BCR signaling is required for posttransplant lymphoproliferative disease in immunodeficient mice receiving human B cells.

Posttransplant lymphoproliferative disease (PTLD) is a major therapeutic challenge that has been difficult to study using human cells because of a lack of suitable models for mechanistic characterization. Here, we show that ex vivo-differentiated B cells isolated from a subset of healthy donors can elicit pathologies similar to PTLD when transferred into immunodeficient mice. The primary driver of PTLD-like pathologies were IgM-producing plasmablasts with Epstein-Barr virus (EBV) genomes that expressed genes commonly associated with EBV latency. We show that a small subset of EBV+ peripheral blood-derived B cells expressing self-reactive, nonmutated B cell receptors (BCRs) expand rapidly in culture in the absence of BCR stimulation. Furthermore, we found that in vitro and in vivo expansion of EBV+ plasmablasts required BCR signaling. Last, treatment of immunodeficient mice with the BCR pathway inhibitor, ibrutinib, delays onset of PTLD-like pathologies in vivo. These data have implications for the diagnosis and care of transplant recipients who are at risk of developing PTLD.

A radical polymer membrane for simultaneous degradation of organic pollutants and water filtration.

Integrating reactive radicals into membranes that resemble biological membranes has always been a pursuit for simultaneous organics degradation and water filtration. In this research, we discovered that a radical polymer (RP) that can directly trigger the oxidative degradation of sulfamethozaxole (SMX). Mechanistic studies by experiment and density functional theory simulations revealed that peroxyl radicals are the reactive species, and the radicals could be regenerated in the presence of O2. Furthermore, an interpenetrating RP network membrane consisting of polyvinyl alcohol and the RP was fabricated to demonstrate the simultaneous filtration of large molecules in the model wastewater stream and the degradation of ~ 85% of SMX with a steady permeation flux. This study offers valuable insights into the mechanism of RP-triggered advanced oxidation processes and provides an energy-efficient solution for the degradation of organic compounds and water filtration in wastewater treatment.

Making waves: Magneto-responsive membranes with special and switchable wettability: new opportunities for membrane distillation.

Membrane distillation (MD) has promising potential in the water purification and wastewater treatment industries; however, fouling and wetting are the main obstacles to its commercialization, and higher fluxes and energy efficiencies are essential. Magneto-responsive membranes (MagMem) with integrated magnetic nanoparticles (MNPs) enable in situ fouling mitigation and switchable separation by nano-mixing or nano-heating, triggered by external magnetic fields, in a range of membrane processes, but not yet been demonstrated in MD. This perspective discussed the potential paths of MagMem utilization in MD based on the research status and dilemmas of MD. It can be envisioned that MagMem will lead to a paradigm shift in MD, especially by in situ fouling/wetting mitigation and enhancing energy efficiency via in-place actuation and localized heating by MNPs. Moreover, remotely controllable pore tuning and specific or switchable wettability can also be anticipated. Overall, MagMem provides attractive opportunities for advanced robust and efficient MD.

Fenton pretreatment to mitigate membrane distillation fouling during treatment of landfill leachate membrane concentrate: Performance and mechanism.

Membrane distillation (MD) is regarded as a promising technology for treatment of landfill leachate membrane concentrate (LLMC) due to its merits of low cost and high rejection of non-volatile components. However, the high concentration of pollutants in the wastewater will cause severe membrane fouling, resulting in costly cleaning and maintenance. In this study, Fenton pretreatment was applied to alleviate membrane fouling during MD treatment of LLMC. Compared to rapid flux decline of 88.2% at concentration factor (CF) of 3 for raw LLMC, MD flux only decreased by 17.4% at CF = 6 for treating acidic Fenton effluent without subsequent pH adjustment (Fe2+ and H2O2 concentration were 600 mg/L and 1457 mg/L, respectively). The pH neutralization of Fenton effluent or merely acidification of LLMC could not achieve such excellent fouling mitigation. It was concluded that both oxidation and acidification were critical and the collaboration mechanism was revealed to explain low membrane fouling. Firstly, Fenton oxidation removed organic contaminants, reduced the hydrophobicity of organic substances and increased the percentage of carboxylic group within LLMC. Thus, hydrophobic (HP) attraction was weakened but multivalent cation bridging became dominant fouling mechanism for neutral Fenton effluent. Then, acidification weakened multivalent cation bridging by inhibiting the deprotonation of carboxylic group, further mitigating membrane fouling. However, acidification of LLMC caused more severe organic fouling due to decrease in electrostatic (EL) repulsion. In addition to low membrane fouling, satisfactory total organic carbon (TOC) rejection rate of 96.23% was achieved during combined Fenton-MD process. This study demonstrated that Fenton pretreatment without pH neutralization could effectively alleviate MD fouling and elucidated the synergistic mechanism between oxidation and acidification for fouling mitigation.

