Tunable Surface Charge of Layered Double Hydroxide Membranes Enabling Osmotic Energy Harvesting from Anion Transport.

Membrane-based osmotic energy harvesting is a promising technology with zero carbon footprint. High-performance ion-selective membranes (ISMs) are the core components in such applications. Recent advancement in 2D nanomaterials opens new avenues for building highly efficient ISMs. However, the majority of the explored 2D nanomaterials have a negative surface charge, which selectively enhances cation transport, resulting in the underutilization of half of the available ions. In this study, ISMs based on layered double hydroxide (LDH) with tunable positive surface charge are studied. The membranes preferentially facilitate anion transport with high selectivity. Osmotic energy harvesting device based on these membranes reached a power density of 2.31 W m-2 under simulated river/sea water, about eight times versus that of a commercial membrane tested under the same conditions, and up to 7.05 W m-2 under elevated temperature and simulated brine/sea water, and long-term stability with consistent performance over a 40-day period. A prototype reverse electrodialysis energy harvesting device, comprising a pair of LDH membranes and commercial cation-selective membranes, is able to simultaneously harvest energy from both cations and anions achieving a power density of 6.38 W m-2 in simulated river/sea water, demonstrating its potential as building blocks for future energy harvesting systems.

Solvated Electrons Generated on the Surface of Na-SPHI for Boosting Visible Light Photocatalytic Hydrogen Evolution with Ultra-High AQE.

Enhancing the utilization of visible-light-active semiconductors with an excellent apparent quantum efficiency (AQE) remains a significant and challenging goal in the realm of photocatalytic water splitting. In this study, a fully condensed sulfur-doped poly(heptazine imide) metalized with Na (Na-SPHI) is synthesized by an ionothermal method by using eutectic NaCl/LiCl mixture as the ionic solvent. Comprehensive characterizations of the obtained Na-SPHI reveal several advantageous features, including heightened light absorption, facilitated exciton dissociation, and expedited charge transfer. More importantly, solvated electron, powerful reducing agents, can be generated on the surface of Na-SPHI upon irradiation with visible light. Benefiting from above advantage, the Na-SPHI exhibits an excellent H2 evolution rate of 571.8 µmol·h-1 under visible light illumination and a super-high AQE of 61.7% at 420 nm. This research emphasizes the significance of the solvated electron on the surface of photocatalyst in overcoming the challenges associated with visible light-driven photocatalysis, showcasing its potential application in photocatalytic water splitting.

Up-regulation of gasdermin C in mouse small intestine is associated with lytic cell death in enterocytes in worm-induced type 2 immunity.

"Taste-like" tuft cells in the intestine trigger type 2 immunity in response to worm infection. The secretion of interleukin-13 (IL-13) from type 2 innate lymphoid cells (ILC2) represents a key step in the tuft cell-ILC2 cell-intestinal epithelial cell circuit that drives the clearance of worms from the gut via type 2 immune responses. Hallmark features of type 2 responses include tissue remodeling, such as tuft and goblet cell expansion, and villus atrophy, yet it remains unclear if additional molecular changes in the gut epithelium facilitate the clearance of worms from the gut. Using gut organoids, we demonstrated that IL-4 and IL-13, two type 2 cytokines with similar functions, not only induced the classical type 2 responses (e.g., tuft cell expansion) but also drastically up-regulated the expression of gasdermin C genes (Gsdmcs). Using an in vivo worm-induced type 2 immunity model, we confirmed the up-regulation of Gsdmcs in Nippostrongylus brasiliensis-infected wild-type C57BL/6 mice. Consistent with gasdermin family members being principal effectors of pyroptosis, overexpression of Gsdmc2 in human embryonic kidney 293 (HEK293) cells triggered pyroptosis and lytic cell death. Moreover, in intestinal organoids treated with IL-4 or IL-13, or in wild-type mice infected with N. brasiliensis, lytic cell death increased, which may account for villus atrophy observed in worm-infected mice. Thus, we propose that the up-regulated Gsdmc family may be major effectors for type 2 responses in the gut and that Gsdmc-mediated pyroptosis may provide a conduit for the release of antiparasitic factors from enterocytes to facilitate the clearance of worms.

