In November 2021, 14 international travel-related severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.529 (omicron) variant of concern (VOC) patients were detected in South Korea. ...Epidemiologic investigation revealed community transmission of the omicron VOC. A total of 80 SARS-CoV-2 omicron VOC-positive patients were identified until December 10, 2021 and 66 of them reported no relation to the international travel. There may be more transmissions with this VOC in Korea than reported.
The switch between stem/progenitor cell expansion and differentiation is critical for organ homeostasis. The mammalian Hippo pathway effector and oncoprotein YAP expands undifferentiated ...stem/progenitor cells in various tissues. However, the YAP-associated transcription factors and downstream targets underlying this stemness-promoting activity are poorly understood. Here we show that the SRF-IL6 axis is the critical mediator of YAP-induced stemness in mammary epithelial cells and breast cancer. Specifically, serum response factor (SRF)-mediated binding and recruitment of YAP to mammary stem cell (MaSC) signature-gene promoters induce numerous MaSC signature genes, among which the target interleukin (IL)-6 is critical for YAP-induced stemness. High SRF-YAP/TAZ expression is correlated with IL6-enriched MaSC/basal-like breast cancer (BLBC). Finally, we show that this high SRF expression enables YAP to more efficiently induce IL6 and stemness in BLBC compared with luminal-type breast cancer. Collectively, our results establish the importance of SRF-YAP-IL6 signalling in promoting MaSC-like properties in a BLBC-specific manner.
mTORC1 plays a key role in autophagy as a negative regulator. The currently known targets of mTORC1 in the autophagy pathway mainly function at early stages of autophagosome formation. Here, we ...identify that mTORC1 inhibits later stages of autophagy by phosphorylating UVRAG. Under nutrient-enriched conditions, mTORC1 binds and phosphorylates UVRAG. The phosphorylation positively regulates the association of UVRAG with RUBICON, thereby enhancing the antagonizing effect of RUBICON on UVRAG-mediated autophagosome maturation. Upon dephosphorylation, UVRAG is released from RUBICON to interact with the HOPS complex, a component for the late endosome and lysosome fusion machinery, and enhances autophagosome and endosome maturation. Consequently, the dephosphorylation of UVRAG facilitates the lysosomal degradation of epidermal growth factor receptor (EGFR), reduces EGFR signaling, and suppresses cancer cell proliferation and tumor growth. These results demonstrate that mTORC1 engages in late stages of autophagy and endosome maturation, defining a broader range of mTORC1 functions in the membrane-associated processes.
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•mTORC1 binds and phosphorylates UVRAG•UVRAG Ser498 phosphorylation by mTORC1 enhances the UVRAG-RUBICON interaction•UVRAG Ser498 phosphorylation suppresses autophagosome and endosome maturation•Prevention of Ser498 phosphorylation enhances the lysosomal degradation of EGFR
mTORC1 is known to regulate early stages of autophagy. In this study, Kim et al. report that mTORC1 also regulates late stages of autophagy as well as endosomal maturation by phosphorylating UVRAG. This finding defines a broad range of mTORC1 functions in the membrane-associated processes.
Background Current guidelines for endoscopic management such as EMR and endoscopic submucosal dissection (ESD) in early gastric cancer (EGC) are in evolution, with broader indication criteria. ...Objective To determine the clinical outcomes of endoscopic treatment, based on absolute indication and extended indication criteria and endoscopic methods. Design Retrospective study. Setting Tertiary-care, academic medical center. Patients EMR or ESD was performed on 1627 cases of EGC in 1447 patients from July 1994 to January 2009. Intervention EMR and ESD. Main Outcome Measurements Clinical outcomes of EGC after EMR or ESD, based on the indication criteria. Results Although the complete resection rate was higher (95.9% vs 88.4%; P < .001), and the complication rate was lower (6.8% vs 9.8%; P = .054) in the absolute than in the extended indication group, there was no between-group difference in the local recurrence rate (0.9% vs 1.1%; P = .783) at a median follow-up period of 32 months (interquartile range 22-48 months). In the extended indication group, ESD resulted in a significantly higher complete resection rate than EMR (83.0% vs 91.1%; P = .006). Limitations Retrospective study. Conclusion ESD in the extended indication group showed acceptable clinical outcomes with a relatively high complete resection rate and a low local recurrence rate.