Microbial density-dependent viral dynamics and low activity of temperate phages in the activated sludge process.

The ecological behavior of bacteriophages (phages), the most abundant biological entity in wastewater treatment systems, is poorly understood, especially that of temperate phages. Here, the temporal dynamics of lytic and temperate phages in a laboratory-scale activated sludge reactor with a sludge bulking issue was investigated using coupled sludge metagenomic and viromic analyses. The lysogenic fragments (prophages) identified were widely distributed in the reconstructed metagenome-assembled genomes (61.7%, n = 227). However, only 12.3% of the identified prophages experienced lysogenic-lytic switching, and the abundance contribution of prophages to free virus communities was only 0.02-0.3%, indicating low activity of temperate phages. Although the sludge community changed dramatically during reactor operation, no massive prophage induction events were detected. Statistical analyses showed strong correlations between sludge concentration and free virus and temperate phage communities, suggesting microbial density-dependent virus dynamics in the sludge microbiota.

New insight into soluble extracellular metabolites during sludge bulking process based on excitation-emission matrix spectroscopy and ultrahigh-performance liquid chromatography-mass spectrometry.

Soluble extracellular metabolites (SEM) produced by microorganisms might significantly change during sludge bulking, which is a major operational problem caused by the excessive growth of filamentous bacteria. However, knowledge remains limited about the dynamics and potential role of SEM in the bulking of sludge. In this study, filamentous bulking was simulated in a laboratory-scale reactor and changes to SEM characteristics during the bulking process were investigated using excitation-emission matrix spectroscopy and ultrahigh-performance liquid chromatography-mass spectrometry. SEM components changed significantly at different phases of sludge bulking. Changes in SEM were closely correlated with the structure of the bacterial community. Based on the EEM profiles, significant increases in fulvic acid-like and humic acid-like substances in SEM were observed with the development of filamentous bulking. The degree of humification in SEM showed a clear increasing trend. Untargeted extracellular metabolomic analysis showed that the intensity of berberine and isorhamnetin in SEM increased significantly during the bulking phase, which might synergistically facilitate the development of filamentous bulking.

Membrane cleaning in membrane distillation of reverse osmosis concentrate generated in landfill leachate treatment.

As a thermally induced membrane separation process, membrane distillation (MD) has drawn more and more attention to the advantages of treating hypersaline wastewaters, especially the concentrate from the reverse osmosis (RO) process. One of the major obstacles in widespread MD application is the membrane fouling. We investigated the feasibility of direct contact membrane distillation (DCMD) for landfill leachate reverse osmosis concentrate (LFLRO) brine treatment and systematically assessed the efficiency of chemical cleaning for DCMD after processing LFLRO brine. The results showed that 80% water recovery rate was achieved when processing the LFLRO brine by DCMD, but membrane fouling occurred during the DCMD process, and manifested as the decreasing of permeate flux and the increasing of permeate conductivity. Analysis revealed that the serious flux reduction was primarily caused by the fouling layer, which consisted of organic matter and inorganic salts. Five cleaning methods were investigated for membrane cleaning, including hydrogen chloride (HCl)-sodium hydroxide (NaOH), ethylene diamine tetraacetic acid (EDTA)-NaOH, citric acid, sodium hypochlorite (NaClO) and sodium dodecyl sulphate (SDS) cleaning. Among the chemical cleaning methods investigated, the 3 wt.% SDS cleaning showed the best efficiency at recovering the performance of fouled membranes.

Recovery and utilization of phosphorus from fruit and vegetable wastewater.