Improved Photo-Excited Carriers Transportation of WS2 -O-Doped-Graphene Heterostructures for Solar Steam Generation.

Two-dimensional (2D) transition metal dichalcogenides and graphene have revealed promising applications in optoelectronic and energy storage and conversion. However, there are rare reports of modifying the light-to-heat transformation via preparing their heterostructures for solar steam generation. In this work, commercial WS2 and sucrose are utilized as precursors to produce 2D WS2 -O-doped-graphene heterostructures (WS2 -O-graphene) for solar water evaporation. The WS2 -O-graphene evaporators demonstrate excellent average water evaporation rate (2.11 kg m-2  h-1 ) and energy efficiency (82.2%), which are 1.3- and 1.2-fold higher than WS2 and O-doped graphene-based evaporators, respectively. Furthermore, for the real seawater with different pH values (pH 1 and 12) and rhodamine B pollutants, the WS2 -O-graphene evaporators show great average evaporation rates (≈2.08 and 2.09 kg m-2  h-1 , respectively) for producing freshwater with an extremely low-grade of dye residual and nearly neutral pH values. More interestingly, due to the self-storage water ability of WS2 -O-graphene evaporators, water evaporation can be implemented without the presence of bulk water. As a result, the evaporation rate reaches 3.23 kg m-2  h-1 , which is ≈1.5 times higher than the regular solar water evaporation system. This work provides a new approach for preparing 2D transition metal dichalcogenides and graphene heterostructures for efficient solar water evaporation.

Lubricin (PRG-4) anti-fouling coating for surface-enhanced Raman spectroscopy biosensing: towards a hierarchical separation system for analysis of biofluids.

Surface-enhanced Raman Spectroscopy (SERS) is a powerful optical sensing technique that amplifies the signal generated by Raman scattering by many orders of magnitude. Although the extreme sensitivity of SERS enables an extremely low limit of detection, even down to single molecule levels, it is also a primary limitation of the technique due to its tendency to equally amplify 'noise' generated by non-specifically adsorbed molecules at (or near) SERS-active interfaces. Eliminating interference noise is thus critically important to SERS biosensing and typically involves onerous extraction/purification/washing procedures and/or heavy dilution of biofluid samples. Consequently, direct analysis within biofluid samples or in vivo environments is practically impossible. In this study, an anti-fouling coating of recombinant human Lubricin (LUB) was self-assembled onto AuNP-modified glass slides via a simple drop-casting method. A series of Raman spectra were collected using rhodamine 6G (R6G) as a model analyte, which was spiked into NaCl solution or unprocessed whole blood. Likewise, we demonstrate the same sensing system for the quantitative detection of L-cysteine spiked in undiluted milk. It was demonstrated for the first time that LUB coating can mitigate the deleterious effect of fouling in a SERS sensor without compromising the detection of a target analyte, even in a highly fouling, complex medium like whole blood or milk. This feat is achieved through a molecular sieving property of LUB that separates small analytes from large fouling species directly at the sensing interface resulting in SERS spectra with low background (i.e., noise) levels and excellent analyte spectral fidelity. These findings indicate the great potential for using LUB coatings together with an analyte-selective layer to form a hierarchical separation system for SERS sensing of relevant analytes directly in complex biological media, aquaculture, food matrix or environmental samples.

Relationship between the Co-Continuous Morphology of Immiscible Polymer Blends and the Structure of an In Situ Formed Graft Copolymer.

