The antimicrobial peptide S100A8/A9 produced by airway epithelium functions as a potent and direct regulator of macrophage phenotype and function.

BACKGROUND: Elevated counts of alveolar macrophages and attenuated phagocytic capacity are associated with chronic obstructive pulmonary disease (COPD). Factors governing macrophage phagocytosis are poorly understood. In this study we aimed to compare the influence of airway epithelial cell secretions from individuals with COPD and without COPD (non-COPD) on macrophage phagocytic activity, and the role of antimicrobial peptides (AMPs). METHODS: Supernatants from non-COPD and COPD small airway epithelial cell (SAEC) cultures exposed to non-typeable Haemophilus influenzae (NTHi) were applied to human monocyte-derived macrophages (MDMs) to assess their influence on phagocytosis. SAECs were analysed for changes in AMP expression by quantitative reverse transcription PCR, and the influence of select AMPs on macrophage phenotype and function was assessed by flow cytometry and metabolic activity assay. RESULTS: Secretions from the apical and basolateral surface of NTHi-exposed SAECs from non-COPD donors elicited superior phagocytic capacity in MDMs. Moreover, NTHi exposure led to a rapid increase in the expression of a range of AMPs by non-COPD SAECs, but this response was delayed in COPD SAECs. We demonstrate that treatment with AMPs ß-defensin 2 and S100 calcium binding protein A8/S100 calcium binding protein A9 (S100A8/A9) improved the phagocytic capacity of MDMs. In-depth analysis of the influence of S100A8/A9 on MDMs revealed a role for this AMP in macrophage phenotype and function. Furthermore, we show that the expression of S100A8 and S100A9 is directly regulated by WNT/ß-catenin signalling, a known deregulated pathway in COPD. CONCLUSION: In conclusion, for the first time, we demonstrate that airway epithelium from patients with COPD has a reduced capacity to support the phagocytic function of macrophages in response to acute NTHi exposure, and we identify the WNT/ß-catenin signalling-modulated and epithelium-derived S100A8/A9 as a potent regulator of macrophage phenotype and function.

Exploring Nanosilver-Coated Hollow Fiber Microfiltration to Mitigate Biofouling for High Loading Membrane Bioreactor.

For the first time, a nanosilver-coated hollow fiber microfiltration (MF) was fabricated by a simple chemical reduction method, then tested for membrane biofouling mitigation study under extreme high mixed liquor suspended solid (MLSS) concentration for long term. This study presents a simple and novel technique to modify a commercially available MF membrane using silver nanoparticles (AgNPs) followed by an investigation of mitigating membrane biofouling potentials using this modified membrane to compare with an unmodified membrane for 60-day operation period. The modified membranes showed that AgNPs was attached to the MF-membrane successfully with a high density of 119.85 ± 5.42 mg/m2. After long-term testing of 60 days in membrane bioreactor with a MLSS concentration of 11,000 mg/L, specific flux of the AgNPs coated MF (AgNPs-MF) decreased 59.7%, while the specific flux of the unmodified membrane dropped 81.8%, resulted from the increase of transmembrane vacuum pressure for the AgNPs-MF was lower than that of the unmodified one. The resistance-in-series model was used to calculate the resistance coefficients of membrane modules, and the result showed that the cake layer resistance coefficient of the unmodified membrane was 2.7 times higher than that of the AgNPs-MF after the 60-day operation, confirming that AgNPs displayed great antimicrobial properties to mitigate membrane biofouling under such high MLSS.

Connective tissue cells, but not muscle cells, are involved in establishing the proximo-distal outcome of limb regeneration in the axolotl.

During salamander limb regeneration, only the structures distal to the amputation plane are regenerated, a property known as the rule of distal transformation. Multiple cell types are involved in limb regeneration; therefore, determining which cell types participate in distal transformation is important for understanding how the proximo-distal outcome of regeneration is achieved. We show that connective tissue-derived blastema cells obey the rule of distal transformation. They also have nuclear MEIS, which can act as an upper arm identity regulator, only upon upper arm amputation. By contrast, myogenic cells do not obey the rule of distal transformation and display nuclear MEIS upon amputation at any proximo-distal level. These results indicate that connective tissue cells, but not myogenic cells, are involved in establishing the proximo-distal outcome of regeneration and are likely to guide muscle patterning. Moreover, we show that, similarly to limb development, muscle patterning in regeneration is influenced by ß-catenin signalling.

Innovative hyper-thermophilic aerobic submerged membrane distillation bioreactor for wastewater reclamation.