Excessive discharge of phosphorus into the water bodies is the key factor to cause eutrophication. The fruit and vegetable wastewater contains large amounts of phosphorus, and it may be directly discharged into water bodies, which has a great burden on the municipal sewage pipe network. Therefore, coagulation was used to remove phosphorus, recovered the phosphorus from the wastewater into the precipitate, and then the precipitate was pyrolyzed as an efficient adsorbent for phosphate removal. By comparing the adsorption effects of adsorbents (XT-300, XT-400, and XT-500) with pyrolysis temperatures of 300 °C, 400 °C, and 500 °C on phosphate in actual phosphorus-containing wastewater and simulated phosphorus-containing wastewater at different adsorbent dosage (4 g/L, 7 g/L, and 10 g/L), it was found that XT-300 had the best performance of adsorption, and the adsorption of phosphate was endothermic and obeyed the Langmuir isotherms and Elovich kinetics. The influence of pH, coexisting anions, and the structure of XT-300 revealed that the removal of phosphate was associated with electrostatic attraction, pore filling, but could not be determined whether it was related to surface precipitation. This study provides a way and method for the recovery and utilization of phosphorus in fruit and vegetable wastewater and proves that the synthetic adsorbent was an efficient phosphorus adsorbent. In the long term, we can try to use the adsorbent after phosphorus adsorption to promote plant growth in agricultural systems.

SMAD4 mutations and cross-talk between TGF-ß/IFNγ signaling accelerate rates of DNA damage and cellular senescence, resulting in a segmental progeroid syndrome-the Myhre syndrome.

SMAD4 encodes a member of the SMAD family of proteins involved in the TGF-ß signaling pathway. Potentially heritable, autosomal dominant, gain-of-function heterozygous variants of SMAD4 cause a rare developmental disorder, the Myhre syndrome, which is associated with a wide range of developmental and post-developmental phenotypes that we now characterize as a novel segmental progeroid syndrome. Whole-exome sequencing of a patient referred to our International Registry of Werner Syndrome revealed a heterozygous p.Arg496Cys variant of the SMAD4 gene. To investigate the role of SMAD4 mutations in accelerated senescence, we generated cellular models overexpressing either wild-type SMAD4 or mutant SMAD4-R496C in normal skin fibroblasts. We found that cells expressing the SMAD4-R496C mutant exhibited decreased proliferation and elevated expression of cellular senescence and inflammatory markers, including IL-6, IFNγ, and a TGF-ß target gene, PAI-1. Here we show that transient exposure to TGF-ß, an inflammatory cytokine, followed by chronic IFNγ stimulation, accelerated rates of senescence that were associated with increased DNA damage foci and SMAD4 expression. TGF-ß, IFNγ, or combinations of both were not sufficient to reduce proliferation rates of fibroblasts. In contrast, TGF-ß alone was able to induce preadipocyte senescence via induction of the mTOR protein. The mTOR inhibitor rapamycin mitigated TGF-ß-induced expression of p21, p16, and DNA damage foci and improved replicative potential of preadipocytes, supporting the cell-specific response to this cytokine. These findings collectively suggest that persistent DNA damage and cross-talk between TGF-ß/IFNγ pathways contribute to a series of molecular events leading to cellular senescence and a segmental progeroid syndrome.

Titanium nitride nanoparticle embedded membrane for photothermal membrane distillation.

To meet the increasing worldwide need for freshwater, it has become critical to exploit non-potable saline water. Solar membrane distillation (MD) is a promising desalination technique, which does not require conventional energy and can reduce the cost of water production. We developed a cost-effective and high-efficiency photothermal membrane that employs TiN nanoparticles as an absorber of sunlight and energy converter. Due to a strong photothermal effect, the solar energy efficiency significantly improved. With optimal membrane and MD operating conditions, we obtained an MD flux of 0.940 kg/m2∙h and a solar efficiency of 64.1% under 1.0 kW/m2 solar irradiation. Compared with a bare poly(vinylidene fluoride) (PVDF) membrane, 65.8% more pure water was produced. Furthermore, the temperature polarization encountered in the conventional MD process was relieved on account of the unique interfacial heating of the photothermal coating, which also contributed to the high solar efficiency. In addition, the membrane was quite stable and the permeate water was of a high, potable quality. The as-prepared photothermal membrane demonstrated a good performance and application prospects for solar MD.

