One-Step Phase Separation and Mineralization Fabrication of Membranes for Oily Wastewater Treatment.

Oily wastewater threatens the environment and the human health. Membrane technology offers a simple and efficient alternative to separating oil and water. However, complex membrane modifications are usually employed to optimize the separation performance. In this research, we develop an extremely simple one-step method to in situ calcium carbonate (CaCO3) nanoparticles onto a porous polyketone (PK) membrane via a nonsolvent induced phase separation (NIPS)-mineralization strategy. We utilized the unique chemical property of PK, which allows it to dissolve in a resorcinol aqueous solution. PK was mixed with tannic acid (TA) and calcium chloride (CaCl2) in a resorcinol aqueous solution to fabricate a casting solution. The activated membrane was cast and immersed into a sodium carbonate (Na2CO3) aqueous solution for taking the one-step NIPS-mineralization process. This proposed NIPS-mineralization mechanism comes to two conclusions: (i) the resulting membrane with comprehensive oleophobic properties and enhanced permeation flux for applications of oil/water separation with ultralow fouling and (ii) simplified the procedure to optimize the membrane performance using regular NIPS steps. The current work explores a one-step NIPS-mineralization technique that offers a novel approach to preparing membranes with highly efficient oil/water separation performance.

Nanochannel Stability of Chemically Converted Graphene Oxide Membranes.

Chemically converted graphene oxide laminate membranes, which exhibit stable interlayered nanochannels in aqueous environments, are receiving increasing attention owing to their potential for selective water and ion permeation. However, how the molecular properties of conversion agents influence the stabilization of nanochannels and how effectively nanochannels are stabilized have rarely been studied. In this study, mono-, di-, and tri-saccharide molecules of glucose (Glu), maltose (Glu2), and maltotriose (Glu3) are utilized, respectively, to chemically modify graphene oxide (GO). The aim is to create nanochannels with different levels of stability and investigate how these functional conversion agents affect the separation performance. The effects of the property differences between different conversion agents on nanochannel stabilization are demonstrated. An agent with efficient chemical reduction of GO and limited intercalation in the resulting nanochannel ensures satisfactory nanochannel stability during desalination. The stabilized membrane nanochannel exhibits a permeance of 0.69 L m-2 h-1 bar-1 and excellent Na2SO4 rejection of 96.42%. Furthermore, this optimized membrane nanochannel demonstrates enhanced stability under varying external conditions compared to the original GO. This study provides useful information for the design of chemical conversion agents for GO nanochannel stabilization and the development of nanochannel membranes for precise separation.

Thin continuous membrane coating with high surface energy for comprehensive antifouling seawater distillation.

Membrane distillation (MD) has prominent advantages such as treating high-salinity wastewater with a low-grade thermal energy, high salt rejection, and zero discharge. However, organic fouling and mineral scaling are two major challenges for hydrophobic MD membranes when used for practical applications. Commonly, improving organic fouling- and mineral scaling-resistance require oppositely enhanced wetting properties of membrane, thus is difficult to simultaneously realize dual resistance with one membrane. Here, we proposed to use underwater thermodynamically stable high-surface-energy coating to modify the hydrophobic membrane with Janus structures comprising different surface energy. The underlayered structure meets the hydrophobicity requirements of the MD membrane, while the coating layer realizes dual resistance to organic and inorganic foulants. Theoretical analysis and experimental proof reveal that the membrane with the high-surface-energy coating layer outperforms the pristine one with approximately 10 times of longevity. This strategy provides a new way for the use of high-surface-energy materials in versatilely fouling-resistant MD process.

Side-Chain-Dependent Functional Intercalations in Graphene Oxide Membranes for Selective Water and Ion Transport.

Subnanometer interlayer space in graphene oxide (GO) laminates is desirable for use as permselective membrane nanochannels. Although the facile modification of the local structure of GO enables various nanochannel functionalizations, precisely controlling nanochannel space is still a challenge, and the roles of confined nanochannel chemistry in selective water/ion separation have not been clearly defined. In this study, macrocyclic molecules with consistent basal plane but varying side groups were used to conjunct with GO for modified nanochannels in laminates. We demonstrated the side-group dependence of both the angstrom-precision tunability for channel free space and the energy barrier setting for ion transport, which challenges the permeability-selectivity trade-off with a slightly decreased permeance from 1.1 to 0.9 L m-2 h-1 bar-1 but an increased salt rejection from 85% to 95%. This study provides insights into the functional-group-dependent intercalation modifications of GO laminates for understanding laminate structural control and nanochannel design.

Effects of Calcium Ions on the Antimicrobial Activity of Gramicidin A.