In order to get stable co-continuous morphology in immiscible polymer blends, besides reducing the interfacial tension, the compatibilizer should not only promote the formation of flat interface between different phases, but also not hinder the coalescence of the dispersed phase. Herein, the relationship between the morphology of the compatibilized polystyrene/nylon 6/styrene-maleic anhydride (PS/PA6/SMA) immiscible polymer blends and the structures of the in-situ formed SMA-g-PA6 graft copolymers as well as the processing conditions are studied. Two kinds of SMA are used: SMA28 (28 wt.% MAH) and SMA11 (11 wt.% MAH). After melt blending with PA6, the in-situ formed copolymer SMA28-g-PA6 has on average of four PA6 side chains, while that of SMA11-g-PA6 has only one. Dissipative particle dynamics simulation results indicate that both SMA28-g-PA6 copolymer and PS/PA6/SMA28 blends tend to form co-continuous structure, while those related to SMA11 intend to form sea-island morphologies. These results are correct only at relatively low rotor speed (60 rpm). When the rotor speed is higher (105 rpm), sea-island morphologies are obtained in SMA28 systems, while that for SMA11 ones are co-continuous. This indicates that higher shear stress can elongate the minor phase domains to form flat interfaces, while the SMA28-g-PA6 copolymers can be pulled out from the interface.

Boosting Osmotic Energy Conversion of Graphene Oxide Membranes via Self-Exfoliation Behavior in Nano-Confinement Spaces.

Introducing alien intercalations to sub-nanometer scale nanochannels is one desirable strategy to optimize the ion transportation of two-dimensional nanomaterial membranes for improving osmotic energy harvest (OEH). Diverse intercalating agents have been previously utilized to realize this goal in OEH, but with modest performance, complex operations, and physicochemical uncertainty gain. Here, we employ the self-exfoliation behavior of oxidative fragments (OFs) from graphene oxide basal plane under an alkaline environment to encapsulate detached OFs in nanochannels for breaking a trade-off between permeability and selectivity, boosting power density from 1.8 to 4.9 W m-2 with a cation selectivity of 0.9 and revealing a negligible decline in power density and trade-off during a long-term operation test (∼168 h). The strategy of membrane design, employing the intrinsically self-exfoliated OFs to decorate the nanochannels, provides an alternative and facile approach for ion separation, OEH, and other nano-fluidic applications.

2D Higher-Metal Nitride Nanosheets for Solar Steam Generation.

Higher-metal (HM) nitrides are a fascinating family of materials being increasingly researched due to their unique physical and chemical properties. However, few focus on investigating their application in a solar steam generation because the controllable and large-scale synthesis of these materials remains a significant challenge. Herein, it is reported that higher-metal molybdenum nitride nanosheets (HM-Mo5 N6 ) can be produced at the gram-scale using amine-functionalized MoS2 as precursor. The first-principles calculation confirms amine-functionalized MoS2 nanosheet effectively lengthens the bonds of MoS leading to a lower bond binding energy, promoting the formation of MoN bonds and production of HM-Mo5 N6 . Using this strategy, other HM nitride nanosheets, such as W2 N3 , Ta3 N5 , and Nb4 N5 , can also be synthesized. Specifically, under one simulated sunlight irradiation (1 kW m-2 ), the HM-Mo5 N6 nanosheets are heated to 80 °C within only ≈24 s (0.4 min), which is around 78 s faster than the MoS2 samples (102 s/1.7 min). More importantly, HM-Mo5 N6 nanosheets exhibit excellent solar evaporation rate (2.48 kg m-2  h-1 ) and efficiency (114.6%), which are 1.5 times higher than the solar devices of MoS2 /MF.

Enhanced Ion Sieving of Graphene Oxide Membranes via Surface Amine Functionalization.