Cell-to-Cell Variation in Gene Expression for Cultured Human Cells Is Controlled in Trans by Diverse Genes: Implications for the Pathobiology of Aging.

Cell-to-cell variation in gene expression increases among homologous cells within multiple tissues during aging. We call this phenomenon variegated gene expression (VGE). Long, healthy life requires robust and coordinated gene expression. We posit that nature may have evolved VGE as a bet-hedging mechanism to protect reproductively active populations. The price we may pay is accelerated aging. That hypothesis will require the demonstration that genetic loci are capable of modulating degrees of VGE. While loci controlling VGE in yeast and genes controlling interindividual variation in gene expression in Caenorhabditis elegans have been identified, there has been no compelling evidence for the role of specific genetic loci in modulations of VGE of specific targets in humans. With the assistance of a core facility, we used a customized library of siRNA constructs to screen 1,195 human genes to identify loci contributing to the control of VGE of a gene with relevance to the biology of aging. We identified approximately 50 loci controlling VGE of the prolongevity gene, SIRT1. Because of its partial homology to FOXO3A, a variant of which is enriched in centenarians, our laboratory independently confirmed that the knockdown of FOXF2 greatly diminished VGE of SIRT1 but had little impact upon the VGE of WRN. While the role of these VGE-altering genes on aging in vivo remains to be determined, we hypothesize that some of these genes can be targeted to increase functionality during aging.

Inactivating Mutations in Exonuclease and Polymerase Domains in DNA Polymerase Delta Alter Sensitivities to Inhibitors of dNTP Synthesis.

POLD1 encodes the catalytic subunit of DNA polymerase delta (Polδ), the major lagging strand polymerase, which also participates in DNA repair. Mutations affecting the exonuclease domain increase the risk of various cancers, while mutations that change the polymerase active site cause a progeroid syndrome called mandibular hypoplasia, deafness, progeroid features, and lipodystrophy (MDPL) syndrome. We generated a set of catalytic subunit of human telomerase (hTERT)-immortalized human fibroblasts expressing wild-type or mutant POLD1 using the retroviral LXSN vector system. In the resulting cell lines, expression of endogenous POLD1 was suppressed in favor of the recombinant POLD1. The siRNA screening of DNA damage-related genes revealed that fibroblasts expressing D316H and S605del POLD1 were more sensitive to knockdowns of ribonuclease reductase (RNR) components, RRM1 and RRM2 in the presence of hydroxyurea (HU), an RNR inhibitor. On the contrary, SAMHD1 siRNA, which increases the concentration of dNTPs, increased growth of wild type, D316H, and S605del POLD1 fibroblasts. Hypersensitivity to dNTP synthesis inhibition in POLD1 mutant lines was confirmed using gemcitabine. Our finding is consistent with the notion that reduced dNTP concentration negatively affects the cell growth of hTERT fibroblasts expressing exonuclease and polymerase mutant POLD1.

Anti-oil-fouling hydrophobic-superoleophobic composite membranes for robust membrane distillation performance.

As a promising thermally driven separation process, membrane distillation (MD) is capable of treating challenging wastewaters. However, the traditional hydrophobic membranes are vulnerable to fouling by non-polar contaminants owing to the strong hydrophobic-hydrophobic interactions. To address this problem, we developed novel anti-oil-fouling MD membranes in this study. The composite membranes with asymmetric wettability were fabricated through electrospinning polyacrylonitrile (PAN) fibrous coating on a hydrophobic polytetrafluoroethylene (PTFE) membrane, followed by hydrolyzing the PAN coating with ethylenediamine (EDA) and NaOH, respectively. These two composite membranes exhibited excellent underwater superoleophobicity, with the underwater oil contact angle >150°, which can be attributed to the fibrous and re-entrant surface structure and the optimized surface hydrophilicity of the electrospun coating. During MD process using saline and oily emulsion as feed, the composite membranes presented robust anti-oil-fouling performance, indicating by stable permeate flux and salt rejection. A novel oil-droplet adhesion force probe was introduced to quasi-quantitatively elucidate oil-membrane interaction and evaluate membrane fouling propensity, the force spectroscopy indicated that the fabricated composite membranes had fairly less attractive to crude oil compared with the PTFE membrane. Our research results suggest that the novel composite membranes with asymmetric wettability were competent to serve as an anti-oil-fouling MD membrane for desalinating challenging saline and oily wastewaters.