Gramicidin A (gA) is a linear antimicrobial peptide that can form a channel and specifically conduct monovalent cations such as H+ across the lipid membrane. The antimicrobial activity of gA is associated with the formation of hydroxyl free radicals and the imbalance of NADH metabolism, possibly a consequence caused by the conductance of cations. The ion conductivity of gramicidin A can be blocked by Ca2+ ions. However, the effect of Ca2+ ions on the antimicrobial activity of gA is unclear. To unveil the role of Ca2+ ions, we examined the effect of Ca2+ ions on the antimicrobial activity of gramicidin A against Staphylococcus aureus (S. aureus). Results showed that the antimicrobial mechanism of gA and antimicrobial activity by Ca2+ ions are concentration-dependent. At the low gA concentration (≤1 µM), the antimicrobial mechanism of gA is mainly associated with the hydroxyl free radical formation and NADH metabolic imbalance. Under this mode, Ca2+ ions can significantly inhibit the hydroxyl free radical formation and NADH metabolic imbalance. On the other hand, at high gA concentration (≥5 µM), gramicidin A acts more likely as a detergent. Gramicidin A not only causes an increase in hydroxyl free radical levels and NAD+/NADH ratios but also induces the destruction of the lipid membrane composition. At this condition, Ca2+ ions can no longer reduce the gA antimicrobial activity but rather enhance the bacterial killing ability of gramicidin A.

The Effect of Calcium and Halide Ions on the Gramicidin A Molecular State and Antimicrobial Activity.

Gramicidin A (gA) forms several convertible conformations in different environments. In this study, we investigated the effect of calcium halides on the molecular state and antimicrobial activity of gramicidin A. The molecular state of gramicidin A is highly affected by the concentration of calcium salt and the type of halide anion. Gramicidin A can exist in two states that can be characterized by circular dichroism (CD), mass, nuclear magnetic resonance (NMR) and fluorescence spectroscopy. In State 1, the main molecular state of gramicidin A is as a dimer, and the addition of calcium salt can convert a mixture of four species into a single species, which is possibly a left-handed parallel double helix. In State 2, the addition of calcium halides drives gramicidin A dissociation and denaturation from a structured dimer into a rapid equilibrium of structured/unstructured monomer. We found that the abilities of dissociation and denaturation were highly dependent on the type of halide anion. The dissociation ability of calcium halides may play a vital role in the antimicrobial activity, as the structured monomeric form had the highest antimicrobial activity. Herein, our study demonstrated that the molecular state was correlated with the antimicrobial activity.

G37V mutation of Aß42 induces a nontoxic ellipse-like aggregate: An in vitro and in silico study.

The glycine zipper motif at the C-terminus of the ß-amyloid (Aß) peptide have been shown to strongly influence the formation of neurotoxic aggregates. A previous study showed that the G37L mutation dramatically reduces the Aß toxicity in vivo and in vitro. However, the primary cause and mechanism of the glycine zipper motif on Aß properties remain unknown. To gain molecular insights into the impact of glycine zipper on Aß properties, we substituted the residue 37 of Glycine by Valine and studied the structural and biochemical properties of G37V mutation, Aß42(37V), by using in vitro and in silico approaches. Unlike G37L mutation, the G37V mutation reduced toxicity substantially but did not significantly accelerate the aggregation rate or change the content of secondary structures. Further TEM analyses showed that the G37V mutation formed an ellipse-like aggregate rather than a network-like fibril as wild type or G37L mutation of Aß42 form. This different aggregation morphology may be highly linked with the reduction of toxicity. To gain the insight for the different properties of Aß42(37V), we studied the structure of Aß42 and G37V mutation using the replica exchange molecular dynamics simulation. Our results demonstrate that although the overall secondary structure population is similar with Aß42 and Aß42(G37V), Aß42(G37V) shows an increase in the ß-turn and ß-hairpin at residues 36-37 and the flexibility of the Asp23-Lys28 salt bridge. These unique structural features may be the possible reason to account for the ellipse-like morphology.

Anti-arrhythmic Medication Propafenone a Potential Drug for Alzheimer's Disease Inhibiting Aggregation of Aß: In Silico and in Vitro Studies.