Membranes based on two-dimensional (2D) nanomaterials have shown great potential to alleviate the worldwide freshwater crisis due to their outstanding performance of freshwater extraction from saline water via ion rejection. However, it is still very challenging to achieve high selectivity and high permeance of water desalination through precise d-spacing control of 2D nanomaterial membranes within subnanometer. Here, we developed functionalized graphene oxide membranes (FGOMs) with nitrogen groups such as amine groups and polarized nitrogen atoms to enhance metal ion sieving by one-step controlled plasma processing. The nitrogen functionalities can produce strong electrostatic interactions with metal ions and result in a mono/divalent cation selectivity of FGOMs up to 90 and 28.3 in single and binary solution, which is over 10-fold than that of graphene oxide membranes (GOMs). First-principles calculation confirms that the ionic selectivity of FGOMs is induced by the difference of binding energies between metal ions and polarized nitrogen atoms. Besides, the ultrathin FGOMs with a thickness of 50 nm can possess a high water flux of up to 120 mol m-2 h-1 without sacrificing rejection rates of nearly 99.0% on NaCl solution, showing an ultrahigh water/salt selectivity of around 4.31 × 103. Such facile and efficient plasma processing not only endows the GOMs with a promising future sustainable water purification, including ion separation and water desalination, but also provides a new strategy to functionalize 2D nanomaterial membranes for specific purposes.

Activation of intestinal tuft cell-expressed Sucnr1 triggers type 2 immunity in the mouse small intestine.

The hallmark features of type 2 mucosal immunity include intestinal tuft and goblet cell expansion initiated by tuft cell activation. How infectious agents that induce type 2 mucosal immunity are detected by tuft cells is unknown. Published microarray analysis suggested that succinate receptor 1 (Sucnr1) is specifically expressed in tuft cells. Thus, we hypothesized that the succinate-Sucnr1 axis may be utilized by tuft cells to detect certain infectious agents. Here we confirmed that Sucnr1 is specifically expressed in intestinal tuft cells but not in other types of intestinal epithelial cells, and demonstrated that dietary succinate induces tuft and goblet cell hyperplasia via Sucnr1 and the tuft cell-expressed chemosensory signaling elements gustducin and Trpm5. Conventional mice with a genetic Sucnr1 deficiency (Sucnr1-/-) showed diminished immune responses to treatment with polyethylene glycol and streptomycin, which are known to enhance microbiota-derived succinate, but responded normally to inoculation with the parasitic worm Nippostrongylus brasiliensis that also produces succinate. Thus, Sucnr1 is required for microbiota-induced but not for a generalized worm-induced type 2 immunity.

Band structure engineering of PTI in C-PTI/ZnO heterostructures for enhanced visible-light-driven H2 evolution.

Polytriazine imide (PTI), a triazine-based carbon nitride has a wider band gap and more positive conduction band (CB) potential compared to those of graphitic carbon nitride (g-C3N4). Therefore, it is highly desired to develop an effective strategy to optimize the band structure of PTI for the enhancement of the photocatalytic performance, especially upshift the conductive band potential. Here, a ternary C-PTI/ZnO (CPZ) photocatalyst was developed via a simple one-step molten salt method. In the obtained CPZ sample, the carbon ring in-plane connects to the triazine ring, leading to the formation of C-PTI nanosheets. The carbon ring incorporation not only efficiently narrows the band gap of PTI, but also shifts its conduction band potential negatively and accelerates the photogenerated electron transport. In addition, ZnO nanoparticles are well dispersed on the C-PTI nanosheets, further promoting the charge carriers transfer and separation. As a result, the CPZ sample presents a photocatalytic H2 evolution rate up to 52 µmol h-1 under visible light, which is 60 and 179 times higher than that of C-PTI and PTI, respectively.

The key structural features governing the free radicals and catalytic activity of graphite/graphene oxide.