For the first time, a hyper-thermophilic aerobic (>60 °C) bioreactor has been integrated with direct submerged membrane distillation (MD), highlighting its potential as an advanced wastewater treatment solution. The hyper-thermophilic aerobic bioreactor, operating up to 65 °C, is tailored for high organic removal, while MD efficiently produces clean water. Throughout the study, high removal rates of 99.5% for organic matter, 96.4% for ammonia, and 100% for phosphorus underscored the impressive adaptability of microorganisms to challenging hyper-thermophilic conditions and a successful combination with the MD process. Despite the extreme temperatures and substantial salinity accumulation reaching up to 12,532 µS/cm, the biomass of microorganisms increased by 1.6 times over a 92-day period, representing their remarkable resilience. The distillation flux ranged from 6.15 LMH to 8.25 LMH, benefiting from the temperature gradient in the hyper-thermophilic setting and the design of the tubular submerged MD membrane module. The system also excels in pH control, utilizing fewer alkali and nutritional resources than conventional systems. Meiothermus, Firmicutes, and Bacteroidetes, the three dominant species, played a crucial role, showcasing their significance in adapting to high salinity and decomposing organic matter.

Gamma-valerolactone biorefinery: Catalyzed birch fractionation and valorization of pulping streams with solvent recovery.

In this study, we propose a full gamma-valerolactone (GVL) organosolv biorefinery concept including the utilization of all pulping streams, solvent recovery, and preliminary material and energy balances. GVL is a renewable and non-toxic solvent that fractionates woody biomass. The silver birch chips were pulped (45-65 wt% GVL, 150 °C, 2 h) under a series of acid-catalyzed conditions (5-12 kg H2SO4/t), and the fully bleached pulp was spun into fibers by the IONCELL® process and knitted into the fabric. The dissolved lignin was precipitated by water from spent liquor (1:1) and processed into polyhydroxyurethane. Most of the dissolved hemicelluloses were in the form of xylose, therefore, the crystallization efficiency of xylose from spent liquor in the presence of residual GVL was studied. The GVL recovery rate in the lab column was 66%, however by increasing the number of equilibrium stages, 99% recovery could be achieved.

High-purity cellulose production from birch wood by γ-valerolactone/water fractionation and IONCELL-P process.

This study presents an environmentally friendly process to produce high-purity cellulose (dissolving pulp) from birch wood by combining γ-valerolactone (GVL)/water fractionation and ionic liquid treatment of pulp, IONCELL-P (IP). A paper grade pulp was produced from optimal GVL cook with a similar composition to birch kraft pulp and was bleached with ECF sequence before the hemicelluloses were removed using the IONCELL-P process. The purity of the GVL-IP pulp significantly exceeded that of commercial prehydrolysis kraft (PHK) and prehydrolysis soda-anthraquinone (PH-Soda-AQ) pulps. IONCELL-P extraction removed more than 90% of the hemicelluloses, resulting in a dissolving pulp with a purity of 96% and a high molecular mass fraction, 2.3 times higher than that of a conventional PHK pulp. GVL-IP pulps are suitable not only for regenerated cellulose fibers or films, but also for high-purity, high-viscosity cellulose acetate and ethers, which cannot be produced in an environmentally friendly way by conventional processes.

Active elimination of intestinal cells drives oncogenic growth in organoids.

Competitive cell interactions play a crucial role in quality control during development and homeostasis. Here, we show that cancer cells use such interactions to actively eliminate wild-type intestine cells in enteroid monolayers and organoids. This apoptosis-dependent process boosts proliferation of intestinal cancer cells. The remaining wild-type population activates markers of primitive epithelia and transits to a fetal-like state. Prevention of this cell-state transition avoids elimination of wild-type cells and, importantly, limits the proliferation of cancer cells. Jun N-terminal kinase (JNK) signaling is activated in competing cells and is required for cell-state change and elimination of wild-type cells. Thus, cell competition drives growth of cancer cells by active out-competition of wild-type cells through forced cell death and cell-state change in a JNK-dependent manner.

A novel thermophilic anaerobic granular sludge membrane distillation bioreactor for wastewater reclamation.

Membrane distillation (MD) has a high heat requirement. Integrating MD with thermophilic bioreactors could remedy this problem. A laboratory-scale thermophilic anaerobic granular sludge membrane distillation bioreactor (ThAGS-MDBR) was used to treat wastewater with a high organic loading rate (OLR). Waste heat from ThAGS was used directly for the MD process to reduce energy consumption. The result demonstrated that the ThAGS-MDBR system achieved a high-efficiency removal of chemical oxygen demand (more 99.5%) and NH4+-N (96.4%). Furthermore, the highest methane production from the proposed system was 332 mL/g CODremoved at OLR of 16 kg COD/m3/day. Specifically, an aggregate of densely packed diverse microbial communities in anaerobic granular sludge was the main mechanism for the enhancement of bioreactor tolerance with environmental changes. High-quality distillate water from ThAGS-MDBR was reclaimed in one step with total organic carbon less than 1.7 mg/L and electrical conductivity less than 120 µS/cm. Furthermore, the result of the DNA extraction kit recorded that Methanosaeta thermophila was a critical archaea for high COD removal and bioreactor stability.

Application of progressive freezing on forward osmosis draw solute recovery.