Alzheimer's disease (AD) is the most common form of dementia caused by the formation of Aß aggregates. So far, no effective medicine for the treatment of AD is available. Many efforts have been made to find effective medicine to cope with AD. Curcumin is a drug candidate for AD, being a potent anti-amyloidogenic compound, but the results of clinical trials for it were either negative or inclusive. In the present study, we took advantages from accumulated knowledge about curcumin and have screened out four compounds that have chemical and structural similarity with curcumin more than 80% from all FDA-approved oral drugs. Using all-atom molecular dynamics simulation and the free energy perturbation method we showed that among predicted compounds anti-arrhythmic medication propafenone shows the best anti-amyloidogenic activity. The in vitro experiment further revealed that it can inhibit Aß aggregation and protect cells against Aß induced cytotoxicity to almost the same extent as curcumin. Our results suggest that propafenone may be a potent drug for the treatment of Alzheimer's disease.

TLR4-dependent internalization of CX3CR1 aggravates sepsis-induced immunoparalysis.

Sepsis, the most severe manifestation of infection, poses a major challenge to health-care systems around the world. Limited ability to clean and remove the pathogen renders difficulty in septic patients to recover from the phase of immunoparalysis. The present study found the vital role of CX3CR1 internalization on sepsis-induced immunoparalysis. A mouse model with cecal ligation and puncture (CLP) and cell model with lipopolysaccharides (LPS) were employed to explore the relationship between CX3CR1 internalization and septic immunoparalysis. Immunoparalysis model in mice was established 4 days after CLP with significantly decreased proinflammatory cytokines. Flow cytometry analysis found a decreased surface expression of CX3CR1 during immunoparalysis, which was associated with reduced mRNA level and increased internalization of CX3CR1. G-protein coupled receptor kinase 2 (GRK2) and ß-arrestin2 were significantly increased during septic immunoparalysis and involved in the internalization of CX3CR1. TLR4-/- or TLR4 inhibitor-treated macrophages exhibited an inhibited expression of GRK2 and ß-arrestin2, along with reduced internalization of CX3CR1. Moreover, the knockdown of GRK2 and ß-arrestin2 inhibited the internalization of CX3CR1 and led to a higher response on the second hit, which was associated with an increased activation of NF-κB. The critical association between internalization of CX3CR1 and immunosuppression in sepsis may provide a novel reference for clinical therapeutics.

Efficacy of dexmedetomidine on postoperative nausea and vomiting: a meta-analysis of randomized controlled trials.

PURPOSE: Postoperative nausea and vomiting (PONV) is a frequent complication in postoperative period. The aim of the current meta-analysis was to assess the efficacy of dexmedetomidine on PONV. METHODS: Two researchers independently searched PubMed, Embase and Cochrane Central Register of Controlled Trials for randomized controlled trials (RCTs). The meta-analysis was performed with Review Manager. RESULTS: Eighty-two trials with 6,480 patients were included in this meta-analysis. Dexmedetomidine reduced postoperative nausea (Risk Ratio (RR) = 0.61, 95% confidence interval (CI): 0.50 to 0.73) and vomiting (RR = 0.48, 95% CI: 0.36 to 0.64) compared with placebo, with an effective dose of 0.5 ug/kg (RR = 0.46, 95% CI: 0.34 to 0.62) and 1.0 ug/kg (RR = 0.29, 95% CI: 0.12 to 0.75), respectively. The antiemetic effect can only be achieved intravenously, not epidurally or intrathecally. The efficacy of dexmedetomidine was similar to that of widely used agents, such as propofol, midazolam etc., but better than opioid analgesics. Moreover, application of dexmedetomidine reduced intraoperative requirement of fentanyl (Standard Mean Difference = -1.91, 95% CI: -3.20 to -0.62). CONCLUSIONS: The present meta-analysis indicates that dexmedetomidine shows superiority to placebo, but not to all other anesthetic agents on PONV. And this efficacy may be related to a reduced consumption of intraoperative opioids.

Efficacy of dexmedetomidine on postoperative nausea and vomiting: a meta-analysis of randomized controlled trials.

PURPOSE: Postoperative nausea and vomiting (PONV) is a frequent complication in postoperative period. The aim of the current meta-analysis was to assess the efficacy of dexmedetomidine on PONV. METHODS: Two researchers independently searched PubMed, Embase and Cochrane Central Register of Controlled Trials for randomized controlled trials (RCTs). The meta-analysis was performed with Review Manager. RESULTS: Eighty-two trials with 6,480 patients were included in this meta-analysis. Dexmedetomidine reduced postoperative nausea (Risk Ratio (RR) = 0.61, 95% confidence interval (CI): 0.50 to 0.73) and vomiting (RR = 0.48, 95% CI: 0.36 to 0.64) compared with placebo, with an effective dose of 0.5 µg/kg (RR = 0.46, 95% CI: 0.34 to 0.62) and 1.0 µg/kg (RR = 0.29, 95% CI: 0.12 to 0.75), respectively. The antiemetic effect can only be achieved intravenously, not epidurally or intrathecally. The efficacy of dexmedetomidine was similar to that of widely used agents, such as propofol, midazolam etc., but better than opioid analgesics. Moreover, application of dexmedetomidine reduced intraoperative requirement of fentanyl (Standard Mean Difference = -1.91, 95% CI: -3.20 to -0.62). CONCLUSIONS: The present meta-analysis indicates that dexmedetomidine shows superiority to placebo, but not to all other anesthetic agents on PONV. And this efficacy may be related to a reduced consumption of intraoperative opioids.