The presence of unpaired electrons (radicals) due to structural defects is believed to contribute to the catalytic reactivity of carbon materials. Graphite oxide and graphene oxide (GO) consist of significant structural defects and hence are considered more reactive than graphite and graphene. However, the relationship between their radical content/reactivity and their physical and chemical structures remains unknown, which limits the fabrication of high efficiency carbon-based catalysts. In this work, we progressively oxidize graphite to achieve graphite oxide and GO with different levels of oxidation and different sizes. It is observed that a maximal radical content can be achieved on graphite oxide with a C/O ratio of ca. 3.0 and a thickness of around 50 nm. Such a graphite oxide contains about 45% of π bonds and 38% of oxygenated bonds, respectively. Thinner or thicker sheets have lower radical contents due to over or insufficient oxidation, respectively. Single GO sheets with high radical contents can only be produced through a combination of oxidation and reduction. The catalytic activity of the graphite/graphene oxide for phenol degradation was found to be linearly correlated to their radical contents. The observations are significant for the advancement of carbon-based metal-free catalysis.

Improving the Resolution and Accuracy of Groundwater Level Anomalies Using the Machine Learning-Based Fusion Model in the North China Plain.

The launch of GRACE satellites has provided a new avenue for studying the terrestrial water storage anomalies (TWSA) with unprecedented accuracy. However, the coarse spatial resolution greatly limits its application in hydrology researches on local scales. To overcome this limitation, this study develops a machine learning-based fusion model to obtain high-resolution (0.25°) groundwater level anomalies (GWLA) by integrating GRACE observations in the North China Plain. Specifically, the fusion model consists of three modules, namely the downscaling module, the data fusion module, and the prediction module, respectively. In terms of the downscaling module, the GRACE-Noah model outperforms traditional data-driven models (multiple linear regression and gradient boosting decision tree (GBDT)) with the correlation coefficient (CC) values from 0.24 to 0.78. With respect to the data fusion module, the groundwater level from 12 monitoring wells is incorporated with climate variables (precipitation, runoff, and evapotranspiration) using the GBDT algorithm, achieving satisfactory performance (mean values: CC: 0.97, RMSE: 1.10 m, and MAE: 0.87 m). By merging the downscaled TWSA and fused groundwater level based on the GBDT algorithm, the prediction module can predict the water level in specified pixels. The predicted groundwater level is validated against 6 in-situ groundwater level data sets in the study area. Compare to the downscaling module, there is a significant improvement in terms of CC metrics, on average, from 0.43 to 0.71. This study provides a feasible and accurate fusion model for downscaling GRACE observations and predicting groundwater level with improved accuracy.

Metal Ions Activate the Human Taste Receptor TAS2R7.

Divalent and trivalent salts exhibit a complex taste profile. They are perceived as being astringent/drying, sour, bitter, and metallic. We hypothesized that human bitter-taste receptors may mediate some taste attributes of these salts. Using a cell-based functional assay, we found that TAS2R7 responds to a broad range of divalent and trivalent salts, including zinc, calcium, magnesium, copper, manganese, and aluminum, but not to potassium, suggesting TAS2R7 may act as a metal cation receptor mediating bitterness of divalent and trivalent salts. Molecular modeling and mutagenesis analysis identified 2 residues, H943.37 and E2647.32, in TAS2R7 that appear to be responsible for the interaction of TAS2R7 with metallic ions. Taste receptors are found in both oral and extraoral tissues. The responsiveness of TAS2R7 to various mineral salts suggests it may act as a broad sensor, similar to the calcium-sensing receptor, for biologically relevant metal cations in both oral and extraoral tissues.

TRIM30 modulates Interleukin-22-regulated papillary thyroid Cancer cell migration and invasion by targeting Sox17 for K48-linked Polyubiquitination.