Progressive freezing is a solvent purification technology with low energy requirements and high concentration efficiency. Although these advantages make it a promising technology, the technique has never been explored for draw solution recovery for forward osmosis (FO). Hence, in this study, the progressive freezing process was used to concentrate three common diluted draw solutions: NaCl, MgCl2, and EDTA-2Na with different ice front speeds, stirring rates, and initial draw solution concentrations. Effective partition and intrinsic partition constants were also evaluated. The results reveal that the freezing process can achieve a draw solution recovery rate of 99.73%, 99.06%, and 98.65% with NaCl, MgCl2, and EDTA-2Na, respectively, using an ice front speed of 0.5 cm/h, a stirring rate of 2.62 m/s, and 30% of percentage of ice phase. Higher concentration efficiency for NaCl and MgCl2 was achieved due to the high solubility of NaCl and MgCl2 increased solute diffusion into the liquid phase solutions. The concentration factors for all three draw solutions exceeded 1.9, indicating that the draw solutes could be reused for the FO process. In addition, the two mass transfer coefficients depended on the ice front speed and the stirring rates were also obtained for scaling up the experiment in the future.

Chemical Recovery of γ-Valerolactone/Water Biorefinery.

We introduce the optimization of the pulping conditions and propose different chemical recovery options for a proven biorefinery concept based on γ-valerolactone (GVL)/water fractionation. The pulping process has been optimized whereby the liquor-to-wood (L:W) ratio could be reduced to 3 L/kg without compromising the pulp properties as raw material for textile fibers production. The recovery of the pulping solvent was performed through combinations of lignin precipitation by water addition, distillation at reduced pressure, and liquid CO2 extraction. With a two-step lignin precipitation coupled with vacuum distillation, more than 90% of lignin and GVL could be recovered from the spent liquor. However, a significant part of GVL remained unrecoverable in the residue, which was a highly viscous liquid with complicated phase behavior. The recovery by lignin precipitation combined with liquid CO2 extraction could recover more than 85% GVL and 90% lignin without forming any problematic residue as in the distillation process. The remaining GVL remained in the raffinate containing a low amount of lignin and other compounds, which can be further processed to isolate the GVL and improve the recovery rate.

Solubility of Organosolv Lignin in γ-Valerolactone/Water Binary Mixtures.

The solubility of lignin in a mixture of γ-valerolactone (GVL) and water at different weight ratios was measured using the Hildebrand solubility parameters. Based on the molecular structure of lignin, its solubility parameter (δ-value) was calculated as 25.5 MPa1/2 . The δ-value for aqueous GVL solvent increased from 23.1 MPa1/2 for pure GVL to 45.6 MPa1/2 for pure water. Therefore, the lignin solubility was predicted to increase with increasing GVL concentration in the aqueous mixture up to approximately 92-96 wt % of GVL. A ternary diagram describing the phase behavior of water-GVL-lignin mixtures at room temperature was constructed based on the experimental results. The three-component system exhibited a complex behavior with a liquid-liquid and solid-liquid-liquid phase split. The efficiency of the selected fractionation trials in a previous work was validated using the ternary solubility diagram. A promising recovery pathway and lignin isolation method were deduced from the results of this work.

Mechanical regulation of transcription controls Polycomb-mediated gene silencing during lineage commitment.

Tissue mechanics drive morphogenesis, but how forces are sensed and transmitted to control stem cell fate and self-organization remains unclear. We show that a mechanosensory complex of emerin (Emd), non-muscle myosin IIA (NMIIA) and actin controls gene silencing and chromatin compaction, thereby regulating lineage commitment. Force-driven enrichment of Emd at the outer nuclear membrane of epidermal stem cells leads to defective heterochromatin anchoring to the nuclear lamina and a switch from H3K9me2,3 to H3K27me3 occupancy at constitutive heterochromatin. Emd enrichment is accompanied by the recruitment of NMIIA to promote local actin polymerization that reduces nuclear actin levels, resulting in attenuation of transcription and subsequent accumulation of H3K27me3 at facultative heterochromatin. Perturbing this mechanosensory pathway by deleting NMIIA in mouse epidermis leads to attenuated H3K27me3-mediated silencing and precocious lineage commitment, abrogating morphogenesis. Our results reveal how mechanics integrate nuclear architecture and chromatin organization to control lineage commitment and tissue morphogenesis.

Patient-specific region-of-interest fluoroscopy device for X-ray dose reduction.

A region-of-interest (ROI) fluoroscopy device that provides an automatically generated ROI filter with an arbitrary shape, as well as digitally compensated images, was built and evaluated. ROI filters were generated by using a deformable attenuation material. Images were compensated by using a compensation ratio and a running average interpolation method. Image compensation parameters were predicted on the basis of the x-ray tube potential used. The image quality with and without an ROI filter was evaluated. This ROI fluoroscopic technique was shown to substantially reduce patient and operator radiation exposure without degrading image quality within the ROI.