Flooding regimes alleviate lead toxicity and enhance phytostabilization of salix: Evidence from physiological responses and iron-plaque formation.

Aggravated metal pollution in wetland and riparian zones has become a global environmental issue, necessitating the identification of sustainable remediation approaches. Salix exhibits great potential as a viable candidate for metal(loid) remediation. However, the underlying mechanisms for its effectiveness in different flooding regimes with Pb pollution have not been extensively studied. In this study, fast-growing Salix×jiangsuensis 'J172' was selected and planted in different Pb polluted soils (control, 400 and 800 mg ∙ kg-1) under non-flooded and flooded (CF: continuous flooding and IF: intermittent flooding) conditions for 60 days. This study aimed to explore the effects of flooding on Salix growth performance, physiological traits, and the relationship between Pb uptake/translocation and root Fe plaques. Salix×jiangsuensis 'J172' exhibited excellent tolerance and adaptation to Pb pollution with a tolerance index (TI) exceeding 0.6, even at the highest Pb levels. Moreover, the TIs under flooded conditions were higher than that under non-flooded conditions, suggesting that flooding could alleviate Pb toxicity under co-exposure to Pb and flooding. Leaf malondialdehyde (MDA) exhibited a dose-dependent response to Pb exposure; however, CF or IF mitigated the oxidative damage induced by Pb toxicity with decreased MDA content (2.2-11.9%). The superoxide dismutase and peroxidase activities were generally enhanced by flooding, but combined stress (flooding and Pb) significantly decreased catalase activity. Pb was predominantly accumulated in Salix roots, and flooding markedly increased root Pb accumulation by 19.2-173.0% compared to non-flooded condition. Additionally, a significant positive correlation was observed between the iron (Fe) content of the root plaque and root Pb accumulation, indicating that the formation of Fe plaque on the root surface could enhance the phytostabilization of Pb in Salix. The current findings highlight that fast-growing woody plants are suitable for phyto-management of metal-polluted wetlands and can potentially minimize the risk of metal mobility in soils.

A solvent-template ethyl cellulose-polydimethylsiloxane crosslinking sponge for rapid and efficient oil adsorption.

Lipophilic adsorbents for oil-water separation are usually synthesized using the template method, in which hydrophobic materials are coated on a ready-made sponge. Herein, a novel solvent-template technique is used to directly synthesize a hydrophobic sponge, by crosslinking polydimethylsiloxane (PDMS) with ethyl cellulose (EC) which plays a vital role in the formation of 3D porous structure. The as-prepared sponge has advantages of strong hydrophobility, high elasticity, as well as excellent adsorption performance. In addition, the sponge can be readily decorated by nano-coatings. After the sponge was simply dipped in nanosilica, the water contact angle increases from 139.2° to 144.5°, and the maximum adsorption capacity for chiroform rises from 25.6 g/g to 35.4 g/g. The adsorption equilibrium can be reached within 3 min, and, the sponge can be regenerated by squeezing, without any change in hydrophobility or evident decline in capacity. The simulation tests of emulsion separation and oil-spill cleanup demonstrate that the sponge has great potential in oil-water separation.

Gasdermin E mediates resistance of pancreatic adenocarcinoma to enzymatic digestion through a YBX1-mucin pathway.

Pancreatic ductal adenocarcinoma (PDAC) originates from normal pancreatic ducts where digestive juice is regularly produced. It remains unclear how PDAC can escape autodigestion by digestive enzymes. Here we show that human PDAC tumour cells use gasdermin E (GSDME), a pore-forming protein, to mediate digestive resistance. GSDME facilitates the tumour cells to express mucin 1 and mucin 13, which form a barrier to prevent chymotrypsin-mediated destruction. Inoculation of GSDME-/- PDAC cells results in subcutaneous but not orthotopic tumour formation in mice. Inhibition or knockout of mucin 1 or mucin 13 abrogates orthotopic PDAC growth in NOD-SCID mice. Mechanistically, GSDME interacts with and transports YBX1 into the nucleus where YBX1 directly promotes mucin expression. This GSDME-YBX1-mucin axis is also confirmed in patients with PDAC. These findings uncover a unique survival mechanism of PDAC cells in pancreatic microenvironments.

