

Polyphenolic-Chemistry-Enabled, Mechanically Robust, Flame Resistant and Superhydrophobic Membrane for Separation of Mixed Surfactant-Stabilized Emulsions.

Superhydrophobic materials hold great promise in emulsion separation, but they have inherent mechanical weakness and are ineffective to separate mixed surfactant-stabilized emulsions. Herein, we combined the adhesion ability of polyphenol-Fe3+ bis-complexes with the high mechanical strength of carbon nanotubes (CNTs) to construct a mechanically robust and superhydrophobic coating on a collagen fiber membrane (CFM). We demonstrated that both CNTs and polyphenolic complexes competed with the surfactants adsorbed onto the emulsion droplets, serving as efficient demulsifiers to various mixed surfactant-stabilized emulsions. CFM has a 3D fibrous structure and a high limiting oxygen index, which provides high flux and flame resistance. The as-prepared superhydrophobic membrane can separate diverse anionic/nonionic and cationic/nonionic surfactant-stabilized micro- and nanoemulsions under gravity, with a separation efficiency and flux up to 99.999 % and 1695 L m-2 h-1 , respectively. The membranes also retained the emulsion separation ability after sandpaper abrasion. These features demonstrate a practical technology for emulsion separation.

Cholesterol derivative-based liposomes for gemcitabine delivery: preparation, in vitro, and in vivo characterization.

As an anti-tumor drug, gemcitabine (Gem) is commonly used for the treatment of non-small cell lung cancer and pancreatic cancer. However, there are several clinical drawbacks to using Gem, including its extremely short plasma half-life and side effects. To prolong its half-life and reduce its side effects, we synthesized a derivative of Gem using cholesterol (Chol). This derivative, called gemcitabine-cholesterol (Gem-Chol), was entrapped into liposomes by a thin-film dispersion method. The particle size of the Gem-Chol liposomes was 112.57 ± 1.25 nm, the encapsulation efficiency was above 99%, and the drug loading efficiency was about 50%. In vitro studies revealed that the Gem-Chol liposomes showed delayed drug release and long-term stability at 4 °C for up to 2 months. In vivo studies also showed the superiority of the Gem-Chol liposomes, and compared with free Gem, the Gem-Chol liposomes had longer circulation time. Moreover, an anti-tumor study in H22 and S180 tumor models showed that liposomal entrapment of Gem-Chol improved the anti-tumor effect of Gem. This study reports a potential formulation of Gem for clinical application.

Histone Ketoamide Adduction by 4-Oxo-2-nonenal Is a Reversible Posttranslational Modification Regulated by Sirt2.

Lipid-derived electrophiles (LDEs) directly modify proteins to modulate cellular signaling pathways in response to oxidative stress. One such LDE, 4-oxo-2-nonenal (4-ONE), has recently been found to target histones and interfere with histone assembly into nucleosomes. Unlike other LDEs that preferentially modify cysteine via nucleophilic Michael addition, 4-ONE reacts with histone lysine residues to form a new histone modification, gamma-oxononanoylation (Kgon). However, it remains unclear whether Kgon can cause irreversible damage or be regulated by enzymes "erasing" this nonenzymatic modification. Here, we report that human Sirt2 catalyzes the removal of histone Kgon. Among the tested human sirtuins, Sirt2 showed robust deacylase activity toward the Kgon-carrying histone peptides in vitro. We use alkynyl-4-ONE as a chemical reporter for Kgon to demonstrate that Sirt2 is responsible for removing histone Kgon in cells. Furthermore, we develop a ketone-reactive chemical probe to detect histones modified by endogenous 4-ONE in macrophages in response to inflammatory stimulation. Using this probe, we show Sirt2 as a deacylase able to control histone Kgon in stimulated macrophages. This study unravels a new mechanism for the regulation of LDE-derived protein posttranslational modifications, as well as a novel role played by Sirt2 as a histone Kgon deacylase in cytoprotective signaling responses.

Prognostic value of endocervical sampling following loop excision of high grade intraepithelial neoplasia.

OBJECTIVE: To assess the role of additional biopsies performed with loop electrosurgical excisional procedure (LEEP) in predicting the likelihood of persistent high grade intraepithelial neoplasia. METHODS: Clinicopathologic data were abstracted from women who underwent excision of high grade intraepithelial lesions between 2001 and 2014. Persistent disease was defined as uninterrupted high grade intraepithelial neoplasia, whereas recurrent disease was defined as disease diagnosed ≥1year after treatment with intervening normal evaluation. Chi-square and Fisher's exact tests were used to examine associations between demographic and histologic parameters and clinical outcomes. RESULTS: A total of 606 women underwent LEEP for high grade intraepithelial neoplasia (HSIL), of whom, 178 (29%) were additionally evaluated by endocervical curettage, 80 (13%), top hat and 99 (16%), both procedures. With mean follow-up of 1.9±1.5years, persistent disease was identified in 87 women (14%) while recurrent disease was diagnosed in 20 (3%). After adjusting for age, HIV status and histologic grade of disease, the presence of disease at the endocervical margin (aOR=2.2, 95% CL 1.8-5.5, p<0.0001), with endocervical curettage (aOR=2.39, 95% CL 1.2-9.9, p=0.025) or on top hat (aOR=4.0, 95% CL 1.1-16.2, p=0.04) correlated with the likelihood of persistent but not recurrent disease. Only endocervical margin status remained predictive (p=0.03) of outcome after controlling for pre-procedure likelihood of endocervical disease. Sensitivity of endocervical margin status for persistent disease was 56.9% with specificity of 72.2%. Positive predictive value (PPV) was 24.9% and negative predictive value (NPV) 90.9%. CONCLUSIONS: Despite frequent use of additional procedures to sample the endocervix, these strategies do not improve the ability of endocervical margin status to predict persistent or recurrent dysplasia.