Phase‐change phenomena have been an attractive research theme for decades due to the dynamic transition of material properties providing extraordinary capabilities for versatile optical device ...applications. Even at the terahertz (THz) frequency regime, phase‐change materials (PCMs) promote the development of dynamic devices, especially when combined with a plasmonic approach delivering strong field enhancement and localization. According to the design of plasmonic metamaterials or hybrid composites, PCMs can actively modulate the electromagnetic properties of THz waves through thermal, electrical, and optical means. In turn, THz waves can affect the PCM properties in the nonlinear regime due to the intense field strength enhancement by plasmonic structures. Here, a few types of PCMs demonstrating promising potential in THz plasmonic applications are introduced. Starting from the best‐known transition metal oxide, vanadium dioxide (VO2), which possesses an insulator‐to‐metal phase transition near room temperature, superconductors, chalcogenides, ferroelectrics, liquid crystals, and liquid metals are covered along with their phase‐change properties and the control mechanisms infused with THz plasmonic applications. The corresponding recent progress presenting how PCMs combined with plasmonic structures can demonstrate effective THz modulation is reviewed. This general overview may provide a better understanding of dynamic THz plasmonics and new ideas for future THz technology.
Phase‐change materials for active terahertz metamaterials are introduced. Recent advances on dynamic terahertz modulation utilizing phase‐change materials combined with plasmonic nano/microstructures are summarized, along with the phase control methods and the designs. The versatility of phase change materials proposes promising future perspectives for the development of multifunctional terahertz devices.
The control of membrane morphology and microstructure is crucial to improve the separation performance of molecular‐sieve membranes. This can be enabled by making thin, dense, and uniform ...seed‐crystal coatings, which are then intergrown into continuous membranes. Herein, we show a novel and simple floating particle coating method can give closely packed monolayers of zeolite nanosheets on nonporous or porous supports. The zeolite nanosheet monolayer is formed at the air–water interface in a conical Teflon trough. As the water in the trough is drained, the monolayer is deposited on a support placed below. Membranes prepared by gel‐free secondary growth of the nanosheets deposited by this method show unprecedented ultra‐selective performance for separation of para‐ from ortho‐xylene (separation factor >10 000).
The membrane drain: A uniform and dense MFI nanosheet monolayer from an air–water interface is transferred onto a porous support by a new monolayer deposition method using a conical trough which drains. The high‐coverage nanosheet seed coating, and subsequent intergrowth gives a thin, oriented, and low‐defect‐density membrane, which exhibits ultra‐selective (separation factor >10 000) performance for xylene isomer separation.
Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is a complex gastrointestinal disorder with a multifactorial etiology, including environmental triggers, autoimmune ...mechanisms, and genetic predisposition. Despite advancements in therapeutic strategies for IBD, its associated mortality rate continues to rise, which is often attributed to unforeseen side effects of conventional treatments. In this context, we explored the potential of
extract (ECE), derived from an edible marine alga known for its anti-inflammatory and antioxidant properties, in mitigating IBD. This study investigated the effectiveness of ECE as a preventive agent in a murine model of dextran sulfate sodium (DSS)-induced colitis. Our findings revealed that pretreatment with ECE significantly ameliorated colitis severity, as evidenced by increased colon length, reduced spleen weight, and histological improvements demonstrated by immunohistochemical analysis. Furthermore, ECE significantly attenuated the upregulation of inflammatory cytokines and mediators and the infiltration of immune cells known to be prominent features of colitis in mice. Notably, ECE alleviated dysbiosis of intestinal microflora and aided in the recovery of damaged intestinal mucosa. Mechanistically, ECE exhibited protective effects against pathogenic colitis by inhibiting the NLRP3/NF-κB pathways known to be pivotal regulators in the inflammatory signaling cascade. These compelling results suggest that ECE holds promise as a potential candidate for IBD prevention. It might be developed into a functional food for promoting gastrointestinal health. This research sheds light on the preventive potential of natural compounds like ECE in the management of IBD, offering a safer and more effective approach to combating this challenging disease.