Repeatable oil-water separation with a highly-elastic and tough amino-terminated polydimethylsiloxane-based sponge synthesized using a self-foaming method.

A 3D porous sponge based on amino-terminated polydimethylsiloxane (PDMS) and graphene oxide (GO) was prepared using a simple one-pot method under mild conditions. Condensing agents combined GO and PDMS with covalent bonds, and simultaneously acted as the pore-foaming agents. Scanning electron microscopy and Mercury intrusion porosimetry revealed that the joint action of GO and condensing agents contributes to the formation of the porous structure. Cyclic compression demonstrated high toughness and elasticity. No deformation occurs after 20 compression cycles at over 80% strain, owing to the assistance of dynamic hydrogen bonds. GO content significantly influences the mechanical strength, hydrophobicity, as well as adsorption capacity for oil. Notably, the sponge can be repeatedly used with a simple squeezing method, and the adsorption capacity can still reach 96.30% of the first adsorption after 30 cycles of adsorption. Besides, the sponge was used to adsorb oil on the seawater surface experimentally. The stable structure, high mechanical strength, and excellent adsorption property suggest the sponge be a promising material for the treatment of oil leakage and oily wastewater purification in practice. This self-foaming method can be a common method for fabricating porous and stable porous materials.

Prominent adsorption of Cr(VI) with graphene oxide aerogel twined with creeper-like polymer based on chitosan oligosaccharide.

Low-density aerogels with three-dimensional porous structure were synthesized using soluble chitosan oligosaccharide (COS) and graphene oxide (GO) as raw materials under mild conditions. Tetraethylenepentamine was used as the crosslinker of COS and the bridge between GO and COS, as well as the provider of functional groups. Structural characterizations revealed that crosslinked COS polymers firmly fixed on the surfaces of GO sheets and abundant amino groups homogeneously distributed in the pores. The adsorption capacity of the aerogel for Cr(VI) can reach up to 519.8 mg/g, while the adsorption efficiency for trace Cr(VI) adsorption can also reach 100% especially. The adsorption mechanism was investigated with X-ray photoelectron spectroscopy and zeta potential analysis. The superb properties suggested that the strategy of using COS as a raw material for the fabrication of adsorbents with controllable structure and form is meaningful.

Removal of Sr(II) from water with highly-elastic carboxymethyl chitosan gel.

A carboxymethyl chitosan (O-CMC) gel was prepared by crosslinking and functionalizing with ethylenediaminetetraacetic acid (EDTA) using a one-pot reaction under mild conditions. Structural characterizations have revealed that the prepared O-CMC/EDTA gel has 3D porous structure with abundant carboxyl groups distributed in the pores. The prepared O-CMC/EDTA gel was used to adsorb Sr(II) ions in water while X-ray photoelectron spectroscopy (XPS) was used to explore the adsorption mechanism. In order to analyze the adsorption process, we performed the adsorption kinetics and isotherms. The results show that the maximum adsorption capacity of O-CMC/EDTA for Sr (II) ions is about 105.81 mg/g at pH = 7. Notably, it exhibited fairly high compression elasticity due to multiple hydrogen bonds in the network. The showed no deformation after 30 continuous compression cycles. The ratio of O-CMC:EDTA significantly influences the adsorption property by affecting the crosslinking degree as well as the number of active sites. The high adsorption capacity, elasticity, and reusability have demonstrated that the prepared material is an effective and promising adsorbent for Sr(II) removal.

Publisher Correction: Chloroquine modulates antitumor immune response by resetting tumor-associated macrophages toward M1 phenotype.

In the originally published version of this Article, images in Fig. 5n were inadvertently replaced with duplicates of images in Fig. 5o during the production process. This has now been corrected in both the PDF and HTML versions of the Article.

Fibrin Stiffness Mediates Dormancy of Tumor-Repopulating Cells via a Cdc42-Driven Tet2 Epigenetic Program.