Non-utilization of the Pap Test Among Women with Frequent Health System Contact.

Despite improvements in health access, many underserved women abstain from cervical cancer screening. A self-administered questionnaire was used to identify factors determining whether medically underserved women attending a safety net health system regularly are screened for cervical cancer. Approximately 11 % of study subjects had never received a Pap test despite an average of nearly four clinic visits in the preceding 12 months. Never screeners were significantly younger, more likely to be Hispanic, non-U.S. born and less likely to have healthcare continuity. In multivariable analysis, odds for never screening were independently lower among women with male partner support (aOR 0.29) and physician's recommendation for screening (aOR 0.34) and higher among women who believed screening visits are too long (aOR 2.53). Educating male partners of Hispanic and immigrant women in addition to addressing recognized situational barriers may help to improve cervical cancer screening rates.

Modulation of LPS-stimulated pulmonary inflammation by Borneol in murine acute lung injury model.

The object of our study is to investigate the protective effects of Borneol on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. To determine the effects of Borneol on the histopathological changes in mice with ALI, inflammatory cell count in bronchoalveolar lavage fluid (BALF) and lung wet/dry weight ratio were measured in LPS-challenged mice, and lung histopathologic changes observed via paraffin section were assessed. Next, cytokine production induced by LPS in BALF and RAW 264.7 cells was measured by enzyme-linked imunosorbent assay (ELISA). To further study the mechanism of Borneol-protective effects on ALI, nuclear factor-kappaB (NF-κB) and mitogen-activated protein kinases (MAPKs) pathways were investigated. In the present study, Borneol obviously alleviated pulmonary inflammation by reducing inflammatory infiltration, histopathological changes, descended cytokine production, and pulmonary edema initiated by LPS. Furthermore, Borneol significantly suppressed phosphorylation of NF-κB/P65, IκBa, p38, JNK, and ERK. Taken together, our results suggest that Borneol suppressed inflammatory responses in LPS-induced acute lung injury through inhibition of the NF-κB and MAPKs signaling pathways. Borneol may be a promising potential preventive agent for acute lung injury treatment.

Role of sortase A in the pathogenesis of Staphylococcus aureus-induced mastitis in mice.

Sortase A (SrtA), a transpeptidase, anchors surface proteins with an LPXTG-motif sorting signal to the cell envelope. To determine the role of SrtA in the pathogenesis of Staphylococcus aureus, we constructed a mutant strain, ∆SrtA, by genetic techniques and identified its functions in a S. aureus-induced mastitis mouse model. The histological and myeloperoxidase (MPO) level results showed that the ∆SrtA strain attenuated the inflammatory reaction in the mammary tissue of mice compared with wild-type S. aureus challenge. Additionally, the ELISA results showed that the ∆SrtA strain impaired the induction of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6), and the Western blot results showed that the mutant strain blocked the activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs) by attenuating the degradation and phosphorylation of signaling pathway molecules such as IκBα, p65 and p38. These results suggest that SrtA is a key virulence factor in the pathogenesis of S. aureus-induced mastitis in mice. It appears that the srtA mutant affected the attachment of S. aureus to host cells, thus attenuating the activation of the NF-κB and MAPK signaling pathways, which regulated the expression of pro-inflammatory cytokines and decreased the susceptibility to mastitis.

Prospective randomized controlled study comparing low-cost LED and conventional phototherapy for treatment of neonatal hyperbilirubinemia.

Our objective was to carry out a prospective, randomized, single-blind study to evaluate whether light emitting diode (LED) phototherapy using a low-cost set of lights is as effective as conventional phototherapy in treating hyperbilirubinemia in neonates. The study included 45 pre-term neonates requiring phototherapy as per American Academy of Pediatrics guidelines; participants were randomized to receive phototherapy using LED-based lights, conventional fluorescent blue lights or conventional halogen lights. There were no statistically significant differences in the average bilirubin levels at the onset, at the maximum and at the end of treatment, nor in the duration of phototherapy treatment and the rate of decrease in bilirubin levels in the neonates receiving conventional fluorescent blue light, conventional halogen light and LED phototherapy. (Differences were considered significant at p < 0.05). The average rate of decrease of bilirubin levels was 0.047 ± 0.037 mg dl(-1) h(-1), 0.055 ± 0.056 mg dl(-1) h(-1) and 0.057 ± 0.045 mg dl(-1) h(-1) in the groups receiving conventional fluorescent blue light, conventional halogen light and LED phototherapy, respectively. The average duration of phototherapy treatment in the three groups was 108.8 ± 85.9 h, 92.8 ± 38.1 h, 110.4 ± 42.6 h, respectively. In this pilot study, LED phototherapy using a simple, low-cost set of lights was as effective as conventional phototherapy in the treatment of neonatal hyperbilirubinemia. LED phototherapy lights that deliver 30-40 µW cm(-2 )nm(-1) can be assembled in small quantities for

Synthesis and cytotoxic evaluation of N-(4-methoxy-1H-benzo[d]imidazol-7-yl)-arylsulfonamide and N-aryl-(4-methoxy-1H-benzo[d]imidazol)-7-sulfonamide analogs of combretastatin A-4.

Two series of novel benzoimidazole sulfonamides as combretastatin A-4 analogs were synthesized. The cytotoxicities of the title compounds were evaluated against five different cancer cell lines. Among the tested compounds, four compounds displayed cytotoxicities against the HCT8 cell line. Compound 6a has shown the strongest potency against the tested human tumor cell lines with an IC50 value ranging from submicromolar to micromolar level.