Efficacy of traditional Chinese medicine on sepsis: a systematic review and Meta-Analysis.

BACKGROUND: Traditional Chinese medicine (TCM) has been used for treatment of sepsis in China, but results still remain equivocal. To evaluate the safety and efficacy of TCM for sepsis, we conducted this Meta-analysis. METHODS: Databases searched included randomized controlled trials (RCTs) published in PubMed, Embase and Cochrane Central Register of Controlled Trials (CENTRAL) (up to December 2014). The studies included used routine therapy treating sepsis in the control group and TCM was added on that basis in the experimental group. Methodological quality was assessed by Cochrane criteria for risk of bias. RESULTS: Ten RCTs with 691 participants were identified and analyzed. In the meta-analysis, TCM plus routine therapy reduced the 28-day mortality compared to routine therapy alone, [RR = 0.67; 95% CI: 0.51~0.87; P = 0.002]; The decrease in length of ICU-stay [MD = -1.82; 95% CI: -2.60~-1.04; P<0.00001]; Acute physiology and chronic health evaluation system (APACHE II) score [MD = -2.95; 95% CI: -3.99~-1.91; P<0.00001]; Serum inflammatory factors concentration after treatment [SMD = -0.50; 95% CI:-0.68~-0.33; P<0.00001], including TNF-α [SMD = -0.61; 95% CI: -0.85~-0.38; P<0.00001] and IL-6 [SMD = -0.40; 95% CI: -0.75~-0.04; P = 0.03] in subgroup analysis all had statistical significance. CONCLUSION: Addition of TCM has better effects in participants with sepsis, while more high-quality studies are needed to draw firm conclusion.

The C-terminus of PARK2 is required for its self-interaction, solubility and role in the spindle assembly checkpoint.

PARK2, an ubiquitin ligase closely correlated with Parkinson's disease and cancer, has been shown to accumulate at centrosomes to ubiquitinate misfolded proteins accumulated during interphase. In the present study, we demonstrated that PARK2 can also localize to centrosomes in mitosis and that the protein does not fluctuate through the S- to M-phase. A C-terminal truncation of PARK2 resulted in a spindle assembly checkpoint defect, characterized by HeLa cells able to bypass mitotic arrest induced by nocodazole and form multinucleated cells when overexpressing the C-terminal truncated PARK2 protein. The spindle assembly checkpoint defect may be due to a change in a biochemical or structural property of PARK2 caused by the C-terminal truncation, resulting in a loss of self-interaction between PARK2 proteins.

Downregulation of Id1 by small interfering RNA in prostate cancer PC3 cells in vivo and in vitro.

Overexpression of helix-loop-helix protein-Id1 in prostate cancer correlates with tumor differentiation, and may play a key role in the development of prostate cancer. Hence, we inactivated the Id1 gene in prostate cancer cells in vitro and in vivo to determine whether the Id1 gene has therapeutic potential in the treatment of prostate cancer. A modified small interfering RNA (siRNA) was used to inactivate the Id1 gene in androgen-independent prostate cancer cell line PC3 and its xenografts in nude mice. Downregulation of Id1 by siRNA was confirmed by real-time PCR. The changes of cell viability, apoptosis and senescence rate in PC3 were individually detected. The mRNA and protein expression of Id1, PCNA and MMP2 in xenografted tumors was further individually assayed by real-time PCR and immunohistochemistry. The mRNA and protein expression of Id1 were obviously inhibited by the siRNA strategy in PC3 cells and their xenografts (P<0.01). The cell viability of PC3 was suppressed obviously (P<0.01); meanwhile, the apoptosis and senescence rates of PC3 were significantly increased by siRNA (P<0.01). Moreover, tumor growth was inhibited by the gene silencing of Id1. Two genes involved in proliferation (PCNA) and tumor invasion (MMP2) were found significantly decreased by siRNA in PC3 xenografts (P<0.01). Our results show that inactivation of Id1 can suppress cell proliferation, induce apoptosis and senescence in PC3. Silencing of the Id1 gene has an in-vivo preventive effect against the development of prostate cancer in a mouse model.