Dormancy is recognized as a critical biological event for tumorigenic cells surviving in an extremely harsh environment. Understanding the molecular process of dormancy can unlock novel approaches to tackle cancers. We recently reported that stem-like tumor-repopulating cells (TRC) sense mechanical signals and rapidly proliferate in a 90 Pa soft fibrin matrix. Here, we show that a stiff mechanical environment induces TRC dormancy via an epigenetic program initiated by translocation of Cdc42, a cytosolic regulator of mechanotransduction, into the nucleus, where it promotes transcription of hydroxymethylating enzyme Tet2. Tet2 epigenetically activated cell-cycle-inhibiting genes p21 and p27 to induce dormancy, but also caused downregulation of integrin ß3 to maintain dormancy. This stiffness-mediated dormancy was recapitulated in mouse models for both murine and primary human melanoma TRCs. These data identify an epigenetic program directed by mechanics, which drives highly tumorigenic TRCs to enter dormancy in a stiff mechanical environment.Significance: A mechanics-directed epigenetic program enables tumor-repopulating cells to enter dormancy in a stiff mechanical environment. Cancer Res; 78(14); 3926-37. ©2018 AACR.

Chloroquine modulates antitumor immune response by resetting tumor-associated macrophages toward M1 phenotype.

Resetting tumor-associated macrophages (TAMs) is a promising strategy to ameliorate the immunosuppressive tumor microenvironment and improve innate and adaptive antitumor immunity. Here we show that chloroquine (CQ), a proven anti-malarial drug, can function as an antitumor immune modulator that switches TAMs from M2 to tumor-killing M1 phenotype. Mechanistically, CQ increases macrophage lysosomal pH, causing Ca2+ release via the lysosomal Ca2+ channel mucolipin-1 (Mcoln1), which induces the activation of p38 and NF-κB, thus polarizing TAMs to M1 phenotype. In parallel, the released Ca2+ activates transcription factor EB (TFEB), which reprograms the metabolism of TAMs from oxidative phosphorylation to glycolysis. As a result, CQ-reset macrophages ameliorate tumor immune microenvironment by decreasing immunosuppressive infiltration of myeloid-derived suppressor cells and Treg cells, thus enhancing antitumor T-cell immunity. These data illuminate a previously unrecognized antitumor mechanism of CQ, suggesting a potential new macrophage-based tumor immunotherapeutic modality.

Tumor-Repopulating Cells Induce PD-1 Expression in CD8+ T Cells by Transferring Kynurenine and AhR Activation.

Despite the clinical successes fostered by immune checkpoint inhibitors, mechanisms underlying PD-1 upregulation in tumor-infiltrating T cells remain an enigma. Here, we show that tumor-repopulating cells (TRCs) drive PD-1 upregulation in CD8+ T cells through a transcellular kynurenine (Kyn)-aryl hydrocarbon receptor (AhR) pathway. Interferon-γ produced by CD8+ T cells stimulates release of high levels of Kyn produced by TRCs, which is transferred into adjacent CD8+ T cells via the transporters SLC7A8 and PAT4. Kyn induces and activates AhR and thereby upregulates PD-1 expression. This Kyn-AhR pathway is confirmed in both tumor-bearing mice and cancer patients and its blockade enhances antitumor adoptive T cell therapy efficacy. Thus, we uncovered a mechanism of PD-1 upregulation with potential tumor immunotherapeutic applications.

STAT3/p53 pathway activation disrupts IFN-ß-induced dormancy in tumor-repopulating cells.

Dynamic interaction with the immune system profoundly regulates tumor cell dormancy. However, it is unclear how immunological cues trigger cancer cell-intrinsic signaling pathways for entering into dormancy. Here, we show that IFN-ß treatment induced tumor-repopulating cells (TRC) to enter dormancy through an indolamine 2,3-dioxygenase/kynurenine/aryl hydrocarbon receptor/p27-dependent (IDO/Kyn/AhR/p27-dependent) pathway. Strategies to block this metabolic circuitry did not relieve dormancy, but led to apoptosis of dormant TRCs in murine and human melanoma models. Specifically, blocking AhR redirected IFN-ß signaling to STAT3 phosphorylation through both tyrosine and serine sites, which subsequently facilitated STAT3 nuclear translocation and subsequent binding to the p53 promoter in the nucleus. Upregulation of p53 in turn disrupted the pentose phosphate pathway, leading to excessive ROS production and dormant TRC death. Additionally, in melanoma patients, high expression of IFN-ß correlated with tumor cell dormancy. Identification of this mechanism for controlling TRC dormancy by IFN-ß provides deeper insights into cancer-immune interaction and potential new cancer immunotherapeutic modalities.