Hydrophobic nanostructured wood membrane for thermally efficient distillation.

Current membrane distillation (MD) is challenged by the inefficiency of water thermal separation from dissolved solutes, controlled by membrane porosity and thermal conductivity. Existing petroleum-derived polymeric membranes face major development barriers. Here, we demonstrate a first robust MD membrane directly fabricated from sustainable wood material. The hydrophobic nanowood membrane had high porosity (89 ± 3%) and hierarchical pore structure with a wide pore size distribution of crystalline cellulose nanofibrils and xylem vessels and lumina (channels) that facilitate water vapor transportation. The thermal conductivity was extremely low in the transverse direction, which reduces conductive heat transport. However, high thermal conductivity along the fiber enables efficient thermal dissipation along the axial direction. As a result, the membrane demonstrated excellent intrinsic vapor permeability (1.44 ± 0.09 kg m-1 K-1 s-1 Pa-1) and thermal efficiency (~70% at 60°C). The properties of thermal efficiency, water flux, scalability, and sustainability make nanowood highly desirable for MD applications.

Fabrication of PVDF nanofibrous hydrophobic composite membranes reinforced with fabric substrates via electrospinning for membrane distillation desalination.

To improve the mechanical properties of the electrospun nanofibrous membrane, the nonwoven fabrics and spacer fabrics were employed as support substrates to fabricate polyvinylidene fluoride (PVDF) nanofibrous composite membranes. The influences of the substrate on membrane morphology, hydrophobicity, pore size and pore size distribution, porosity, mechanical strength and permeability were comprehensive evaluated. The electrospun composite membranes had a three dimension bead-fiber interconnected open structure and a rough membrane surface. The membrane surface presented a multilevel re-entrant structure and all the water contact angles were above 140°. In contrast with the pure PVDF nanofibrous membrane, the stress at break and the elastic modulus of the composite membranes increased by 4.5-16 times and 17.5-37 times, respectively. Since the spacer fabrics had less resistance to mass transfer, the membranes composited with spacer fabrics exhibited greater permeate fluxes compared with the composite membranes with the nonwoven fabrics as substrates. During the membrane distillation test, the highest permeate flux was up to 49.3kg/m2/hr at the feed temperature of 80°C. The long-time and repeat operation of membrane distillation desalination indicated the fabricated membrane with a good resistance to scaling and wetting. The results suggested the potential of the electrospun composite membrane for membrane distillation application.

Development of a composite membrane with underwater-oleophobic fibrous surface for robust anti-oil-fouling membrane distillation.

Membrane fouling caused by non-polar foulants is a challenging problem for hydrophobic membranes, which hinders the industrial implementation of membrane distillation (MD). The hydrophilic coating can create a hydration layer at solid-water interface, thereby the hydrophilic surfaces are expected to supply a barrier inhibiting adhesion of hydrophobic foulants. Hence, it should be possible to develop anti-fouling composite membranes through constructing a hydrophilic skin layer onto hydrophobic MD membranes. Herein, we fabricated a novel composite membrane for excellent anti-oil-fouling performance in MD process by electrospinning polyetherimide (PEI) nanofibers on the hydrophobic polyvinylidene fluoride (PVDF) membrane surface, followed by cross-linking with ethanediamine (EDA). The membrane morphology and structure properties, surface zeta potential and wettability, thermal stability were all systematically characterized, and force spectroscopy was used to quasi-quantitatively evaluate oil-membrane adhesion force. Compared with the PVDF membrane, the PVDF/PEI-EDA composite membrane exhibited strong resistance to crude oil with underwater oil contact angle of about 145° and low oil-membrane adhesion force, which contributed to the stable performance during MD desalinating an oily and saline solution. The fabricated composite membrane with underwater-oleophobic fibrous surface can effectively mitigate oil-fouling in MD and promote MD to treat highly saline wastewater with high concentration of hydrophobic foulants.

Enhancement of energy utilization using nanofluid in solar powered membrane distillation.