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Ulcerative colitis (UC) is an inflammatory bowel disease accompanied by abdominal pain, diarrhea, and rectal bleeding. The aim of this study was to investigate whether puerarin, one ...of the main components of the root of Pueraria lobata, exerts anti-inflammatory and anti-oxidative effects against UC. To examine the anti-inflammatory and anti-oxidative effects of puerarin against colitis, we used a mouse model of dextran sulfate sodium (DSS)-induced colitis. Administration of puerarin alleviated colon shortening, pathological damage to the colon, and myeloperoxidase (MPO) activity. Puerarin significantly inhibited inflammation through the down-regulation of nuclear factor-κB (NF-κB) and the secretion of pro-inflammatory mediators. Moreover, puerarin showed anti-oxidative effects through the regulation of the expression of the NF-E2 p45-related factor 2 (Nrf2) pathway and antioxidant enzymes. Puerarin inhibited intestinal epithelial barrier dysfunction by increasing the expression of tight junction proteins. These results suggest that puerarin has anti-inflammatory and anti-oxidative effects in the mouse model of colitis.
Terahertz (THz) shielding becomes increasingly important with the growing development of THz electronics and devices. Primarily materials based on carbon nanostructures or polymer–carbon ...nanocomposites have been explored for this application. Herein, significantly enhanced THz shielding efficiencies for 2D titanium carbide (Ti3C2 MXene) thin films with nanoscale THz metamaterials are presented. Nanoscale slot antenna arrays with strong resonances at certain frequencies enhance THz electromagnetic waves up to three orders of magnitude in transmission, which in turn enormously increases the shielding performance in combination with MXene films. Drop‐casting of a colloidal solution of MXene (a few micrograms of dry material) can produce an ultrathin film (several tens of nanometers in thickness) on a slot antenna array. Consequently, THz waves strongly localized in the near‐field regime by the slot antenna undergo enhanced absorption through the film with a magnified effective refractive index. Finally, the combination of an ultrathin MXene film and a nano‐metamaterial shows excellent shielding performance in the THz range.
Greatly enhanced terahertz (THz) shielding efficiencies are presented using nano‐scale THz metamaterials coated by ultrathin film of 2D titanium carbide (MXene). The THz nano‐metamaterials combined with Ti3C2Tx efficiently block incident THz electromagnetic waves up to three orders of magnitude in transmission, by simply repetitive drop‐casting of MXene thin film.
ULK1 (unc-51 like autophagy activating kinase 1), the key mediator of MTORC1 signaling to autophagy, regulates early stages of autophagosome formation in response to starvation or MTORC1 inhibition. ...How ULK1 regulates the autophagy induction process remains elusive. Here, we identify that ATG13, a binding partner of ULK1, mediates interaction of ULK1 with the ATG14-containing PIK3C3/VPS34 complex, the key machinery for initiation of autophagosome formation. The interaction enables ULK1 to phosphorylate ATG14 in a manner dependent upon autophagy inducing conditions, such as nutrient starvation or MTORC1 inhibition. The ATG14 phosphorylation mimics nutrient deprivation through stimulating the kinase activity of the class III phosphatidylinositol 3-kinase (PtdIns3K) complex and facilitates phagophore and autophagosome formation. By monitoring the ATG14 phosphorylation, we determined that the ULK1 activity requires BECN1/Beclin 1 but not the phosphatidylethanolamine (PE)-conjugation machinery and the PIK3C3 kinase activity. Monitoring the phosphorylation also allowed us to identify that ATG9A is required to suppress the ULK1 activity under nutrient-enriched conditions. Furthermore, we determined that ATG14 phosphorylation depends on ULK1 and dietary conditions in vivo. These results define a key molecular event for the starvation-induced activation of the ATG14-containing PtdIns3K complex by ULK1, and demonstrate hierarchical relations between the ULK1 activation and other autophagy proteins involved in phagophore formation.
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