BACKGROUND: Interleukin-22 (IL-22) belongs to the IL-10 cytokine family and is mainly produced by activated Th1 cells. Although IL-22 expression is reported to be elevated in many cancers, and increased IL-22 expression correlates with tumor progression and poor prognosis, little is known about the role of IL-22 in papillary thyroid cancer (PTC). We previously demonstrated that IL-22 promotes PTC cell migration and invasion through the microRNA-595/Sox17 axis. METHODS: We used qRT-PCR and western blot to determine TRIM30, Sox17 and ß-catenin expression in PTC cells. Knockdown and overexpression were performed to detect the role of TRIM30/Sox17/ß-catenin axis on the migration and invasion PTC cells. Co-IP were used to determine the interaction between TRIM30 and Sox17. FINDINGS: In this study, we demonstrated that IL-22 triggered tripartite-motif protein 30 (TRIM30) association with Sox17, thereby mediating K48-linked polyubiquitination of Sox17. We then demonstrated that TRIM30 was a positive regulator of IL-22-regulated migration and invasion of PTC cells. We also found that IL-22 induced the transcriptional activity of ß-catenin and translocation of ß-catenin from cytosol to the nucleus. Upon investigating the mechanisms behind this event, we found that IL-22 disrupted Sox17/ß-catenin interactions by inducing TRIM30/Sox17 interactions, leading to promotion of ß-catenin-dependent signaling. The analysis of hundreds of clinical specimens revealed that IL-22, TRIM30 and ß-catenin levels were upregulated in PTC tissues compared with normal thyroid, and that their expression levels were closely correlated. Taken together, under the influence of IL-22, by sequestration of Sox17, TRIM30 promotes ß-catenin-dependent signaling that promotes PTC cell proliferation.

Adhesion and Self-Assembly of Lubricin (PRG4) Brush Layers on Different Substrate Surfaces.

Lubricin (LUB, aka PRG4), a mucin-like glycoprotein, is best known for the significant role it plays in the boundary lubrication, wear protection, and adhesion control systems in human joints. However, LUB exhibits a number of diverse and useful properties, including a remarkable ability to self-assemble into a telechelic brush structure onto virtually any substrate. This self-assembly behavior has spawned the emergence of numerous nontraditional applications of LUB coatings in numerous areas such as microfluidics, electrochemical sensors, contact lenses, antifouling surfaces, and bionic neural interfaces. Although LUB will readily self-assemble on most substrates, it has become apparent that the substrate has a significant influence on the LUB layer's demonstrated lubrication, antiadhesion, electrokinetic, and size-selective transport properties; however, investigations into LUB-substrate interactions and how they influence the self-assembled LUB layer structure remain a neglected aspect of LUB research. This study utilizes AFM force spectroscopy to directly assess the adhesion energy of LUB molecules adsorbed to a wide variety of different substrates which include inorganic, polymeric, and metallic materials. An analysis of the steric repulsive forces measured on approach provides a qualitative assessment of the LUB layer's mechanical modulus, related to the chain packing density, across substrates. These modulus measurements, combined with characteristic features and the dwell time dependence of the LUB adhesion forces provide insight into the organization and uniformity of the LUB brush structure. The results of these measurements indicate that LUB interactions with different substrates are highly variable and substrate-specific, resulting in a surprisingly broad spectrum of adhesion energies and layer properties (i.e., chain density, uniformity, etc.) which are not, themselves, correlated or easily predicted by substrate properties. In addition, this study finds exceptionally poor LUB adhesion to both mica and poly(methyl methacrylate) surfaces that remain widely used substrates for constructing model surfaces in fundamental tribology studies which may have significant implications for the findings of a number of foundational studies into LUB tribology and molecular synergies.

Self-healable poly(acrylic acid-co-maleic acid)/glycerol/boron nitride nanosheet composite hydrogels at low temperature with enhanced mechanical properties and water retention.