Nanofluids have excellent solar energy utilization efficiency due to the localized surface plasmon resonance phenomenon. In this study, photothermal nanofluids were employed as the feed solution for energy harvesting in solar powered membrane distillation. Ten different nanofluids were compared and TiN (titanium nitride) was chosen following UV-Vis-NIR-waveband (ultraviolet-visible-near-infrared) optical absorption analysis, zeta potential measurement, and membrane distillation flux testing. Desalination experiments were conducted using a range of TiN concentrations and solar radiation powers. The results showed that water flux and solar energy utilization efficiency increased with increasing TiN content. Compared to the base fluid (35 g/L NaCl aqueous solution), flux increased from 0.47 to 0.74 kg/(m2∙h), while energy utilization efficiency improved from 32.1% to 50.5% for 100 mg/L TiN nanofluid. Flux also increased with the increasing of solar radiation power markedly. With 5 kW/m2 solar radiation power, the flux reached 2.77 kg/(m2∙h). Furthermore, the permeate water produced was of excellent quality contained less than 10 mg/L salinity when using 35 g/L NaCl feed solution. And no nanoparticles were detected transport through the membrane during the process. The nanofluid enhanced solar powered membrane distillation represents a promising perspective for better solar energy utilization.

Domestic wastewater treatment by forward osmosis-membrane distillation (FO-MD) integrated system.

In this study, real domestic wastewater treatment by forward osmosis-membrane distillation (FO-MD) integrated system was investigated in laboratory scale. The integrated membrane system presented a good separation performance and the removal efficiency of most contaminants in the domestic wastewater was higher than 90%. High molecular weight contaminants were completely removed, while a few low molecular weight contaminants permeated through the membrane. The FO membrane fouling layer mainly consisted of organic substances like polysaccharides and proteins, and was very loose and could be effectively removed by rinsing the membrane surface with tap water. By comparison, the MD membrane fouling was mainly induced by inorganic salts and was not as severe as that of the FO membrane. During 120 h continuous operation, the FO-MD integrated system exhibited satisfying performance stability and maintained a high water yield and high product water quality. The results indicated the potential of the FO-MD integrated system for municipal wastewater treatment in coastal cities, water purification and desalination.

Ozone mass transfer behaviors on physical and chemical absorption for hollow fiber membrane contactors.

To understand the mass transfer behaviors in hollow fiber membrane contactors, ozone fluxes affected by various conditions and membranes were investigated. For physical absorption, mass transfer rate increased with liquid velocity and the ozone concentration in the gas. Gas flow rate was little affected when the velocity was larger than the critical value, which was 6.1 × 10-3m/s in this study. For chemical absorption, the flux was determined by the reaction rate between ozone and the absorbent. Therefore, concentration, species, and pH affected the mass transfer process markedly. For different absorbents, the order of mass transfer rate was the same as the reaction rate constant, which was phenol, sodium nitrite, hydrogen peroxide, and oxalate. Five hydrophobic membranes with various properties were employed and the mass transfer behavior can be described by the Graetz-Lévèque equation for the physical absorption process. The results showed the process was controlled by liquid film and the gas phase conditions, and membrane properties did not affect the ozone flux. For the chemical absorption, gas film, membrane and liquid film affected the mass transfer together, and none of them were negligible.

Fabrication and performance of PET mesh enhanced cellulose acetate membranes for forward osmosis.

Polyethylene terephthalate mesh (PET) enhanced cellulose acetate membranes were fabricated via a phase inversion process. The membrane fabrication parameters that may affect the membrane performance were systematically evaluated including the concentration and temperature of the casting polymer solution and the temperature and time of the evaporation, coagulation and annealing processes. The water permeability and reverse salt flux were measured in forward osmosis (FO) mode for determination of the optimal membrane fabrication conditions. The optimal FO membrane shows a typical asymmetric sandwich structure with a mean thickness of about 148.2µm. The performance of the optimal FO membrane was tested using 0.2mol/L NaCl as the feed solution and 1.5mol/L glucose as the draw solution. The membrane displayed a water flux of 3.47L/(m(2)·hr) and salt rejection of 95.48% in FO mode. While in pressure retarded osmosis (PRO) mode, the water flux was 4.74L/(m(2)·hr) and salt rejection 96.03%. The high ratio of water flux in FO mode to that in PRO mode indicates that the fabricated membrane has a lower degree of internal concentration polarization than comparable membranes.