Many living tissues possess excellent mechanical properties and water retention which enable them to self-heal at room temperature even below the freezing temperature of water. To mimic the unique features of living tissue, a poly(acrylic acid-co-maleic acid) composite hydrogel with enhanced mechanical properties and remarkable water retention was fabricated under accessible conditions. The hydrogel is functionalized by amino group modified boron nitride nanosheets (BNNS-NH2)/glycerol and exhibits self-healing abilities at low temperature. The self-healing process occurs through the re-establishing of hydrogen bonds and metal coordination interactions at the damaged surfaces. Its anti-freezing abilities enable the hydrogel to self-heal at -15 °C, and the self-healing efficiency based on tensile strength reaches up to ∼70%. Moreover, glycerol also endows the hydrogel with long-lasting water retention, which remains a water content of ∼99 wt% for more than 30 days. Meanwhile, the simultaneous introduction of BNNS-NH2 and glycerol significantly improved the mechanical properties of the hydrogel, which displays great stretchability (∼474%), tensile strength (∼151.3 kPa), stiffness (Young's modulus of ∼62.75 kPa) and toughness (∼355.13 kJ m-3). It is anticipated that these novel hydrogels will develop many fields and be exploited for new applications in extensive external environments.

High-Performance Biscrolled MXene/Carbon Nanotube Yarn Supercapacitors.

Yarn-shaped supercapacitors (YSCs) once integrated into fabrics provide promising energy storage solutions to the increasing demand of wearable and portable electronics. In such device format, however, it is a challenge to achieve outstanding electrochemical performance without compromising flexibility. Here, MXene-based YSCs that exhibit both flexibility and superior energy storage performance by employing a biscrolling approach to create flexible yarns from highly delaminated and pseudocapacitive MXene sheets that are trapped within helical yarn corridors are reported. With specific capacitance and energy and power densities values exceeding those reported for any YSCs, this work illustrates that biscrolled MXene yarns can potentially provide the conformal energy solution for powering electronics beyond just the form factor of flexible YSCs.

High and Stable Ionic Conductivity in 2D Nanofluidic Ion Channels between Boron Nitride Layers.

Achieving a high rate of ionic transport through porous membranes and ionic channels is important in numerous applications ranging from energy storage to water desalination, but it still remains a challenge. Herein we show that ions can quickly pass through interlayer spaces in hydrated boron nitride (BN) membranes. Measurements of surface-charge governed ionic currents between BN nanosheets in a variety of salt solutions (KCl, NaCl and CaCl2) at low salt concentrations (<10-4 M) showed several orders of magnitude higher ionic conductivity compared to that of the bulk solution. Moreover, due to the outstanding chemical and thermal stability of BN, the ionic conduits remain fully functional at temperatures up to 90 °C. The BN conduits can operate in acidic and basic environments and do not degrade after immersing in solutions with extreme pH (pH ∼ 0 or 14) for 1 week. Those excellent properties make the BN ionic conduits attractive for applications in nanofluidic devices and membrane separation.

Type III Collagen Directs Stromal Organization and Limits Metastasis in a Murine Model of Breast Cancer.

Breast cancer metastasis is the leading cause of cancer-related deaths in women worldwide. Collagen in the tumor microenvironment plays a crucial role in regulating tumor progression. We have shown that type III collagen (Col3), a component of tumor stroma, regulates myofibroblast differentiation and scar formation after cutaneous injury. During the course of these wound-healing studies, we noted that tumors developed at a higher frequency in Col3(+/-) mice compared to wild-type littermate controls. We, therefore, examined the effect of Col3 deficiency on tumor behavior, using the murine mammary carcinoma cell line 4T1. Notably, tumor volume and pulmonary metastatic burden after orthotopic injection of 4T1 cells were increased in Col3(+/-) mice compared to Col3(+/+) littermates. By using murine (4T1) and human (MDA-MB-231) breast cancer cells grown in Col3-poor and Col3-enriched microenvironments in vitro, we found that several major events of the metastatic process were suppressed by Col3, including adhesion, invasion, and migration. In addition, Col3 deficiency increased proliferation and decreased apoptosis of 4T1 cells both in vitro and in primary tumors in vivo. Mechanistically, Col3 suppresses the procarcinogenic microenvironment by regulating stromal organization, including density and alignment of fibrillar collagen and myofibroblasts. We propose that Col3 plays an important role in the tumor microenvironment by suppressing metastasis-promoting characteristics of the tumor-associated stroma.